10-12G/A

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Amendment No.1

to

FORM 10

GENERAL FORM FOR REGISTRATION OF SECURITIES

Pursuant to Section 12(b) or (g) of The Securities Exchange Act of 1934 

 

NuGenerex Immuno-Oncology, Inc.

(Exact name of registrant as specified in its charter)

Delaware	04-3208418
(State or other jurisdiction of incorporation or organization)	(I.R.S. Employer Identification No.)

10102 USA Today Way, Miramar, Florida 33025

(Address of principal executive offices) (Zip code)

(416) 364-2551

(Registrant’s telephone number, including area code)

Securities to be Registered Under Section 12(b) of the Act: None

Securities to be Registered Under Section 12(g) of the Act:

Common Stock, Par Value $0.001

(Title of class)

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

Large accelerated filer	☐	Accelerated filer	☐
Non-accelerated filer	☐	Smaller reporting company	☒
		Emerging growth company	☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐

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INDEX TO FORM 10

Introductory Comment	3
Cautionary Note Regarding Forward-Looking Statements	3
Item 1.                   Business	4
Item1A.                 Risk Factors	12
Item 2.                   Financial Information	12
Item 3.                   Properties
Item 4.                   Security Ownership of Certain Beneficial Owners and Management	15
Item 5.                   Directors and Executive Officers	15
Item 6.                   Executive Compensation	19
Item 7.                   Certain Relationships and Related Transactions, and Director Independence	19
Item 8.                   Legal Proceedings	19
Item 9.                   Market Price of and Dividends on the Registrant's Common Equity and Related Stockholder Matters	20
Item 10.                 Recent Sales of Unregistered Securities	20
Item 11.                 Description of Registrant's Securities to be Registered	20
Item 12.                 Indemnification of Directors and Officers	21
Item 13.                 Financial Statements and Supplementary Data	22
Item 14.                 Changes in and Disagreements with Accountants on Accounting and Financial Disclosure	22
Item 15.                 Financial Statements and Exhibits	22

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Introductory Comment

We are filing this General Form for Registration of Securities on Form 10 to register our common stock pursuant to Section 12(g) of the Exchange Act. Once this registration statement is deemed effective, we will be subject to the requirements of Section 13(a) under the Exchange Act, which will require us to file annual reports on Form 10-K (or any successor form), quarterly reports on Form 10-Q (or any successor form), and current reports on Form 8-K, and we will be required to comply with all other obligations of the Exchange Act applicable to issuers filing registration statements pursuant to Section 12(g) of the Exchange Act.

Throughout this registration statement, unless the context otherwise requires, the terms “NGIO,” “we,” “us,” “our,” the “Company” and “our company” refer to NuGenerex Immuno-Oncology, Inc., a Delaware corporation, formerly Antigen Express, Inc.

Cautionary Note Regarding Forward-Looking Statements

This registration statement on Form 10 contains “forward-looking statements” concerning our future results, future performance, intentions, objectives, plans, and expectations, including, without limitation, statements regarding the plans and objectives of management for future operations, any statements concerning our proposed services, any statements regarding future economic conditions or performance, and any statements of assumptions underlying any of the foregoing. All forward-looking statements included in this document are made as of the date hereof and are based on information available to us as of such date. We assume no obligation to update any forward-looking statements. In some cases, forward-looking statements can be identified by the use of terminology such as “may,” “will,” “expects,” “plans,” “probable,” “possible,” “anticipates,” “intends,” “believes,” “estimates,” “should,” “potential,” or “continue,” or the negative thereof or other comparable terminology. Although we believe that the expectations reflected in the forward-looking statements contained herein are reasonable, there can be no assurance that such expectations or any of the forward-looking statements will prove to be correct, and actual results could differ materially from those projected or assumed in the forward-looking statements. Future financial condition and results of operations, as well as any forward-looking statements are subject to inherent risks and uncertainties, including those discussed elsewhere in this Form 10.

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Item 1. Business.

Corporate History

NuGenerex Immuno-Oncology, Inc., a Delaware corporation formed on October 8, 1993 and formerly known as Antigen Express, Inc. (“NGIO”) is an oncology company focused on the modulation of the immune system to treat cancer. To that end, we are developing immunotherapeutic products and vaccines based on our proprietary, patented platform technology, Ii-Key. The Ii-Key is a peptide derived from the major histocompatibility complex (“MHC”) Class II associated invariant chain (Ii) that regulates the formation, trafficking, and antigen-presenting functions of MHC class II complexes, essential for the activation of T cells in the immune response. T cells recognize antigenic epitopes when they are ‘presented’ to them by specific molecules, termed (MHC) on the surface of infected or malignant cells. This interaction activates the T cells, stimulating a multicellular cascade of actions that eliminates the diseased cell and protects against future disease recurrence.

All of our capital stock was acquired by Generex Biotechnology Corporation (“Generex”) in August of 2003. Generex currently owns approximately 90.41% of our common stock.

Business Overview

NGIO is an oncology company focused on the modulation of the immune system to treat cancer. To that end, we are developing immunotherapeutic products and vaccines based on our proprietary, patented platform technology, Ii-Key. The Ii-Key is a peptide derived from the major histocompatibility complex (MHC) Class II associated invariant chain (Ii) that regulates the formation, trafficking, and antigen-presenting functions of MHC class II complexes, essential for the activation of T cells in the immune response. T cells recognize antigenic epitopes when they are ‘presented’ to them by specific molecules, termed (MHC) on the surface of infected or malignant cells. This interaction activates the T cells, stimulating a multicellular cascade of actions that eliminates the diseased cell and protects against future disease recurrence. We have developed a number of Ii-Key Hybrid peptides for the immunotherapeutic targeting of tumor associated antigens (TAAs) in cancer and for vaccines against infectious diseases. Ii-Key hybrid peptides can also be used to selectively activate Th2 responses and thereby induce tolerance to antigens involved in harmful immune reactions, with therapeutic applications in major market segments including diabetes, arthritis, allergy, transplant rejection, and other autoimmune diseases. We have been established to not only to advance the Ii-Key core technology, but also to expand our portfolio in the field of immunotherapy and personalized medicine through partnerships and acquisitions.

AE37 – Ii-Key/HER2/neu Hybrid Immunotherapeutic Vaccine

NGIO is currently developing AE37 (Ii-Key-HER2/neu peptide immunotherapeutic vaccine) for the treatment of cancer, including breast, bladder, prostate, and potentially other indications. In 2005 and 2006, the company conducted a Phase I trial of AE37 in breast cancer. NGIO has also conducted a Phase II trial of AE37 for prevention of recurrence of breast cancer. The company is currently working with the National Surgical Bowel & Breast Project (NSABP) to conduct a Phase II trial of AE37 in combination with Merck’s Keytruda (pembrolizumab) for the treatment of triple negative breast cancer. Details of the AE37 clinical trials are provided in the following paragraphs.

Our most advanced immunotherapy vaccine is AE37, an Ii-Key-Hybrid molecule that contains the HER2/neu antigenic peptide linked to the Ii-Key to enhance immune stimulation against HER2, which is expressed in numerous cancers, including breast, prostate, and bladder cancers. In 2006 we completed a Phase I clinical trial of AE37 in breast cancer, including a phase Ib safety and immunology study of AE37 in combination with GM-CSF in 16 breast cancer patients who had completed all first-line therapies and who were disease-free at the time of enrollment to the study (Holmes et al. Results of the first phase I clinical trial of the novel Ii-Key hybrid preventive HER-2/neu peptide (AE37) vaccine. J Clin Oncol 2008;26:3426-33). The subjects of the trial were given intradermally 500 micrograms of AE37 and 125 micrograms of GM-CSF or 1000 micrograms AE37 without GM-CSF. The phase I trial was conducted by Dr. George Peoples, MD from 2005 through 2006 at the Walter Reed Army Medical Center in Washington D.C. Both the primary endpoint of safety and the secondary endpoint of immunogenicity were achieved. No serious adverse events were reported in this trial.

In April of 2007 we commenced  a Phase IIb trial of AE37 in combination with GM-CSF on 300 patients that was completed in November of 2019 in the prevention of cancer recurrence in women who were at high risk of recurrence after undergoing successful primary standard of care breast cancer therapies and were disease free at time of enrollment. The dosages of 500 microns and 125 microns was administered intradermally. The trial was conducted by Dr. Elizabeth A. Mittendorf, MD, F.A.C.S. at 14 sites both in the US and Europe.  The subjects of the trial were given intradermally 500 micrograms of AE37 combined with 125 micrograms GM-CSF. Both the primary endpoint of safety and the secondary endpoint of immunogenicity were achieved.  The results of the Phase IIb clinical trial for the prevention of recurrence of breast cancer were published on April 22, 2020 in the peer-reviewed journal, Breast Cancer Research & Treatment (the “Peer-reviewed Publication”). In the AE37 arm of this trial, the investigators found that patients with advanced stage, HER2 low-expression, and triple negative breast cancer may benefit from AE37 vaccination, and those with both advanced stage and low HER2 expression have a significant clinical benefit to AE37 vaccination, demonstrating earlier DFS plateau may be maintained for up to the ten years of follow-up. There were two serious adverse events in this phase II trial. There was a grade 3 serious adverse event reported for a patient in the GM-CSF arm of the trial that had a drop in ejection fraction from 50% to 45% more than two months after completion of protocol treatments. It was noted that the patient had received one full year of Herceptin adjuvant treatment prior to starting on any protocol treatments, and had reported a similar ejection fraction decline episode in while on Herceptin treatment. Another patient in the AE37 plus GM-CSF arm had serious, unexpected grade 2 bladder pain that the investigator considered serious. The investigators concluded in the Peer-reviewed publication that the similar toxicity profiles between the AE37/GM-CSF treatment and GM-CSF alone control groups indicate that the majority of the toxicity can be attributed to the immunoadjuvant, GM-CSF.

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Based on the results from the Phase II trial described above, NGIO entered into a Clinical Trial Collaboration and Supply Agreement (the “Collaboration Agreement”) on June 28, 2017 with Merck Sharpe & Dohme B.V. (“Merck”) to evaluate the safety and efficacy of AE37 in combination with the anti-PD-1 therapy, KEYTRUDA (pembrolizumab) in patients with metastatic triple-negative breast cancer. NGIO is sponsoring the NSABP FB-14 clinical trial protocol. Since then, the Company has initiated the study at 5 clinical research sites, and completed the first 3-patient safety cohort to allow for expanded enrollment. The Phase II trial began enrolling patients in September of 2019, and is expected to enroll 29 patients; however, the SARS-CoV-2 epidemic has temporarily paused enrollment. The Collaboration Agreement provides for NGIO to sponsor the study and to make the regulatory filings for approval of the trial. Merck will supply NGIO with Keytruda® for the trial. NGIO will provide its AE37 cancer vaccine and will generally be responsible for the costs of the trial. All Clinical Data shall be jointly owned by NGIO and Merck. Merck and NGIO assigned to each other an undivided one-half interest in, to and under the Clinical Data. The trial will require additional funding estimated at roughly $1.5 million over the next three years. In connection with the Collaboration Agreement, on November 20, 2018, NGIO entered into a Clinical Trial Agreement (the “Clinical Trial Agreement”) with NSABP Foundation, Inc. (“NASBP”), which provides for NASBP conducting a Phase II trial clinical trial on the safety and efficacy of AE37 in combination with KEYTRUDA (pembrolizumab) as described above. NGIO has also signed a Pharmacovigilance Agreement among Merck, NSABP and NGIO to ensure the clinical monitoring of the trial.

The FB-14 is an open label, phase II study using pembrolizumab in combination with AE37 peptide vaccine (AE37) in patients with metastatic triple-negative breast cancer. This study will have a Simon two-stage design. In Stage I (safety cohort), 13 patients will receive combination therapy of AE37 vaccine (without granulocyte macrophage-colony stimulating factor GM-CSF adjuvant) 1000 micrograms in two split intradermal injections on Day 1 of cycles 1 through 5 and pembrolizumab 200 mg intravenous infusion (IV) given Day 1 of each cycle for 2 years (1 cycle equals 21 days). As the clinical trial continues, NGIO will be obligated to pay NSABP, pursuant to the Clinical Trial Agreement, additional amounts during each completed phase in the increments and at the times set forth in the agreement in four primary phases: Start-Up Activities, Accrual and Treatment Period, Follow-up Period and Primary Endpoint. The future payments required under the Clinical Trial Agreement will be funded through the proceeds received from a licensing agreement with Shenzhen BioScien Pharmaceuticals Co., Ltd., (“Shenzhen”) described below.  All Clinical Data shall be jointly owned by NGIO and Merck.

In addition to the breast cancer program, NGIO completed a Phase I clinical trial of AE37 in combination with GM-CSF in prostate cancer in April of 2009. This Phase I trial commenced in November of 2007 and enrolled thirty-two HER-2/neu+, castrate-sensitive, and castrate-resistant prostate cancer patients to demonstrate safety and strong immunological response to AE37. The trial was administered by Dr. Sonya Perez, MD and Dr. Anastastios Thanos, MD, PhD at the Saint Savas Cancer Hospital in Athens, Greece. Both the primary endpoint of safety and the secondary endpoint of immunogenicity were achieved. There were no serious adverse events. We are advancing AE37 for the treatment of prostate cancer through a License and Research Agreement (the “License Agreement”) dated November 29, 2017 with Shenzhen. Under the License Agreement, NGIO granted Shenzhen an exclusive license (the “License”) to use NGIO’s patents, know-how, data and other intellectual property relating to NGIO’s AE37 peptide to develop and sell products for the prevention and treatment of prostate cancer in China (including Taiwan, Hong Kong and Macau). In exchange for exclusive rights to AE37 for prostate cancer in China, Shenzen is financing and conducting the Phase II and Phase III trials globally under International Commission on Harmonization (“ICH”) guidelines, with us retaining the rights to all clinical data for regulatory submissions and commercialization in the rest of the world outside China. Further, Shenzhen has agreed, inter alia, to the following financial consideration:

• a $700,000 non-refundable initial payment;

• milestone payments of $1,000,000 each upon completion of Phase II and Phase III studies;

• a milestone payment of $2,000,000 upon regulatory approval of a product covered by the License; and

• a 10% royalty on net sales, provided the patents are in force and there are no approved generic equivalents.

Shenzhen, generally, will be responsible for conducting clinical trials, securing Chinese regulatory approvals, and marketing in China for all products developed under the License Agreement.

In exchange for exclusive rights to AE37 for prostate cancer in China, Shenzen is financing and conducting the Phase II trials in the European Union and Phase III trials globally under ICH guidelines, with NGIO retaining the rights to all clinical data for regulatory submissions and commercialization in the rest of the world outside China. . If Shenzhen Bioscien is successful in completing positive results in the prostate cancer development program, we will evaluate the data and make determinations on a commercialization strategy.

In addition to the AE37 clinical program in cancer, NGIO has conducted a Phase I clinical trial of an Ii-Key-H5N1 peptide vaccine for avian influenza. The trial was conducted by Dr. Alexander Abdelnoor, MD in 2007 and 2008 in Lebanon at the Lebanese Canadian Hospital, enrolling 120 subjects who were randomized to receive intramuscularly 500 micrograms of Ii-Key peptide vaccine or placebo. Ten Ii-Key-H5N1 epitope peptides were tested for safety and immunogenicity (10 subjects per cohort). The trial demonstrated the safety and measured T-Cell responses to the Ii-Key peptides. After the Phase I trial was completed, however, interest in the avian influenza vaccine waned because the virus disappeared before becoming a serious global pandemic. The pandemic flu research program was discontinued following the swine flu scare, which faded into the background ten years ago.

We plan to continue the development of AE37 for breast, prostate and other cancers including bladder cancer. Upon funding we plan to initiate a Phase II trial of AE37 in bladder cancer at a premier cancer institute. Discussions on confidential trial design and conduct are ongoing.

In regard to commercialization of AE37 in cancer, NGIO plans to identify and engage pharmaceutical companies like Merck that have checkpoint inhibitors; there are currently six pharmaceutical companies with approved checkpoint inhibitor products on the market. The goal is to partner the Ii-Key vaccines either through co-development, licensing, or sale of the product to a major pharmaceutical company that has the financial, operational, and commercial resources to fund at least $200,000,000 for research, development, manufacturing, marketing and sales typically required to bring immunotherapeutic cancer products to market. If we are unable to identify a large pharmaceutical company as a partner, we will have to raise the funds necessary for NGIO to commercialize the product. It is expected that FDA approval will take from 5 to 7 years, provided the funding is available to complete Phase III registration trials and the filing of a New Drug Application (“NDA”).

To address the current COVID-19 pandemic, Generex and NGIO have resurrected the pandemic research program using its proprietary, patented Ii-Key immune system activation technology that holds promise for the rapid development of a complete SARS-COV-2 Ii-Key peptide vaccine. The plan includes the conduct of a master protocol design that includes a Phase I/II dose escalation trial, with and without adjuvant, followed by a Phase III trial using the target commercial dose and formulation. This master protocol design will be conducted with healthy adult volunteers followed by cohorts in different age and risk categories. The commercial development program is budgeted for roughly $400 million and it is estimated that it will take 12 to 18 months for completion, depending on FDA emergency regulatory decisions during the pandemic. To accomplish these goals, Generex and NGIO have partnered with globally recognized industry leaders for each of the program’s key activities, to ensure world-class science, strategy and execution. Our objective is to provide government funding agencies with every degree of confidence in the ability of our team to execute and mitigate program risks. Generex has made applications to BARDA in the U.S. and with Health Canada and Malaysian health authorities to support the clinical and commercial development program.

The funding for the development of a vaccine of SARS-CoV-2 virus is in advanced discussions and currently expected that the development costs will be borne by the U.S. and foreign government agencies and without additional external funding, Generex will not pursue these projects.

 There is always uncertainty and risk associated with the development of any vaccine, medical treatment or therapy, but the continued development depends upon completing the trials under various collaboration agreements and associated potential commercialization of the product, FDA approval and/or licensing agreements. Any collaborator with whom we may enter into such collaboration agreements may not support fully our research and commercial interests since our program may compete for time, attention and resources with such collaborator's internal programs. Therefore, these collaborators may not commit sufficient resources to our program to move it forward effectively, or that the program will advance as rapidly as it might if we had retained complete control of all research, development, regulatory and commercialization decisions. During the pandemic COVID-19, it is anticipated that delays will occur, but the full impact of any slow down due to COVID-19 has not been determined.

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The primary increase in research and development costs incurred by NGIO during the year ending July 31, 2019 was related the initial payment by the Company of $340,000 to for the Clinical Trial Agreement for the start-up activities of the Phase II Study being conducted by NASBP, paid during the quarter ending January 31, 2020.

Clinical Development Plans for Ii-Key Immunotherapeutic Peptides

NGIO plans to expand the company’s clinical development program to evaluate AE37 immunotherapeutic peptide in combination with immune checkpoint inhibitors for the treatment of bladder cancer in cooperation with a major oncology research center focused on the role of HER-2/neu in bladder and urothelial cancer. The clinical & translational research program is designed to evaluate the ability of AE37 to activate a CD-4 response in conjunction with a checkpoint inhibitor and the effect of the combination therapy on the tumor microenvironment.

Additionally, NGIO is working with another major oncology research center to rebuild the company’s long-dormant melanoma program, which includes Ii-Key hybrid peptides for GP-100 and Tyrosinase (TYR). We are working with a long-term clinical advisor at the research institute to establish a translational research program that incorporates gene expression profiling, tumor microenvironment immunology, and clinical biomarker evaluation, coordinating with their newly established immune-oncology clinical research center.

Intellectual Property

Platform Patents. The foundational “Platform Patents” for Ii-Key technology focus on methods of increasing the antigen-specific activation of CD4⁺ T cells. This cell type is a critical component of the immune system, involved both in the recognition of new pathogenic agents as well as in autoimmune syndromes. The first technology platform (Ii-Key hybrid) relates to a means for increasing the vaccine potency of virtually any protein and while the second (Ii-suppression) relates to generation of an effective cell-based vaccine (REH-2017-01, REH 2017-02).

Oncology Patents. This group of patents relate more specifically to the use of the platform technologies for generating anti-cancer vaccines. We have generated Ii-Key hybrid compounds specifically for patients with breast, prostate, bladder, melanoma and HPV-related cancers (AEX-2001, AEX-2006, AEX-2007).

We hold five U.S. patents and one patent in Japan. The U.S. patent numbers are7,935,350 (expiring Novemeber 3, 2022), 8,748,130 (expiring on December 10, 2025), 8889143 (expiring on May 18, 2026), 928945 (expiring on September 22, 2027), 8,815,249 (expiring on February 26, 2026). Japan patent number is 5707326 (expiring September 1, 2029). These patents cover:

• Compositions and Methods Related to Ii Technology

• Ii hybrid peptides used for the enhancement of antigen presentation

• Constructs for the expression of Ii-Key/antigen epitope fusion peptides

• Hybrid Ii-Key/antigen epitope fusion peptides

• Methods for inhibiting Ii expression

We also have U.S. patents on the Ii-Key technology have expired, we are in discussions with third parties to extend the patent coverage of the Ii-Key technology for cancer immunotherapy. The expiration dates of the immune-oncology applications of the Ii-Key hybrid technologies extend to 2031. The company is exploring the development of new immunotherapeutic peptide vaccines against additional tumor antigens, and plans to use computer algorithms to identify epitopes of tumor antigens that can be linked to the Ii-Key to develop new IP and products based on the Ii-Key platform technology.

Our long-term success will substantially depend upon our ability to obtain patent protection for our technology and our ability to protect our technology from infringement, misappropriation, discovery and duplication. We cannot be sure that any of our pending patent applications will be granted, or that any patents which we own or obtain in the future will fully protect our position. Our patent rights and the patent rights of biotechnology and pharmaceutical companies in general, are highly uncertain and include complex legal and factual issues. We believe that our existing technology and the patents which we hold or for which we have applied do not infringe anyone else's patent rights. We believe our patent rights will provide meaningful protection against others duplicating our proprietary technologies. We cannot be sure of this, however, because of the complexity of the legal and scientific issues that could arise in litigation over these issues.

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We also rely on trade secrets and other unpatented proprietary information. We seek to protect this information, in part, by confidentiality agreements with our employees, consultants, advisors and collaborators.

The US Patent and Trademark Office (“PTO”) compensates patentees with additional patent in-force days if there are delays by the US PTO during prosecution. These additional days are called patent term adjustment (“PTA”) days and they allow a patentee to keep its patent in force after the expiration date of the patent for a period of time that the US PTO has provided as PTA.

In addition to patent protection, we plan to seek marketing exclusivity under other laws and regulations. Our success for preserving market exclusivity for our product candidate relies on our ability to obtain and maintain a regulatory period of data exclusivity for an approved biologic, currently 12 years from the date of marketing approval, obtaining orphan designation in the major markets and to preserve effective patent coverage. Once any regulatory period of data exclusivity expires, depending on the status of our patent coverage, we may not be able to prevent others from marketing and selling biosimilar versions of our product candidates. We are also dependent upon the diligence of third parties, which control the prosecution of pending domestic and foreign patent applications and maintain granted domestic and foreign patents.

We may be unable to obtain, maintain and protect the intellectual property rights necessary to conduct our business, and we may be subject to claims that we infringe or otherwise violate the intellectual property rights of others, which could materially harm our business.

Seasonality

Our products and services are not subject to seasonality.

Competition

The major pharmaceutical companies, including Novartis, Inc., Bristol-Myers Squibb (And acquisition Celgene), Merck, Sanofi, and Pfizer, GlaxoSmithKline PLC, MedImmune Inc. (a subsidiary of Astra-Zeneca, Inc.) and others, also compete in the oncology, immunomedicine and vaccine markets. These companies have greater experience and expertise in securing government contracts and grants to support research and development efforts, conducting testing and clinical trials, obtaining regulatory approvals to market products, as well as manufacturing and marketing approved products. As such, they are also considered significant competitors in these fields of pharmaceutical products and therapies. There are also many smaller companies which are pursuing similar technologies in these fields and are considered to be our competitors. With significant research and development effort in the field, the cancer immunotherapy market has been forecasted to be $128.3 billion^[1], $152.829 billion^[2] and $173 billion^[3] by the mid-2020’s.

While the size of the future market remains unknown, what is certain is that immuno-oncology is growing, and that its lead products enjoy blockbuster ($1 billion-plus/year in sales) status several times over. According to Genetic Engineering News (February 25, 2019), the biggest-selling cancer immunotherapies in 2018 were Celgene’s Revlimid (lenalidomide), which generated $9.685 billion; Opdivo® (nivolumab), which generated $7.570 billion, Merck’s Keytruda® (pembrolizumab), which generated $7.171 billion, Bristol-Myers Squibb, which generated $6.735 billion and Ono Pharmaceutical, which generated $835 million.

There are a limited number of commercialized products in the immunotherapy field, but that has not deterred the investment community, which recognizes the huge potential for cancer immunotherapy, and supplies hundreds of millions of dollars in development funding annually. According to the Cancer Research Institute, there are 3,394 immuno-oncology therapies in the current global development pipeline, with 1,287 of them in clinical studies. The major pharmaceutical companies have significant research and development efforts in the immuno-oncology field.

Competitive Position

As described in “Business Overview” above where we discuss certain clinical trials, NGIO has years of experience in cancer immunotherapy, having completed a Phase IIb clinical trial of the HER2/neu Ii-Key hybrid peptide vaccine, AE37 for the prevention of breast cancer recurrence in over 300 women. The company has also conducted Phase I trials with AE37 in breast and prostate cancers and has conducted pre-clinical work to support additional peptide vaccines for the treatment of melanoma.

^[1] KBV Research

^[2] Meticulous Research

^[3] Market Research Engine

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NGIO has a research agreement with Merck and is conducting a Phase II clinical trial of AE37 in combination with Keytruda for the treatment of triple negative breast cancer, a multi-billion market with significant medical need.

NGIO has licensed AE37 for the treatment of prostate cancer in China to Shenzhen Bioscien, a Chinese Pharmaceutical company. As part of the licensing agreement, Shezhen Bioscien is paying for the development of the immunotherapeutic vaccine and conducting the clinical trials under ICH guidelines in Europe as well as in China. NGIO retains global rights to AE37 for the treatment of prostate cancer outside of China and has exclusive rights to the clinical trial data to support regulatory filings in the US, EU, Japan, and other ex-China markets.

With a late phase clinical asset, a research partnership with a major pharmaceutical company, a licensing deal with an international pharmaceutical company, and a pipeline of immunotherapeutic products, NGIO is positioned to become a participant in the immuno-oncology field.

Employees

As of the date of this registration statement, we had six full time employees, including the Joseph Moscato, Chief Executive Officer; Eric von Hofe, President and Chief Scientific Officer; Mark Corrao, Interim Chief Financial Officer; Jason B. Terell, Chief Medical Officer; Richard Purcell, Executive Vice President, R&D and Anthony Crisci, Chief Legal Officer and Secretary. In the future, we plan to hire additional employees, including a Financial Controller and support staff. In the meantime, we plan to continue utilizing key consultants and contractors for certain operations, such as finance and accounting, business development, clinical development, regulatory affairs, statistical consulting, and manufacturing. We believe our relationships with our employees and contractors are good.

Government Regulation and Product Approval

Our research and development activities and the manufacturing and marketing of our medical device, biologic, and pharmaceutical products are subject to extensive regulation by the FDA in the United States, Health Canada in Canada, the European Medicines Evaluation Agency in Europe, and comparable designated regulatory authorities in other countries. Among other things, extensive regulations require us to satisfy numerous conditions before we can bring products to market. While these regulations apply to all competitors in our industry, having a technology that is unique and novel extends the requisite review period by the various divisions within the FDA and other regulators. Also, other companies in our industry are not limited primarily to products which still need to be approved by government regulators, as we are now.

If requisite regulatory approvals are not obtained and maintained, our business will be substantially harmed. In many cases, we expect that extant and prospective development partners will participate in the regulatory approval process. The following discussion summarizes the principal features of food and drug regulation in the United States and other countries as they affect our business.

United States. All aspects of our research, development and foreseeable commercial activities relating to medical device, biologic, and pharmaceutical products are subject to extensive regulation by the FDA and other regulatory authorities in the United States. United States federal and state statutes and regulations govern, among other things, the testing, manufacturing, safety, efficacy, labeling, storage, record keeping, approval, advertising and promotion of pharmaceutical products. The regulatory approval process, including clinical trials, usually takes several years and requires the expenditure of substantial resources. If regulatory approval of a product is granted, the approval may include significant limitations on the uses for which the product may be marketed.

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The steps required before a medical device, biologic or pharmaceutical product may be marketed in the United States include:

• Conducting appropriate pre-clinical laboratory evaluations, including animal studies, in compliance with the FDA’s Good Laboratory Practice (“GLP”) requirements, to assess the potential safety and efficacy of the product, and to characterize and document the product’s chemistry, manufacturing controls, formulation and stability;

• Submitting the results of these evaluations and tests to the FDA, along with manufacturing information, analytical data, and protocols for clinical studies, in an Investigational New Drug (“IND”) application, and receiving approval from the FDA that the clinical studies proposed under the IND are allowed to proceed;

• Obtaining approval of Institutional Review Boards (“IRBs”) to administer the product to humans in clinical studies; conducting adequate and well-controlled human clinical trials in compliance with the FDA’s Good Clinical Practice (“GCP”) requirements that establish the safety and efficacy of the product candidate for the intended use;

• Developing manufacturing processes which conform to the FDA’s current Good Manufacturing Practices (“cGMPs”), as confirmed by FDA inspection;

• Submitting to the FDA the results of pre-clinical studies, clinical studies, and adequate data on chemistry, manufacturing and control information to ensure reproducible product quality batch after batch, in an NDA, FDA Section 510(K) application, PMA or Biologics License Application (“BLA”); and

• Obtaining FDA approval of the NDA, BLA, PMA, or FDA Section 510(K) application, including inspection and approval of the product manufacturing facility as compliant with cGMP requirements, prior to any commercial sale or shipment of the pharmaceutical agent.

Quality and pre-clinical tests and studies include: laboratory evaluation of drug substance and drug product chemistry, formulation/manufacturing, and stability profiling, as well as a large number of animal studies to assess the potential safety and efficacy of each product. 

The results of the quality and pre-clinical tests/studies, in addition to any non-clinical pharmacology, are submitted to the FDA along with the initial clinical study protocol (see descriptive of process below) as part of the initial IND and are reviewed by the FDA before the commencement of human clinical trials. Unless the FDA objects to it, the IND becomes effective 30 days following its receipt by the FDA. The FDA reviews all protocols, protocol amendments, adverse event reports, study reports, and annual reports in connection with a new pharmacological product.

The Physician’s Investigational New Drug Application for the Phase 1 and Phase II trial of AE37, NGIO’s synthetic peptide vaccine designed to stimulate a potent and specific immune response against tumors expressing the HER-2/neu oncogene, in patients with stage II HER-2/neu positive breast cancer became effective in March 2006. Dr. George Peoples filed the original IND for Phase I and II. The Company took over as sponsor of the Phase II trial and the IND from Dr. Peoples in 2013. The Company has no current relationship with Dr. Peoples.

The Investigational New Drug Application for the Phase II trial of AE37 in combination with pembrolizumab (Merck’s KeytrudaÒ) for treatment of triple negative breast cancer became effective in December 2018, and the trial is expected to continue enrolling patients through 2020. NSABP filed the IND on our behalf for this trial.

Clinical trials involve the administration of a new drug to humans under the supervision of qualified investigators. The protocols for the trials must be submitted to the FDA as part of the IND. Also, each clinical trial must be approved and conducted under the auspices of an IRB, which considers, among other things, ethical factors, the safety of human subjects, and the possible liability of the institution conducting the clinical trials.

Clinical trials are typically conducted in three sequential phases (Phase I, Phase II, and Phase III), but the phases may overlap. Phase I clinical trials test the drug on healthy human subjects for safety and other aspects, but usually not effectiveness. Phase II clinical trials are conducted in a limited patient population to gather evidence about the efficacy of the drug for specific purposes, to determine dosage tolerance and optimal dosages, and to identify possible adverse effects and safety risks. When a compound has shown evidence of efficacy and acceptable safety in Phase II evaluations, Phase III clinical trials are undertaken to evaluate and confirm clinical efficacy and to test for safety in an expanded patient population at clinical trial sites in different geographical locations. The FDA and other regulatory authorities require that the safety and efficacy of therapeutic product candidates be supported through at least two adequate and well-controlled Phase III clinical trials (known as “Pivotal Trials”). The successful completion of Phase III clinical trials is a mandatory step in the approval process for the manufacturing, marketing, and sale of products.

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In the United States, the results of quality, pre-clinical studies and clinical trials, if successful, are submitted to the FDA in an NDA to seek approval to market and commercialize the drug product for a specified use. The NDA is far more specific than the IND and must also include proposed labeling and detailed technical sections based on the data collected. The FDA is governed by the Prescription Drug User Fee Act (“PDUFA”) regarding response time to the application, which is generally 12 months (and shorter for a priority application). It may deny a NDA if it believes that applicable regulatory criteria are not satisfied. The FDA also may require additional clarifications on the existing application or even additional testing for safety and efficacy of the drug. We cannot be sure that any of our proposed products will receive FDA approval. The multi-tiered approval process means that our products could fail to advance to subsequent steps without the requisite data, studies, and FDA approval along the way. Even if approved by the FDA, our products and the facilities used to manufacture our products will remain subject to review and periodic inspection by the FDA.

To supply drug products for use in the United States, foreign and domestic manufacturing facilities must be registered with, and approved by, the FDA. Manufacturing facilities must also comply with the FDA’s cGMPs, and such facilities are subject to periodic inspection by the FDA. Products manufactured outside the United States are inspected by regulatory authorities in those countries under agreements with the FDA.  To comply with cGMPs, manufacturers must expend substantial funds, time and effort in the area of production and quality control. The FDA stringently applies its regulatory standards for manufacturing. Discovery of previously unknown problems with respect to a product, manufacturer or facility may result in consequences with commercial significance. These include restrictions on the product, manufacturer or facility, suspensions of regulatory approvals, operating restrictions, delays in obtaining new product approvals, withdrawals of the product from the market, product recalls, fines, injunctions and criminal prosecution.

One final hurdle that is closely associated with the cGMP inspections is the pre-approval inspection that the FDA carries out prior to the issuance of a marketing license. FDA inspectors combine cGMP compliance with a review of research and development documents that were used in the formal NDA. A close inspection of historic data is reviewed to confirm data and to demonstrate that a company has carried out the activities as presented in the NDA. This is generally a long inspection and requires a team of individuals from the Company to “host” the FDA inspector(s).

Foreign Countries

Before we are permitted to market any of our products outside of the United States, those products will be subject to regulatory approval by foreign government agencies similar to the FDA. These requirements vary widely from country to country. Generally, however, no action can be taken to market any drug product in a country until an appropriate application has been submitted by a sponsor and approved by the regulatory authorities in that country. Again, similar to the FDA, each country will mandate a specific financial consideration for the Marketing Application dossiers being submitted. Although an important consideration, FDA approval does not assure approval by other regulatory authorities. The current approval process varies from country to country, and the time spent in gaining approval varies from that required for FDA approval. The Canadian regulatory process is substantially similar to that of the United States. To date, we have received a number of foreign regulatory approval for our product candidates, as listed below, however we are not manufacturing, marketing, nor distributing products in these regions based upon these approvals. There are no current plans to pursue these markets with these products, as we have redirected its efforts to more profitable business opportunities.

• Applications were filed and approvals obtained in May 2007 for a Phase I prostate cancer trial using AE37 in Athens, Greece from the Hellenic Organization of Drugs. This Phase I trial was completed in August 2009.

• Applications were filed and approvals obtained in May 2007 for a Phase I prostate cancer trial using AE37 in Athens, Greece from the Hellenic Organization of Drugs. This Phase I trial was completed in August 2009.

Environmental Compliance

Our research and development activities have involved the controlled use of hazardous materials and chemicals. We believe that our procedures for handling and disposing of these materials comply with all applicable government regulations. However, we cannot eliminate the risk of accidental contamination or injury from these materials. If an accident occurred, we could be held liable for damages, and these damages could severely impact our financial condition. We are also subject to many environmental, health and workplace safety laws and regulations, particularly those governing laboratory procedures, exposure to blood-borne pathogens, and the handling of hazardous biological materials. Violations and the cost of compliance with these laws and regulations could adversely affect us. However, we do not believe that compliance with applicable environmental laws will have a material effect on us in the foreseeable future.

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 Compliance with the JOBS Act

The Company is, and expects to remain, an “emerging growth company,” as defined in the Jumpstart Our Business Startups Act, as it may be amended from time to time (the “JOBS Act”), until the earliest of:

• the last day of the fiscal year in which the Company’s total annual gross revenues first meet or exceed $1.07 billion;

• the date on which the Company has, during the prior three-year period, issued more than $1.0 billion in non-convertible debt;

• the last day of the fiscal year in which the Company (1) has an aggregate worldwide market value of common stock held by non-affiliates of $700 million or more (measured at the end of each fiscal year) as of the last business day of the Company’s most recently completed second fiscal quarter and (2) has been an Exchange Act reporting company for at least one year (and filed at least one annual report under the Exchange Act); or

• the last day of the fiscal year following the fifth anniversary of the date of the first sale of common stock of the Company pursuant to an effective registration statement under the Securities Act.

As an “emerging growth company” we may take advantage of certain exemptions from various reporting requirements that are applicable to other public companies that are not “emerging growth companies” including, but not limited to:

• not being required to comply with the auditor attestation requirements of Section 404 of the Sarbanes-Oxley Act; which would require that the Company’s independent registered public accounting firm provide an attestation report on the effectiveness of the Company’s internal control over financial reporting. This may increase the risk that material weaknesses or other deficiencies in the Company’s internal control over financial reporting go undetected

• reduced disclosure obligations regarding executive compensation in our periodic reports and proxy statements;

• exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and stockholder approval of any golden parachute payments; and

• extended transition periods available for complying with new or revised accounting standards.

We have chosen to take advantage of all of the benefits available under the JOBS Act, including the exemptions listed above. We cannot predict if investors will find our common stock less attractive because we may rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock price may be more volatile.

As an “emerging growth company” under the definition of the JOBS Act, our financial statements may not be comparable to other companies that have fully complied with public company effective dates due to our election to take advantage of the extended transition period for complying with new or revised accounting standards under the JOBS Act .

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Item 1A. Risk Factors.

Not required due to the Company’s status as a smaller reporting company.

Item 2. Financial Information.

We are a smaller reporting company, as defined in Rule 12b-2 of the Exchange Act. Accordingly, we have omitted certain information called for by this Item as permitted by applicable scaled disclosure rules.

Management’s Discussion and Analysis of Financial Condition and Results of Operations

The following discussion and analysis of financial condition and results of operations should be read together with our financial statements and accompanying notes appearing elsewhere in this registration statement. This Management’s Discussion and Analysis contains forward-looking statements that involve risks and uncertainties. Please see “Cautionary Note Regarding Forward-Looking Statements” set forth in the beginning of this registration statement. Operating results are not necessarily indicative of results that may occur in future periods.

Overview

We are an oncology company focused on the modulation of the immune system to treat cancer. To that end, we are developing immunotherapeutic products and vaccines based on our proprietary, patented platform technology, Ii-Key. The Ii-Key is a peptide derived from the major histocompatibility complex (“MHC”) Class II associated invariant chain (Ii) that regulates the formation, trafficking, and antigen-presenting functions of MHC class II complexes, essential for the activation of T cells in the immune response. T cells recognize antigenic epitopes when they are 'presented' to them by specific molecules, termed (MHC) on the surface of infected or malignant cells. This interaction activates the T cells, stimulating a multicellular cascade of actions that eliminates the diseased cell and protects against future disease recurrence.

The following discussion and analysis by management provides information with respect to our financial condition and results of operations for the fiscal year ended July 31, 2019 and 2018, and the three months ended October 31, 2019 and 2018.

Results of Operations

Three months ended January 31, 2020 compared to Three months ended January 31, 2019

We reported a net loss of $292,367 and $517,544 for the three-month periods ended January 31, 2020 and 2019, respectively, reflecting a reduction in the reported net loss of $225,177 or 43%. The decrease in the net loss resulted from a $338,500 or 99% reduction in research and development offset by a $79,158 increase in general and administrative expense plus an increase of $34,165 or 20% in interest expense.

Research and development expenses for the three months ended January 31, 2020 resulted from costs incurred to support the Phase II clinical trial on the safety and efficacy of AE37 in combination with KEYTRUDA for treatment of metastatic triple negative breast cancer being performed by NSABP (our only ongoing research and development project) . For the three months ended January 31,2019, we expensed the $340,000 for start-up activities related to the NSABP clinical trial agreement. For the three months ended January 31, 2020 we did not incur any expenses related to the NSABP clinical trial agreement. Other research and development costs were de minimis.

The $79,158 increase in general and administrative expenses for the three months ended January 31, 2020 versus the comparative period in the prior year is due to increased professional fees incurred in connection to the 2019 and 2018 audits as well as the Form 10 registration statement.

Our interest expense for the three months ended January 31, 2020 increased by $34,165 compared to the months ended January 31, 2019 due to the additional principal resulting from the compounding of interest accrued on the payable to foundation.

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Six months ended January 31, 2020 Compared to Six months ended January 31, 2019

We reported a net loss of $775,631 and $704,642 for the six month periods ended January 31, 2020 and January 31, 2019, respectively, reflecting an increase in the reported net loss of $70,989 or 10%. The increased net loss resulted from a $102,886 increase in general and administrative expense and an increase of $66,838 or 20 % in interest expense offset by a $98,735 or 28% reduction in research and development

For the six months ended January 31, 2020, we incurred costs of $251,459 for the first 5 patients to be enrolled in the Phase II trial clinical tri on the safety and efficacy of AE37 in combination with KEYTRUDA for treatment of metastatic triple negative breast cancer conducted by NASBP Foundation, Inc. on our behalf. For the six months ended January 31, 2019 we expensed $340,000 related to the NSABP clinical trial agreement. For the six months ended January 31. 2020 and 2019 other research and development costs were de minimis.

The $102,886 increase in general and administrative expenses for the six months ended January 31, 2020 versus the comparative period in the prior year is due to professional fees incurred in connection to the 2019 and 2018 audits as well as the Form 10 registration system.

Our interest expense for the six months ended January 31, 2020 increased by $66,838 compared to the six months ended January 31, 2019 due to the additional principal resulting from the compounding of interest accrued on the payable to foundation.

Year ended July 31, 2019 Compared to Year ended July 31, 2018

We reported a net loss for the years ended July 31, 2019 and 2018 in the amount $1,108,016 and $173,255, respectively, reflecting a 540%, or $934,761 increase from the prior fiscal year. The increase in net loss was primarily attributable the Company not recognizing revenue for the year ended July 31, 2019 compared to the one-time recognition of $700,000 during the year ended July 31, 2018 from a non-refundable license fee as part of a research and development agreement for AE37. Research and development costs related to our AE37 peptide increased from $234,317 for the year ended July 31, 2018 to $354,000 for the year ended July 31, 2019 because we incurred $340,000 as related to the start-up of our clinical trial agreement with NSABP. In 2018 we incurred clinical costs related to our development of AE 37.

Interest expense increased 20% or $117,028 for the year ended July 31, 2019 to $715,275 from $598,247 for year ended July 31, 2018 due to the additional principal resulting from the compounding interest on payable to the foundation. The interest payable to the foundation was $3,055,945, and $2,340,670, as of July 31, 2019 and 2018, respectively.

Financial Condition, Liquidity and Resources

Sources of Liquidity

COVID-19

The ongoing coronavirus outbreak which began in China at the beginning of 2020 has impacted various businesses throughout the world, including travel restrictions and the extended shutdown of certain businesses in impacted geographic regions. If the coronavirus outbreak situation should continue to worsen, we may experience disruptions to our business including, but not limited disruptions of our ongoing clinical trials and the operations of our partners.

While we expect delays in our research and development plans, the extent to which the coronavirus impacts our operations or those of our third-party partners will depend on future developments, which are highly uncertain and cannot be predicted with confidence, including the duration of the outbreak, new information that may emerge concerning the severity of the coronavirus and the actions to contain the coronavirus or treat its impact, among others. Any such disruptions or losses we incur could have a material adverse effect on our financial results and our ability to conduct business as expected.

Sources of Liquidity

To date, we have financed our activities primarily through capital contributions from Generex, our majority shareholder. Generex in the past has raised capital for our operations through private placements of Generex common stock, securities convertible into Generex common stock, and investor loans. We will require additional funds to support our working capital requirements and any development or other activities or will need to curtail its research and development and other planned activities or suspend operations. While Generex owns over 90% of our common stock, going forward, we will rely both on financing from third parties and from Generex, which may sell shares of our common stock, to fund our operations, development and other activities.

As an public company, NGIO will begin to incur costs for corporate activities such as executives, corporate accounting for external reporting, and investor relations. Reasonable estimates of such costs are not available.

As of June 11, 2020, our cash position is not sufficient for twelve months of operations. Generex has financed our activities to date. Our cash balances have been low throughout fiscal 2020.

Management may seek to meet all or some of our operating cash flow requirements through financing activities, such as private placement of our common stock, preferred stock offerings and offerings of debt and convertible debt instruments as well as through merger or acquisition opportunities.

In addition, management is actively pursuing financial and strategic alternatives, including strategic investments and divestitures, industry collaboration activities, and potential strategic partners.

We will continue to require substantial funds to continue research and development, including preclinical studies and clinical trials of our product candidates, further clinical trials for AE37 and to commence sales and marketing efforts if the FDA or other regulatory approvals are obtained.  Currently, the phase II clinical study using AE37 in combination with pembrolizumab (Keytruda ®) for treatment of metastatic triple negative breast cancer is our only ongoing research and development project In this regard, we have committed to provide the NASBP Foundation, Inc. financial support for clinical research using AE37 in combination with pembrolizumab (Keytruda ®) up to $2,118,461 upon NASBP achieving certain milestones. As of January 31, 2020, we have incurred $591,459 against this commitment.

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Cash Flows for the Six Months ended January 31, 2019

For the six months ended January 31, 2020, we used $215 in cash from operating activities. There were no cash flows from financing or investing activities. The use for operating activities included a net loss of $775,631, offset by an increase in interest payable to foundation of $408,512, and an increase in accounts payable and accrued expenses,of $366,904.

Cash Flows for the Year ended July 31, 2019

For the year ended July 31, 2019, we used $636 in cash in our operating activities. There were no cash flows from financing or investing activities. The use for operating activities included a net loss of $1,108,016, offset by an increase in interest payapbe to foundation of $715,275, and an increase in accounts payable and accrued expenses of, $392,105.

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Item 4. Security Ownership of Certain Beneficial Owners and Management.

 The table below sets forth information regarding the beneficial ownership of our common stock by (i) our directors and named executive officers; (ii) all the named executives and directors as a group and (iii) any other person or group that to our knowledge beneficially owns more than five percent of our outstanding shares of common stock. Except as indicated below, the address of each holder is c/o Generex Biotechnology Corporation, 10102 USA Today Way, Miramar, Florida 33025.

The information contained in this table is as of June 10, 2020. At that date, 400,000,000 shares of our common stock were outstanding.

A person is deemed to be a beneficial owner of shares if he has the power to vote or dispose of the shares. This power can be exclusive or shared, direct or indirect. In addition, a person is considered by SEC rules to beneficially own shares underlying options or warrants that are presently exercisable or that will become exercisable within sixty (60) days. Except as otherwise indicated, we believe that the persons named in this table have sole voting and investment power with respect to all shares of common stock held by them. To our knowledge, none of the shares listed below are held under a voting trust or similar agreement, except as noted. There is no arrangement, including any pledge by any person of securities of the Company, the operation of which may at a subsequent date result in a change in control of the Company.

Name of Beneficial Owner	Number of Shares			Percent of Class
Named Executives and Directors
Joseph Moscato		2,997,295	*		**
Mark Corrao		—			**
Eric Von Hofe		—			**
Craig Eagle		—			**
Anthony Crisci		—			**
Richard Purcell		—			**
Thomas Leonard		—			**
Marvin Hausman		—			**
Brian McGee		—			**
Jason Terrell		—			**
Carol Nacy		—			**
S. Gail Eckhardt		—			**
Named Executives and Directors as a group (12 persons)		2,997,295
Holders of 5% of Common Stock					**
Generex Biotechnology Corporation		361,642,962			90.41	%

*2,793,975 shares of which are owned by Friends of Generex Biotech Investment Trust, of which Joe Moscato is trustee.

**Represents less than 1%.

Item 5. Directors and Executive Officers.

The following are our executive officers and directors and their respective ages and positions as of June 10, 2020.

Name	Position	Age
Executive Officers:
Joseph Moscato	Chief Executive Officer	57
Eric von Hofe, Ph.D	President and Chief Scientific Officer	62
Mark Corrao	Interim Chief Financial Officer	62
Dr. Jason B. Terrell, MD	Chief Medical Officer	48
Anthony Crisci, Esq., CPA	Chief Legal Officer and Secretary	50
Richard Purcell	Executive Vice President, R&D	59
Directors:
Joseph Moscato	Chairman of the Board	57
Richard Purcell	Director	59
Dr. Craig Eagle, MD	Director	57
Dr. Marvin Hausman, MD	Director	78
Carol Nacy, Ph.D	Director	72
Thomas Leonard, MPA	Director	46
Brian T. McGee	Director	59
S. Gail Eckhardt, MD	Director	62
Anthony Crisci, Esq.	Director	50

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Joseph Moscato. Mr. Moscato is currently the Chief Executive Officer, President, and Chairman of the Board for Generex since January 2017.  Mr. Moscato has over 30 years of experience in healthcare, sales and marketing, distribution management, and finance.  Mr. Moscato brings his marketing and advertising acumen to drug discovery and diagnostic & treatment development and commercialization.  Since 2009, Mr. Moscato has been working as an exclusive consultant to the Company.  Mr. Moscato has originated and negotiated several licensing deals with the top biopharmaceutical companies; has advised on equity financings totaling over $300 million, and has implemented the broad strategic vision for the Company.  Mr. Moscato has worked and consulted for Pfizer in several capacities from sales and marketing to new drug discovery & development for licensing.  He has worked with other biopharmaceutical companies such as GlaxoSmithKline, Johnson & Johnson, Parke-Davis, Amgen and others.  Mr. Moscato has consulted for several healthcare focused private equity, hedge funds and family offices.

Mr. Moscato also owned several advertising and marketing agencies focused on media, entertainment, and healthcare with clients ranging from Motorola, Chadmoore Wireless, Nextel, Cannon, Sharp, GlaxoSmithKline, Pfizer, and other biopharmaceutical companies.  Mr. Moscato’s agency was acquired by William Douglas McAdams, one of the largest independent healthcare advertising and marketing agencies.

Mark Corrao. Mr. Corrao is currently the Chief Financial Officer, Treasurer for Generex since January 2017. Mr. Corrao has experience in financial management with a proven track record of raising capital and extraordinary bottom line management. He has been involved in the initial registration of numerous public companies and subsequent SEC quarterly and annual reporting and has developed, authored and presented numerous business plans and models inclusive of budgets, forecasts, cash flow, cash management and investment strategies. From 2012 to present he has affiliated with of The Mariner Group LLC, which merged with the CFO Squad, creating a much larger and diverse multi-talented organization. The CFO Squad is a financial and business advisory firm providing outsourced and part-time CFO services for emerging to midsized companies (both private and public) in a wide range of businesses and industries. He is the Chief Financial Officer for Kannalife, Inc., a pharmaceutical company specializing in the research and development of novel and new therapeutic agents designed to reduce oxidative stress and act as immune modulators and Neuroprotectants. From 2010-12, he served as Chief Financial Officer of New York Business Efficiency Experts, Inc. which provides professional services in the financial areas of accounting, taxation, auditing, venture capital and SEC registrations (reporting). He served as a Director and Chief Financial Officer for a manufacturer of proprietary software for the prevention of identity theft and the protection of computer systems from unauthorized access.

Eric von Hofe, Ph.D. Dr. von Hofe has extensive experience with technology development projects, including his previous position at Millennium Pharmaceuticals as Director of Programs & Operations, Discovery Research and is also President of Antigen Express. Prior to that, Dr. von Hofe was Director, New Targets at Hybridon, Inc., where he coordinated in-house and collaborative research that critically validated gene targets for novel antisense medicines. Dr. von Hofe also held the position of Assistant Professor of Pharmacology at the University of Massachusetts Medical School, where he received a National Cancer Institute Career Development Award for defining mechanisms by which alkylating carcinogens create cancers. He received his Ph.D. from the University of Southern California in Experimental Pathology and was a postdoctoral fellow at both the University of Zurich and Harvard School of Public Health. His work has been published in forty-eight articles in peer-reviewed journals, and he has been an inventor on four patents.

Dr. Jason B. Terrell, MD. Dr. Terrell is also the Chief Scientific Officer and Chief Medical Officer of Generex, providing scientific and medical due diligence for partnerships and mergers/acquisitions, and providing clinical oversight for subsidiary operations and product development strategies. Since 2017, he has also served as Assistant Clinical Professor of Oncology, University of Texas at Austin Dell Medical School as an industry and clinical expert advisor to researchers, innovators, and entrepreneurs for accelerating the translation of innovations to health products for Texas Health Catalyst. Since 2017, he has also been Lead Independent Director and Non-Executive Chairman of Kiromic Biopharma Inc, providing guidance for corporate formation, business development, product development and commercialization strategies. Since 2016, Dr. Terrell has served as CEO and Chief Medical Officer for Volition America Inc. From 2010 to 2015 he was Corporate Medical Director for AnyLabTestNow, Dr. Terrell is a summa cum laude graduate from Hardin-Simmons University with a degree in Biochemistry. He graduated as recipient of the Holland Medal of Honor for the top graduate in the School of Science and Mathematics. Dr. Terrell was honored with the Hardin-Simmons University Outstanding Young Alumni Award and currently serves on the University’s Board of Development. Dr. Terrell attended The University of Texas School of Medicine in Houston and received General Medicine Internship and Pathology Residency training at the Texas Tech University Health Sciences Center.

Anthony S. Crisci, Esq., C.P.A. Mr. Crisci is currently the Chief Legal Officer for Generex since August 2019. Mr. Crisci is an attorney and certified public accountant with over twenty (20) years of experience in tax, accounting, finance, corporate, health care and employee benefit matters. Mr. Crisci has built a stellar career as a business legal executive across a number of regulated industries.

From November 2018, Mr. Crisci was Corporate Counsel for Generex and remains as the Chief Administrative Officer and Chief Legal Counsel for Generex’s wholly owned subsidiary, NuGenerex Distribution Solutions, where he oversees business, accounting, and legal matters for NuGenerex’s distribution enterprise. Most recently, Mr. Crisci was General Counsel, COO, CFO, and Controller for a publicly traded holding company, specializing in financial services and technology software companies. Previously, he served as Corporate Counsel for a major health system with $1 Billion in annual revenues, and General Counsel for a National Pharmacy Benefit Management Company that includes mail and specialty drug dispensing.

Mr. Crisci brings a broad range of capabilities with his legal, business, financial, and regulatory background, and his expertise is instrumental in the execution of Generex’s strategic objectives, including mergers & acquisitions, joint venture and development agreements, in-licensing and out-licensing agreements, and most importantly, long term supply and distributorship agreements for nation-wide pharmacy, laboratory, and medical management services. Mr. Crisci holds a Bachelor of Business Administration degree in Accounting from Hofstra University and a Juris Doctor degree, with distinction, from Hofstra University School of Law. He is a licensed CPA and a Member of the New York State and New Jersey State Bar Associations.

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Richard Purcell. Mr. Purcell currently is and has been the Executive Vice-President of Research & Drug Development for Generex since January 2017. Mr. Purcell has managed a consulting practice, DNA Healthlink, Inc. advising emerging biopharmaceutical and technology companies on new business strategy, operations management, and clinical development of novel compounds. Mr. Purcell has been the SVP of R&D for RespireRx Pharmaceuticals since 2014. From 2011 to 2017, Mr. Purcell was the President and founder of a Healthcare IT startup, IntelliSanté. Mr. Purcell graduated with a degree in Biochemical Sciences from Princeton University, and attended Rutgers Graduate School of Management majoring in marketing and finance. He is also an Adjunct Professor of Biology at Monmouth University.

Dr. Craig Eagle, MD. Dr. Eagle is currently the Vice President of Medical Affairs Oncology for Genentech where he oversees the medical programs across the oncology portfolio. Prior to his current role, Dr Eagle worked at Pfizer in several positions including as the oncology business lead in United Kingdom and Canada delivering significant business growth. Previously, Dr Eagle was the global lead for Oncology Strategic Alliances and Partnerships based in New York at Pfizer Inc. and was involved in multiple deals on both the sell and buy side. Dr Eagle started work in Pfizer New York as the global head of the Oncology Therapeutic Area Global Medical and Outcomes Group for Pfizer, including the US oncology business, in this role he oversaw an extensive oncology clinical trial program, health outcomes assessments and scientific collaborations with key global research organizations like the  National Cancer Institute (NCI), and EORTC. As part of this role Dr Eagle lead the worldwide development of several compounds including celecoxib, aromasin, irinotecan, dalteparin and ozagomicin, Concurrently Dr. Eagle has been a Member of Scientific Advisory Board at Generex Biotechnology Corp. since August 2010. He has served on the scientific advisory committee and board of directors for several start up biotechnology companies.

Dr. Eagle attended Medical School at the University of New South Wales, Sydney, Australia and received his general internist training at Royal North Shore Hospital in Sydney. He completed his hemato-oncology and laboratory hematology training at Royal Prince Alfred Hospital in Sydney. He was granted Fellowship in the Royal Australasian College of Physicians (FRACP) and the Royal College of Pathologists Australasia (FRCPA). After his training, Dr. Eagle performed basic research at the Royal Prince of Wales hospital to develop a new monoclonal antibody to inhibit platelets.

Dr. Marvin S. Hausman, MD. Dr. Hausman is an Immunologist and Board-Certified Urological Surgeon with more than 30 years of drug research and development experience with various pharmaceutical companies, including Bristol-Myers International, Mead-Johnson Pharmaceutical Co., E.R. Squibb, Medco Research, and Axonyx. Dr. Hausman currently serves as Chairman of the Board & Chief Science and Technology Officer of Entia Biosciences, Inc.  Previously, Dr. Hausman was a co-founder of Medco Research Inc., a NYSE clinical research organization and biotechnology company specializing in adenosine products that was subsequently acquired by King Pharmaceuticals. Dr. Hausman was also a co-founder of Axonyx, and served in various capacities as President, Chief Executive Officer and Chairman of the Board until the company merged into Torrey Pines Therapeutics in 2006. He has also served as a director of Arbios Technologies and of Regent Assisted Living, Inc. Dr. Hausman has done residencies in General Surgery at Mt. Sinai Hospital in New York, and in Urological Surgery at UCLA Medical Center. He received his medical degree from New York University School of Medicine.

Dr. Carol Nacy, PhD. Dr. Nacy is a founder and the Chief Executive Officer of Sequella, Inc., a privately held pharmaceutical company that discovers and develops new and more effective treatments for life threatening infectious diseases. Previously, Dr. Nacy was Executive Vice President and Chief Scientific Officer at EntreMed,Inc. from 1993 through its successful public offering in June 1996. Prior to her career in biotechnology, Dr. Nacy worked for 17 years at the Walter Reed Army Institute of Research in Washington, DC, where she studied tropical infectious diseases. She has published over 165 scientific papers to date. Dr. Nacy has a long and successful career in infectious disease research and has been widely recognized for her achievements in the biotechnology industry. She was singled out as a Top 50 Innovator in the U.S. by Inc. Magazine in 2002, named Entrepreneur of the Year by Women in BIO in 2004, the state of Maryland named her in its Top 100 Business Women in 2005, and the Washington Business Journal named her as a top 25 female executive in the Washington DC metropolitan area in 2005. In 2006, she received a National Leadership Award in Healthcare from the National Urban Technology Center in New York City, and in 2007 she was honored with a Special Outstanding Achievement Award for Clinical Trials by Women in BIO. In 2009 she was awarded the Humanitarian Award, Hope is a Vaccine, by the Global Alliance for Immunization against Aids (GAIA) for her work to create new drugs for TB. She is an Editor for the American Academy of Microbiology journal, mBio, and an adjunct faculty member of the Department of Tropical Diseases at the George Washington University, Washington, DC. She earned her A.B., M.S., and Ph.D. degrees from the Catholic University of America in Washington, DC, which awarded Dr. Nacy with a Lifetime Achievement Award in Science.

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Thomas Leonard, MPA. Mr. Leonard has had a long and successful career at Bristol Myers Squibb in pharmaceutical sales, marketing, and management across multiple segments of the healthcare delivery system, most recently as the Northeast Business Manager for Oncology. Mr. Leonard brings a deep understanding of the current oncology market, having responsibility for cutting edge immunotherapy products including Opdivo (PD1 inhibitor), Yervoy (CTLA4 inhibitor), and Empliciti, as well as small molecule cancer drugs like Sprycel. He has worked across the oncology landscape, with experience in Lung/NSCLC, Head/Neck, Liver, CML, Kidney/Renal Cell Carcinoma, Bladder, Urothelial, Melanoma, and Colorectal Cancers. He also brings to NGIO a broad network of clinical oncologists with whom he has developed relationships over his career, and who will help guide the NGIO clinical development programs for our Ii-Key peptide immunotherapeutic vaccines. In addition to his work in oncology, Mr. Leonard has extensive experience interacting with the healthcare payor sector, leading the market access pull through programs and specialty pharmacy strategy at major payors nationwide and as a core team member for major regional Integrated Delivery Networks (IDNs) and Organized Customer Groups (OCGs) including Duke, Kaiser Permanente, Cleveland Clinic, Mayo Clinic, Northwell Health. Mr. Leonard received a master’s degree in Public Administration, Business and Health Management from New York University and graduated St. John’s University with a B.S. in Business and Healthcare Administration.

Brian T. McGee. Mr. McGee serves as an independent Director of Generex since 2004. Mr. McGee has served as Chairman of the Generex Audit Committee and a member of the Generex Compensation and Corporate Governance and Nominating Committees. Mr. McGee has been a partner of Zeifmans LLP ("Zeifmans") since 1995. Mr. McGee began working at Zeifmans shortly after receiving a B.A. degree in Commerce from the University of Toronto in 1985. Zeifmans is a Chartered Accounting firm based in Toronto, Ontario. A significant element of Zeifmans’ business is public corporation accounting and auditing. Mr. McGee is a Chartered Accountant. Throughout his career, Mr. McGee has focused on, among other areas, public corporation accounting and auditing. In 1992, Mr. McGee completed courses focused on International Taxation and Corporation Reorganizations at the Canadian Institute of Chartered Accountants and in 2003, Mr. McGee completed corporate governance courses on compensation and audit committees at Harvard Business School. In April 2004 Mr. McGee received his CPA designation from The American Institute of Certified Public Accountants. Mr. McGee has received a certificate in International Financial Reporting Standards issued by The Institute of Chartered Accountants in England and Wales in 2010. The Board believes that Mr. McGee’s knowledge and understanding of accounting and finance, his education and training in accounting and corporate governance, and his extensive experience in the accounting industry.

S. Gail Eckhardt, MD. Dr. Eckhardt is a tenured professor at The University of Texas at Austin’s Dell Medical School where she is also the inaugural director of the Livestrong Cancer Institutes, chair of the Department of Oncology, and associate dean of cancer programs. She has been a faculty member at the institution since January of 2017. Prior to joining UT Austin, Eckhardt was at the University of Colorado School of Medicine where she was division head of medical oncology from 2006-2014, associate director for translational research at the University of Colorado Comprehensive Cancer Center and director of the Phase I Program and Fellowship.

Dr. Eckhardt has served on numerous committees/study sections, including the ASCO Molecular Oncology Task Force, the ASCO Board of Directors, the FDA Oncology Drugs Advisory Committee and the NCI Cancer Centers Study Section. She is a member of the NCI Investigational Drug Steering Committee, serves on 10 External Advisory Boards of NCI designated Cancer Centers, is currently on the Board of the Association of American Cancer Institutes (AACI) and was a lead mentor in ASCO’s Leadership Development Program. Dr. Eckhardt is the Principal Investigator on grants involving early clinical trials and colorectal cancer research, has conducted numerous phase I and II clinical trials and has published over 200 manuscripts. She is a Research Scholar of the Cancer Prevention and Research Institute of Texas (CPRIT).

Dr. Eckhardt’s expertise is in the preclinical and early clinical development of novel agents and she has over 25 years of drug development experience. Dr. Eckhardt earned her undergraduate degree in chemistry from Stephen F. Austin State University and her medical degree from the University of Texas Medical Branch in Galveston, TX. She conducted her internship and residency in Internal Medicine at the University of Virginia Medical School in Charlottesville, VA followed by a post-doctoral research fellowship in experimental and molecular medicine at Scripps Research Institute in La Jolla, CA and a fellowship in medical oncology at the University of California, San Diego.

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Item 6. Executive Compensation.

In fiscal 2018 and 2019, due to limited resources, we did not pay any cash or non-cash compensation to executive officers or directors and the Company’s board of directors does not have a compensation committee.

The Company has no outstanding options or warrants.

Item 7. Certain Relationships and Related Transactions, and Director Independence.

Related Party Transactions

As of January 31, 2020, the only related party transactions are capital transactions between the Company and its parent Generex.

Director Independence

Our board of directors are composed of six “independent directors” as defined under the rules of Nasdaq. We use the definition of “independence” of Nasdaq to make this determination. Nasdaq Listing Rule 5605(a)(2) provides that an “independent director” is a person other than an officer or employee of the company or any other individual having a relationship which, in the opinion of the Company’s Board, would interfere with the exercise of independent judgment in carrying out the responsibilities of a director. The Nasdaq listing rules provide that a director cannot be considered independent if:

• the director is, or at any time during the past three (3) years was, an employee of the company;

• the director or a family member of the director accepted any compensation from the company in excess of $120,000 during any period of twelve (12) consecutive months within the three (3) years preceding the independence determination (subject to certain exemptions, including, among other things, compensation for board or board committee service);

• the director or a family member of the director is a partner in, controlling shareholder of, or an executive officer of an entity to which the company made, or from which the company received, payments in the current or any of the past three fiscal years that exceed 5% of the recipient’s consolidated gross revenue for that year or $200,000, whichever is greater (subject to certain exemptions);

• the director or a family member of the director is employed as an executive officer of an entity where, at any time during the past three (3) years, any of the executive officers of the company served on the compensation committee of such other entity; or

• the director or a family member of the director is a current partner of the company’s outside auditor, or at any time during the past three (3) years was a partner or employee of the company’s outside auditor, and who worked on the company’s audit.

Under such definitions, our Board has undertaken a review of the independence of each director. Based on information provided by each director concerning his or her background, employment and affiliations, our Board has determined that Dr. Craig Eagle, MD and Dr. Marvin S. Hausman, MD, Thomas Leonard, Dr. Carol Nacy, Ph.D, Brian McGee and Dr. S. Gail Eckhardt, MD are all independent directors of the Company. However, our common stock is not currently quoted or listed on any national exchange or interdealer quotation system with a requirement that a majority of our Board be independent and, therefore, the Company is not subject to any director independence requirements.

Audit Committee

We have established an audit committee consisting of Brian McGee and Anthony Crisci. In addition, our Board has determined that Brian McGee is an audit committee financial expert within the meaning of Item 407(d) of Regulation S-K under the Securities Act. The audit committee’s duties, which are specified in our Audit Committee Charter, include, but are not limited to:

● reviewing and discussing with management and the independent auditor the annual audited financial statements, and recommending to the board whether the audited financial statements should be included in our annual disclosure report;

● discussing with management and the independent auditor significant financial reporting issues and judgments made in connection with the preparation of our financial statements;

● discussing with management major risk assessment and risk management policies;

● monitoring the independence of the independent auditor;

● verifying the rotation of the lead (or coordinating) audit partner having primary responsibility for the audit and the audit partner responsible for reviewing the audit as required by law;

● reviewing and approving all related-party transactions;

● inquiring and discussing with management our compliance with applicable laws and regulations;

● pre-approving all audit services and permitted non-audit services to be performed by our independent auditor, including the fees and terms of the services to be performed;

● appointing or replacing the independent auditor;

● determining the compensation and oversight of the work of the independent auditor (including resolution of disagreements between management and the independent auditor regarding financial reporting) for the purpose of preparing or issuing an audit report or related work;

● establishing procedures for the receipt, retention and treatment of complaints received by us regarding accounting, internal accounting controls or reports which raise material issues regarding our financial statements or accounting policies; and

● approving reimbursement of expenses incurred by our management team in identifying potential target businesses.

Item 8. Legal Proceedings.

We are not currently a party to any material legal proceedings, nor, to our knowledge, is any material legal proceeding threatened against us.

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Item 9. Market Price of and Dividends on the Registrant’s Common Equity and Related Stockholder Matters.

We are a smaller reporting company, as defined in Rule 12b-2 of the Exchange Act. Accordingly, we have omitted certain information called for by this Item as permitted by applicable scaled disclosure rules.

(a) Market information

Our common stock is not trading on any stock exchange, quoted on any interdealer quotation system and there is no established public trading market for the class of common equity.

(b) Holders.

As of June 10, 2020, there are approximately 477 record holders of an aggregate of 400,000,000 shares of our common stock issued and outstanding.

(c) Dividends.

We have not paid any cash dividends to date and do not anticipate or contemplate paying dividends in the foreseeable future. It is the president intention of management to utilize all available funds for the development of the Registrant’s business.

(d) Securities authorized for issuance under equity compensation plans.

None

Item 10. Recent Sales of Unregistered Securities.

The Company has not sold any of its securities within the past three years.

Item 11. Description of Registrant’s Securities to be Registered.

The following description of our capital stock is qualified by reference to our certificate of incorporation, as amended, which is filed as exhibits to this registration statement.

Authorized Capital Stock

Our authorized capital stock consists of 750,000,000 shares of common stock, $0.001 par value and 10,000,000 shares of preferred stock, $0.001 par value. As of June 10, 2020, there were 400,000,000 shares of common stock outstanding and no preferred stock is outstanding. As of June 10, 2020, there were approximately 477 holders of record of our common stock.

Common Stock

Holders of common stock are entitled to one vote for each share owned as of record on all matters on which shareholders may vote. Holders of common stock do not have cumulative voting rights in the election of directors. Therefore, holders of more than 50% of the outstanding shares can elect the entire Board of Directors. The holders of common stock are entitled, upon liquidation or dissolution of the Company, to receive pro rata all remaining assets available for distribution to stockholders after payment to any preferred shareholders who may have preferential rights. The common stock has no preemptive or other subscription rights, and there are no conversion rights or redemption provisions. All outstanding shares of common stock are validly issued, fully paid, and nonassessable.

Preferred Stock

Our Certificate of Incorporation, as amended, authorizes our Board of Directors to issue up to 10,000,000 shares of preferred stock from time to time with such designations, preferences, conversion or other rights, voting powers, restrictions, dividends or limitations as to dividends or other distributions, qualifications or terms or conditions of redemption as shall be determined by the Board of Directors for each class or series of stock. There are currently no shares of preferred stock outstanding.

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Item 12. Indemnification of Directors and Officers.

Subsection (a) of Section 145 of the General Corporation Law of Delaware, or the DGCL, empowers a corporation to indemnify any person who was or is a party or is threatened to be made a party to any threatened, pending or completed action, suit or proceeding, whether civil, criminal, administrative or investigative (other than an action by or in the right of the corporation) by reason of the fact that he is or was a director, employee or agent of the corporation or is or was serving at the request of the corporation as a director, officer, employee or agent of another corporation, partnership, joint venture, trust or other enterprise, against expenses (including attorneys’ fees), judgments, fines and amounts paid in settlement actually and reasonably incurred by him in connection with such action, suit or proceeding if he acted in good faith and in a manner he reasonably believed to be in or not opposed to the best interests of the corporation and, with respect to any criminal action or proceeding, had no reasonable cause to believe his conduct was unlawful.

Subsection (b) of Section 145 of the DGCL empowers a corporation to indemnify any person who was or is a party or is threatened to be made a party to any threatened, pending or completed action or suit by or in the right of the corporation to procure a judgment in its favor by reason of the fact that such person acted in any of the capacities set forth above, against expenses (including attorneys’ fees) actually and reasonably incurred by him in connection with the defense or settlement of such action or suit if he acted in good faith and in a manner he reasonably believed to be in or not opposed to the best interests of the corporation and except that no indemnification may be made with respect to any claim, issue or matter as to which such person shall have been adjudged to be liable to the corporation unless and only to the extent that the Court of Chancery or the court in which such action or suit was brought shall determine upon application that, despite the adjudication of liability but in view of all of the circumstances of the case, such person is fairly and reasonably entitled to indemnity for such expenses which the Court of Chancery or such other court shall deem proper.

Section 145 of the DGCL further provides that to the extent a director, officer, employee or agent of a corporation has been successful on the merits or otherwise in the defense of any action, suit or proceeding referred to in subsections (a) and (b) or in the defense of any claim, issue or matter therein, he shall be indemnified against expenses (including attorneys’ fees) actually and reasonably incurred by him in connection therewith; that indemnification or advancement of expenses provided for by Section 145 shall not be deemed exclusive of any other rights to which the indemnified party may be entitled; and empowers the corporation to purchase and maintain insurance on behalf of a director, officer, employee or agent of the corporation against any liability asserted against him or incurred by him in any such capacity or arising out of his status as such whether or not the corporation would have the power to indemnify him against such liabilities under Section 145.

Reference is also made to Section 102(b)(7) of the DGCL, which enables a corporation in its certificate of incorporation to eliminate or limit the personal liability of a director for monetary damages for violations of a director’s fiduciary duty, except for liability (i) for any breach of the director’s duty of loyalty to the corporation or its stockholders, (ii) for acts or omissions not in good faith or which involve intentional misconduct or a knowing violation of law, (iii) under Section 174 of the DGCL (providing for liability of directors for unlawful payment of dividends or unlawful stock purchases or redemptions) or (iv) for any transaction from which the director derived an improper personal benefit. Our amended and restated certificate of incorporation provides that a director of the Company will not be personally liable for monetary damages for breach of fiduciary duty as a director, except:

• for any breach of duty of loyalty to us or to our stockholders;

• for acts or omissions not in good faith or that involve intentional misconduct or a knowing violation of law;

• for unlawful payment of dividends or unlawful stock repurchases or redemptions; or

• for any transaction from which the director derived an improper personal benefit.

In addition, our bylaws provide that:

• we are required to indemnify our directors and executive officers to the fullest extent not prohibited by Delaware law or any other applicable law, subject to limited exceptions;

• we may indemnify our other officers, employees and other agents as set forth in Delaware law or any other applicable law;

• we are required to advance expenses to our directors and executive officers as incurred in connection with legal proceedings against them for which they may be indemnified; and

• the rights conferred in the amended and restated bylaws are not exclusive.

21

Item 13. Financial Statements and Supplementary Data.

Our Financial Statements begin on page F-1 and are incorporated in this Item 13 by reference.

Item 14. Changes in and Disagreements with Accountants on Accounting and Financial Disclosure.

Not applicable.

Item 15. Financial Statements and Exhibits.

15(a) Financial Statements: The financial statements filed herewith are set forth on the Index to Consolidated Financial Statements on page F-1 of the separate financial section which accompanies this registration statement, which is incorporated herein by reference.

15(b) Exhibits: The exhibits listed in the Exhibit Index below are filed as part of this registration statement.

Exhibit Number	Description
3.1	Amended and Restated Certificate of Incorporation of the registrant. *
3.2	Restated By-Laws of the registrant.*
10.1	Clinical Trial Collaboration and Supply Agreement dated June 28, 2017 by and among Merck Sharp & Dohme B.V. and NuGenerex Immuno-Oncology, Inc. (formerly Antigen Express, Inc.).
10.2	Clinical Trial Agreement dated November 20, 2018 between NSABP Foundation, Inc. and NuGenerex Immuno-Oncology, Inc. (formerly Antigen Express, Inc.).
10.3	License and Research Agreement dated November 29, 2017 between NuGenerex Immuno-Oncology, Inc. (formerly Antigen Express, Inc.) and Shenzhen Bioscien Pharmaceuticals Co. Ltd.
23.1	Consent of Independent Registered Public Accounting Firm

* Filed as an exhibit to the Registration Statement on Form 10 filed on March 12, 2020

22

SIGNATURES

Pursuant to the requirements of Section 12 of the Securities Exchange Act of 1934, the registrant has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized.

	NUGENEREX IMMUNO-ONCOLOGY, INC.
Date: June 12, 2020	By:	/s/Joseph Moscato
		Joseph Moscato
		Chief Executive Officer

23

INDEX TO FINANCIAL STATEMENTS
AUDITED FINANCIAL STATEMENTS
Report of Independent Registered Public Accounting Firm	F-2
Balance Sheets as of July 31, 2019 and 2018	F-3
Statements of Operations for the years ended July 31, 2019 and 2018	F-4
Statements of Changes in Stockholders’ Deficit for the years ended July 31, 2019 and 2018	F-5
Statements of Cash Flows for the and years ended July 31, 2019 and 2018	F-6
Notes to Financial Statements	F-7 - F-12
INTERIM FINANCIAL INFORMATION (Unaudited)
Condensed Balance Sheets as of January 31, 2020 (Unaudited) and July 31, 2019	F-13
Condensed Statements of Operations for the three and six months ended January 31, 2020 and 2019 (Unaudited)	F-14
Condensed Statements of Stockholders’ Deficit for the six months ended January 31, 2019 and 2020 (Unaudited)	F-15
Condensed Statements of Cash Flows for the six months ended January 31, 2020 and 2019 (Unaudited)	F-16
Notes to condensed financial information (Unaudited)	F-17 - F-20

F-1

REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM

To the Board of Directors and Stockholders of NuGenerex Immuno-Oncology, Inc.

Opinion on the Financial Statements

We have audited the accompanying balance sheets of NuGenerex Immuno-Oncology, Inc. (the “Company”) as of July 31, 2019 and 2018, and the related statements of operations, changes in stockholders’ deficit, and cash flows for each of the two years in the period ended July 31, 2019, and the related notes (collectively referred to as the “financial statements”). In our opinion, the financial statements present fairly, in all material respects, the financial position of the Company as of July 31, 2019 and 2018, and the results of their operations and their cash flows for the years then ended, in conformity with accounting principles generally accepted in the United States of America.

Explanatory Paragraph Regarding Going Concern

The accompanying financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in Note 1 to the financial statements, the Company has incurred significant operating losses from inception and has both a working capital deficiency and accumulated deficit of $36,834,887 at July 31, 2019. The Company is dependent on obtaining necessary funding from their parent Company, as well as other outside sources, including obtaining additional funding from private placements of its common stock, and issuances of debt and convertible debt instruments in order to continue their operations. These conditions raise substantial doubt about its ability to continue as a going concern. Management’s plans regarding those matters also are described in Note 1. The financial statements do not include any adjustments that might result from the outcome of this uncertainty.

Basis for Opinion

These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s financial statements based on our audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (PCAOB) and are required to be independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the PCAOB.

We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audits to obtain reasonable assurance about whether the financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits, we are required to obtain an understanding of internal control over financial reporting, but not for the purpose of expressing an opinion on the effectiveness of the Company’s internal control over financial reporting. Accordingly, we express no such opinion.

Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also included evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe that our audits provide a reasonable basis for our opinion.

/s/ Mazars USA LLP

We have served as the Company’s auditor since 2019

Edison, NJ

March 12, 2020

F-2

NUGENEREX IMMUNO-ONCOLOGY, INC.
BALANCE SHEETS
	July 31,
	2019			2018
ASSETS
Current Assets:
Cash and total current assets	$	389		$	1,025
LIABILITIES AND STOCKHOLDERS’ DEFICIT
Current Liabilities:
Accounts payable and accrued expenses	$	12,528		$	7,753
Payable to Foundation for services		1,315,817			1,315,817
Interest payable to foundation		3,055,945			2,340,670
Total Current Liabilities		4,384,290			3,664,240
Commitments and Contingencies		—			—
Stockholders’ Deficiency
Common stock, $0.001 par value, 400,000,000 shares authorized, issued, and outstanding		400,000			400,000
Additional paid-in capital		32,050,986			31,663,656
Accumulated deficit		(36,834,887	)		(35,726,871	)
Total Stockholders’ Deficiency		(4,383,901	)		(3,663,215	)
TOTAL LIABILITIES AND STOCKHOLDERS’ DEFICIENCY	$	389		$	1,025
The accompanying notes are an integral part of these financial statements

F-3

NUGENEREX IMMUNO-ONCOLOGY, INC.
STATEMENTS OF OPERATIONS
YEARS ENDED JULY 31,
	2019			2018
Revenue
Licensing revenue	$	—		$	700,000
Operating expenses
Research and development		354,000			234,317
General and administrative		38,741			40,691
Total operating expenses		392,741			275,008
Operating (loss) income		(392,741	)		424,992
Other Expense:
Interest expense		(715,275	)		(598,247	)
Net Loss	$	(1,108,016	)	$	(173,255	)
Net Loss per Common Share – basic and diluted	$	0.00		$	0.00
Shares Used to Compute Net Loss per Share – basic and diluted		400,000,000			400,000,000
The accompanying notes are an integral part of these financial statements

F-4

NUGENEREX IMMUNO-ONCOLOGY, INC.
STATEMENTS OF STOCKHOLDERS’ DEFICIT
YEARS ENDED JULY 31, 2019 and 2018
	Common Stock
	Shares		Amount		Additional Paid-in Capital			Accumulated Deficit			Total Stockholders’ Deficit
Balance as of July 31, 2017	400,000,000	$	400,000	$	32,059,639		$	(35,553,616	)	$	(3,093,977	)
Distribution to Generex					(700,000	)					(700,000	)
Contributions from Generex					304,017						304,017
Net loss	—		—		—			(173,255	)		(173,255	)
Balance as of July 31, 2018	400,000,000		400,000		31,663,656			(35,726,871	)		(3,663,215	)
Contributions from Generex					387,330						387,330
Net loss	—		—					(1,108,016	)		(1,108,016	)
Balance as of July 31, 2019	400,000,000	$	400,000	$	32,050,986		$	(36,834,887	)	$	(4,383,901	)

The accompanying notes are an integral part of these financial statements 

F-5

NUGENEREX IMMUNO-ONCOLOGY, INC.
STATEMENTS OF CASH FLOWS
YEARS ENDED JULY 31,
		2019			2018
CASH FLOWS FROM OPERATING ACTIVITES:
Net Loss	$	(1,108,016	)	$	(173,255	)
Adjustments to reconcile net loss to net cash used in operating activities:
Changes in operating assets and liabilities:
Interest payable to foundation		715,275			598,247
Accounts payable and accrued expenses		392,105			(424,054	)
Net (decrease) increase in cash and cash equivalents		(636	)		938
Cash, beginning of period		1,025			87
Cash, end of period	$	389		$	1,025
SUPPLEMENTAL CASH FLOW INFORMATION:
Cash paid for interest	$	—		$	—
Cash paid of income taxes	$	—		$	—
NON-CASH INVESTING AND FINANCING ACTIVITES:
Expenses paid by parent as non-cash capital contributions	$	387,330		$	304,017
Revenue received by parent as distribution to parent	$	—		$	700,000

The accompanying notes are an integral part of these financial statements

F-6

NUGENEREX IMMUNO-ONCOLOGY, INC.

NOTES TO FINANCIAL STATEMENTS

Note 1 – Organization of Business and Going Concern:

NuGenerex Immuno-Oncology, Inc., a Delaware corporation formed in October of 1993 and formerly known as Antigen Express, Inc. (“NGIO” or the “Company”) and for all periods presented Generex Biotechnology Corporation (“Generex”) held a controlling financial interest in the Company. NGIO is an oncology company focused on the modulation of the immune system to treat cancer. To that end, the Company is developing immunotherapeutic products and vaccines based on our proprietary, patented platform technology.

As part of its strategy, Generex has elected to spin-out NuGenerex Immuno-Oncology, Inc. as a separate, publicly traded Company.

Going Concern

The accompanying financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America (“US GAAP”), which contemplates continuation of the Company as a going concern. The Company has experienced recurring net losses and negative cash flows from operations since inception and has accumulated deficits of approximately $36.8 million as of July 31, 2019. Additionally, the Company has a working capital deficiency of approximately $4.4 million as of July 31, 2019. The Company’s parent, Generex Biotechnology Corporation (“Generex”) has funded substantially all the Company’s underlying working capital deficiencies. These conditions raise substantial doubt about the Company’s ability to continue as a going concern.

The Company will continue to require substantial funds to implement its business plans.  Management’s plans in order to meet its operating cash flow requirements include financing activities such as private placements of its common stock, preferred stock offerings, and issuances of debt and convertible debt instruments. There are no assurances that such additional funding will be achieved and that the Company will succeed in its future operations. Management is also actively pursuing financial and strategic alternatives, including strategic investments and divestitures, industry collaboration activities and strategic partners.

These financial statements do not include any adjustments to the recoverability and classification of recorded assets amounts and classification of liabilities that might be necessary should the Company not be able to continue as a going concern. The Company’s inability to obtain required funding in the near future or its inability to obtain funding on favorable terms will have a material adverse effect on its operations and strategic development plan for future growth. If the Company cannot successfully raise additional capital and implement its strategic development plan, its liquidity, financial condition and business prospects will be materially and adversely affected, and the Company may have to cease operations.

F-7

Note 2 – Summary of Significant Accounting Policies:

Basis of Presentation

The Company’s financial statements have been included in the consolidated financial statements of its parent, Generex, and the Company has been dependent on Generex to fund its operations. Generex does not have costs centralized or shared services departments serving all its subsidiaries, accordingly, no allocations of centralized or shared service are necessary or included in the financial statements, as they are de-minimums.

The accompanying financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America (“U.S. GAAP”).

Use of Estimates

The preparation of consolidated financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets and liabilities and disclosure of contingent assets and liabilities at the dates of the consolidated financial statements and the reported amounts of revenues and expenses during the reporting periods.

Research and Development Costs

Expenditures for research and development are expensed as incurred and include, among other costs, those related to the production of experimental drugs, including payroll costs, and amounts incurred for conducting clinical trials. Amounts expected to be received from governments under research and development tax credit arrangements are offset against current research and development expense.

Income Taxes

NGIO is included in the Generex consolidated federal tax return. All tax provisions and the related tax liabilities and assets have been computed using the separate return method, as if the company was the legal taxpayer.

Income taxes are accounted for under the asset and liability method prescribed by FASB Accounting Standards Codification (“ASC”) Topic 740. These standards require a company to determine whether it is more likely than not that a tax position will be sustained upon examination based upon the technical merits of the position. If the more likely than not threshold is met, a company must measure the tax position to determine the amount to recognize in the financial statements. Deferred income taxes are recorded for temporary differences between financial statement carrying amounts and the tax basis of assets and liabilities. Deferred tax assets and liabilities reflect the tax rates expected to be in effect for the years in which the differences are expected to reverse. A valuation allowance is provided if it is more likely than not that some or all the deferred tax asset will not be realized.

F-8

Revenue

The Company generated revenue from licenses to access its intellectual property. During the fiscal year ended July 31, 2018, the Company recognized revenue related to a nonrefundable, up-front license fee for $700,000.

If a license to the Company’s intellectual property is determined to be distinct from the other performance obligations identified in the arrangement, the Company recognizes revenues attributed to the license when the license is transferred to the customer and the customer is able to use and benefit from the license. For licenses that are bundled with other promises, the Company utilizes judgement to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time. At the inception of each arrangement that contain development milestones, the Company evaluates whether the development milestones included are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the control of the Company or the licensee, such as regulatory approvals, are not generally considered probable of being achieved until those approvals are received.

New Accounting Standards

The Company has reviewed the FASB issued Accounting Standards Update (“ASU”) accounting pronouncements and interpretations thereof that have effective dates during the periods reported and in future periods. The Company does not believe that any new or modified principles will have a material impact on the Company’s reported financial position or operations in the near term. The applicability of any standard is subject to the formal review of our financial management and certain standards are under consideration.

In February 2016, the FASB issued ASU No. 2016-02, Leases (“ASU 2016-02”). In January 2018, the FASB issued ASU 2018-01, which provides additional implementation guidance on the previously issued ASU 2016-02. Under the new guidance, lessees will be required to recognize the following for all leases (with the exception of short-term leases) at the commencement date: (1) a lease liability, which is a lessee's obligation to make lease payments arising from a lease, measured on a discounted basis; and (2) a right-of-use asset, which is an asset that represents the lessee's right to use, or control the use of, a specified asset for the lease term. The Company is required to adopt ASU 2016-02 for fiscal years, and for interim periods within those fiscal years, beginning after December 15, 2018. This ASU will be effective for us in the first quarter of 2019 which begins with interim period ending October 31, 2019. We do not anticipate the adoption of this ASU to have a material impact to our financial statements.

Note 3 - Commitments and Contingencies:

Commitments

On November 29, 2017, the Company entered into a clinical trial agreement (“CTA”) with a shanghai based, contract research organization (“CRO”) for a four-year Phase II study of AE37 for the treatment of metastatic triple negative breast cancer. In accordance with the CTA, the Company agrees to pay the CRO amounts not to exceed $5,747,039, unless approved in writing by both parties, upon completion of certain milestones and achievements over the four-year study.

On November 20, 2018, the Company entered into a clinical trial agreement with NSABP Foundation, Inc. (“NSABP”) under which NSABP will conduct clinical research using the Company’s AE37 peptide immunotherapeutic vaccine in combination with pembrolizumab (Ketruda®) for the treatment of metastatic triple negative breast cancer. The Company has agreed to pay NSABP an amount not to exceed $2,118,461 based on NAABP achieving various milestones.

The Company recognized $340,000 as research and development related to the clinical trial agreement with NSABP in the year ended July 31, 2019.

F-9

Payable to Foundation

On February 1, 2007, the Company entered into a clinical study agreement (the “CSA”) with a Henry J. Jackson Foundation for “Foundation”).for two phase II clinical trials to determine if a vaccine containing AE37 plus another compound improved patient outcomes compared to the other compounds alone. The Foundation conducted the study, under the sponsorship of an institute affiliated with the United States Military. In consideration for the study the Company agreed to total compensation of $2,700,000 payable as follows:

i.	Initial payments of:
	a. $250,000 on February 1, 2007; and
	b. $250,000 on March 1, 2007

ii. Ongoing payments of $150,000 per quarter for three years beginning first quarter of 2007.

iii. Final payments: $200,000 upon enrollment of the final subject and $200,000 upon completion of all subjects and receipt and acceptance of by the Company of all required documents.

Upon written notice either party could terminate the agreement for insolvency or proceedings under bankruptcy law. The Company could Terminate the CSA without cause upon written notice to the Foundation. Although the Agreement has not been terminated, the Foundation has not provided the Company with a final clinical study report as required under the terms of the CSA.

On September 1, 2013 the Foundation and the Company entered into a forbearance agreement (the “Forbearance Agreement”) under which the Company acknowledged they were $1,315,817 in arrears in its payment and interest obligations to the Foundation under the CSA (the “Original Forbearance Amount”). Pursuant to the Forbearance Agreement, the Company and the Foundation in exchange for the Foundations deferring the Company’s overdue payments, future payments and interest, the Company agreed, among other things to pay the Foundation certain royalties and accelerated payments (“Forbearance Payments”) as further described below.

1) The Company agreed to pay the final $200,000 payment due upon completion of all subjects and acceptance by the company of all documents, out of and a first charge any amounts received by the foundation or the Company from a third party in respect of or relating to the continued clinical development and commercialization of the breast cancer indication of the vaccine.

2) A royalty equal to five percent (5%) of the Net third party sales of the Vaccine.

3) The Original Forbearance Amount will continue to accrue interest at one- and one-half percent (1.5%) per month.

Once the Company has repaid the Original Forbearance Amount and interest through the royalty mechanism described above the Company may buy-out its continuing obligation to make Forbearance Payments my making the following payments:

i. Period 1 (Effective date of the Forbearance Agreement through fifteenth month after the effective date of the Forbearance Agreement) buyout for $200,000

ii. Period 2 (First following the end of period 1 through the twenty-fourth month after the effective date of the Forbearance Agreement) Buyout for $500,000

iii. Period 3 (the beginning of the third year following the Effective Date through the end of the fifth year following the effective date of the Forbearance Agreement) Buyout for $1,000,000

iv. Period 4 (any time after the beginning of the sixth year following the effective date of the Forbearance Agreement) Buyout for $2,000,000.

The Company has not made any buy-out payments under the Forbearance Agreement. The Foundation May terminate the Forbearance Agreement, in its sole discretion upon giving written notice the Company of any of the following:

i. If the Company fails to make a payment under the Forbearance Agreement (including interest) and fails to cure such nonpayment with thirty days after receiving written notice of such non-payment by the Foundation or;

ii. if the Company is unable to repay its debts, makes a general assignment for the benefit of its creditors, has a petition in bankruptcy or a suit seeking reorganization, liquidation, dissolution, or similar relief filed against or files or permits the filing seeking relief under bankruptcy or;

iii. the Company is in default in the performance of any of its obligations under the Forbearance Agreement and such default is not cured within thirty days after receiving written notice from the foundation of such default.

The Foundation has not notified the Company that it is default of any of its obligations under the Forbearance agreement.

Effective August 1, 2015, the Company capitalized all outstanding unpaid interest on the outstanding balance. The. For the years ended July 31, 2019 and 2018, the Company recorded interest expense in the amount of $715,275 and $598,247, respectively, in the statements of operations. As of July 31, 2019, and 2018 the Company has recorded accrued interest of $3,055,945and $2,340,670, respectively.

F-10

Related Party

During the year ended July 31, 2018, Generex collected on behalf of the Company, $700,000 in revenue from the non-refundable license fee. (See Note 2) Company did not collect any cash from Generex related to this transaction, accordingly, the Company treated cash it was due from this transaction as distribution to Generex.

Expenses paid by Generex on behalf of the Company have been treated as Capital contributions from Generex as Generex will not be reimbursed by the Company for these expenses. On behalf of the Company Generex paid expenses of $387,330 and $304,017 for the years ended July 31, 2019 and 2018, respectively.

Note 5 - Stockholders’ Deficiency:

Common Stock

On February 21, 2019, the Company issued a 4,000 to 1 stock split, in which all shares outstanding have been presented retrospectively for all periods presented. The Company has 400,000,000 authorized, issued, and outstanding shares of common stock with a $0.001 par value (the “Common Stock”). The holders of Common Stock are entitled to one vote per share of Common Stock held at the time of vote.

 Note 6 – Income Taxes:

The Company has incurred losses since inception, which have generated net operating loss carryforwards. Pre-tax losses were $1,108,016 and $173,225 for the years ended July 31, 2019 and 2018, respectively.

As of July 31, 2019, the Company has net operating loss carryforwards of approximately $35.9 million, available to reduce future federal and state taxable income. The carryforwards may be limited in future years due as a result of ownership changes. The net operating losses of approximately $1.3 million relating to the tax years after July 31, 2017 may be carried forward indefinitely, however, its use is limited to 80% of taxable income. The remaining net operating loss carryforwards prior to the tax years ending July 31, 2018 of approximately $34.6 million can be carried forward for 20 years with its use limited to 100% of taxable income in any given year. Carryforwards for tax years ending prior to July 31, 2018 will begin to expire next year.

Net deferred tax assets approximated the following: 

	July 31,
	2019			2018
Net operating loss carryforwards	$	9,821,000		$	9,643,000
Valuation Allowance		(9,821,000	)		(9,643,000	)
Net Deferred Tax assets	$	—		$	—

On December 22, 2017, the Tax Cuts and Jobs Act (“The Act”), was signed into law by President Trump. The Act includes several provisions, including the lowering of the U.S. corporate tax rate from 34 percent to 21 percent, effective January 1, 2018 and the establishment of a territorial-style system for taxing foreign-source income of domestic multinational corporations. The Company remeasured its deferred tax assets and liabilities as of July 31, 2018, applying the reduced corporate income tax rate and recorded a provisional decrease to the deferred tax assets of approximately $4,208,000, with a corresponding adjustment to the valuation allowance. In the fourth quarter of fiscal year ended July 31, 2019, we completed our analysis to determine the effect of the Tax Act and there were no material adjustments as of July 31, 2019. The change in the valuation allowance approximated an increase of $178,000 for the fiscal year ended July 31, 2019.

As of July 31, 2019, and 2018, the Company had no unrecognized tax benefits or accrued interest, or penalties related to uncertain tax positions. Accordingly, the Company has not recognized any adjustment to its financial position, results of operations or cash flows. The Company does not expect that unrecognized tax benefits will increase within the next twelve months. The Company has not recognized any penalties or interest. The Company will recognize interest and penalties related to tax matters within other expense. Generally, tax years 2016 to 2019 remain open to examination by the Internal Revenue Agency or other tax jurisdictions to which the Company is subject.

F-11

A reconciliation of the United States Federal Statutory rate to the Company’s effective tax rate for the years ended July 31, 2019 and 2018 is as follows: 

	July 31,
	2019			2018
Benefit at Federal rate		(21.0	)%		(26.4	)%
State rate, net of Federal		(6.3	)		(5.3	)
Tax rate change		—			2,429.1
Expiration of NOL		11.3			—
Valuation allowance		16.0			(2,397.4	)
Effective tax rate		—	%		—	%

Note 7–Securities Registration:

The Company intends to file a Registration Statement on Form 10 under the Securities Exchange Act of 1934 (the Exchange Act”). The registration statement registers the Company’s common stock under the Exchange Act.

Note 8 – Subsequent Events:

The Company has evaluated subsequent events occurring after the balance sheet date through the date the audited annual consolidated financial statements were issued.

On March 10, 2020, the Company increased the number of authorized shares from 400,000,000 to 760,000,000, which consists of 750,000,000 shares of common stock, par value $0.001 per share and 10,000,000 shares of preferred stock, par value $0.001 per share.  The preferred stock may be issued in one of more series and may have preferences as to dividends and to liquidation of the Company.

F-12

NUGENEREX IMMUNO-ONCOLOGY, INC.
CONDENSED BALANCE SHEETS
		January 31, 2020			July 31, 2019
		(Unaudited)
ASSETS
Current Assets:
Cash and total current assets	$	174		$	389
LIABILITIES AND STOCKHOLDERS’ DEFICIENCY
Accounts payable and accrued expenses	$	349,732		$	12,528
Payable to foundation for services		1,315,817			1,315,817
Interest payable to foundation		3,464,457			3,055,945
Total Current Liabilities		5,130,006			4,384,290
Commitments and Contingencies		—			—
Stockholders’ Deficiency
Common stock, $0.001 par value, 400,000,000 shares authorized, issued, and outstanding		400,000			400,000
Additional paid-in capital		32,080,686			32,050,986
Accumulated deficit		(37,610,518	)		(36,834,887	)
Total Stockholders’ Deficiency		(5,129,832	)		(4,383,901	)
TOTAL LIABILITIES AND STOCKHOLDERS’ DEFICIENCY	$	174		$	389
The accompanying notes are an integral part of these condensed financial statements

F-13

NUGENEREX IMMUNO-ONCOLOGY, INC.
CONDENSED STATEMENTS OF OPERATIONS
(UNAUDITED)
	Three Months Ended						Six Months Ended
	January 31, 2020			January 31, 2019			January 31, 2020			January 31, 2019
Revenue
Licensing revenue	$	—		$	—		$	—		$	—
Operating expenses
Research and development		3,500			342,000			255,265			354,000
General and administrative		80,050			892			111,854			8,968
Total operating expenses		83,550			342,892			367,119			362,968
Operating loss		(83,550	)		(342,892	)		(367,119	)		(362,968	)
Other Expense
Interest expense		(208,817	)		(174,652	)		(408,512	)		(341,674	)
Net Loss	$	(292,367	)	$	(517,544	)	$	(775,631	)	$	(704,642	)
Net Loss per Common Share – basic and diluted	$	0.00		$	0.00		$	0.00		$	0.00
Shares Used to Compute Net Loss per Share – basic and diluted		400,000,000			400,000,000			400,000,000			400,000,000

The accompanying notes are an integral part of these condensed financial statements

F-14

NUGENEREX IMMUNO-ONCOLOGY, INC.
CONDENSED STATEMENTS OF STOCKHOLDERS’ DEFICIT (Unaudited)
	Common Stock
	Shares		Amount		Additional Paid in Capital		Accumulated Deficit			Total Stockholders’ Deficit
Balance as of July 31, 2018	400,000.000	$	400,000	$	31,663,656	$	(35,726,871	)	$	(3,663,215	)
Contribution from Generex					18,317					18,317
Net Loss							(187,098	)		(187,098	)
Balance October 31, 2018	400,000,000		400,000		31,681,973		(35,913,969	)		(3,831,996	)
Contribution from Generex					342,847					342,847
Net Loss							(517,544	)		(517,544	)
Balance as of January 31, 2019	400,000,000	$	400,000	$	32,024,820	$	(36,431,513	)	$	(4,006,693	)
Balance as of July 31, 2019	400,000,000	$	400,000	$	32,050,986	$	(36,834,887	)	$	(4,383,901	)
Contributions from Generex	—		—		26,586		—			26,586
Net loss	—		—		—		(483,264	)		(483,264	)
Balance as of October 31, 2019	400,000,000		400,000		32,077,572		(37,318,151	)		(4,840,579	)
Contributions from Generex	—		—		3,114		—			3,114
Net loss	—		—		—		(292,367	)		(292,367	)
Balance as of January 31, 2020	400,000,000	$	400,000	$	32,080,686	$	(37,610,518	)	$	(5,129,832	)

The accompanying notes are an integral part of these condensed financial statements

F-15

NUGENEREX IMMUNO-ONCOLOGY, INC.
CONDENSED STATEMENTS OF CASH FLOWS (Unaudited)
	Six Months Ended,
	January 31, 2020		January 31, 2019
CASH FLOWS FROM OPERATING ACTIVITES:
Net loss	$	(775,631)	$	(704,642)
Adjustments to reconcile net loss to net cash used in operating activities:
Changes in operating assets and liabilities:
Interest payable to foundation		408,512		341,675
Accounts payable and accrued expenses		366,904		362,421
Net cash used in operating activities and decrease in cash and cash equivalents		(215)		(546)
Cash, beginning of period		389		1,025
Cash, end of period	$	174	$	479
SUPPLEMENTAL CASH FLOW INFORMATION:
Cash paid for interest	$	-	$	-
Cash paid for income taxes	$	-	$	-
NON-CASH INVESTING AND FINANCING ACTIVITES:
Expenses paid by parent as non-cash capital contributions	$	29,700	$	361,164

The accompanying notes are an integral part of these condensed financial statements

F-16

NUGENEREX IMMUNO-ONCOLOGY, INC.

NOTES TO INTERIM FINANCAL INFORMATION

(Unaudited)

Note 1 Going Concern:

Going Concern

The accompanying financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America (“U.S. GAAP”), which contemplates continuation of the Company as a going concern. The Company has experienced recurring net losses and negative cash flows from operations since inception and has both accumulated deficits of approximately $37.6 and a working capital deficiency of approximately $5.1 million as of January 31, 2020. The Company’s parent, Generex Biotechnology Corporation (“Generex”) has funded substantially all the Company’s underlying working capital deficiencies. The uncertain economic fallout from the COVID -19 pandemic may also adversely affect our operations (See Commitments and Contingencies) These conditions raise substantial doubt about the Company’s ability to continue as a going concern.

The Company will continue to require substantial funds to implement its business plans.  Management’s plans, to meet its operating cash flow requirements, include financing activities such as private placements of its common stock, preferred stock offerings, and issuances of debt and convertible debt instruments. There are no assurances that such additional funding will be achieved and that the Company will succeed in its future operations. Management is also actively pursuing financial and strategic alternatives, including strategic investments and divestitures, industry collaboration activities and strategic partners.

These financial statements do not include any adjustments to the recoverability and classification of recorded assets amounts and classification of liabilities that might be necessary should the Company not be able to continue as a going concern. The Company’s inability to obtain required funding in the near future or its inability to obtain funding on favorable terms will have a material adverse effect on its operations and strategic development plan for future growth. If the Company cannot successfully raise additional capital and implement its strategic development plan, its liquidity, financial condition, and business prospects will be materially and adversely affected, and the Company may have to cease operations.

Note 2 – Summary of Significant Accounting Policies:

Basis of Presentation

The Company’s financial statements have been included in consolidated financial statements of its parent, Generex and the Company has been dependent on Generex to fund its operations. Generex does not have costs centralized or shared services departments serving all its subsidiaries, accordingly, no allocations of centralized or shared service are necessary or included in the financial statements, as they are de-minimis.

The accompanying unaudited condensed financial statements of the Company have been prepared in accordance with accounting principles generally accepted in the United States of America (“U.S. GAAP”) for interim financial information and with the instructions to Form 10-Q and Article 10 of Regulation S-X. Accordingly, they do not include all of the information and footnotes required by U.S. GAAP for complete financial statements. In the opinion of management, all adjustments, which include only normal recurring adjustments, considered necessary for a fair presentation have been included.

F-17

The Company’s fiscal year ends on July 31 of each calendar year. Each reference below to a fiscal year refers to the fiscal year ending in the calendar year indicated.

 Operating results for the three and six months ended January 31, 2020 are not necessarily indicative of the results that may be expected for the fiscal year ending July 31, 2020. The balance sheet at January 31, 2020 does not include all of the information and footnotes required by U.S. GAAP for complete financial statements. Therefore, these condensed financial statements should be read in conjunction with the Company’s audited financial statements and notes thereto included elsewhere in this registration statement.

Research and Development Costs

Expenditures for research and development are expensed as incurred and include, among other costs, those related to the production of experimental drugs, and amounts incurred for conducting clinical trials. Amounts expected to be received from governments under research and development tax credit arrangements are offset against current research and development expense.

Income Taxes

NGIO is included in the Generex consolidated federal tax return. All tax provisions and the related tax liabilities and assets have been computed using the separate return method, as if the company was the legal taxpayer.

Revenue

The Company expects to generate revenue from licenses to access its intellectual property.

If a license to the Company’s intellectual property is determined to be distinct from the other performance obligations identified in the arrangement, the Company recognizes revenues attributed to the license when the license is transferred to the customer and the customer is able to use and benefit from the license. For licenses that are bundled with other promises, the Company utilizes judgement to assess the nature of the combined performance obligation to determine whether the combined performance obligation is satisfied over time or at a point in time. At the inception of each arrangement that contain development milestones, the Company evaluates whether the development milestones included are considered probable of being reached and estimates the amount to be included in the transaction price using the most likely amount method. If it is probable that a significant revenue reversal would not occur, the associated milestone value is included in the transaction price. Milestone payments that are not within the control of the Company or the licensee, such as regulatory approvals, are not generally considered probable of being achieved until those approvals are received.

New Accounting Standards

The Company has reviewed the FASB issued Accounting Standards Update (“ASU”) accounting pronouncements and interpretations thereof that have effective dates during the periods reported and in future periods. The Company does not believe that any new or modified principles will have a material impact on the Company’s reported financial position or operations in the near term. The applicability of any standard is subject to the formal review of our financial management and certain standards are under consideration.

F-18

In February 2016, the FASB issued Accounting Standards Update (ASU) No. 2016-02, Leases (“ASU 2016-02”). In January 2018, the FASB issued ASU 2018-01, which provides additional implementation guidance on the previously issued ASU 2016-02. Under the new guidance, lessees will be required to recognize the following for all leases (with the exception of short-term leases) at the commencement date: (1) a lease liability, which is a lessee's obligation to make lease payments arising from a lease, measured on a discounted basis; and (2) a right-of-use asset, which is an asset that represents the lessee's right to use, or control the use of, a specified asset for the lease term. The Company is required to adopt ASU 2016-02 for fiscal years, and for interim periods within those fiscal years, beginning after December 15, 2018. This ASU was effective for us in the first quarter of fiscal 2020 which begins with interim period ending October 31, 2019. Implementation of this guidance did not impact our financial statements

Note 3 - Commitments and Contingencies:

Commitments

On November 29, 2017, the Company entered into a clinical trial agreement (“CTA”) with a shanghai based, contract research organization (“CRO”) for a four-year Phase II study of AE37 for the treatment of metastatic triple negative breast cancer. In accordance with the CTA, the Company agrees to pay the CRO amounts not to exceed $5,747,039, unless approved in writing by both parties, upon completion of certain milestones and achievements over the four-year study

On November 20, 2018, the Company entered into a clinical trial agreement with NSABP Foundation, Inc. (“NSABP”) under which NSABP will conduct clinical research using the Company’s AE37 peptide immunotherapeutic vaccine in combination with pembrolizumab (Ketruda®) for the treatment of metastatic triple negative breast cancer. The company has agreed to pay NSABP an amount not to exceed $2,118,461 based on NSABP achieving various milestones.

The Company recognized $251,459 and $340,000 as research and development related to the clinical trial agreement with NSABP for the six-month periods ended January 31, 2020 and 2019, respectively. For the three-month periods ended January 31,2020 and 2019 the Company recognized $0 and $340,000 of research and development expense related to the NSABP clinical trial agreement, respectively.

Payable to Foundation

On February 1, 2007, the Company entered into a clinical study agreement with the Henry J. Jackson Foundation (the “Foundation” for the clinical research and development of AE37 for the treatment of breast cancer). The Company agreed to pay the foundation total compensation of $2,700,00 payable at various intervals over the term of the agreement.

On September 9, 2013, the Company entered into a forbearance agreement (the “Forbearance Agreement”) with the Foundation and under which the Company n acknowledged that they were in arrears on its payment and interest obligations to the Foundation in the amount of $1,315,817. Pursuant to the Forbearance Agreement, the Company and the Foundation agreed that in exchange for deferring the overdue payments the Company would among other matters, pay the foundation (i) the final $200,000 upon completion of the study and acceptance of all study documents, 274 (ii) for a royalty of 5% of net third party sales and (iii) the original forbearance amount will continue to bear interest at 1.5% per month, compounded. The Foundation may terminate the Forbearance Agreement by providing the Company written notice should the Company, among other matters, fail to make payments due under the Forbearance Agreement. The foundation has not provided the study documents to the Company.

As of January 31, 2020, and July 31, 2020, the Company’s payable to the foundation for services was $1,315,817. Interest payable to the Foundation was $3,464,457 and $3,055,945 as of January 31, 2020 and July 31, 2019, respectively. Interest accrued related to the payable to the foundation was $208,817 and $174,652, respectively for the three months ended January 31, 2020 and 2019; and $408,512 and $341,674, respectively, for the six months ended January 31, 2020 and 2019, respectively.

F-19

Related Party

Expenses paid by Generex on behalf of the Company have been treated as Capital contributions from Generex as Generex will not be reimbursed by the Company for these expenses. For the six-month periods ended January 31, 2020 and 2019, Generex paid expenses of $29,700 and $361,164, respectively.

COVID-19

The ongoing coronavirus outbreak which began in China at the beginning of 2020 has impacted various businesses throughout the world, including travel restrictions and the extended shutdown of certain businesses in impacted geographic regions. If the coronavirus outbreak situation should continue to worsen, we may experience disruptions to our business including, but not limited disruptions of our ongoing clinical trials and the operations of our partners.

The extent to which the coronavirus impacts our operations or those of our third-party partners will depend on future developments, which are highly uncertain and cannot be predicted with confidence, including the duration of the outbreak, new information that may emerge concerning the severity of the coronavirus and the actions to contain the coronavirus or treat its impact, among others. Any such disruptions or losses we incur could have a material adverse effect on our financial results and our ability to conduct business as expected.

Note 4 - Stockholders’ Deficiency:

Common Stock

On February 21, 2019, the Company issued a 4,000 to 1 stock split, in which all shares outstanding have been presented retrospectively for all periods presented. The Company has 400,000,000 authorized, issued, and outstanding shares of common stock with a $0.001 par value (the “Common Stock”). The holders of Common Stock are entitled to one vote per share of Common Stock held at the time of vote.

Note 5–Income taxes:

Deferred tax assets and liabilities are recognized for the future tax consequences attributable to differences between the financial statement carrying amounts of existing assets and liabilities and their respective tax bases and operating loss and tax credit carry forwards. Deferred tax assets and liabilities are measured using enacted tax rates expected to apply to taxable income in the years in which those temporary differences are expected to be recovered or settled. The effect on net deferred tax assets and liabilities of a change in tax rates is recognized in income in the period that includes the enactment date. At January 31,2020, the Company had a full valuation allowance against its deferred tax assets, accordingly the Company did not recognize an income tax benefit for losses incurred during the three and six-month periods ended January 31, 2020.

F-20

EX-10.1

EXECUTION COPY

CLINICAL TRIAL COLLABORATION AND SUPPLY AGREEMENT

by and among

Merck Sharp & Dohme B.V.

and

Antigen Express, Inc.

Dated: June 28, 2017

-i-

Page

1.	Definitions	1
2.	Scope of the Agreement	8
2.1. Generally		8
2.2. Manufacturing Delay		8
2.3. Compound Commitments		8
2.4. Delegation of Obligations		9
2.5. Compounds		9
3.	Conduct of the Study	9
3.1. Sponsor and Combination IND		9
3.2. Performance		10
3.3. Debarred Personnel; Exclusions Lists		10
3.4. Regulatory Matters		10
3.5. Documentation		10
3.6. Copies		10
3.7. Samples		11
3.8. Ownership and Use of Clinical Data		11
3.9. Regulatory Submission		12
3.10. Joint Development Committee		12
3.11. Final Study Report		13
3.12. Relationship		13
3.13. Licensing		13
3.14. Subsequent Study		13
4.	Protocol and Certain Other Documents	14
4.1. Protocol		14
4.2. Informed Consent		15
4.3. Financial Disclosure.		15
4.4. Transparency Reporting		15
5.	Adverse Event Reporting	16
5.1. Pharmacovigilance Agreement		16
5.2. Transmission of SAEs		17
6.	Term and Termination.	17
6.1. Term		17
6.2. Merck Termination Right for Safety		17

6.3. Termination for Material Breach	17
6.4. Termination for Patient Safety	17
6.5. Termination for Regulatory Action; Other Reasons	18
6.6. Return of Merck Compound	18
6.7. Termination Related to Anti-Corruption	18
6.8. Survival	18
6.9. No Prejudice	18
6.10. Confidential Information	18
6.11. Manufacturing Costs	19
7. Costs of Study	19
8. Supply and Use of the Compounds	19
8.1. Supply of the Compounds	19
8.2. Clinical Quality Agreement	20
8.3. Minimum Shelf Life Requirements	20
8.4. Provision of Compounds	20
8.5. Labeling and Packaging; Use, Handling and Storage	21
8.6. Product Specifications	21
8.7. Changes to Manufacturing	21
8.8. Product Testing; Noncompliance	21
8.9. Investigations	23
8.10. Shortage; Allocation	23
8.11. Records; Audit Rights	23
8.12. Quality	23
8.13. Quality Control	23
8.14. Audits and Inspections	23
8.15. Recalls	24
8.16. VAT	24
9. Confidentiality	24
9.1. Confidential Information	24
9.2. Inventions	25
9.3. Personal Identifiable Data	25
10. Intellectual Property	25
10.1. Joint Ownership and Prosecution	25
10.2. Inventions Owned by	27
10.3. Inventions Owned by Merck	27
10.4. Mutual Freedom to Operate for Combination Inventions	28
11. Reprints; Rights of Cross-Reference	28
12. Publications; Press Releases	28
12.1. Clinical Trial Registry	28
12.2. Publication	29
12.3. Press Releases	29
13. Representations and Warranties; Disclaimers	29
13.1. Due Authorization	29
13.2. Compounds	29
13.3. Results	30
13.4. Anti-Corruption	30
13.5. DISCLAIMER	32
14. Insurance; Indemnification; Limitation of Liability	32
14.1. Insurance	32
14.2. Indemnification	32
14.3. LIMITATION OF LIABILITY	33
15. Use of Name	33
16. Force Majeure	33
17. Entire Agreement; Amendment; Waiver	34
18. Assignment and Affiliates	34
19. Invalid Provision	34
20. No Additional Obligations	34
21. Governing Law; Dispute Resolution	35
22. Notices	35
23. Relationship of the Parties	36
24. Counterparts and Due Execution	36
25. Construction	36

-ii-

EXECUTION COPY

CLINICAL TRIAL COLLABORATION AND SUPPLY AGREEMENT

by and among

Merck Sharp & Dohme B.V.

and

Antigen Express, Inc.

Dated: June 28, 2017

TABLE OF CONTENTS

Page

1. Definitions 1

2. Scope of the Agreement 8

2.1. Generally 8

2.2. Manufacturing Delay 8

2.3. Compound Commitments 8

2.4. Delegation of Obligations 9

2.5. Compounds 9

3. Conduct of the Study 9

3.1. Sponsor and Combination IND 9

3.2. Performance 10

3.3. Debarred Personnel; Exclusions Lists 10

3.4. Regulatory Matters 10

3.5. Documentation 10

3.6. Copies 10

3.7. Samples 11

3.8. Ownership and Use of Clinical Data 11

3.9. Regulatory Submission 12

3.10. Joint Development Committee 12

3.11. Final Study Report 13

3.12. Relationship 13

3.13. Licensing 13

3.14. Subsequent Study 13

4. Protocol and Certain Other Documents 14

4.1. Protocol 14

4.2. Informed Consent 15

4.3. Financial Disclosure. 15

4.4. Transparency Reporting 15

5. Adverse Event Reporting 16

5.1. Pharmacovigilance Agreement 16

5.2. Transmission of SAEs 17

6. Term and Termination. 17

6.1. Term 17

6.2. Merck Termination Right for Safety 17

6.3. Termination for Material Breach 17

6.4. Termination for Patient Safety 17

6.5. Termination for Regulatory Action; Other Reasons 18

6.6. Return of Merck Compound 18

6.7. Termination Related to Anti-Corruption 18

6.8. Survival 18

6.9. No Prejudice 18

6.10. Confidential Information 18

6.11. Manufacturing Costs 19

7. Costs of Study 19

8. Supply and Use of the Compounds 19

8.1. Supply of the Compounds 19

8.2. Clinical Quality Agreement 20

8.3. Minimum Shelf Life Requirements 20

8.4. Provision of Compounds 20

8.5. Labeling and Packaging; Use, Handling and Storage 21

8.6. Product Specifications 21

8.7. Changes to Manufacturing 21

8.8. Product Testing; Noncompliance 21

8.9. Investigations 23

8.10. Shortage; Allocation 23

8.11. Records; Audit Rights 23

8.12. Quality 23

8.13. Quality Control 23

8.14. Audits and Inspections 23

8.15. Recalls 24

8.16. VAT 24

9. Confidentiality 24

9.1. Confidential Information 24

9.2. Inventions 25

9.3. Personal Identifiable Data 25

10. Intellectual Property 25

10.1. Joint Ownership and Prosecution 25

10.2. Inventions Owned by 27

10.3. Inventions Owned by Merck 27

10.4. Mutual Freedom to Operate for Combination Inventions 28

11. Reprints; Rights of Cross-Reference 28

12. Publications; Press Releases 28

12.1. Clinical Trial Registry 28

12.2. Publication 29

12.3. Press Releases 29

13. Representations and Warranties; Disclaimers 29

13.1. Due Authorization 29

13.2. Compounds 29

13.3. Results 30

13.4. Anti-Corruption 30

13.5. DISCLAIMER 32

14. Insurance; Indemnification; Limitation of Liability 32

14.1. Insurance 32

14.2. Indemnification 32

14.3. LIMITATION OF LIABILITY 33

15. Use of Name 33

16. Force Majeure 33

17. Entire Agreement; Amendment; Waiver 34

18. Assignment and Affiliates 34

19. Invalid Provision 34

20. No Additional Obligations 34

21. Governing Law; Dispute Resolution 35

22. Notices 35

23. Relationship of the Parties 36

24. Counterparts and Due Execution 36

25. Construction 36

Appendices

Appendix A

Appendix B

Schedules

Schedule I

CLINICAL TRIAL COLLABORATION AND SUPPLY AGREEMENT

This CLINICAL TRIAL COLLABORATION AND SUPPLY AGREEMENT (this

“Agreement”), made as of June 28, 2017 (the “Effective Date”), is by and between Merck Sharp & Dohme B.V., having a place of business at Waarderweg 39, 2031 BN Haarlem, Netherlands (“Merck”), and Antigen Express, Inc., having a place of business at 33 Redwing Road, Wellesley, MA, 02481 (“Antigen Express”). Merck and Antigen Express are each referred to herein individually as “Party” and collectively as “Parties”.

RECITALS

A.                 Merck is developing the Merck Compound for the treatment of certain tumor types.

B.                 Antigen Express is developing the Antigen Express Compound (as defined below) for the treatment of certain tumor types.

C.                 Antigen Express desires to sponsor a clinical trial in which the Antigen Express Compound and the Merck Compound would be dosed concurrently or in combination.

D.                 Merck and Antigen Express, consistent with the terms of this Agreement, desire to collaborate as more fully described herein, including by providing the Merck Compound and the Antigen Express Compound for the Study (as defined below).

NOW, THEREFORE, in consideration of the premises and of the following mutual promises, covenants and conditions, the Parties, intending to be legally bound, mutually agree as follows:

1. Definitions.

For all purposes of this Agreement, the capitalized terms defined in this Article 1 and throughout this Agreement shall have the meanings herein specified.

1.1.    “Affiliate” means, with respect to either Party, a firm, corporation or other entity which directly or indirectly owns or controls said Party, or is owned or controlled by said Party, or is under common ownership or control with said Party. The word “control” as used in this definition means (i) the direct or indirect ownership of fifty percent (50%) or more of the outstanding voting securities of a legal entity, or (ii) possession, directly or indirectly, of the power to direct the management or policies of a legal entity, whether through the ownership of voting securities, contract rights, voting rights, corporate governance or otherwise.

1.2.    “Agreement” means this agreement, as amended by the Parties from time to time, and as set forth in the preamble.

1.3. “Alliance Manager” has the meaning set forth in Section 3.10.

1.4. “Antigen Express” has the meaning set forth in the preamble.

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1.5. “Antigen Express Background Patents” has the meaning set forth in Section

10.4.1.

1.6. “Antigen Express Class Compound” means any Ii-Key modified cancer peptide

vaccine.

1.7.    “Antigen Express Compound” means AE37, an Ii-Key HER2776-790 cancer peptide vaccine, excluding, however, any biosimilar version of AE37 other than a biosimilar version Controlled by Antigen Express or its Affiliate.

1.8. “Antigen Express Inventions” has the meaning set forth in Section 10.2.

1.9.    “Applicable Law” means all federal, state, local, national and regional statutes, laws, rules, regulations and directives applicable to a particular activity hereunder, including performance of clinical trials, medical treatment and the processing and protection of personal and medical data, that may be in effect from time to time, including those promulgated by the United States Food and Drug Administration (“FDA”), national regulatory authorities, the European Medicines Agency (“EMA”) and any successor agency to the FDA or EMA or any agency or authority performing some or all of the functions of the FDA or EMA in any jurisdiction outside the United States or the European Union (each a “Regulatory Authority” and collectively, “Regulatory Authorities”), and including cGMP and GCP (each as defined below); all data protection requirements such as those specified in the EU Data Protection Directive and the regulations issued under the United States Health Insurance Portability and Accountability Act of 1996 (“HIPAA”); export control and economic sanctions regulations which prohibit the shipment of United States-origin products and technology to certain restricted countries, entities and individuals; anti-bribery and anti-corruption laws pertaining to interactions with government agents, officials and representatives; laws and regulations governing payments to healthcare providers; and any United States or other country’s or jurisdiction’s successor or replacement statutes, laws, rules, regulations and directives relating to the foregoing.

1.10.   “Business Day” means any day other than a Saturday, Sunday or a day on which commercial banks located in the country where the applicable obligations are to be performed are authorized or required by law to be closed.

1.11.   “cGMP” means the current Good Manufacturing Practices officially published and interpreted by EMA, FDA and other applicable Regulatory Authorities that may be in effect from time to time and are applicable to the Manufacture of the Compounds.

1.12.   “Clinical Data” means all data (including raw data) and results generated by or on behalf of either Party or at either Party’s direction, or by or on behalf of the Parties together or at their direction, in the course of each such Party’s performance of the Study; provided however, that Clinical Data does not include Sample Testing Results.

1.13. “Clinical Quality Agreement” has the meaning set forth in Section 8.2.

1.14.   “CMC” means “Chemistry Manufacturing and Controls” as such term of art is used in the pharmaceutical industry.

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1.15.   “Combination” means the use or method of using the Merck Compound and the Antigen Express Compound in concomitant or sequential administration.

1.16.   “Compounds” means the Merck Compound and the Antigen Express Compound. A “Compound” means either the Merck Compound or the Antigen Express Compound, as applicable.

1.17.   “Confidential Information” means any information, Know-How or other proprietary information or materials furnished to one Party (“Receiving Party”) by or on behalf the other Party (“Disclosing Party”) in connection with this Agreement, except to the extent that such information or materials: (a) was already known to the Receiving Party, other than under an obligation of confidentiality, at the time of disclosure by the Disclosing Party, as demonstrated by competent evidence; (b) was generally available to the public or otherwise part of the public domain at the time of its disclosure to the Receiving Party; (c) became generally available to the public or otherwise part of the public domain after its disclosure and other than through any act or omission of the Receiving Party in breach of this Agreement; (d) was disclosed to the Receiving Party by a Third Party who had no obligation to the Disclosing Party not to disclose such information to others; or (e) was subsequently developed by the Receiving Party without use of the Disclosing Party Confidential Information, as demonstrated by competent evidence.

1.18. “Continuing Party” has the meaning set forth in Section 10.1.3.

1.19.   “Control” or “Controlled” means, with respect to particular information or intellectual property, that the applicable Party owns or has a license to such information or intellectual property and has the ability to grant a right, license or sublicense to the other Party as provided for herein without violating the terms of any agreement or other arrangement with any Third Party.

1.20.   “CTA” means an application to a Regulatory Authority for purposes of requesting the ability to start or continue a clinical trial, which CTA may consist of, or include, and IND.

1.21.   “Data Sharing/Sample Testing Schedule” means the schedule attached hereto as Schedule I.

1.22. “Defending Party” has the meaning set forth in Section 14.2.3.

1.23.   “Delivery” with respect to the Merck Compound has the meaning set forth in Section 8.4.1, and with respect to the Antigen Express Compound, the meaning set forth in Section 8.4.2.

1.24. “Direct Manufacturing Costs” has the meaning set forth in Section 6.11.

1.25.   “Disclosing Party” has the meaning set forth in the definition of Confidential Information.

1.26. “Disposition Package” has the meaning set forth in Section 8.8.1.

1.27. “Effective Date” has the meaning set forth in the preamble.

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1.28. “EMA” has the meaning set forth in the definition of Applicable Law.

1.29. “Exclusions List” has the meaning set forth in the definition of Violation.

1.30. “FDA” has the meaning set forth in the definition of Applicable Law.

1.31.   “Field” means the concomitant and/or sequenced administration of the Merck Compound and the Antigen Express Compound in patients with metastatic triple negative breast cancer.

1.32. “Filing Party” has the meaning set forth in Section 10.1.3.

1.33. “Final Study Report” has the meaning set forth in Section 3.11.

1.34. “Force Majeure” has the meaning set forth Section 16.

1.35. “GAAP” has the meaning set forth in Section 6.11.

1.36.   “GCP” means the Good Clinical Practices officially published by EMA, FDA and the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH) that may be in effect from time to time and are applicable to the testing of the Compounds.

1.37.   “Government Official” means: (a) any officer or employee of a government or any department, agency or instrument of a government; (b) any Person acting in an official capacity for or on behalf of a government or any department, agency, or instrument of a government; (c) any officer or employee of a company or business owned in whole or part by a government; (d) any officer or employee of a public international organization such as the World Bank or United Nations; (e) any officer or employee of a political party or any Person acting in an official capacity on behalf of a political party; and/or (f) any candidate for political office; who, when such Government Official is acting in an official capacity, or in an official decision- making role, has responsibility for performing regulatory inspections, government authorizations or licenses, or otherwise has the capacity to make decisions with the potential to affect the business of either of the Parties.

1.38. “HIPAA” has the meaning set forth in the definition of Applicable Law.

1.39.   “IND” means any Investigational New Drug Application filed or to be filed with the FDA as described in Title 21 of the U.S. Code of Federal Regulations, Part 312, and the equivalent application in the jurisdictions outside the United States, including an “Investigational Medicinal Product Dossier” filed or to be filed with Regulatory Authorities in the European Union.

1.40. “Indirect Manufacturing Costs” has the meaning set forth in Section 6.11.

1.41.   “Inventions” means all inventions and discoveries, whether or not patentable, that are made, conceived, or first actually reduced to practice by or on behalf of a Party, or by or on behalf of the Parties together, (i) in the design or performance of the Study, or in the design or

4 

performance of any Subsequent Study for the Combination performed pursuant to Section 3.14, or (ii) through use of unpublished Clinical Data

1.42.   “Joint Development Committee” or “JDC” has the meaning set forth in Section 3.10.

1.43. “Joint Patent Application” has the meaning set forth in Section 10.1.3.

1.44.   “Joint Patent” means a patent, extension, registration, supplementary protection certificate or the like that issues from a Joint Patent Application.

1.45. “Jointly Owned Invention” has the meaning set forth in Section 10.1.1.

1.46.   “Know-How” means any proprietary invention, innovation, improvement, development, discovery, computer program, device, trade secret, method, know-how, process, technique or the like, including manufacturing, use, process, structural, operational and other data and information, whether or not written or otherwise fixed in any form or medium, regardless of the media on which contained and whether or not patentable or copyrightable, that is not generally known or otherwise in the public domain.

1.47. “Liability” has the meaning set forth in Section 14.2.1.

1.48.   “Manufacture,” “Manufactured,” or “Manufacturing” means all activities related to the manufacture of a Compound, including planning, purchasing, manufacture, processing, compounding, storage, filling, packaging, waste disposal, labeling, leafleting, testing, quality assurance, sample retention, stability testing, release, dispatch and supply, as applicable.

1.49.   “Manufacturer’s Release” or “Release” has the meaning ascribed to such term in the Clinical Quality Agreement.

1.50.   “Manufacturing Site” means the facilities where a Compound is Manufactured by or on behalf of a Party, as such Manufacturing Site may change from time to time in accordance with Section 8.7.

1.51. “Merck” has the meaning set forth in the preamble.

1.52. “Merck Background Patents” has the meaning set forth in Section 10.4.2.

1.53.   “Merck Compound” means pembrolizumab, a humanized anti-human PD-1 monoclonal antibody, excluding, however, any biosimilar version of pembrolizumab other than a biosimilar version Controlled by Merck or its Affiliate.

1.54. “Merck Inventions” has the meaning set forth in Section 10.3.

1.55.   “NDA” means a New Drug Application, Biologics License Application, Marketing Authorization Application, filing pursuant to Section 510(k) of the United States Federal Food, Drug and Cosmetic Act, or similar application or submission for a marketing

5 

authorization of a product filed with a Regulatory Authority to obtain marketing approval for a biological, pharmaceutical or diagnostic product in that country or in that group of countries.

1.56.   “Non-Conformance” means, with respect to a given unit of Compound, (i) an event that deviates from an approved cGMP requirement with respect to the applicable Compound, such as a procedure, Specification, or operating parameter, or that requires an investigation to assess impact to the quality of the applicable Compound or (ii) that such Compound failed to meet the applicable representations and warranties set forth in Section 2.3. Classification of the Non-Conformance is detailed in the Clinical Quality Agreement.

1.57. “Non-Filing Party” has the meaning set forth in Section 10.1.3.

1.58. “Other Party” has the meaning set forth in Section 14.2.3.

1.59. “Opting-out Party” has the meaning set forth in Section 10.1.3.

1.60. “Party” has the meaning set forth in the preamble.

1.61.   “PD-1 Antagonist” means any small or large molecule that blocks binding of PD- L1 and/or PD-L2 to PD-1.

1.62.   “Person” means any individual, sole proprietorship, partnership, corporation, business trust, joint stock company, trust, unincorporated organization, association, limited liability company, institution, public benefit corporation, joint venture, entity or governmental entity.

1.63. “Pharmacovigilance Agreement” has the meaning set forth in Section 5.1.

1.64. “Project Manager” has the meaning set forth in Section 3.10.

1.65.   “Protocol” means the written documentation that describes the Study and sets forth specific activities to be performed as part of the conduct of the Study, which is attached hereto as Appendix A.

1.66.   “Receiving Party” has the meaning set forth in the definition of Confidential Information.

1.67.   “Regulatory Approvals” means, with respect to a Compound, any and all permissions (other than the Manufacturing approvals) required to be obtained from Regulatory Authorities and any other competent authority for the development, registration, importation and distribution of such Compound in the United States, Europe or other applicable jurisdictions for use in the Study.

1.68.   “Regulatory Authorities” has the meaning set forth in the definition of Applicable Law.

1.69.   “Regulatory Documentation” means, with respect to the Compounds, all submissions to Regulatory Authorities in connection with the development of such Compounds,

6 

including all INDs and amendments thereto, NDAs and amendments thereto, drug master files, correspondence with regulatory agencies, periodic safety update reports, adverse event files, complaint files, inspection reports and manufacturing records, in each case together with all supporting documents (including documents that include Clinical Data).

1.70.   “Related Agreements” means the Pharmacovigilance Agreement and the Clinical Quality Agreement.

1.71.   “Right of Reference” means the “right of reference” defined in 21 CFR 314.3(b), including with regard to a Party, allowing the applicable Regulatory Authority in a country to have access to relevant information (by cross-reference, incorporation by reference or otherwise) contained in Regulatory Documentation (and any data contained therein) filed with such Regulatory Authority with respect to a Party’s Compound, only to the extent necessary for the conduct of the Study in such country or as otherwise expressly permitted or required under this Agreement to enable a Party to exercise its rights or perform its obligations hereunder.

1.72. “SAEs” has the meaning set forth in Section 5.2.

1.73.   “Samples” means biological specimens collected from subjects participating in the Study, including urine, blood and tissue samples.

1.74.   “Sample Testing” means the analyses to be performed by each Party using the applicable Samples, as described in the Data Sharing/Sample Testing Schedule.

1.75.   “Sample Testing Results” means those data and results arising from the Sample Testing performed by a Party.

1.76.   “Specifications” means, with respect to a given Compound, the set of requirements for such Compound as set forth in the Clinical Quality Agreement.

1.77.   “Study” means a Phase I dose escalation study to evaluate the safety, pharmacokinetics, pharmacodynamics and preliminary efficacy of the concomitant and/or sequenced administration of the combination of the Antigen Express Compound and the Merck Compound in patients with triple negative breast cancer.

1.78. “Study Completion” has the meaning set forth in Section 3.11.

1.79. “Subcontractors” has the meaning set forth in Section 2.4.

1.80. “Subsequent Study” has the meaning set forth in Section 3.14.1.

1.81. “Term” has the meaning set forth in Section 6.1.

1.82.   “Third Party” means any Person or entity other than Antigen Express, Merck or their respective Affiliates.

7 

1.83.   “Toxicity & Safety Data” means all clinical adverse event information and/or patient-related safety data included in the Clinical Data, as more fully described in the Pharmacovigilance Agreement.

1.84. “VAT” has the meaning set forth in Section 8.16.

1.85.   “Violation” means that a Party or any of its officers or directors or any other personnel (or other permitted agents of a Party performing activities hereunder) has been: (1) convicted of any of the felonies identified among the exclusion authorities listed on the U.S. Department of Health and Human Services, Office of Inspector General (OIG) website, including 42 U.S.C. 1320a-7(a) (http://oig.hhs.gov/exclusions/authorities.asp); (2) identified in the OIG List of Excluded Individuals/Entities (LEIE) database (http://exclusions.oig.hhs.gov/) or listed as having an active exclusion in the System for Award Management (http://www.sam.gov); or (3) listed by any US Federal agency as being suspended, proposed for debarment, debarred, excluded or otherwise ineligible to participate in Federal procurement or non-procurement programs, including under 21 U.S.C. 335a (http://www.fda.gov/ora/compliance_ref/debar/) ( (1), (2) and (3) collectively the “Exclusions Lists”).

2. Scope of the Agreement.

2.1.    Generally. Each Party shall: (a) contribute to the Study such resources as are necessary to fulfill its obligations set forth in this Agreement; and (b) act in good faith in performing its obligations under this Agreement and each Related Agreement to which it is a Party.

2.2.    Manufacturing Delay. Each Party shall notify the other Party as promptly as possible in the event of any Manufacturing delay that is likely to adversely affect supply of its Compound as contemplated by this Agreement.

2.3. Compound Commitments.

2.3.1.   Antigen Express agrees to Manufacture and supply the Antigen Express Compound for purposes of the Study in accordance with Article 8, and Antigen Express hereby represents and warrants to Merck that, at the time of Delivery of the Antigen Express Compound, such Antigen Express Compound shall have been Manufactured and supplied in compliance with: (i) the Specifications for the Antigen Express Compound; (ii) the Clinical Quality Agreement; and (iii) all Applicable Law, including cGMP and health, safety and environmental protections.

2.3.2.   Merck agrees to Manufacture and supply the Merck Compound for purposes of the Study in accordance with Article 8, and Merck hereby represents and warrants to Antigen Express that, at the time of Delivery of the Merck Compound, such Merck Compound shall have been Manufactured and supplied in compliance with: (i) the Specifications for the Merck Compound; (ii) the Clinical Quality Agreement; and (iii) all Applicable Law, including cGMP and health, safety and environmental protections.

8 

2.3.3.    Without limiting the foregoing, each Party is responsible for obtaining all regulatory approvals (including facility licenses) that are required to Manufacture its Compound in accordance with Applicable Law (provided that, for clarity, Antigen Express shall be responsible for obtaining Regulatory Approvals for the Study as set forth in Section 3.4).

2.4.    Delegation of Obligations. Each Party shall have the right to delegate any portion of its obligations hereunder as follows: (a) to such Party’s Affiliates, without the other Party’s consent; (b) to Third Parties that (i) are conducting clinical trials of such Party’s Compound as of the Effective Date and are set forth in the Protocol as performing such Study activities, or (ii) are conducting Sample Testing for such Party, provided in each of (i) and (ii) that both Parties have approved the use of such Third Parties in the performance of such activities; (c) without restriction to the extent related to the Manufacture of such Party’s Compound; and (d) upon the written consent of the other Party. Any and all Third Parties to whom a Party delegates any of its obligations hereunder are referred to as “Subcontractors.” Notwithstanding any delegation of its obligations hereunder, each Party shall remain solely and fully liable for the performance of its Affiliates and Subcontractors to which such Party delegates the performance of its obligations under this Agreement. Each Party shall ensure that each of its Affiliates and Subcontractors performs such Party’s obligations pursuant to the terms of this Agreement, including the Appendices and Schedules attached hereto. Each Party shall use reasonable efforts to obtain and maintain copies of documents relating to the obligations performed by such Affiliates and Subcontractors that are required to be provided to the other Party under this Agreement.

2.5.    Compounds. Except as expressly set forth in Section 3.14, this Agreement does not create any obligation on the part of Merck to provide the Merck Compound for any activities other than the Study, nor does it create any obligation on the part of Antigen Express to provide the Antigen Express Compound for any activities other than the Study.

3. Conduct of the Study.

3.1.    Sponsor and Combination IND. Antigen Express shall act as the sponsor of the Study. Antigen Express shall conduct the Study under a new IND specific for the Combination (“Combination IND”), which will be prepared and submitted to FDA by Antigen Express and will include a Right of Reference to the IND of the Merck Compound as further described in Section 3.4. The Combination IND shall be filed with a request for a waiver that exempts Merck from any requirement to notify FDA of any Suspected Unexpected Serious Adverse Reactions (a “SUSAR Waiver”) related to administration of the Merck Compound in any clinical study other than as part of the Study. At Merck’s request, Merck shall have the right to review all relevant documentation in connection with the Combination IND. Notwithstanding the above, if FDA refuses to grant such SUSAR Waiver under the Combination IND, Antigen Express shall instead sponsor the Study under its existing IND for the Antigen Express Compound with a Right of Reference to the IND of the Merck Compound as further described in Section 3.4; provided, however, that in no event shall Antigen Express file an additional IND for the Study, other than the Combination IND, unless required by Regulatory Authorities to do so. If a Regulatory Authority requests such an additional IND for the Study, the Parties shall meet and mutually agree on an approach to address such requirement.

9 

3.2.    Performance. Antigen Express shall ensure that the Study is performed in accordance with this Agreement, the Protocol and all Applicable Law, including GCP.

3.3.    Debarred Personnel; Exclusions Lists. Notwithstanding anything to the contrary contained herein, Antigen Express shall not employ or subcontract with any Person that is excluded, debarred, suspended, proposed for suspension or debarment, in Violation or otherwise ineligible for government programs for the performance of the Study or any other activities under this Agreement or the Related Agreements. Antigen Express hereby certifies that it has not employed or otherwise used in any capacity and will not employ or otherwise use in any capacity, the services of any Person suspended, proposed for debarment, or debarred under United States law, including 21 USC 335a, or any foreign equivalent thereof, in performing any portion of the Study or other activities under this Agreement or the Related Agreements and that Antigen Express has, as of the Effective Date, screened itself, and its officers and directors, against the Exclusions Lists and that it has informed Merck whether it or any of its officers or directors has been in Violation. Antigen Express shall notify Merck in writing immediately if any such suspension, proposed debarment, debarment or Violation occurs or comes to its attention, and shall, with respect to any Person so suspended, proposed for debarment, debarred or in Violation, promptly remove such Person from performing activities, function or capacity related to the Study or otherwise related to activities under this Agreement or the Related Agreements.

3.4.    Regulatory Matters. Antigen Express shall: (a) obtain, prior to initiating the Study, all Regulatory Approvals from all Regulatory Authorities, ethics committees and/or institutional review boards with jurisdiction over the Study prior to initiating the Study; and (b) follow all directions from any such Regulatory Authorities, ethics committees and/or institutional review boards. Merck shall have the right (but not the obligation) to participate in any discussions with a Regulatory Authority regarding matters related to the Merck Compound. If a Right of Reference is necessary, each Party shall provide to the other a cross-reference letter or similar communication to the applicable Regulatory Authority if needed to effectuate the Right of Reference. Notwithstanding anything to the contrary in this Agreement, neither Party shall have any right to access the other Party’s CMC data with respect to such other Party’s Compound. Merck shall authorize FDA and other applicable Regulatory Authorities to cross- reference the appropriate Merck Compound INDs and CTAs to provide data access to Antigen Express sufficient to support conduct of the Study. If Merck’s CTA is not available in a given country, Merck will file its CMC data with the Regulatory Authority for such country, referencing Antigen Express’ CTA as appropriate (however, Antigen Express shall have no right to directly access the CMC data).

3.5.    Documentation. Antigen Express shall maintain reports and all related documentation in good scientific manner and in compliance with Applicable Law. Antigen Express shall provide to Merck all Study information and documentation reasonably requested by Merck to enable Merck to (a) comply with any of its legal, regulatory and/or contractual obligations, or any request by any Regulatory Authority, related to the Merck Compound and (b) determine whether the Study has been performed in accordance with this Agreement.

3.6.    Copies. Antigen Express shall provide to Merck copies of all Clinical Data, in electronic form or other mutually agreeable alternate form and on the timelines specified in the

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Data Sharing/Sample Testing Schedule (if applicable) or upon mutually agreeable timelines; provided, however, that and a complete copy of the Clinical Data shall be provided to Merck no later than thirty (30) days following Study Completion. Antigen Express shall ensure that all patient authorizations and consents required under HIPAA, the EU Data Protection Directive (to the extent any part of the Study is done in Europe), or any other similar Applicable Law in connection with the Study permit such sharing of Clinical Data with Merck.

3.7. Samples.

3.7.1.   Antigen Express shall provide Samples to Merck as specified in the Protocol or as agreed to by the Joint Development Committee. Each Party shall (a) use the Samples only for the Sample Testing and (b) conduct the Sample Testing solely in accordance with the Data Sharing/Sample Testing Schedule and the Protocol.

3.7.2.   Merck shall own all Sample Testing Results arising from Sample Testing performed by or on behalf of Merck. Solely to the extent specified on the Data Sharing/Sample Testing Schedule as being shared, Merck shall provide to Antigen Express the Sample Testing Results for the Sample Testing conducted by or on behalf of Merck, in electronic form or other mutually agreeable alternate form, on the timelines specified in the Data Sharing/Sample Testing Schedule or as otherwise mutually agreed.

3.7.3.   Antigen Express shall own all Sample Testing Results arising from Sample Testing performed by or on behalf of Antigen Express. Solely to the extent specified on the Data Sharing/Sample Testing Schedule as being shared, Antigen Express shall provide to Merck the Sample Testing Results for the Sample Testing conducted by or on behalf of Antigen Express, in electronic form or other mutually agreeable alternate form, on the timelines specified in the Data Sharing/Sample Testing Schedule or as otherwise mutually agreed.

3.7.4.   Except to the extent otherwise agreed in a writing signed by authorized representatives of each Party, each Party may use and disclose the Sample Testing Results owned by the other Party and shared by such other Party in accordance with the Data Sharing/Sample Testing Schedule solely for the purposes of (i) seeking Regulatory Approval for the use of its respective Compound in the Combination and (ii) filing and prosecuting Joint Patent Applications and enforcing any Joint Patents in accordance with Article 10.

3.8. Ownership and Use of Clinical Data.

3.8.1.   All Clinical Data shall be jointly owned by Antigen Express and Merck. Merck hereby assigns to Antigen Express an undivided one-half interest in, to and under the Clinical Data. Antigen Express hereby assigns to Merck an undivided one-half interest in, to and under the Clinical Data. If such assignment cannot or does not occur, including in circumstances where such assignment is precluded by law, the Party with the obligation to assign hereby grants the other Party a non-exclusive license, with the right to grant sublicenses and to assign its license rights to the Clinical Data to any Person, in each case without the consent of the granting Party and without any accounting to such Party. Antigen Express shall maintain the Clinical Data in its internal database; provided, however, that at all times during the Term, Antigen

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Express shall grant Merck access to all Clinical Data and any portions of Antigen Express’ database that include Clinical Data.

3.8.2.   Notwithstanding the foregoing, and subject to the remaining provisions of this Section 3.8, before publication of the Clinical Data in accordance Article 12, (a) neither Party may disclose the Clinical Data publicly or to a Third Party without the consent of the other Party; and (b) in no event may (i) Merck use Clinical Data, directly or indirectly, to research, develop or commercialize a compound that is an Antigen Express Class Compound (whether as a monotherapy or in a combination other than pursuant to this Agreement) or (ii) Antigen Express use Clinical Data, directly or indirectly, to research, develop or commercialize a PD-1 Antagonist (whether as a monotherapy or in a combination other than pursuant to this Agreement). Each Party’s use of unpublished Clinical Data is restricted to (A) seeking regulatory approval for use of such Party’s Compound in the Combination; (B) prosecuting and enforcing Jointly Owned Inventions; (C) conducing Subsequent Studies; and (D) internal purposes related to its own Compound; provided, however, that the foregoing shall not limit or restrict either Party’s ability to (x) use or disclose the unpublished Clinical Data as may be necessary to comply with Applicable Law or with such Party’s internal policies and procedures with respect to pharmacovigilance and adverse event reporting, or (y) share with Third Parties or Affiliates Toxicity & Safety Data where because of severity, frequency or lack of reversibility either Party needs to use such Toxicity & Safety Data with respect to its own Compound or the Combination to ensure patient safety.

3.9.    Regulatory Submission. It is understood and acknowledged by the Parties that positive Clinical Data could be used to obtain label changes for the Compounds, and each Party may propose a Subsequent Study (as defined below) in connection therewith in accordance with Section 3.14.

3.10.   Joint Development Committee. The Parties shall form a joint development committee (the “Joint Development Committee” or “JDC”) made up of an equal number of representatives of Merck and Antigen Express, with Antigen Express members having one vote and Merck members having one vote, which shall have responsibility for coordinating all regulatory and other activities under, and pursuant to, this Agreement. Each Party shall designate a project manager (the “Project Manager”) who shall be responsible for implementing and coordinating activities and facilitating the exchange of information between the Parties with respect to the Study and shall be a member of the JDC. Other JDC members will be agreed by both Parties. The JDC shall meet as soon as practicable after the Effective Date and then no less than twice yearly, and more often as reasonably considered necessary at the request of either Party, to provide an update on the progress of the Study. The JDC may meet in person or by means of teleconference, Internet conference, videoconference or other similar communications equipment. Prior to any such meeting, the Antigen Express Project Manager shall provide an update in writing to the Merck Project Manager, which update shall contain information about the overall progress of the Study, recruitment status, interim analysis (if results available), final analysis and other information relevant to the conduct of the Study. In addition to a Project Manager, each Party shall designate an alliance manager (the “Alliance Manager”), who shall endeavor to ensure clear and responsive communication between the Parties and the effective exchange of information and shall serve as the primary point of contact for any issues arising under this Agreement. The Alliance Managers shall have the right to

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attend all JDC meetings and may bring to the attention of the JDC any matters or issues either of them reasonably believes should be discussed and shall have such other responsibilities as the Parties may mutually agree in writing. In the event that an issue arises and the Alliance Managers cannot or do not, after reasonable efforts, reach agreement on such issue, or if there is a decision to be made by the JDC on which the members of the JDC cannot unanimously agree, the issue shall be elevated to the Vice President of Clinical Oncology for Merck and the Chief Operating Officer for Antigen Express. In the event such escalation does not result in resolution or consensus: (a) Merck shall have final decision-making authority with respect to issues related to Merck Compound; and (b) Antigen Express shall have final decision-making authority with respect to issues related to Antigen Express Compound.

3.11.   Final Study Report. Antigen Express shall provide Merck with an electronic draft of the final study report promptly following Study Completion, and Merck shall have thirty (30) days after receipt of such draft to provide comments thereon. Antigen Express shall reasonably consider any comments provided by Merck on the draft final study report and shall not include any statements relating to the Merck Compound that have not been approved by Merck. Antigen Express shall deliver to Merck a final version of the final study report promptly following finalization thereof (the “Final Study Report”). “Study Completion” shall occur upon database lock of the Study results.

3.12.   Relationship. Except as expressly set forth in this Agreement, nothing in this Agreement shall: (a) prohibit either Party from performing clinical studies other than the Study relating to its own Compound, either individually or in combination with any other compound or product, in any therapeutic area; or (b) create an exclusive relationship between the Parties with respect to any Compound. Each Party acknowledges and agrees that nothing in this Agreement shall be construed as a representation or inference that the other Party will not develop for itself, or enter into business relationships with other Third Parties regarding, any products, programs, studies (including combination studies), technologies or processes that are similar to or that may compete with the Combination or any other product, program, technology or process, including Antigen Express Class Compound or PD-1 Antagonists, provided that the Clinical Data, Confidential Information, Jointly Owned Inventions and Sample Testing Results are not used or disclosed in connection therewith in violation of this Agreement.

3.13.   Licensing. Nothing in this Agreement shall prohibit or restrict a Party from licensing, assigning or otherwise transferring to an Affiliate or Third Party such Party’s Compound or any Inventions, Confidential Information or Sample Testing Results owned solely by such Party. A Party may license, assign or transfer to an Affiliate or Third Party such Party’s interest in the Clinical Data, Confidential Information owned jointly by the Parties and/or Jointly Owned Inventions, and in connection therewith share the shared Sample Testing Results owned by the other Party, solely to the extent such licensee, assignee or transferee agrees in writing to be bound by the terms of this Agreement with respect to such Clinical Data, Confidential Information, Jointly Owned Inventions, and shared Sample Testing Results. For purposes of clarity, any assignment or transfer of this Agreement must comply with Section 18 of this Agreement.

3.14. Subsequent Study.

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3.14.1.  During the Term and for a period of twelve (12) months thereafter, either Party shall have the option to propose additional studies for the purpose of conducting a registration study for the Combination in the same indication as the Study (each a “Subsequent Study”) by sending a written proposal to the other Party. Antigen Express must offer Merck the option of participating in a Subsequent Study prior to entering into an agreement with a Third Party to conduct a registration study in the same indication and line of therapy as the Study of the Antigen Express Compound in concomitant and/or sequential administration with a PD-1 Antagonist.

3.14.2.  If the receiving Party desires to engage in discussions around the proposed Subsequent Study, such Party shall notify the other Party, in writing, no later than ninety (90) days after receipt of the written proposal. Following such notification, the Parties shall negotiate in good faith the terms of an amendment to this Agreement and the Related Agreements or a new agreement (a “Subsequent Study Agreement”), as appropriate, but will have no obligation to agree upon the details of, or execute, such amendment or Subsequent Study Agreement. Any such amendment or Subsequent Study Agreement would include the following:

(a) the Party that would sponsor such Subsequent Study:

(b) a full and final protocol;

(c) how costs would be allocated;

(d) that the Parties will jointly own all data (including raw data) and results generated by or on behalf of either Party or at either Party’s direction, or by or on behalf of the Parties together or at their direction in the course of each such Party’s performance of the Subsequent Study (excluding any data and results arising from a Party’s sample testing) and that the sponsor Party will provide the other Party the unpublished summary data and results from the Subsequent Study as promptly as reasonable after the data is available; and

(e) that the Parties shall jointly own the Jointly Owned Inventions.

4. Protocol and Certain Other Documents.

4.1.    Protocol. A protocol and statistical analysis plan for the Study, entitled “A Phase II Clinical Trial of Pembrolizumab in combination with the AE37 Peptide Vaccine in Patients with Metastatic Triple Negative Breast Cancer,” has been agreed to by the Parties as of the Effective Date and is attached hereto as Appendix A (the “Protocol”). The Protocol may be amended with the approval of the JDC, subject to each Party’s decision making rights set forth in this Section 4.1. To the extent there is a disagreement between the Parties regarding the contents of the Protocol, Antigen Express shall have final decision-making authority; provided, however, that any material changes to any draft of the Protocol (other than material changes relating solely to the Antigen Express Compound) from the draft of the Protocol previously provided to Merck, any material changes to the approved final Protocol (other than material changes relating solely to the Antigen Express Compound), and any changes to any draft of the Protocol or approved

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final Protocol (whether or not material) relating to the Merck Compound (including with respect to the quantities and/or presentations of Merck Compound to be provided for the Study and/or the timing for Delivery thereof), shall require Merck’s prior written consent. Any such proposed changes will be sent in writing to Merck’s Project Manager and Merck’s Alliance Manager. Merck will provide such consent, or a written explanation for why such consent is being withheld, within fifteen (15) Business Days after Merck receives a copy of Antigen Express’ requested changes.

4.1.1.   Notwithstanding anything to the contrary contained herein, Merck, in its sole discretion, shall have the sole right to determine the dose and dosing regimen for the Merck Compound and shall have the final decision on all matters relating to the Merck Compound (including quantities of Merck Compound to be supplied pursuant to Article 8) and any information regarding the Merck Compound included in the Protocol.

4.1.2.   Notwithstanding anything to the contrary contained herein, Antigen Express, in its sole discretion, shall have the sole right to determine the dose and dosing regimen for the Antigen Express Compound and shall have the final decision on all matters relating to the Antigen Express Compound (including quantities of Antigen Express Compound to be supplied pursuant to Article 8) and any information regarding the Antigen Express Compound included in the Protocol.

4.2.    Informed Consent. Antigen Express shall prepare the patient informed consent form for the Study (which shall include provisions regarding the use of Samples in Sample Testing) in consultation with Merck (it being understood and agreed that the portion of the informed consent form relating to the Sample Testing of the Merck Compound shall be provided to Antigen Express by Merck). Any proposed changes to such form that relate to the Merck Compound, including Sample Testing of the Merck Compound, shall be subject to Merck’s prior written consent. Any such proposed changes will be sent in writing to Merck’s Project Manager and Merck’s Alliance Manager. Merck will provide such consent, or a written explanation for why such consent is being withheld, within fifteen (15) Business Days after Merck receives a copy of Antigen Express’ requested changes.

4.3.    Financial Disclosure. Antigen Express shall (a) track and collect financial disclosure information from all “clinical investigators” involved in the Study and (b) prepare and submit the certification and/or disclosure of the same in accordance with all Applicable Law, including, but not limited to, Part 54 of Title 21 of the United States Code of Federal Regulations (Financial Disclosure by Clinical Investigators) and related FDA Guidance Documents. Prior to the initiation of clinical activities under the Study, but in any event within 60 days after the Effective Date, the parties shall determine whether Antigen Express shall track and collect from all “clinical investigators” involved in the Study separate certification and/or disclosure forms for each of Merck and Antigen Express or one (1) “combined” certification and/or disclosure form for both Merck and Antigen Express. For purposes of this Section 4.3, the term “clinical investigators” shall have the meaning set forth in Part 54.2(d) of Title 21 of the United States Code of Federal Regulations.

4.4. Transparency Reporting.

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4.4.1.   With respect to any annual reporting period in which Antigen Express is not an entity that is required to make a Transparency Report under Applicable Law, Antigen Express will: (a) notify Merck, in writing, within thirty (30) days after the commencement of such reporting period that Antigen Express is not so required; and (b) during such reporting period Antigen Express will track and provide to Merck data regarding “indirect” payments or other transfers of value by Antigen Express to such health care professionals to the extent such payments or other transfers of value were required, instructed, directed or otherwise caused by Merck pursuant to this Agreement in the format requested by Merck and provided on a basis to be agreed upon by both Parties. Antigen Express represents and warrants that any data provided by Antigen Express to Merck pursuant to Section 4.4.1(b) above will be complete and accurate to the best of Antigen Express knowledge.

4.4.2.   With respect to any annual reporting period in which Antigen Express is required to make a Transparency Report under Applicable Law, Antigen Express will provide to Merck, in writing, Antigen Express’ point of contact for purposes of receiving information from Merck pursuant to this Section 4.4, along with such contact’s full name, email address, and telephone number. Antigen Express may update such contact from time to time by notifying Merck in writing pursuant to Article 22 (Notices). Where applicable, Merck will provide to such Antigen Express contact all information regarding the value of the Merck Compound provided for use in the Study required for such reporting. In the event that the value of the Merck Compound provided pursuant to this Section 4.4.2 changes, Merck shall notify Antigen Express of such revised value and the effective date thereof.

4.4.3.   For purposes of this Section 4.4, “Transparency Report” means a transparency report in connection with reporting payments and other transfers of value made to health care professionals, including, without limitation, investigators, steering committee members, data monitoring committee members, and consultants in connection with the Study in accordance with reporting requirements under Applicable Law, including, without limitation, the Physician Payment Sunshine Act and state gift laws, and the European Federation of Pharmaceutical Industries and Associations Disclosure Code, or a Party’s applicable policies.

5. Adverse Event Reporting.

5.1.    Pharmacovigilance Agreement. Antigen Express will be solely responsible for compliance with all Applicable Laws pertaining to safety reporting for the Study and related activities. The Parties (or their respective Affiliates) will execute a pharmacovigilance agreement (the “Pharmacovigilance Agreement”) prior to the initiation of clinical activities under the Study, but in any event within sixty (60) days after the Effective Date, to ensure the exchange of relevant safety data within appropriate timeframes and in an appropriate format to enable the Parties to fulfill local and international regulatory reporting obligations and to facilitate appropriate safety reviews. In the event of any inconsistency between the terms of this Agreement and the Pharmacovigilance Agreement, the terms of this Agreement shall control. The Pharmacovigilance Agreement will include safety data exchange procedures governing the coordination of collection, investigation, reporting, and exchange of information concerning any adverse experiences, pregnancy reports, and any other safety information arising from or related to the use of the Merck Compound and Antigen Express Compound in the Study, consistent with Applicable Law. Such guidelines and procedures shall be in accordance with, and enable the

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Parties and their Affiliates to fulfill, local and international regulatory reporting obligations to Government Authorities.

5.2.    Transmission of SAEs. Antigen Express will transmit to Merck all serious adverse events (“SAEs”) as follows:

5.2.1.   For drug-related fatal and life-threatening SAEs, Antigen Express will send a completely processed case (on a CIOMS-1 form in English) within three (3) calendar days after receipt by Antigen Express of such SAEs.

5.2.2.   For all other SAEs, including non-drug-related fatal and life-threatening SAEs, Antigen Express will send a completely processed case (on a CIOMS-1 form in English) within five (5) calendar days after receipt by Antigen Express of such SAEs.

6. Term and Termination.

6.1.    Term. The term of this Agreement shall commence on the Effective Date and shall continue in full force and effect until the earlier of (i) delivery of the Final Study Report and (ii) Study Completion plus three (3) months, or until terminated by either Party pursuant to this Article 6 (the “Term”).

6.2.    Merck Termination Right for Safety. In the event that Merck in good faith believes that the Merck Compound is being used in the Study in an unsafe manner and notifies Antigen Express in writing of the grounds for such belief, and Antigen Express fails to promptly incorporate changes into the Protocol requested by Merck to address such issue or to otherwise address such issue reasonably, Merck may terminate this Agreement and the supply of the Merck Compound immediately upon written notice to Antigen Express.

6.3.    Termination for Material Breach. Either Party may terminate this Agreement if the other Party commits a material breach of this Agreement, and such material breach continues for thirty (30) days after receipt of written notice thereof from the non-breaching Party; provided that if such material breach cannot reasonably be cured within thirty (30) days, the breaching Party shall be given a reasonable period of time to cure such breach; provided further, that if such material breach is incapable of cure, then the notifying Party may terminate this Agreement effective after the expiration of such thirty (30) day period.

6.4.    Termination for Patient Safety. If either Party reasonably determines, based on a review of the Clinical Data, Sample Testing Results or other Study-related Know-How or other information, that the Study may unreasonably affect patient safety, such Party shall promptly notify the other Party of such determination. The Party receiving such notice may propose modifications to the Study to address the safety issue identified by the other Party and, if the notifying Party agrees, shall act to implement immediately such modifications; provided, however, that if the notifying Party, in its sole discretion, believes that there is imminent danger to patients, such Party need not wait for the other Party to propose modifications and may instead terminate this Agreement immediately upon written notice to such other Party. Furthermore, if the notifying Party, in its sole discretion, believes that any modifications proposed by the other Party will not resolve the patient safety issue, such Party may terminate this Agreement effective upon written notice to such other Party.

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6.5.    Termination for Regulatory Action; Other Reasons. Either Party may terminate this Agreement immediately upon written notice to the other Party in the event that any Regulatory Authority takes any action, or raises any objection, that prevents the terminating Party from supplying its Compound for purposes of the Study. Additionally, either Party shall have the right to terminate this Agreement immediately upon written notice to the other Party in the event that it determines in its sole discretion to withdraw any applicable Regulatory Approval for its Compound or to discontinue development of its Compound, for medical, scientific or legal reasons.

6.6.    Return of Merck Compound. In the event that this Agreement is terminated, or in the event Antigen Express remains in possession (including through any Affiliate or Subcontractor) of Merck Compound at the time this Agreement expires, Antigen Express shall, at Merck’s sole discretion, promptly either return or destroy all unused Merck Compound pursuant to Merck’s instructions. If Merck requests that Antigen Express destroy the unused Merck Compound, Antigen Express shall provide written certification of such destruction.

6.7.    Termination Related to Anti-Corruption. Either Party shall have the right to terminate this Agreement immediately upon written notice to the other Party, if such other Party fails to perform any of its obligations under Section 13.4 or breaches any representation or warranty contained in Section 13.4. Except as set forth in Section 6.11, the non-terminating Party shall have no claim against the terminating Party for compensation for any loss of whatever nature by virtue of the termination of this Agreement in accordance with this Section 6.7.

6.8.    Survival. The provisions of Sections 3.4 through 3.8 (inclusive), 3.9, 3.13, 4.3, 6.6 through 6.11 (inclusive), 8.5.2, 8.11, 8.14 through 8.16 (inclusive), 13.4.6, 14.2, and 14.3, and Articles 1, 5, 9 through 12 (inclusive), 17, and 20 through 25 (inclusive) shall survive the expiration or termination of this Agreement.

6.9.    No Prejudice. Termination of this Agreement shall be without prejudice to any claim or right of action of either Party against the other Party for any prior breach of this Agreement.

6.10.   Confidential Information. Upon termination of this Agreement, each Party and its Affiliates shall promptly return to the Disclosing Party or destroy any Confidential Information of the Disclosing Party (other than Clinical Data, Sample Testing Results and Inventions) furnished to the Receiving Party by the Disclosing Party; provided, however that the Receiving Party may retain one copy of such Confidential Information in its confidential files, solely for purposes of exercising the Receiving Party’s rights hereunder, satisfying its obligations hereunder or complying with any legal proceeding or requirement with respect thereto, and provided further that the Receiving Party shall not be required to erase electronic files created in the ordinary course of business during automatic system back-up procedures pursuant to its electronic record retention and destruction practices that apply to its own general electronic files and information so long as such electronic files are (i) maintained only on centralized storage servers (and not on personal computers or devices), (ii) not accessible by any of its personnel (other than its information technology specialists), and (iii) are not otherwise accessed subsequently except with the written consent of the Disclosing Party or as required by law or

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legal process. Such retained copies of Confidential Information shall remain subject to the confidentiality and non-use obligations herein.

6.11.   Manufacturing Costs. In the event of termination by Merck pursuant to Section 6.2, 6.3 or 6.7 above, Merck shall be entitled to reimbursement by Antigen Express for the Direct Manufacturing Costs and Indirect Manufacturing Costs (as defined herein) incurred by Merck for its Compound Delivered for the Study. “Direct Manufacturing Costs” shall be calculated consistent with Generally Accepted Accounting Principles (“GAAP”) and include manufacturing fees, raw materials, direct labor, freight and duty, and factory overhead costs that can be directly attributed to the Compound, including but not limited to equipment maintenance and repair, supplies, ongoing stability program costs, other plant services, indirect labor and depreciation on direct capital assets. “Indirect Manufacturing Costs” shall be calculated consistent with GAAP and include allocations of indirect factory overhead and site support costs, including but not limited to utilities, quality, planning, engineering, maintenance, safety, site science and technology, and depreciation on indirect capital assets, procurement, warehousing, and corporate services. Allocations shall be based on each Compound’s utilization relative to a manufacturing site’s total activity. In the event of termination by Antigen Express pursuant to Section 6.3 or 6.7 above, and in order to complete the Study it is necessary for Antigen Express to purchase Merck Compound, Merck shall reimburse Antigen Express’ out of pocket costs for the purchase of Merck Compound (from a Third Party) necessary to complete the Study as contemplated by the Protocol; provided, however, that in no event shall Merck’s obligation to reimburse Antigen Express subject to this sentence exceed one hundred thousand US Dollars ($100,000) in the aggregate.

7. Costs of Study.

The Parties agree that: (a) Merck shall provide the Merck Compound for use in the Study, as described in Article 8 below; (b) each Party will be responsible for its own internal costs and expenses to support the Study and the costs of any Sample Testing conducted by such Party in connection with the Study; and (c) Antigen Express shall bear all other costs associated with the conduct of the Study, including that Antigen Express shall provide the Antigen Express Compound for use in the Study, as described in Article 8 below. For the avoidance of doubt, Antigen Express will not be required to reimburse Merck for any costs or expenses incurred by Merck or its Affiliates in connection with the Study (except as provided in Section 6.11) and Merck will not be required to reimburse Antigen Express for any costs or expenses incurred by Antigen Express or its Affiliates in connection with the Study.

8. Supply and Use of the Compounds.

8.1.    Supply of the Compounds. Subject to the terms and conditions of this Agreement, each of Antigen Express and Merck will use commercially reasonable efforts to supply, or cause to be supplied, the quantities of its respective Compound as are set forth in Appendix B, on the timelines set forth in Appendix B, in each case for use in the Study; provided, however, in the event the Study will be conducted under a Combination IND in accordance with Section 3.1, no Merck Compound shall be supplied until after the SUSAR Waiver has been obtained. If the initial supply timelines in Appendix B need to be altered as a result of a delay in obtaining the SUSAR Waiver or the need to re-submit the Study to FDA under a supplement to the existing

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IND of the Antigen Express Compound, such timelines may be altered without amending the Agreement, by mutual consent of the Parities in writing via email. If the Protocol is changed in accordance with Section 4 in such a manner that may affect the quantities of Compound to be provided or the timing for providing such quantities, the Parties shall amend Appendix B to reflect any changes required to be consistent with the Protocol. Each Party shall also provide to the other Party a contact person for the supply of its Compound under this Agreement. Notwithstanding the foregoing, or anything to the contrary herein, in the event that either Party is not supplying its Compound in accordance with the terms of this Agreement, or is allocating under Section 8.10, then the other Party shall have no obligation to supply its Compound, or may allocate proportionally.

8.2.    Clinical Quality Agreement. Within forty five (45) days from the Effective Date of this Agreement, but in any event before any supply under this Agreement of the Merck Compound, the Parties (or their respective Affiliates) shall enter into a quality agreement that shall address and govern issues related to the quality of clinical drug supply to be supplied by the Parties for use in the Study (the “Clinical Quality Agreement”). In the event of any inconsistency between the terms of this Agreement and the Clinical Quality Agreement, the terms of this Agreement shall control. The Clinical Quality Agreement shall, among other things:

(i)   detail classification of any Compound found to have a Non-Conformance; (ii) include criteria for Manufacturer’s Release and related certificates and documentation; (iii) include criteria and timeframes for acceptance of Merck Compound; (iv) include procedures for the resolution of disputes regarding any Compounds found to have a Non-Conformance; and (v) include provisions governing the recall of Compounds.

8.3.    Minimum Shelf Life Requirements. Each Party shall use commercially reasonable efforts to supply its Compound hereunder with an adequate remaining shelf life at the time of Delivery to meet the Study requirements.

8.4. Provision of Compounds.

8.4.1.   Merck will deliver the Merck Compound DAP (INCOTERMS 2010) to Antigen Express’, or its designee’s, location as specified by Antigen Express (“Delivery” with respect to such Merck Compound). Title and risk of loss for the Merck Compound shall transfer from Merck to Antigen Express at Delivery. All costs associated with the subsequent transportation, warehousing and distribution of Merck Compound shall be borne by Antigen Express. Antigen Express will, or will cause its designee to: (i) take delivery of the Merck Compound supplied hereunder; (ii) perform the acceptance (including testing) procedures allocated to it under the Clinical Quality Agreement; (iii) subsequently label and pack the Merck Compound (in accordance with Section 8.5), and promptly ship the Merck Compound to the Study sites for use in the Study, in compliance with cGMP, GCP and other Applicable Law and the Clinical Quality Agreement; and (iv) provide, from time to time at the reasonable request of Merck, the following information: any applicable chain of custody forms, in-transport temperature recorder(s), records and receipt verification documentation, such other transport or storage documentation as may be reasonably requested by Merck, and usage and inventory reconciliation documentation related to the Merck Compound.

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8.4.2.   Antigen Express is solely responsible, at its own cost, for supplying (including all Manufacturing, acceptance and release testing) the Antigen Express Compound for the Study, and the subsequent handling, storage, transportation, warehousing and distribution of the Antigen Express Compound supplied hereunder. Antigen Express shall ensure that all such activities are conducted in compliance with cGMP, GCP and other Applicable Law and the Clinical Quality Agreement. For purposes of this Agreement, the “Delivery” of a given quantity of the Antigen Express Compound shall be deemed to occur when such quantity is packaged for shipment to a Study site.

8.5. Labeling and Packaging; Use, Handling and Storage.

8.5.1.   The Parties’ obligations with respect to the labeling and packaging of the Compounds are as set forth in the Clinical Quality Agreement. Notwithstanding the foregoing or anything to the contrary contained herein, Merck shall provide the Merck Compound to Antigen Express in the form of unlabeled vials, and Antigen Express shall be responsible for labeling, packaging and leafleting such Merck Compound in accordance with the terms and conditions of the Clinical Quality Agreement and otherwise in accordance with all Applicable Law, including cGMP, GCP, and health, safety and environmental protections.

8.5.2.   Antigen Express shall: (i) use the Merck Compound solely for purposes of performing the Study; (ii) not use the Merck Compound in any manner that is inconsistent with this Agreement or for any commercial purpose; and (iii) label, use, store, transport, handle and dispose of the Merck Compound in compliance with Applicable Law and the Clinical Quality Agreement, as well as all instructions of Merck. Antigen Express shall not reverse engineer, reverse compile, disassemble or otherwise attempt to derive the composition or underlying information, structure or ideas of the Merck Compound, and in particular shall not analyze the Merck Compound by physical, chemical or biochemical means except as necessary to perform its obligations under the Clinical Quality Agreement.

8.6.    Product Specifications. A certificate of analysis shall accompany each shipment of the Merck Compound to Antigen Express. Upon request, Antigen Express shall provide Merck with a certificate of analysis covering each shipment of Antigen Express Compound used in the Study.

8.7.    Changes to Manufacturing. Each Party may make changes from time to time to its Compound or the Manufacturing Site, provided that such changes shall be in accordance with the Clinical Quality Agreement.

8.8. Product Testing; Noncompliance.

8.8.1.   After Manufacturer’s Release. After Manufacturer’s Release of the Merck Compound and concurrently with Delivery of the Compound to Antigen Express, Merck shall provide Antigen Express with such certificates and documentation as are described in the Clinical Quality Agreement (“Disposition Package”). Antigen Express shall, within the time defined in the Clinical Quality Agreement, perform with respect to the Merck Compound, the acceptance (including testing) procedures allocated to it under the Clinical Quality Agreement. Antigen Express shall be solely responsible for taking all steps necessary to determine that

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Merck Compound or Antigen Express Compound, as applicable, is suitable for release before making such Merck Compound or Antigen Express Compound, as applicable, available for human use, and Merck shall provide cooperation or assistance as reasonably requested by Antigen Express in connection with such determination with respect to the Merck Compound. Antigen Express shall be responsible for storage and maintenance of the Merck Compound until it is tested and/or released, which storage and maintenance shall be in compliance with (a) the Specifications for the Merck Compound, the Clinical Quality Agreement and Applicable Law and (b) any specific storage and maintenance requirements as may be provided by Merck from time to time. Antigen Express shall be responsible for any failure of the Merck Compound to meet the Specifications to the extent caused by shipping, storage or handling conditions after Delivery to Antigen Express hereunder.

8.8.2. Non-Conformance.

(a)                              In the event that either Party becomes aware that any Compound may have a Non-Conformance, despite testing and quality assurance activities (including any activities conducted by the Parties under Section 8.8.1), such Party shall immediately notify the other Party in accordance with the procedures of the Clinical Quality Agreement. The Parties shall investigate any Non-Conformance in accordance with Section 8.9 (Investigations) and any discrepancy between them shall be resolved in accordance with Section 8.8.3.

(b)                             In the event that any proposed or actual shipment of the Merck Compound (or portion thereof) shall be agreed to have a Non-Conformance at the time of Delivery to Antigen Express, then unless otherwise agreed to by the Parties, Merck shall replace such Merck Compound as is found to have a Non-Conformance (with respect to Merck Compound that has not yet been administered in the course of performing the Study). Unless otherwise agreed to by the Parties in writing, the sole and exclusive remedies of Antigen Express with respect to any Merck Compound that is found to have a Non-Conformance at the time of Delivery shall be (i) replacement of such Merck Compound as set forth in this Section 8.8.2(b), (ii) indemnification under Section 14.2.2 (to the extent applicable), and (iii) termination of this Agreement pursuant to Section 6.3 (to the extent applicable, but subject to the applicable cure periods set forth therein); provided that, for clarity, Antigen Express shall not be deemed to be waiving any rights under Section 8.15. In the event Merck Compound is lost or damaged by Antigen Express after Delivery, Merck shall provide additional Merck Compound (if available for the Study) to Antigen Express; provided that Antigen Express shall reimburse Merck for the Direct Manufacturing Costs and Indirect Manufacturing Costs (as such terms are defined in Section 6.11) of such replaced Merck Compound; and provided further that Merck shall have no obligation to provide additional Merck Compound more than once. Except as set forth in the foregoing sentence, Merck shall have no obligation to provide replacement Merck Compound for any Merck Compound supplied hereunder other than such Merck Compound as has been agreed or determined to have a Non-Conformance at the time of Delivery to Antigen Express.

(c)                              Antigen Express shall be responsible for, and Merck shall have no obligation or liability with respect to, any Antigen Express Compound supplied hereunder that is found to have a Non-Conformance. Antigen Express shall replace any Antigen Express Compound as is found to have a Non-Conformance (with respect to Antigen Express Compound that has not yet been administered in the course of performing the Study). Unless otherwise

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agreed to by the Parties in writing, the sole and exclusive remedies of Merck with respect to any Antigen Express Compound that is found to have a Non-Conformance at the time of Delivery shall be (i) replacement of such Antigen Express Compound as set forth in this Section 8.8.2(c),

(ii)   indemnification under Section 14.2.1 (to the extent applicable), and (iii) termination of this Agreement pursuant to Section 6.3 (to the extent applicable, but subject to the applicable cure periods set forth therein); provided that, for clarity, Merck shall not be deemed to be waiving any rights under Section 8.15.

8.8.3.   Resolution of Discrepancies. Disagreements regarding any determination of Non-Conformance by Antigen Express shall be resolved in accordance with the provisions of the Clinical Quality Agreement.

8.9.    Investigations. The process for investigations of any Non-Conformance shall be handled in accordance with the Clinical Quality Agreement.

8.10.   Shortage; Allocation. In the event that a Party’s Compound is in short supply such that a Party reasonably believes that it will not be able to fulfill its supply obligations hereunder with respect to its Compound, such Party will provide prompt written notice to the other Party thereof (including the shipments of Compound hereunder expected to be impacted and the quantity of its Compound that such Party reasonably determines it will be able to supply) and the Parties will promptly discuss such situation (including how the quantity of Compound that such Party is able to supply hereunder will be allocated within the Study). In such event, the Party experiencing such shortage shall (i) use its commercially reasonable efforts to remedy the situation giving rise to such shortage and to take action to minimize the impact of the shortage on the Study, and (ii) allocate to the other Party an amount of Compound at least proportionate to the total amount of the Compound shipments hereunder expected to be impacted by the shortage divided by the total demand for the Compound for the impacted time period.

8.11.   Records; Audit Rights. Antigen Express shall keep complete and accurate records pertaining to its use and disposition of Merck Compound (including its storage, shipping (cold chain) and chain of custody activities) and, upon request of Merck, shall make such records open to review by Merck for the purpose of conducting investigations for the determination of Merck Compound safety and/or efficacy and Antigen Express’ compliance with this Agreement with respect to the Merck Compound.

8.12.   Quality. Quality matters related to the Manufacture of the Compounds shall be governed by the terms of the Clinical Quality Agreement in addition to the relevant quality provisions of this Agreement.

8.13.   Quality Control. Each Party shall implement and perform operating procedures and controls for sampling, stability and other testing of its Compound, and for validation, documentation and release of its Compound and such other quality assurance and quality control procedures as are required by the Specifications, cGMPs and the Clinical Quality Agreement.

8.14.   Audits and Inspections. The Parties’ audit and inspection rights related to this Agreement shall be governed by the terms of the Clinical Quality Agreement.

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8.15.   Recalls. Recalls of the Compounds shall be governed by the terms of the Clinical Quality Agreement.

8.16. VAT.

8.16.1.  It is understood and agreed between the Parties that any payments made and any other consideration given under this Agreement are each exclusive of any value added or similar tax (“VAT”), which shall be added thereon as applicable and at the relevant rate. Subject to Section 8.16.2, where VAT is properly charged by the supplying Party and added to a payment made or other consideration provided (as applicable) under this Agreement, the Party making the payment or providing the other consideration (as applicable) will pay the amount of VAT properly chargeable only on receipt of a valid tax invoice from the supplying Party issued in accordance with the laws and regulations of the country in which the VAT is chargeable. Each Party agrees that it shall provide to the other Party any information and copies of any documents within its Control to the extent reasonably requested by the other Party for the purposes of (i) determining the amount of VAT chargeable on any supply made under this Agreement, (ii) establishing the place of supply for VAT purposes, or (iii) complying with its VAT reporting or accounting obligations.

8.16.2.  Where one Party or its Affiliate (the “First Party”) is treated as making supply of goods or services in a particular jurisdiction (for VAT purposes) for non-cash consideration, and the other Party or its Affiliate (the “Second Party”) is treated as receiving such supply in the same jurisdiction, thus resulting in an amount of VAT being properly chargeable on such supply, the Second Party shall only be obliged to pay to the First Party the amount of VAT properly chargeable on such supply (and no other amount). The Second Party shall pay such VAT to the First Party on receipt of a valid VAT invoice from the First Party (issued in accordance with the laws and regulations of the jurisdiction in which the VAT is properly chargeable). Each Party agrees to (i) use its reasonable efforts to determine and agree the value of the supply that has been made and, as a result, the corresponding amount of VAT that is properly chargeable and (ii) provide to the other Party any information or copies of documents in its Control as are reasonably necessary to evidence that such supply will take, or has taken, place in the same jurisdiction (for VAT purposes).

9. Confidentiality.

9.1.    Confidential Information. Subject to Section 13.4.8, Antigen Express and Merck agree to hold in confidence any Confidential Information provided by or on behalf of the other Party, and neither Party shall use Confidential Information of the other Party except to fulfill such Party’s obligations under this Agreement or exercising its rights. Without limiting the foregoing, the Receiving Party may not, without the prior written permission of the Disclosing Party, disclose any Confidential Information of the Disclosing Party to any Third Party except to the extent disclosure (i) is required by Applicable Law; (ii) is pursuant to the terms of this Agreement; or (iii) is necessary for the conduct of the Study, and in each case ((i) through (iii)) provided that the Receiving Party shall provide reasonable advance notice to the Disclosing Party before making such disclosure. For the avoidance of doubt, Antigen Express may, without Merck’s consent, disclose Confidential Information to clinical trial sites and clinical trial investigators performing the Study, the data safety monitoring and advisory board relating to the

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Study, and Regulatory Authorities working with Antigen Express on the Study, in each case to the extent necessary for the performance of the Study and provided that such Persons (other than governmental entities) are bound by an obligation of confidentiality at least as stringent as the obligations contained herein.

9.2.    Inventions. Notwithstanding the foregoing: (i) Inventions that constitute Confidential Information and are jointly owned by the Parties, shall constitute the Confidential Information of both Parties and each Party shall have the right to use and disclose such Confidential Information consistent with Articles 10, 11 and 12; and (ii) Inventions that constitute Confidential Information and are solely owned by one Party shall constitute the Confidential Information of that Party and each Party shall have the right to use and disclose such Confidential Information consistent with Articles 10, 11 and 12.

9.3.    Personal Identifiable Data. All Confidential Information containing personal identifiable data shall be handled in accordance with all data protection and privacy laws, rules and regulations applicable to such data.

10. Intellectual Property.

10.1.   Joint Ownership and Prosecution.

10.1.1.  All rights to all Inventions relating to, or covering, the combined use of the Antigen Express Compound and the Merck Compound that are not Merck Inventions or Antigen Express Inventions (each a “Jointly Owned Invention”) shall be owned jointly by Antigen Express and Merck. Merck hereby assigns to Antigen Express an undivided one-half interest in, to and under the Jointly Owned Inventions that are invented or created solely by Merck or by Persons having an obligation to assign such rights to Merck. Antigen Express hereby assigns to Merck an undivided one-half interest in, to and under any Jointly Owned Inventions that are invented or created solely by Antigen Express or by Persons having an obligation to assign such rights to Antigen Express. For those countries where a specific license is required for a joint owner of a Jointly Owned Invention to practice such Jointly Owned Invention in such countries: (i) Merck hereby grants to Antigen Express a perpetual, irrevocable, non-exclusive, worldwide, royalty-free, fully paid-up license, transferable and sublicensable, under Merck’s right, title and interest in and to all Jointly Owned Inventions to use such Inventions in accordance with the terms of this Agreement; and (ii) Antigen Express hereby grants to Merck a perpetual, irrevocable, non-exclusive, worldwide, royalty-free, fully paid-up license, transferable and sublicensable, under Antigen Express’ right, title and interest in and to all Jointly Owned Inventions to use such Inventions in accordance with the terms of this Agreement. For clarity, the terms of this Agreement do not provide Antigen Express or Merck with any rights, title or interest or any license to the other Party’s intellectual property except as necessary to conduct the Study and as expressly provided under this Agreement, including as set forth in Section 10.4.

10.1.2.  Each Party shall have the right to freely exploit each Jointly Owned Invention both within and outside the scope of the Study, without accounting to or any other obligation to the other Party; provided, however, that Merck may not use the Jointly Owned Inventions, directly or indirectly, to research, develop or commercialize a compound that is an

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Antigen Express Class Compound, and Antigen Express may not use the Jointly Owned Inventions, directly or indirectly, to research, develop or commercialize a PD-1 Antagonist.

10.1.3.  Promptly following the Effective Date, but in any event as soon as practicable after the discovery of a Jointly Owned Invention, patent representatives of each of the Parties shall meet (in person or by telephone) to discuss the patenting strategy for any Jointly Owned Inventions that may arise. In particular, the Parties shall discuss which Party will file and prosecute a patent application (including any provisional, substitution, divisional, continuation, continuation in part, reissue, renewal, reexamination, extension, supplementary protection certificate and the like) in respect of any Jointly Owned Invention (each, a “Joint Patent Application”) and whether the Parties wish to appoint counsel that is mutually acceptable to the Parties. In any event, the Parties shall consult and reasonably cooperate with one another in the preparation, filing, prosecution (including prosecution strategy) and maintenance of such patent application and shall equally share the expenses associated with the Joint Patent Applications and any corresponding Joint Patents. In the event that one Party (the “Filing Party”) wishes to file a patent application for a Jointly Owned Invention and the other Party (the “Non-Filing Party”) does not want to file a patent application for such Jointly Owned Invention or does not want to file in a particular country, the Non-Filing Party shall execute in a timely manner and at the Filing Party’s reasonable expense an assignment of such Jointly Owned Invention to the Filing Party (in such country or all countries, as applicable) and any additional documents as may be reasonably necessary to allow the Filing Party to file and prosecute such patent application. If a Party (the “Opting-out Party”) wishes to discontinue the prosecution and maintenance (or sharing in the costs with respect thereto) of a Joint Patent Application or Joint Patent (in one or more countries), the other Party, at its sole option (the “Continuing Party”), may continue such prosecution and maintenance. In such event, the Opting-out Party shall execute in a timely manner and at the Continuing Party’s reasonable expense an assignment of such Joint Patent Application or Joint Patent to the Continuing Party (in such country or all countries, as applicable) and any additional documents as may be necessary to allow the Continuing Party to prosecute and maintain such Joint Patent Application or Joint Patent. Any Jointly Owned Invention, Joint Patent Application or Joint Patent so assigned shall thereafter be owned solely by the Continuing Party or Filing Party (as applicable), shall no longer be considered jointly owned, and the Non-Filing Party or Opting-out Party (as applicable) shall have no right to practice under such Joint Patent Application or Joint Patent in the applicable country or countries.

10.1.4.  Except as expressly provided in Section 10.1.3 and in furtherance and not in limitation of Section 9.1, each Party agrees to make no patent application based on the other Party’s Confidential Information, and to give no assistance to any Third Party for such application, without the other Party’s prior written authorization.

10.1.5.  Antigen Express shall have the first right to initiate legal action to enforce all Joint Patents against infringement and to protect all Jointly Owned Inventions from misappropriation by any Third Party, where such infringement or misappropriation results from the development or sale of a product that includes an Antigen Express Class Compound but not a PD-1 Antagonist or to defend any declaratory judgment action relating thereto, at its sole expense. In the event that Antigen Express fails to initiate or defend such action within thirty

(30) days after being first notified of such infringement, Merck shall have the right to do so at its 26

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sole expense. Merck shall have the first right to initiate legal action to enforce all Joint Patents against infringement and to protect all Jointly Owned Inventions from misappropriation by any Third Party, where such infringement or misappropriation results from the development or sale of a product that includes a PD-1 Antagonist but not an Antigen Express Class Compound or to defend any declaratory judgment action relating thereto, at its sole expense. In the event that Merck fails to initiate or defend such action within thirty (30) days after being first notified of such infringement, Antigen Express shall have the right to do so at its sole expense. The Parties shall reasonably cooperate to coordinate legal action to enforce all Joint Patents against infringement, and to protect all Jointly Owned Inventions from misappropriation, by any Third Party where such infringement or misappropriation results from the development or sale of a product that includes both a PD-1 Antagonist and an Antigen Express Class Compound, or to defend any declaratory judgment action relating thereto, and shall share the costs and expenses of such litigation equally.

10.1.6.  If one Party brings any prosecution or enforcement action or proceeding against a Third Party with respect to any Joint Patent, the second Party agrees to be joined as a party plaintiff where necessary and to give the first Party reasonable assistance and authority to file and prosecute the suit. The costs and expenses of the Party bringing suit under Section

10.1.5 shall be borne by such Party, and any damages or other monetary awards recovered shall be shared as follows: (i) the amount of such recovery actually received by the Party controlling such action shall be first applied to the out-of-pocket costs of each Party in connection with such action; and then (ii) any remaining proceeds shall be divided evenly between Antigen Express and Merck. A settlement or consent judgment or other voluntary final disposition of a suit under Section 10.1.5 may not be entered into without the consent of the Party not bringing the suit.

10.2.   Inventions Owned by Antigen Express. Notwithstanding anything to the contrary contained in Section 10.1, the Parties agree that all rights to Inventions relating solely to, or covering solely, the Antigen Express Compound or an Antigen Express Class Compound, and any improvements related thereto, regardless of whether such Invention or improvement was invented solely by Antigen Express or Merck or jointly by the Parties, are the exclusive property of Antigen Express (“Antigen Express Inventions”). Antigen Express shall be entitled to file and prosecute in its own name relevant patent applications and to own resultant patent rights for any Antigen Express Invention. For the avoidance of doubt, any Invention generically encompassing the Antigen Express Compound or another Antigen Express Class Compound (and not the Merck Compound) within its scope, even where the Antigen Express Compound or Antigen Express Class Compound is not disclosed per se, is an Antigen Express Invention. Merck hereby assigns its right, title and interest to any and all Antigen Express Inventions to Antigen Express.

10.3.   Inventions Owned by Merck. Notwithstanding anything to the contrary contained in Section 10.1, the Parties agree that all rights to Inventions relating solely to, or covering solely, the Merck Compound or a PD-1 Antagonist, and any improvements related thereto, regardless of whether such Invention or improvement was invented solely by Merck or Antigen Express or jointly by the Parties, are the exclusive property of Merck (“Merck Inventions”). Merck shall be entitled to file and prosecute in its own name relevant patent applications and to own resultant patent rights for any Merck Invention. For the avoidance of doubt, any Invention

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generically encompassing the Merck Compound or another PD-1 Antagonist (and not the Antigen Express Compound) within its scope, even where the Merck Compound or other PD-1 Antagonist is not disclosed per se, is a Merck Invention. Antigen Express hereby assigns its right, title and interest to any and all Merck Inventions to Merck.

10.4. Mutual Freedom to Operate for Combination Inventions.

10.4.1.  Antigen Express License to Merck. Antigen Express hereby grants to Merck a non-exclusive, worldwide, royalty-free, fully paid-up license, transferable and sublicensable, to any patent Controlled by Antigen Express that (a) has a priority claim that is earlier than the initiation of the Study (i.e., first dosing of the first patient in the Study) and (b) claims the Combination (the “Antigen Express Background Patents”) solely for the purpose of conducting the Study; provided, however, that in no event shall Merck have the right to use Antigen Express Background Patents to commercialize the Antigen Express Compound or any Antigen Express Class Compound.

10.4.2.  Merck License to Antigen Express. Merck hereby grants to Antigen Express a non-exclusive, worldwide, royalty-free, fully paid-up license, transferable and sublicensable, to any patent Controlled by Merck that (a) has a priority claim that is earlier than the initiation of the Study (i.e., first dosing of the first patient in the Study) and (b) claims the Combination (the “Merck Background Patents”) solely for the purpose of conducting the Study; provided, however, that in no event shall Antigen Express have the right to use Merck Background Patents to commercialize the Merck Compound or any PD-1 Antagonist.

10.4.3.  No Other Rights. For clarity, the terms of this Section 10.4 do not provide Merck or Antigen Express with any rights, title or interest or any license to the other Party’s intellectual property rights that do not have a priority claim that is earlier than the initiation of the Study or do not claim the Combination (i.e., intellectual property owned or licensed by either Party that does not constitute an Invention and does not claim or cover the Combination), except as necessary to conduct the Study.

10.4.4.  Termination. Any and all licenses granted under this Section 10.4 shall terminate upon the latest of (i) the termination of this Agreement and (ii) the completion of the Study or any Subsequent Study conducted pursuant to Section 3.14.

11. Reprints; Rights of Cross-Reference.

Consistent with applicable copyright and other laws, each Party may use, refer to, and disseminate reprints of scientific, medical and other published articles and materials from journals, conferences and/or symposia relating to the Study that disclose the name of a Party, provided, however, that such use does not constitute an endorsement of any commercial product or service by the other Party.

12. Publications; Press Releases.

12.1.   Clinical Trial Registry. Antigen Express shall register the Study with the Clinical Trials Registry located at www.clinicaltrials.gov and is committed to timely publication of the results following Study Completion, after taking appropriate action to secure intellectual

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property rights (if any) arising from the Study. The publication of the results of the Study will be in accordance with the Protocol.

12.2.   Publication. Each Party shall use reasonable efforts to publish or present scientific papers dealing with the Study in accordance with accepted scientific practice. The Parties agree that prior to submission of the results of the Study for publication or presentation or any other dissemination of such results including oral dissemination, the publishing Party shall invite the other to comment on the content of the material to be published, presented, or otherwise disseminated according to the following procedure:

12.2.1.  At least forty-five (45) days prior to submission for publication of any paper, letter or any other publication, or thirty (30) days prior to submission for presentation of any abstract, poster, talk or any other presentation, the publishing Party shall provide to the other Party the full details of the proposed publication, presentation, or dissemination in an electronic version (cd-rom or email attachment). Upon written request from the other Party, the publishing Party agrees not to submit data for publication/presentation/dissemination for an additional ninety (90) days in order to allow for actions to be taken to preserve rights for patent protection.

12.2.2.  The publishing Party shall give reasonable consideration to any request by the other Party made within the periods mentioned in Section 12.2.1 to modify the publication and the Parties shall work in good faith and in a timely manner to resolve any issue regarding the content for publication.

12.2.3.  The publishing Party shall remove all Confidential Information of the other Party before finalizing the publication.

12.3.   Press Releases. Unless otherwise required by Applicable Law, neither Party shall make any public announcement concerning this Agreement or the Study or otherwise communicate with any news media without the prior written consent of the other Party. To the extent a Party desires to make such public announcement, such Party shall provide the other Party with a draft thereof at least seven (7) Business Days prior to the date on which such Party would like to make the public announcement.

13. Representations and Warranties; Disclaimers.

13.1.   Due Authorization. Each of Antigen Express and Merck represents and warrants to the other that: (i) it has the corporate power and authority and the legal right to enter into this Agreement and perform its obligations hereunder; (ii) it has taken all necessary corporate action on its part required to authorize the execution and delivery of this Agreement and the performance of its obligations hereunder; and (iii) this Agreement has been duly executed and delivered on behalf of such Party and constitutes a legal, valid and binding obligation of such Party that is enforceable against it in accordance with its terms.

13.2. Compounds.

13.2.1.  Antigen Express Compound. Antigen Express hereby represents and warrants to Merck that: (i) Antigen Express has the full right, power and authority to grant all of

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the licenses granted to Merck under this Agreement; and (ii) Antigen Express Controls the Antigen Express Compound.

13.2.2.  Merck Compound. Merck hereby represents and warrants to Antigen Express that: (i) Merck has the full right, power and authority to grant all of the licenses granted to Antigen Express under this Agreement; and (ii) Merck Controls the Merck Compound.

13.3.   Results. Antigen Express does not undertake that the Study shall lead to any particular result, nor is the success of the Study guaranteed. Neither Party shall be liable for any use that the other Party may make of the Clinical Data nor for advice or information given in connection therewith.

13.4. Anti-Corruption.

13.4.1.  In performing their respective obligations hereunder, the Parties acknowledge that the corporate policies of Antigen Express and Merck and their respective Affiliates require that each Party’s business be conducted within the letter and spirit of the law. By signing this Agreement, each Party agrees to conduct the business contemplated herein in a manner that is consistent with all Applicable Law, including the Stark Act, Anti-Kickback Statute, Sunshine Act, and the U.S. Foreign Corrupt Practices Act, good business ethics, and its ethics and other corporate policies and agrees to abide by the spirit of the other Party’s guidelines, which may be provided by such other Party from time to time.

13.4.2.  Specifically, each Party represents and warrants that it has not, and covenants that it, its Affiliates, and its and its Affiliates’ directors, employees, officers, and anyone acting on its behalf, will not, in connection with the performance of this Agreement, directly or indirectly, make, promise, authorize, ratify or offer to make, or take any action in furtherance of, any payment or transfer of anything of value for the purpose of influencing, inducing or rewarding any act, omission or decision to secure an improper advantage; or improperly assisting it in obtaining or retaining business for it or the other Party, or in any way with the purpose or effect of public or commercial bribery.

13.4.3.  Neither Party shall contact, or otherwise knowingly meet with, any Government Official for the purpose of discussing activities arising out of or in connection with this Agreement, without the prior written approval of the other Party, except where such meeting is consistent with the purpose and terms of this Agreement and in compliance with Applicable Law.

13.4.4.  Each Party represents and warrants that it (i) is not excluded, debarred, suspended, proposed for suspension or debarment, in Violation or otherwise ineligible for government programs; and (ii) has not employed or subcontracted with any Person for the performance of the Study who is excluded, debarred, suspended, proposed for suspension or debarment, or is in Violation or otherwise ineligible for government programs.

13.4.5.  Each Party represents and warrants that, except as disclosed to the other in writing prior to the Effective Date, such Party: (1) does not have any interest that directly or indirectly conflicts with its proper and ethical performance of this Agreement; (2) shall maintain arm’s length relations with all Third Parties with which it deals for or on behalf of the other in

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performance of this Agreement; and (3) has provided complete and accurate information and documentation to the other Party, the other Party’s Affiliates and its and their personnel in the course of any due diligence conducted by the other Party for this Agreement, including disclosure of any officers, employees, owners or Persons directly or indirectly retained by such Party in relation to the performance of this Agreement who are Government Officials or relatives of Government Officials. Each Party shall make all further disclosures to the other Party as are necessary to ensure the information provided remains complete and accurate throughout the Term. Subject to the foregoing, each Party agrees that it shall not hire or retain any Government Official to assist in its performance of this Agreement, with the sole exception of conduct of or participation in clinical trials under this Agreement, provided that such hiring or retention shall be subject to the completion by the hiring or retaining Party of a satisfactory anti-corruption and bribery (e.g., FCPA) due diligence review of such Government Official. Each Party further covenants that any future information and documentation submitted to the other Party as part of further due diligence or a certification shall be complete and accurate.

13.4.6. Each Party shall have the right during the Term, and for a period of two

(2) years following termination of this Agreement, to conduct an investigation and audit of the other Party’s activities, books and records, to the extent they relate to that other Party’s performance under this Agreement, to verify compliance with the terms of this Section 13.4. Such other Party shall cooperate fully with such investigation or audit, the scope, method, nature and duration of which shall be at the sole reasonable discretion of the Party requesting such audit.

13.4.7.  Each Party shall use commercially reasonable efforts to ensure that all transactions under the Agreement are properly and accurately recorded in all material respects on its books and records and that each document upon which entries in such books and records are based is complete and accurate in all material respects. Each Party further represents, warrants and covenants that all books, records, invoices and other documents relating to payments and expenses under this Agreement are and shall be complete and accurate and reflect in reasonable detail the character and amount of transactions and expenditures. Each Party shall maintain a system of internal accounting controls reasonably designed to ensure that no off-the-books or similar funds or accounts will be maintained or used in connection with this Agreement.

13.4.8.  Each Party agrees that in the event that the other Party reasonably believes that there has been a possible violation of any provision of Section 13.4, such other Party may make full disclosure of such belief and related information needed to support such belief at any time and for any reason to any competent government bodies and agencies, and to anyone else such Party determines in good faith has a legitimate need to know.

13.4.9.  Each Party shall comply with its own ethical business practices policy and any corporate integrity agreement (if applicable) to which it is subject, and shall conduct its Study-related activities in accordance with Applicable Law. Each Party shall ensure that all of its employees involved in performing its obligations under this Agreement are made specifically aware of the compliance requirements under this Section 13.4. In addition, each Party shall ensure that all such employees participate in and complete mandatory compliance training to be conducted by each Party, including specific training on anti-bribery and corruption, prior to his/her performance of any obligations or activities under this Agreement. Each Party shall

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certify its continuing compliance with the requirements under this Section 13.4 on a periodic basis during the Term in such form as may be reasonably specified by the other Party.

13.4.10.      Each Party shall have the right to terminate this Agreement immediately upon violation of this Section 13.4 in accordance with Section 6.7.

13.5.   DISCLAIMER. EXCEPT AS EXPRESSLY PROVIDED HEREIN, MERCK MAKES NO WARRANTIES, EXPRESS OR IMPLIED, INCLUDING ANY WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, WITH RESPECT TO THE MERCK COMPOUND, AND ANTIGEN EXPRESS MAKES NO WARRANTIES, EXPRESS OR IMPLIED, INCLUDING ANY WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, WITH RESPECT TO THE ANTIGEN EXPRESS COMPOUND.

14. Insurance; Indemnification; Limitation of Liability.

14.1.   Insurance. Each Party warrants that it maintains a policy or program of insurance or self-insurance at levels sufficient to support the indemnification obligations assumed herein. Upon request, a Party shall provide evidence of such insurance.

14.2. Indemnification.

14.2.1.  Indemnification by Antigen Express. Antigen Express agrees to defend, indemnify and hold harmless Merck, its Affiliates, and its and their employees, directors, subcontractors and agents from and against any loss, damage, reasonable costs and expenses (including reasonable attorneys’ fees and expenses) incurred in connection with any claim, proceeding, or investigation by a Third Party arising out of this Agreement or the Study (a “Liability”), except to the extent that such Liability was directly caused by (i) negligence or willful misconduct on the part of Merck (or any of its Affiliates, or its and their employees, directors, subcontractors or agents); (ii) a breach on the part of Merck of any of its representations and warranties or any other covenants or obligations of Merck under this Agreement; or (iii) a breach of Applicable Law by Merck.

14.2.2.  Indemnification by Merck. Merck agrees to defend, indemnify and hold harmless Antigen Express, its Affiliates, and its and their employees, directors, Subcontractors and agents from and against any Liability to the extent such Liability was directly caused by (i) negligence or willful misconduct on the part of Merck (or any of its Affiliates, or its and their employees, directors, subcontractors or agents); (ii) a breach on the part of Merck of any of its representations and warranties or any other covenants or obligations of Merck under this Agreement; or (iii) a breach of Applicable Law by Merck.

14.2.3.  Procedure. The obligations of Merck and Antigen Express under this Section 14.2 are conditioned upon the delivery of written notice to Merck or Antigen Express, as the case might be, of any potential Liability within a reasonable time after a Party becomes aware of such potential Liability. The indemnifying Party will have the right to assume the defense of any suit or claim related to the Liability (using counsel reasonably satisfactory to the indemnified Party) if it has assumed responsibility for the suit or claim in writing; provided that the indemnified Party may assume the responsibility for such defense to the extent the

32 

indemnifying Party does not do so in a timely manner). The indemnified Party may participate in (but not control) the defense thereof at its sole cost and expense. The Party controlling such defense (the “Defending Party”) shall keep the other Party (the “Other Party”) advised of the status of such action, suit, proceeding or claim and the defense thereof and shall consider recommendations made by the Other Party with respect thereto. The Defending Party shall not agree to any settlement of such action, suit, proceeding or claim without the prior written consent of the Other Party, which shall not be unreasonably withheld. The Defending Party, but solely to the extent the Defending Party is also the indemnifying Party, shall not agree to any settlement of such action, suit, proceeding or claim or consent to any judgment in respect thereof that does not include a complete and unconditional release of the Other Party from all liability with respect thereto or that imposes any liability or obligation on the Other Party without the prior written consent of the Other Party.

14.2.4.  Study Subjects. Antigen Express shall not offer compensation on behalf of Merck to any Study subject or bind Merck to any indemnification obligations in favor of any Study subject. Merck shall not offer compensation on behalf of Antigen Express to any Study subject or bind Antigen Express to any indemnification obligations in favor of any Study subject.

14.3.   LIMITATION OF LIABILITY. IN NO EVENT SHALL EITHER PARTY (OR ANY OF ITS AFFILIATES OR SUBCONTRACTORS) BE LIABLE TO THE OTHER PARTY UNDER ANY THEORY FOR, NOR SHALL ANY INDEMNIFIED PARTY HAVE THE RIGHT TO RECOVER, ANY SPECIAL, INDIRECT, INCIDENTAL, PUNITIVE OR CONSEQUENTIAL DAMAGES (INCLUDING LOST PROFITS OR DAMAGES FOR LOST OPPORTUNITIES), WHETHER IN CONTRACT, WARRANTY, NEGLIGENCE, TORT, STRICT LIABILITY OR OTHERWISE, ARISING OUT OF (X) THE MANUFACTURE OR USE OF ANY COMPOUND SUPPLIED HEREUNDER OR (Y) ANY BREACH OF OR FAILURE TO PERFORM ANY OF THE PROVISIONS OF THIS AGREEMENT OR ANY REPRESENTATION, WARRANTY OR COVENANT CONTAINED IN OR MADE PURSUANT TO THIS AGREEMENT, EXCEPT THAT SUCH LIMITATION SHALL NOT APPLY TO DAMAGES PAID OR PAYABLE TO A THIRD PARTY BY AN INDEMNIFIED PARTY FOR WHICH THE INDEMNIFIED PARTY IS ENTITLED TO INDEMNIFICATION HEREUNDER OR WITH RESPECT TO DAMAGES ARISING OUT OF OR RELATED TO A PARTY’S BREACH OF ITS OBLIGATIONS UNDER THIS AGREEMENT WITH RESPECT TO USE, DISCLOSURE, LICENSE, ASSIGNMENT OR OTHER TRANSFER OF CLINICAL DATA, CONFIDENTIAL INFORMATION, JOINTLY-OWNED INVENTIONS AND SAMPLE TESTING RESULTS.

15. Use of Name.

Except as otherwise provided herein, neither Party shall have any right, express or implied, to use in any manner the name or other designation of the other Party or any other trade name, trademark or logo of the other Party for any purpose in connection with the performance of this Agreement without the other Party’s prior written consent.

16. Force Majeure.

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If, in the performance of this Agreement, one of the Parties is prevented, hindered or delayed by reason of any cause beyond such Party’s reasonable control (e.g., war, riots, fire, strike, acts of terror, governmental laws), such Party shall be excused from performance to the extent that it is necessarily prevented, hindered or delayed (“Force Majeure”). The non- performing Party shall notify the other Party of such Force Majeure within ten (10) days after such occurrence by giving written notice to the other Party stating the nature of the event, its anticipated duration, and any action being taken to avoid or minimize its effect. The suspension of performance will be of no greater scope and no longer duration than is necessary and the non- performing Party shall use commercially reasonable efforts to remedy its inability to perform.

17. Entire Agreement; Amendment; Waiver.

This Agreement, together with the Appendices and Schedules hereto and the Related Agreements, constitutes the sole, full and complete agreement by and between the Parties with respect to the subject matter of this Agreement, and all prior agreements, understandings, promises and representations, whether written or oral, with respect thereto are superseded by this Agreement. In the event of a conflict between a Related Agreement and this Agreement, the terms of this Agreement shall control. No amendments, changes, additions, deletions or modifications to or of this Agreement shall be valid unless reduced to writing and signed by the Parties hereto. Any term or condition of this Agreement may be waived at any time by the Party that is entitled to the benefit thereof, but no such waiver shall be effective unless set forth in a written instrument duly executed by or on behalf of the Party waiving such term or condition. The waiver by either Party of any right hereunder or of the failure to perform or of a breach by the other Party shall not be deemed a waiver of any other right hereunder or of any other breach or failure by said other Party whether of a similar nature or otherwise.

18. Assignment and Affiliates.

Neither Party shall assign or transfer this Agreement without the prior written consent of the other Party; provided, however, that either Party may assign all or any part of this Agreement to one or more of its Affiliates without the other Party’s consent, and any and all rights and obligations of either Party may be exercised or performed by its Affiliates, provided that such Affiliates agree to be bound by this Agreement.

19. Invalid Provision.

If any provision of this Agreement is held to be illegal, invalid or unenforceable, the remaining provisions shall remain in full force and effect and will not be affected by the illegal, invalid or unenforceable provision. In lieu of the illegal, invalid or unenforceable provision, the Parties shall negotiate in good faith to agree upon a reasonable provision that is legal, valid and enforceable to carry out as nearly as practicable the original intention of the entire Agreement.

20. No Additional Obligations.

Antigen Express and Merck have no obligation to renew this Agreement or apply this Agreement to any clinical trial other than the Study. Nothing in this Agreement obligates the Parties to enter into any other agreement (other than the Related Agreements) at this time or in the future.

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21. Governing Law; Dispute Resolution.

21.1.   The Parties shall attempt in good faith to settle all disputes arising out of or in connection with this Agreement in an amicable manner. Any claim, dispute or controversy arising out of or relating to this Agreement, including the breach, termination or validity hereof or thereof, shall be governed by and construed in accordance with the substantive laws of the State of New York, without giving effect to its choice of law principles.

21.2.   Nothing contained in this Agreement shall deny either Party the right to seek injunctive or other equitable relief from a court of competent jurisdiction in the context of a bona fide emergency or prospective irreparable harm, and such an action may be filed or maintained notwithstanding any ongoing discussions between the Parties.

22. Notices.

All notices or other communications that are required or permitted hereunder shall be in writing and delivered personally, sent by facsimile (and promptly confirmed by personal delivery or overnight courier), or sent by internationally-recognized overnight courier addressed as follows:

If to Antigen Express, to:

Antigen Express, Inc. 33 Redwing Road

Wellesley, MA 02481 Attention: Eric von Hofe

If to Merck, to:

Merck Sharp & Dohme B.V. Waarderweg 39

2031 BN Haarlem Netherlands Attention: Director

Facsimile: +31 23 514 8677

With copies (which shall not constitute notice) to: Merck Sharp & Dohme Corp.

One Merck Drive PO Box 100

Whitehouse Station, NJ 08889-0100 Attention: Office of Secretary

Merck Sharp & Dohme Corp. 351 North Sumneytown Pike Mailstop UG4CD-16

35 

North Wales, PA 19454-2505

Attention: Senior Vice President, Research Science

Merck Sharp & Dohme Corp. 2000 Galloping Hill Road Mailstop K-1-3045 Kenilworth, NJ 07033-1310

Attention: Assistant General Counsel, Corporate Transactions

23. Relationship of the Parties.

The relationship between the Parties is and shall be that of independent contractors, and does not and shall not constitute a partnership, joint venture, agency or fiduciary relationship. Neither Party shall have the authority to make any statements, representations or commitments of any kind, or take any actions, that are binding on the other Party, except with the prior written consent of the other Party to do so. All Persons employed by a Party will be the employees of such Party and not of the other Party and all costs and obligations incurred by reason of any such employment shall be for the account and expense of such Party.

24. Counterparts and Due Execution.

This Agreement and any amendment may be executed in any number of counterparts (including by way of facsimile or electronic transmission), each of which shall be deemed an original, but all of which together shall constitute one and the same instrument, notwithstanding any electronic transmission, storage and printing of copies of this Agreement from computers or printers. When executed by the Parties, this Agreement shall constitute an original instrument, notwithstanding any electronic transmission, storage and printing of copies of this Agreement from computers or printers. For clarity, facsimile signatures and signatures transmitted via PDF shall be treated as original signatures.

25. Construction.

Except where the context otherwise requires, wherever used, the singular will include the plural, the plural the singular, the use of any gender will be applicable to all genders, and the word “or” is used in the inclusive sense (and/or). Whenever this Agreement refers to a number of days, unless otherwise specified, such number refers to calendar days. The captions of this Agreement are for convenience of reference only and in no way define, describe, extend or limit the scope or intent of this Agreement or the intent of any provision contained in this Agreement. The term “including” as used herein shall be deemed to be followed by the phrase “without limitation” or like expression. The term “will” as used herein means shall. The terms “hereof”, “hereto”, “herein” and “hereunder” and words of similar import when used in this Agreement refer to this Agreement as a whole and no to any particular provision of this Agreement. References to “Article,” “Section”, “Appendix” or “Schedule” are references to the numbered sections of this Agreement and the appendices attached to this Agreement, unless expressly stated otherwise. Except where the context otherwise requires, references to this “Agreement” shall include the appendices attached to this Agreement. The language of this Agreement shall

36 

be deemed to be the language mutually chosen by the Parties and no rule of strict construction will be applied against either Party hereto.

[Remainder of page intentionally left blank.]

37 

IN WITNESS WHEREOF, the respective representatives of the Parties have executed this Agreement as of the Effective Date.

 

Merck Sharp & Dohme B.V.

By: _ _

_ _ _

_ _ _

_ _ _

Name

Title

38 

IN WITNESS WHEREOF , the respective representatives of the Parties have executed this Agreement as of the Effective Date.

Antigen Express, Inc.

By:

Name: Eric von Hofe

Title: President

39 

Appendix A PROTOCOL

 DRAFT PROTOCOL NSABP B-001_v05-11

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NSABP PROTOCOL B-001

A Phase II Clinical Trial of Pembrolizumab in Combination with the AE37 Peptide Vaccine in Patients with Metastatic Triple Negative Breast Cancer

NSABP Foundation, Inc.

Nova Tower 2 − Two Allegheny Center – Suite 1200 Pittsburgh, PA 15212

TELEPHONE:	1-800-270-3165
E-MAIL:	industry.trials@nsabp.org
CLINICAL QUESTIONS:	1-800-270-3165

KEY STUDY PERSONNEL

NSABP Chair:	Norman Wolmark, MD
Protocol Chair:	Shannon Puhalla, MD
Protocol Officer:	Samuel Jacobs, MD
Protocol Statistician:	Greg Yothers, PhD
Clinical Research Scientist:	TBD

Protocol B-001 IND #XXXX sponsored by NSABP Foundation, Inc.

Version Date: May 11, 2017

CONFIDENTIAL

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TABLE OF CONTENTS

Information Resources		iii
Glossary of Abbreviations and Acronyms		iv
1.0	OVERVIEW OF STUDY DESIGN
2.0	BACKGROUND	10
2.1	Background	10
2.2	Rationale for Immune checkpoint therapy in triple-negative breast cancer	10
2.3	Rationale for HER2 vaccine in triple-negative breast cancer	11
2.4	Pembrolizumab background and clinical trials	12
2.5	HER2 vaccine, AE37	13
3.0	STUDY AIMS AND ENDPOINTS	14
3.1	Co-Primary aims and endpoints	14
3.2	Secondary aims and endpoints	14
3.3	Exploratory translational science	14
4.0	PATIENT ELIGIBILITY AND INELIGIBILITY	15
4.1	Conditions for patient eligibility	15
4.2	Conditions for patient ineligibility	16
5.0	REQUIREMENT FOR STUDY ENTRY AND DURING TREATMENT AND FOLLOW-UP	21
6.0	PATHOLOGY AND CORRELATIVE SCIENCE STUDIES	21
6.1	Overview of requirements	21
6.2	Use of specimens	21
6.3	Tumor and blood sample submissions	22
6.4	Rationale for correlative science studies	23
7.0	STUDY THERAPY	24
7.1	AE37 Vaccine	24
7.2	Study regimen	25
7.3	Supportive therapy	26
7.4	Contraindications and precautions	26
7.5	Contraception	27
7.6	Pregnancy	27
7.7	Participation in other clinical trials	27
8.0	TREAMENT MANAGEMENT	28
8.1	General instructions	28
8.2	Treatment management for study therapy	28
8.3	Supportive care guidelines for pembrolizumab	33
8.4	Liver dysfunction (Hy's Law)	35
9.0	DRUG INFORMATION	37
9.1	AE37 peptide vaccine	37
9.2	Pembrolizumab (MK-3475, KEYTRUDAÒ) (NSC-776864)	38
9.3	Study therapy procurement	39
9.4	Study therapy storage	40
9.5	Transfer of study therapy	40
9.6	Destruction of study therapy vials	40
9.7	Drug inventory records	40
9.8	Drug accountability	40
10.0	ADVERSE EVENT REPORTING REQUIREMENTS	42
10.1	Definition of an AE	42

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10.2	Definition of an SAE	42
10.3	Events requiring expedited reporting	43
10.4	Pregnancy	44
10.5	Grading the severity of the AE	45
10.6	Expedited reporting instructions	45
10.7	Time period and frequency for routine reporting of AEs	46
10.8	Documentation requested following death	46
11.0	ASSESSMENT OF EFFECT	47
11.1	Definitions	47
11.2	Response criteria	48
11.3	Evaluation of best overall response	48
11.4	Symptomatic deterioration	49
12.0	PATIENT ENTRY PROCEDURES	50
12.1	Patient consent form	50
12.2	Study entry	50
12.3	Patient study number and treatment assignment	50
12.4	Investigator-initiated discontinuation of study therapy	50
12.5	Patient-initiated discontinuation of study therapy	50
12.6	Patient-initiated withdrawal from the study	51
13.0	DATA HANDLING AND RECORDKEEPING	52
14.0	STATISTICAL CONSIDERATION	53
14.1	Sample size determination and protocol duration for the primary endpoint	53
14.2	Statistical analysis plan	53
14.3	Monitoring	53
15.0	PUBLICATION INFORMATION	54
16.0	REFERENCES	55
APPENDEX A DETERMINIATION OF PERFORMANCE STATUS		59
APPENDIX B CONTRACEPTION		60

INFORMATION RESOURCES	iii
GLOSSARY OF ABBREVIATIONS AND ACRONYMS	iv
Table 1. B-001 Safety Run-In (N=13 patients)	7
Figure 1 B-001 Schema	9
Table 2. Tests, exams, and other requirements prior to study entry	18
Table 3. Tests, exams, and other requirements following study entry	19
Table 4. Summary of patient sample submission requirements	21
Table 5: Safety Cohort Study Therapy	25
Table 6: Expansion Cohort Study Therapy	26
Table 7. AE37 vaccine local reaction assessment	29
Table 8. Dose levels for AE37 vaccine	29
Table 9. Dose modification and toxicity management guidelines for immune-related AEs associated with pembrolizumab	30
Table 10. Infusion Reaction Treatment Guidelines	34
Table 11. Determination of response	48

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INFORMATION RESOURCES

NSABP Department of Site and Study Management NSABP Operations Center Nova Tower 2 Nova Tower 2 − Two Allegheny Center– Suite 1200 Pittsburgh, PA 15212 Phone: 1-800-270-3165 E-mail: industry.trials@nsabp.org
For questions regarding: •         IRB review & informed consent •         Submission of IRB approval •         Study entry information •         Eligibility •         Treatment regimen •         Dose modifications/delays •         Other clinical aspects of the trial •         Adverse event reporting including SAE reporting •         eCRF completion	Department of Site and Study Management (DSSM)	Phone: 1-800-270-3165 E-mail: industry.trials@nsabp.org
For questions regarding data management	Department of Site and Study Management (DSSM)	Phone: 1-800-270-3165 E-mail: industry.trials@nsabp.org
Request for research sample collection kits	NSABP Division of Pathology 1307 Federal Street – Suite 303 Pittsburgh, PA 15212	Phone: 412-697-6611 E-mail: pathology.questions@nsabp.org Refer to the B-001Pathology and Correlative Science Instructions
Requests for study drug	Department of Site and Study Management (DSSM)	E-mail: B001.drugorders@nsabp.org
Questions regarding drug shipment	Department of Site and Study Management (DSSM)	Phone: 1-800-270-3165 E-mail: industry.trials@nsabp.org

44 

GLOSSARY OF ABBREVIATIONS AND ACRONYMS

AE		adverse event
ALT (SGPT)		alanine aminotransferase
ANC		absolute neutrophil count
ASCO		American Society of Clinical Oncology
AST (SGOT)		aspartate aminotransferase
BP		blood pressure
BSA		body surface area
BUN		blood urea nitrogen
CA	Canada
CAP		College of American Pathologists
CBC		complete blood count
CD3ζ		cluster of differentiation zeta chain
CD4		cluster of differentiation 4
CD8		cluster of differentiation 8
CD28		cluster of differentiation 28
CDK4,6		cyclin-dependent kinase 4,6
CHF		congestive heart failure
CI		confidence interval
CR	complete response
CT	computed tomography
CTCAE v4.0		Common Terminology Criteria for Adverse Events Version 4.0 CTEP Cancer Therapy Evaluation Program
DLT		dose-limiting toxicity
DSSM		Department of Site and Study Management
DTH		delayed type hypersensitivity
ECG		electrocardiogram
ECOG		Eastern Cooperative Oncology Group
eCRF		electronic case report form
ELISA		enzyme-linked immunosorbent assay
ER	estrogen receptor
ErbB		epidermal growth factor receptor
FDA		Food and Drug Administration
FFPE		formalin fixed paraffin embedded
FNA		fine needle aspiration
FoxP3+		Forkhead Box protein p3
GCP		Good Clinical Practice
G-CSF		granulocyte colony stimulating factor
GM-CSF		granulocyte macrophage-colony stimulating factor H&P history and physical
HER2		human epidermal growth factor receptor 2
HIV		human immunodeficiency virus
HLA		human leucocyte antigen
HR	hazard ratio
HRT		hormone replacement therapy
IB	Investigator's Brochure
IBC		Institutional Biosafety Committee
ID	identification
IDO		indolamine-2, 3-dioxygenase

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GLOSSARY OF ABBREVIATIONS AND ACRONYMS (continued)

IFNγ	Interferon gamma
IHC	immunohistochemistry
IND	investigational new drug
INR	international normalized ratio
irAE	immune-related adverse event
IRB	institutional review board
IV	intravenous
KEYNOTE-001	Study of Pembrolizumab (MK-3475) in Participants With Progressive Locally Advanced or Metastatic Carcinoma, Melanoma, or Non-small Cell Lung Carcinoma (P07990/MK-3475-001/KEYNOTE-001)
kg	kilogram
LD	longest diameter
LFT	liver function test
LLN	lower limit of normal
LRMK	N-terminal-linked with Ii-Key tetramer
mAb	monoclonal antibody
mg	milligram
MHC	major histocompatibility complex
MRI	magnetic resonance imaging
mTNBC	metastatic triple-negative breast cancer
NCCN	National Comprehensive Cancer Network
NCI	National Cancer Institute
NSABP	NSABP Foundation, Inc.
NSCLC	non-small cell lung cancer
ORR	overall response rate
OTC	over-the-counter
p	probability
PBMC	peripheral blood mononuclear cells
pCR	pathologic complete response
PD	progressive disease
PDs	pharmacodynamics
PD-1	Programmed cell death-1, proficient
PD-L1	programmed death ligand-1
PET	positron emission tomography
PFS	progression-free survival
PK	pharmacokinetic
PO	by mouth
PR	partial response
PT	prothrombin time
q	every
Q2W	every 2 weeks
Q3W	every 3 weeks
RECIST	Response Evaluation Criteria in Solid Tumors
RNA	Ribonucleic acid
RT	radiation therapy
SABCS	San Antonio Breast Cancer Symposium
SAE	serious adverse event
SC	subcutaneous
SD	stable disease
TILS	tumor-infiltrating lymphocytes

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GLOSSARY OF ABBREVIATIONS AND ACRONYMS (continued)

T-cell	T lymphocyte
TGFβ	Transforming growth factor beta
TNBC	triple negative breast cancer
ULN	upper limit of normal
US	United States (of America)
WOCBP	women of childbearing potential

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1.0 OVERVIEW OF STUDY DESIGN

The B-001 is an open label, phase II study using pembrolizumab in combination with AE37 peptide vaccine (AE37) in patients with metastatic triple negative breast cancer (mTNBC). The primary objectives for this study are to establish the recommended biologic dose of AE37 in combination with pembrolizumab that will enhance the tumor-specific immune response and demonstrate efficacy in patients with advanced triple negative breast cancer.

This study will have a Simon two-stage design. In Stage I (safety cohort), 13 patients will receive combination therapy of AE37 vaccine (without GM-CSF adjuvant) 1000 micrograms in two split intradermal injections on Day 1 of cycles 1 through 5 and pembrolizumab 200 mg intravenous infusion (IV) given Day 1 of each cycle for 2 years (1 cycle =21 days). See Table 1.

During a safety run-in, the first 3 patients will be closely followed for 6 weeks following the first dose of study therapy (2 cycles) without further accrual of patients. If one or less of the first 3 patients experience ≥ Grade 3 systemic toxicity attributable to study therapy during the observation period, the safety run-in portion of the study will proceed to full enrollment at the proposed study therapy dose (AE37 1000 micrograms and pembrolizumab 200 mg IV infusion). If there are two or more patients in the safety run-in with ≥ Grade 3 systemic toxicities requiring a

≥ 2 week delay in starting Cycle 2, the dose of AE37 will be decreased to dose level −1 (500 micrograms) to complete stage I accrual.

If Grade 3 systemic toxicity attributable to the vaccine is observed during the safety run-in or in > 25% (4 or more) of patients in Stage I, the AE37 dose will be de-escalated to 500 micrograms (dose level −1) for all patients to complete stage I accrual. If systemic toxicity occurs in ≥ 3 patients at dose level −1 accrual will be halted and the toxicity reviewed by the study team. .

Table 1. B-001 Safety Run-In (N=13 patients)

AE37 1000mcg
Patient # 1-13	DLT/ patients		AE37 Dose modification
1	0/1 or 1/1		Continue at 1000mcg
2	0/2 or 1/2		Continue at 1000mcg
	2/2		Decrease Dose level -1 (500mcg)
3	0/3, 1/3		Continue at 1000mcg
	2/3		Decrease Dose level -1 (500mcg)
All subsequent patients*	0/13, 1/13, 2/13, 3/13		Continue at 1000mcg
if 4 or more patients experience Grade 3 systemic toxicity attributable to the AE37 vaccine, the starting dose will be decreased to Dose Level −1 (500mcg) for all subsequent patients enrolled to the study and the Safety Run-In will commence as outlined below.
AE37 500mcg
Patient #		DLT/ patients		AE37 Dose modification
1st  patient on 500mcg		0/1, 1/1		Continue at 500mcg
2nd  patient on 500mcg		0/2, 1/2		Continue at 500mcg
		2/2		Hold AE37
3rd  patient on 500mcg		0/3, 1/3,		Continue at 500mcg
		2/3		Hold AE37
All subsequent patients		0, 1, 2**		Continue at 500mcg
**If 3 or more patients experience Grade 3 systemic toxicity at AE37 500mcg attributable to the AE37 vaccine, the trial will be halted and reevaluated.

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If > 2 patients in the first stage have an objective response, the study will proceed to Stage II (expansion cohort). The expansion cohort will enroll 16 additional patients to receive the combination therapy: AE37 (at the dose established in the initial safety cohort [i.e., 1000 micrograms or 500 micrograms]) x on Day 1 for five cycles, and pembrolizumab 200mg IV on Day 1 of every cycle x 2 years. If ≥ 8 patients have objective response, the study therapy will be considered for further testing.

All patients (safety and expansion cohorts) will receive two delayed type hypersensitivity inoculations (DTH): the first within one week prior to beginning study therapy and the second approximately 42 days after the last AE37 vaccine dose.

Toxicity will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events version 4.0. Oversight and determination/attribution of all AEs during the safety run-in and the subsequent study will be reviewed by NSABP Department of Site and Study Management at monthly intervals.

There will be up to 29 evaluable patients; accrual will occur over 24 months. Trial duration is about 4 years.

Correlative science includes the submission of archived primary tumor tissue and blood samples as a study requirement for all patients and two optional tissue sample collections from consenting patients.

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Figure 1

B-001 Schema

 

50 

2.0 BACKGROUND

2.1 Background

Triple-negative breast cancers (TNBC) are defined as tumors with low expression of estrogen receptor, progesterone receptor, and HER2. Approximately 20% of women with breast cancer have triple- negative disease. As a group, these patients have a relatively poor prognosis.

Chemotherapy is the mainstay of therapy as these tumors lack a biomarker for targeted therapy such as endocrine treatment or traditional anti-HER2 therapy (e.g., trastuzumab). TNBC more frequently occurs in younger women of < 40 years of age and is more common in black women than in white women. Recurrence after initial diagnosis and treatment more often occurs within the first few years of diagnosis compared to hormone positive disease in which late recurrences are frequent. Because targeted therapies are ineffective in triple-negative disease, survival after recurrence is often short.

2.2 Rationale for Immune checkpoint therapy in triple-negative breast cancer

The use of immune checkpoint therapy has recently joined the other modalities of therapy as one of the pillars of modern cancer treatment. The development of agents that target immune checkpoints has dramatically altered treatment in many difficult to treat cancers such as lung cancers, melanoma, specific subpopulations of colorectal cancer, bladder cancer, chemo- refractory Hodgkin's disease, and others. Immune surveillance in controlling outgrowth of neoplastic transformation has been recognized for decades (Disis 2010). Accumulating evidence shows a correlation between tumor-infiltrating lymphocytes (TILs) in cancer tissue and favorable prognosis in various malignancies (Dong 2002; Sharpe 2002; Brown 2003; Francisco 2010; Thompson 2007). The magnitude of lymphocytic infiltration is not the only factor modulating disease progression as the phenotype of the lymphocytic infiltrate may be most important

(Stanton 2016). In particular, the presence of CD8+ T-cells and the ratio of the CD8+ effector T- cells/FoxP3+ regulatory T-cells seems to correlate with improved prognosis and long-term

survival in many solid tumors. In breast cancer there is variation in the incidence and magnitude of TILs. TNBC demonstrates the highest incidence of TILs. CD8+ T-cell infiltrates indicative of type 1immunity were found in 60% of TNBC. There are many factors that may contribute to the magnitude of TILs in TNBC. For example, hormone receptor negative cancers have been shown to have more genomic instability and more chromosomal instability than hormone-receptor- positive tumors (Disis 2015; Stephens 2012). A greater number of mutations raise the chance that mutated protein sequences will be expressed and potentially be recognized as novel antigens by the immune system.

In addition, PD-L1 is expressed on many cancer and immune cells and in doing so plays an important role in disrupting cancer surveillance and maintaining an immunosuppressive

microenvironment. A recent study of 43 breast tumors demonstrated that 89% of PD-L1+ cancers were associated with increased TIL infiltration compared with 24% of PD-L1− tumors. The PD-L1 receptor-ligand interaction is a major pathway hijacked by tumors to suppress

immune control. The normal function of PD-1, expressed on the cell surface of activated T-cells under healthy conditions, is to down-modulate unwanted or excessive immune responses, including autoimmune reactions.

Blocking PD-1 pathway invigorated the immune system, for example by enhancing tumor antigen-specific CD8+ T cell responses. Pembrolizumab is a humanized monoclonal antibody

that binds to the PD-1 receptor and blocks interactions with its ligands, PD-L1 and PD-L2. This in turn releases the immune inhibitory effects of PD-1 and can enhance anti-tumor immune response.

In a phase 1 trial in heavily treated TNBC patients (20% had ≥ 5 or more lines of therapy) (n=32) selected for PD-L1+ staining in the tumor or tumor stroma, the response to pembrolizumab was

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encouraging: 18.5% (1 complete response [CR] and 2 partial responses [PRs]). The median time to response was 18 weeks and the duration of response was not reached. The 6 month progression free survival (PFS) rate was 23.3% (Nanda 2016). While encouraging, there is still low overall response to single agent immune therapy in TNBC. This is further demonstrated in a recent study of avelumab, a PD-1 targeted agent presented at SABCS in 2015. This trial had a low objective response rate of 5.4% in the entire cohort; however in the TNBC cohort tumors with PD-L1 expressing immune cells in the tumor, there were 44.4% of patients receiving PR (Dirix 2015). Because of the durability in response, current strategies are aimed at increasing the number of responsing patients.

2.3 Rationale for HER2 vaccine in triple-negative breast cancer

The HER2/neu protein was shown to be a tumor antigen that stimulates immune responses, as evidenced by specific antibodies and T cells against HER2/neu detected in blood samples from breast cancer patients (Disis 1994). The multiple immunogenic epitopes within the HER2/neu protein led to the discovery of specific HER2/neu peptides that stimulate cytotoxic T lymphocytes to recognize and eliminate HER2/neu expressing breast and ovarian cancer cells (Peoples 1995). Two peptide vaccines, E75 and GP2, containing epitopes derived from HER2/neu, have been shown in Phase I and II trials to safely and effectively stimulate antigen-

specific immune responses and cytolytic activity via CD8+ T cells in tumors of breast cancer

patients expressing HER2/neu (Benavides 2009; Mittendorf 2006). However, these first generation peptide vaccines are HLA-A2 restricted and require booster vaccinations as they do not demonstrate sustained-immunity.

AE37, which is not HLA-A2 restricted, has been tested in Phase I and II clinical trials with breast and prostate cancer patients determined to express any level of the HER2/neu protein. Significant increases in T cell proliferation were detected 1 month post-vaccination and long term (6 months after completion of vaccinations [3 years after completion in our Phase I prostate cancer study, see below]) with DTH reactions noted for all patients that received vaccine. The vaccine was well tolerated with 73% experiencing Grade 1 systemic toxicities (fatigue, nausea, myalgias, rhinitis, diarrhea, headache and cough) and 13% experiencing Grade 2 toxicities (joint pain and stiffness). In the larger Phase II breast cancer study, Grade 3 toxicities were observed in 1% of 298 patients enrolled (Mittendorf 2016). This was a controlled, randomized and single blinded study comparing the AE37 vaccine plus GM-CSF versus GM-CSF alone. The toxicities were observed equally both in the AE37 plus GM-CSF as well as the GM-CSF only arms of the study, indicating that toxicities were attributable to GM-CSF and not AE37. Given that AE37 on its own is sufficient to generate a T cell response, the current study will employ AE37 without GM-CSF.

AE37 was also tested in a Phase 1 study of 32 castrate-sensitive and castrate resistant prostate cancer patients with any level of HER2/neu expression at 500 micrograms AE37 peptide/125 micrograms GM-CSF in 6 monthly intradermal inoculations (Perez 2010). The vaccine was very well tolerated with mild Grade 1 and 2 toxicities attributed largely to GM-CSF. In vitro immune responses were noted in 72% of patients demonstrated by increases in the percentages of circulating CD4+ and CD8+ T cells as well as increased production of IFN-γ noted post vaccination and long term. Interestingly, in vitro immune responses were significantly higher in patients expressing low levels of HER2/neu (IHC 1+ or 2+) which is consistent with results seen in the E75 vaccine trial in breast cancer patients (Benavides 2009). Importantly, it has been shown that tumor cells with low level HER2 expression are still good targets for killing by activated T cells (Weidanz 2006). This is because activated T cells recognize target protein peptides in the context of MHC molecules as opposed to the native target protein as is the case for monoclonal antibodies. The limiting factor is thus more closely dependent upon the level of expression of MHC molecules rather than the level of target protein expression. As patients in this category are considered HER2 negative by ASCO/CAP guidelines (Nitta 2016) they are represented in the triple negative breast cancer population. In addition to establishing a specific

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activation of both CD4+ and CD8+ T cells, the Phase I trial of AE37 also demonstrated a reduction in circulating T regulatory cells as well as TGFβ. This is significant as it suggests that AE37 treatment reduces immune suppressive function as it increases specific effector function.

2.4 Pembrolizumab background and clinical trials

Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD 1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Based on preclinical in vitro data, pembrolizumab has high affinity and potent receptor blocking activity for PD 1. Pembrolizumab has an acceptable preclinical safety profile and is in clinical development as an intravenous (IV) immunotherapy for advanced malignancies.

Keytruda™ (pembrolizumab) is indicated for the treatment of patients across a number of indications. For more details on specific indications refer to the Investigator brochure.

2.4.1       Rationale for pembrolizumab dose selection

The dose of pembrolizumab planned to be studied in this trial is 200 mg Q3W. The dose recently approved in the United States and several other countries for treatment of melanoma subjects is 2 mg/kg Q3W. Information on the rationale for selecting 200 mg Q3W is summarized below.

In KEYNOTE-001, an open-label Phase I study conducted to evaluate the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD), and anti-tumor activity of pembrolizumab when administered as monotherapy. The dose escalation portion of this trial evaluated three dose levels, 1 mg/kg, 3 mg/kg and 10 mg/kg, administered every 2 weeks (Q2W) and dose expansion cohorts evaluated 2 mg/kg Q3W and 10 mg/kg Q3W in subjects with advanced solid tumors. All dose levels were well tolerated and no dose- limiting toxicities were observed. This first-in-human study of pembrolizumab showed evidence of target engagement and objective evidence of tumor size reduction at all dose levels. No maximum tolerated dose (MTD) has been identified. In addition, two randomized cohort evaluations of melanoma subjects receiving pembrolizumab at a dose of 2 mg/kg versus 10 mg/kg Q3W have been completed, and one randomized cohort evaluating 10 mg/kg Q3W versus 10 mg/kg Q2W has also been completed. The clinical efficacy and safety data demonstrate a lack of important differences in efficacy or safety profile across doses.

An integrated body of evidence suggests that 200 mg every 3 weeks (Q3W) is expected to provide similar response to 2 mg/kg Q3W, 10 mg/kg Q3W and 10 mg/kg Q2W. Previously, a flat pembrolizumab exposure-response relationship for efficacy and safety has been found in subjects with melanoma in the range of doses between 2 mg/kg and 10 mg/kg. Exposures for 200 mg Q3W are expected to lie within this range and will be close to those obtained with 2 mg/kg Q3W dose.

A population pharmacokinetic (PK) model, which characterized the influence of body weight and other patient covariates on exposure, has been developed. The PK profile of pembrolizumab is consistent with that of other humanized monoclonal antibodies, which typically have a low clearance and a limited volume of distribution. The distribution of exposures from the 200 mg fixed dose are predicted to considerably overlap those obtained with the 2 mg/kg dose and importantly will maintain individual patient exposures within the exposure range established in melanoma as associated with maximal clinical response. Pharmacokinetic properties of pembrolizumab, and specifically the weight-dependency in clearance and volume of distribution are consistent with no meaningful advantage to weight-based dosing relative to fixed dosing.

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In translating to other tumor indications, similarly flat exposure-response relationships for efficacy and safety as observed in subjects with melanoma can be expected, as the anti-tumor effect of pembrolizumab is driven through immune system activation rather than through a direct interaction with tumor cells, rendering it independent of the specific tumor type. In addition, available PK results in subjects with melanoma, NSCLC, and other tumor types support a lack of meaningful difference in pharmacokinetic exposures obtained at tested doses among tumor types. Thus the 200 mg Q3W fixed-dose regimen is considered an appropriate fixed dose for other tumor indications as well.

A fixed dose regimen will simplify the dosing regimen to be more convenient for physicians and to reduce potential for dosing errors. A fixed dosing scheme will also reduce complexity in the logistical chain at treatment facilities and reduce wastage. The existing data suggest 200 mg Q3W as the appropriate dose for pembrolizumab.

2.5 HER2 vaccine, AE37

The HER2/neu proto-oncogene is a tumor associated antigen that has been investigated in many types of cancers including breast, prostate, and ovarian. HER2/neu codes for a 185kD

trans-membrane protein in the epidermal growth factor receptor family which is found to be over- expressed in 20-30% of breast cancers and has also been correlated with more aggressive tumor behavior (Slamon 1989). It has been shown to be expressed in an additional 50% of breast cancers at low to intermediate levels.

AE37 is a fifteen amino-acid peptide from the HER2 protein to which the four amino-acid sequence LRMK has been added, it is produced by a solid-phase peptide synthesis. The peptide sequence is AC-LRMK-GVGSPYVSRLLGICL-NH2. Studies have demonstrated that the AE37 peptide stimulates a robust helper T-cell response leading to effective cytotoxic T lymphocyte (CTL) activity against tumors expressing even low levels of HER2 regardless of HLA status.

AE37 is a hybrid Ii-Key/HER2 peptide. Ii-Key hybrids have been shown to display >250 times potency in terms of T-cell stimulation in vitro compared to the unmodified naturally-occurring peptide. AE37 has been shown to be recognized both by CD4+ T helper cells as well as CD8+ CTLs (HER2 Hybrid Peptide AE37 IB).

Antigen Express has developed a novel method for dramatically increasing antigen-specific stimulation of T helper cells. This involves the addition of a small portion of the major histocompatibility complex (MHC) class II-associated Ii protein (termed Ii-Key) to class II epitopes (Lee 2000). The Ii-Key segment of the Ii protein was found to bind to an allosteric site on MHC class II molecules, thereby facilitating the direct charging of a vaccine peptide into the antigenic peptide-binding site of MHC class II molecules (Sotiriadou 2007). The resulting Ii- Key/antigenic epitope hybrid displays up to 250 times greater potency in vitro compared to the unmodified class II epitope (Sotiriadou 2007). Studies have shown that Ii-Key hybrid peptides derived from a variety of disease-related antigens more potently activate CD4+ T helper cells in vivo as well as in vitro when compared to epitope only peptides. The consequence of this increased yet specific T helper cell stimulation is more robust CTL activation and the production of immunological memory.

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3.0 STUDY AIMS AND ENDPOINTS

3.1 Co-Primary aims and endpoints

3.1.1 Determination of recommended dose for further study

Aim: To evaluate the safety and tolerability of AE37 peptide vaccine given in combination with pembrolizumab in patients with metastatic triple negative breast cancer

Endpoint: Recommended dose of AE37 that can safely be administered with pembrolizumab as a combination in an expanded cohort

3.1.2 Response rate

Aim: Objective response rate (ORR)

Endpoint: Overall objective response rate as measured by RECIST 1.1 with modifications for progressive disease confirmation

3.2 Secondary aims and endpoints

3.2.1 Progression-free survival (PFS)

Aim: To evaluate the progression free survival (PFS) with pembrolizumab in combination with AE37 peptide vaccine at the recommended biologic dosage

Endpoint: Time to progression or death from any cause

3.2.2 Overall Survival (OS)

Aim: To determine OS rate at 1 year

Endpoint: Time from study entry through 1 year

3.2.3 Toxicity

Aim: To evaluate the overall toxicity of AE37 peptide vaccine in combination with pembrolizumab

Endpoint: Frequency and severity of adverse events categorized using the NCI Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v4.0).

3.3 Exploratory translational science

Aim: Exploratory analysis of immune parameters

Aim: To determine presence of in vivo responses to DTH

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4.0 PATIENT ELIGIBILITY AND INELIGIBILITY

Investigators should consider each of these factors when selecting patients for this trial. Investigators should also consider all other relevant factors (medical and non-medical), as well as the risks and benefits of the study therapy, when deciding if a patient is an appropriate candidate for this trial.

4.1 Conditions for patient eligibility

A patient cannot be considered eligible for this study unless all of the following conditions are met:

4.1.1 In order to be eligible for participation in this trial, the patient must be willing and able to provide written informed consent for the trial.

4.1.2 Be female and ≥ 18 years of age on day of signing informed consent.

4.1.3 Have a performance status of 0 or 1 on the ECOG Performance Scale. (See Appendix A.)

4.1.4 Patients must have histologic or cytologic confirmation of the diagnosis of invasive adenocarcinoma of the breast.

4.1.5 The primary or metastatic tissue must be triple negative (ER/PR < 9%, HER2 negative by ASCO/CAP guidelines).

4.1.6 There must be documentation that the patient has evidence of measurable

metastatic breast cancer based on RECIST 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Histologic confirmation of metastatic disease is not required.

4.1.7 At least 1 of the tumor sites must be amenable to core needle biopsy.

4.1.8 Patients with treated, stable, asymptomatic metastatic disease to the brain not requiring chronic corticosteroids are eligible (per discretion of the treating investigator).

4.1.9 Patient must have resolution of toxic effect(s) of the most recent chemotherapy ≤ to Grade 1 (except alopecia). If the patient has received major surgery or radiation therapy of > 30 Gy, they must have recovered from the toxicity and/or complication from the intervention.

4.1.10 Demonstrate adequate organ function, all screening labs should be performed within two weeks of treatment initiation.

• ANC count ≥ 1,500/mm3

• Platelets ≥ 100,000/mm3

• Hemoglobin ≥ 9 g/dL

• Creatinine ≤ 1.5x upper limit of normal (ULN) OR measured or calculated creatinine clearance (CrCl) ≥ 60mL/min for patients with creatinine levels > 1.5x institutional ULN. (Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl.)

• Total bilirubin ≤ 1.5x ULN OR Direct bilirubin ≤ ULN for patients with total bilirubin levels > 1.5 x ULN.

• AST (SGOT) and ALT (SGPT) ≤ 2.5 x ULN OR ≤ 5 x ULN for patients with liver metastases.

4.1.11 A ≤ Grade 1 skin reaction to the first DTH inoculation is required to begin study therapy. See Section 7.1 and Table 7.

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4.1.12 International normalized ratio (INR) or prothrombin time (PT) must be ≤1.5xULN unless the patient is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants. Partial Thromboplastin Time (aPTT) and

≤1.5xULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants

4.1.13 Female patients of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

4.1.14 Study patients of childbearing potential should be willing to use an adequate method of contraception as outlined in (Section 7.5 and Appendix B) or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Patients of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.

4.2 Conditions for patient ineligibility

Any patient with one or more of the following conditions will be ineligible for this study:

4.2.1 Greater than 4 prior lines of therapy for metastatic disease.

4.2.2 Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.

4.2.3 Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment. The use of physiologic doses of corticosteroids must be discussed with DSSM.

4.2.4 A ≥ Grade 2 skin reaction to the first DTH inoculation will exclude that patient from beginning study therapy.

4.2.5 Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.

4.2.6 Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Patients with alopecia are an exception to this criterion and may qualify for the study.

4.2.7 Blood products (including platelets or red blood cells) or administration of colony stimulating factors (including G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks prior to beginning study therapy.

4.2.8 Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy, or in situ cancers.

4.2.9 Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment.

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4.2.10 Has an active autoimmune disease that has required systemic treatment within the past

2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency and bone anti-resorptive agents etc.) is not considered a form of systemic treatment.

4.2.11 Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis.

4.2.12 Has a history of or active interstitial lung disease, autoimmune lung disease, severe asthma requiring daily medication.

4.2.13 Malabsorption syndrome, ulcerative colitis, inflammatory bowel disease, resection of the stomach or small bowel, or other disease or condition significantly affecting gastrointestinal function.

4.2.14 Has an active infection requiring systemic therapy.

4.2.15 Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with a patient’s participation for the full duration of the trial, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.

4.2.16 Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.

4.2.17 Is pregnant or breastfeeding, or expecting to conceive a child within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

4.2.18 Prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) is not allowed.

4.2.19 Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

4.2.20 Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).

4.2.21 Has received a live vaccine within 30 days prior to the first dose of trial treatment. Seasonal flu vaccines are permitted.

4.2.22 Has severe hypersensitivity to pembrolizumab and/or any of its excipients.

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5.0 REQUIREMENT FOR STUDY ENTRY AND DURING TREATMENT AND FOLLOW-UP

Tests and exams required before study entry are listed on Table 2. Requirements following study entry are outlined on Table 3.

Table 2. Tests, exams, and other requirements prior to study entry

Requirements	Prior to Study Entry
Consent form for the B-001 trial signed by the patient	X
Agreement of local pathology department to release the primary tumor tissue slides from the diagnostic biopsy or other previous surgerya	X
History & physical examb	X	Within 2 weeks
Performance status (see Appendix A)	X
Height & weight	X
CBC/differential/platelet count	X
Total bilirubin/AST (SGOT)/ALT (SGPT), alkaline phosphatase, serum sodium, chloride, potassium, CO2, calcium, protein, glucose, creatininec, BUN (e.g., Comprehensive metabolic panel)	X
Thyroid function tests: TSHd	X
Imaging of cheste	X	Within 4 weeks
Imaging of abdomen and pelvisf	X
Pregnancy testg	X	After patient signs consent and within 1 week of planned start of study therapy
Required study blood samplesh	X
Vaccine allergen skin test (DTH)i	X
a        The archived primary tumor tissue from the previous surgery must be requested and the pathology department must agree before study entry to release these slides or an archived paraffin tumor block if slides are unavailable (see Section 6.0). Submit the tumor tissue within 60 days after study entry. b       Complete H&P by physician or other healthcare professional (on FDA Form 1572). c        Serum creatinine OR measured or calculated creatinine clearance (CrCl) > 60mL/min for patients with creatinine levels > 1.5 x institutional ULN. (Glomerular filtration rate (GFR) can also be used in place of creatinine or CrCl.) d        If TSH abnormal, (outside normal range) obtain free triiodothyronine (T3) and thyroxine (T4). e        Preferred imaging options for chest: CT scan with contrast or PET/CT scan with contrast. f          Preferred imaging for abdomen and pelvis: CT scan with contrast or PET/CT with or without contrast; MRI with contrast. (MRI with contrast can be substituted for CT scan.) g        For WOCBP should have a negative urine or serum pregnancy within 72 hours prior to receiving the first delayed type hypersensitivity (DTH). Pregnancy testing should be performed according to institutional standards h       Blood samples collected for research study purposes should be drawn concurrently with blood samples required for study entry. See Section 6.0. For all blood and tissue sample collections and submissions see B-001 Pathology and Correlative Science Instructions. i         The DTH inoculation is to be performed within one week prior to beginning study therapy. DTH inoculation sites are to be assessed for hypersensitivity reactions within 48-72 hours after the inoculation. A negative response is required for study entry. See Section 7.1 and Table 7.

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Table 3. Tests, exams, and other requirements following study entry

Requirements	Within 72 hours before Day 1 of Cycle 1	Within 72 hours before Day 1 of Cycle 2	Within 72 hours before Day 1 of Cycle 3	Within 72 hours before Day 1 of Cycle 4	Within 72 hours before Day 1 of Cycle 5	Within 72 hours before Day 1 of Cycle 6	Within 72 hours before Day 1 of Cycle 7	Within 72 hours before Day 1 of Cycles 8 through 34	Follow-up 30 days following discontinuation of study therapy (Within +/- 7 days)
History & physical exama, b	X	X	X	X	X	X	X	X	X
Vital signs	X	X	X	X	X	X	X	X	X
Adverse event Assessmentc, d	X (And within 48 -72 hours after Day 1)	X (And within 48 -72 hours after Day 1)	X (And within 48 -72 hours after Day 1)	X (And within 48 -72 hours after Day 1)	X (And within 48 -72 hours after Day 1)		X (And within 48 -72 hours after Day 1)		X
DTH intradermal inoculatione							X (On Day 1)
CBC/differential/platelet countf		X	X	X	X	X	X	X	X
Total bilirubin/AST (SGOT)/ALT (SGPT), alkaline phosphatase Serum sodium, chloride, potassium, CO2, calcium, protein, glucose, creatinine, BUN (e.g., Comprehensive metabolic panel)f		X	X	X	X	X	X	X	X
Thyroid function tests: g		X		X		X		X (Cycle 8 and every even cycle)	X
Measurement of target lesionsh			X			X		X (Cycle 9 and then every 3 cycles)	X
Pregnancy testi		X	X	X	X	X	X	X
Blood samplesj	X (Required)			X (Required)			X (Required)		X (Optional upon disease progression)
Tumor tissue samplek,l	X (Required)			Xl (Required)					Xl (Optional: upon disease progression)

Table 3 continues on next page

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Table 3. Tests, exams, and other requirements following study entry (continued)

a At the discretion of the investigator, additional exams, bloodwork, x-rays, ECGs, scans, and other testing may be performed as clinically indicated.

b Updated H&P with exams, adverse event assessment, and assessments during therapy and follow-up by physician or other appropriate healthcare professional (on FDA Form 1572).

c The AE37 intradermal injection sites (DTH and study therapy dose) are to be assessed for hypersensitivity reactions within 48-72 hours after each dose (e.g., DTH inoculations on Days 3 or 4; AE37 vaccinations: on Days 3 or 4). Note: An assessment of a negative response is required from initial DTH inoculation for the patient to enter the study. See Section 7.1

d Should the patient stop study therapy (e.g. due to disease progression or second primary) and begin a new treatment prior to the last dose of study therapy AE assessments should be collected only up to the date the new therapy begins. See Section 10.0. SAE/AE assessments 90 days (+/− 14 days) after the last dose of study therapy.

e The second DTH inoculation will be given approximately 42 days after the last AE37 vaccination (e.g., Day 1 Cycle 7). See Section 7.1.

f CBC/Diff, blood chemistries, LFTs done at screening may be used as baseline assessment results for Cycle 1/Day 1.

g Beginning with Cycle 2, obtain thyroid function tests: TSH, free triiodothyronine (T3) and thyroxine (T4) every 6 weeks (e.g., every even Cycle).

h The same imaging method (PET/CT scan, CT scan or MRI), used at baseline should be used every 3 cycles from start of therapy. Assessment of measurable disease is every 3 cycles by RECIST 1.1. See Section 11.0.

i WOCBP should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. Pregnancy testing should be performed monthly according to institutional standards.

j A required research blood sample will be collected from all patients prior to starting study therapy and within 72 hours of beginning Cycle 4 (with biopsy), and within 72 hours of cycle 7. Optional research blood samples will be collected from consenting patients at the time of disease progression. Blood samples collected for research study purposes should be drawn concurrently with blood samples required for the study. See Section 6.0.

k Tumor tissue requirement: A tissue core biopsy from an accessible metastatic site will be collected prior to starting study therapy and within 72 hours of beginning Cycle 4. See Section 6.0.

l Optional blood samples and tumor tissue core biopsies from an accessible metastatic site will be collected from consenting patients upon disease progression.

See Section 6.0.

For all blood and tissue sample collections and submissions see B-001 Pathology and Correlative Science Instructions.

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6.0 PATHOLOGY AND CORRELATIVE SCIENCE STUDIES

6.1 Overview of requirements

Collection and submission of all patient samples (blood, tumor) listed below is a requirement for all patients participating in the NSABP B-001 study. By signing the B-001 consent form, the patient has agreed to all required sample collections and submissions.

Non-submission of required patient samples will be a protocol violation. Patient samples will be collected at the specified time points as outlined in Table 3 and Table 4. (See B-001 Pathology and Correlative Science Instructions for tumor and blood sample processing and submission).

Table 4. Summary of patient sample submission requirements

Study requirements for ALL patients	Prior to beginning study therapy	Prior to Day 1 of Cycle 4	Prior to Day 1 of Cycle 7	At the time of disease progression
Submission of archived primary tumor tissuea	YES (Required)
Collection and submission of blood samplesb	YES (Required)	YES (Required)	YES (Required)
Collection and submission of tissue samplesc,d	YES (Required)	YES (Required)		YES (Optional)
a       Archived paraffin block of primary tumor tissue is preferable. See Section 6.3.1. b        Required blood sample collections: Blood samples collected for research study purposes should be drawn concurrently with blood samples required for study: prior to beginning study therapy and Day 1 of Cycle 7. See Section 6.3.1. c        Required tissue biopsy procurement: Core biopsy specimens (2 to 4 cores) from an accessible metastatic site will be collected from all patients prior to starting study therapy and within 72 hours prior to beginning Cycle 4 and Cycle 7. Samples should be submitted on the same day as procurement d        Optional tissue and blood samples: Blood samples and procurement of core biopsy specimens (2 to 4 cores) from an accessible metastatic site and at disease progression should be requested and collected from consenting patients. Samples should be submitted on the same day as procurement NOTE: Refer to the B-001 Pathology and Correlative Science Instructions for tumor and blood sample submission instructions.

6.2 Use of specimens

The blood and tumor samples collected in this study will be used for B-001 studies as described in Section 6.4 and for analyses to be conducted in the future related to the purposes of the B-001 study but not currently described in the protocol document. Additionally, the specimens procured may be used for future studies involving gene and protein conferring susceptibility to cancer or other diseases. If hereditary genetic studies are conducted, an anonymization process will be used. Results of the correlative science studies, including raw sequencing data, will not be reported directly to the patient or the physician and will not have any bearing on patient treatment.

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The results of the study will be communicated through publication, in peer reviewed scientific literature and/or through presentations at scientific meetings. Anonymized or de-identified research data (as deemed appropriate by the NSABP), including genome sequencing data, may be submitted to public research databases for data sharing with controlled access to scientific researchers outside of the NSABP.

6.3 Tumor and blood sample submissions

6.3.1 Required tissue and blood samples

• Archived primary tumor tissue block: Use of the archived paraffin block of primary tumor tissue is permitted; however submission of a fresh core biopsy specimen is preferred. Refer to the B-001 Pathology and Correlative Science Instructions for tumor tissue submission instructions.

• Required tissue samples: Core biopsy specimens (2 to 4 cores) from an accessible metastatic site will be collected from all patients:

− prior to starting study therapy, and

− within 72 hours of beginning Day 1 of Cycle 4.

• Study blood samples: Peripheral blood may be analyzed for AE37 antigen-specific T cell immune responses in peripheral blood. Blood samples will be collected:

− prior to initiation of pembrolizumab plus AE37 peptide vaccine therapy and

− prior to receiving study therapy on Day 1 of cycle 7.

Note: Refer to the B-001 Pathology and Correlative Science Instructions for study blood sample collection, processing, and submission instructions.

6.3.2 Optional tissue and blood samples

• Optional tumor tissue samples should be collected from consenting patients at the time of disease progression.

Note: When disease progression has been confirmed by imaging per RECIST criteria, biopsy specimens are to be collected from consenting patients preferably from a new accessible metastatic lesion or one that increased in size when compared to the previous imaging scan result from consenting patients. Biopsy specimens at the time of progression must be collected prior to initiating any new therapy and within 30 days following discontinuation from study therapy.

• Optional research blood samples should be collected optional blood sample from consenting patients at time of progression.

All tissue and blood samples will be submitted to the NSABP Division of Pathology (see Information Resources) where the samples will be logged into the database and assigned a unique code number. The samples will be stripped of any remaining patient identifiers (except the NSABP B-001 Patient ID numbers), processed, and stored. A portion of the samples may be shipped to collaborating laboratories including Merck & Co. Inc. and their vendor who will perform assay for PDL-1 expression and PanCancer nanostring mRNA assay including approximately 800 genes. Refer to the B-001 Pathology and Correlative Science Instructions for tissue and blood specimen collection and submission instructions.

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6.4 Rationale for correlative science studies

6.4.1 AE37 antigen-specific T cell immune responses in peripheral blood

To determine whether pembrolizumab plus AE37 Peptide Vaccine in study patients induces AE37 antigen-specific T cell immune responses in peripheral blood and enhances T cell immune responses in tumor tissues, peripheral blood may be analyzed for AE37 antigen-specific T cell immune responses (Fourcade 2014; Hamid 2013.

Fourcade 2012; Fourcade 2010; Fourcade 2009). These include:

• Analysis of AE37 antigen-specific T cell immune responses in peripheral blood.

− Intracellular cytokine ex-vivo assay: The frequency of AE37 antigen-specific CD4+ and CD8+ T cells in peripheral blood will be analyzed by ex-vivo intracellular cytokine assays for IFN-g, TNF, IL-2, and IL-21 as previously reported (Fourcade 2014; Hamid 2013. Fourcade 2012; Fourcade 2010; Fourcade 2009).

− Ex-vivo CD107a degranulation assays: CD107a cell surface expression as a surrogate of lytic function will be investigated using overlapping peptides from AE37 antigens as previously reported (Fourcade 2014).

• Change of CD4+CD25+FOXP3+ Treg cells in peripheral blood lymphocytes (Gates 2010).

• To determine potential correlation between TGF-β levels in plasma samples by ELISA and clinical tumor response (Perez 2014; Perez 2013; Perez 2010).

• To determine potential correlation between HLA-A*24 and/or HLA-DRB1*11 and clinical tumor response (Anastasopoulou 2015).

6.4.2 Tissue studies

• Optional tumor biopsy prior to initiation of pembrolizumab plus AE37 Peptide vaccine therapy and prior to cycle 4 may be used for the following:

− Evaluation of CD8+ T cell infiltrates in tumor tissues using the Immunoscore. The distribution and density of CD8+ T cells may be analyzed by quantitative IHC analysis for standard T-cell subsets using antibodies to CD3, CD4, and CD8 in the invasive tumor margin and within the tumor parenchyma, as previously reported (Tumeh 2014; Galon 2006; Pages 2005; Llosa 2015).

− IHC analysis of genes involved in immune checkpoint pathways in tumor tissues: IHC analysis of PD-1, PD-L1, LAG-3, CTLA-4 and IDO1 in tumor tissues may be performed, as previously reported (Tumeh 2014; Llosa 2015; Pierer 2007; Irie 2005).

• Analysis of TCR β-chain usage in tumor infiltrating lymphocytes (TILs):

A more restricted TCR β-chain usage reflects a T-cell population that is less diverse in repertoire and more clonal in nature, and is significantly correlated with clinical response to pembrolizumab plus AE37 Peptide vaccine therapy (Tumeh 2014;Zhu 2013).

To determine whether the frequency of mutation-associated neoantigens in tumor tissue correlates with tumor response to prior to initiation of pembrolizumab plus AE37 Peptide vaccine therapy, tumor tissues collected prior to initiation of pembrolizumab plus AE37 Peptide vaccine therapy may be analyzed for tumor gene mutations. Analysis of the frequency of mutation-associated neoantigens in tumor tissues (Vogelstein 2013; Alexandrov 2013; Snyder 2014; Yadav 2014; Le 2015; Rizvi 2015).

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7.0 STUDY THERAPY

7.1 AE37 Vaccine

7.1.1 Delayed type hypersensitivity (DTH) monitoring

Each enrolled patient will receive a delayed type hypersensitivity (DTH) intradermal injection (100 mcg AE37 peptide/0.5 ml normal saline) at two times during the study:

• Within one week prior to the first dose of study therapy (see Section 4.1.11 and Table 3); and

• Approximately 42 days after delivery of the final inoculation (e.g., Cycle 7/Day 1).

Note: Women of child bearing potential must have a negative pregnancy test within 72 hours of each DTH inoculation.

7.1.2 DTH inoculation administration

The contents of the first AE37 DTH vial for a newly enrolled patient’s inoculation regimen will be administered in the following manner:

• One frozen, sterile AE37 DTH vial containing 100 micrograms is removed from the -20ºC freezer and thawed at room temperature (RT). The thawed solution is withdrawn into a single-dose, sterile syringe and immediately administered by intradermal injection on the left anterior thigh approximately 9 inches superior to the knee. See Section 9.1.6.

• After the above is accomplished, 0.5 ml of normal sterile saline is withdrawn into a single-dose, sterile syringe. The 0.5 ml inoculum is immediately administered by intradermal injection on the right anterior thigh approximately 9 inches superior to the knee. (This second inoculum of sterile saline is administered to serve as a negative control for the DTH test).

7.1.3 DTH reaction assessment

The DTH reaction will be measured in 2 dimensions at 48-72 hours post inoculation and compared between peptide and sterile saline and between pre-inoculation and post- inoculation. The low dose of peptide used in the DTH test is not expected to induce a long term immune response; however, any response that is induced is expected to be transitory in nature.

Patients are to be monitored post-injection for 1 hour to note any local or systemic reactions to the vaccine and are required to return to the clinic within 48-72 hours after inoculation for assessment of local and/or systemic reactions. A photograph of the DTH response will be obtained for the purpose of documentation and reporting. These results will also be recorded in the response database. See Section 8.2.3 and Table 7.

Additionally, patients should be given the phone number to the treatment clinic, and emergency department in case of reaction/side effects, and educated about the local and systemic signs of infection. If any adverse events occur, these will be reported per the protocol. If infection is detected, then vaccinations will be halted and the sterility of the remaining single dose vials re-confirmed. The patient will be medically treated as appropriate.

Note: A ≤ Grade 1 skin reaction DTH response is required to begin study therapy. See

4.1.11 and Table 7.

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7.1.4 Dose-limiting toxicity for AE37

If Grade 3 systemic toxicity that require a ≥ 2 week delay in starting Cycle 2 is observed during the safety run-in or in > 25% (4 or more) of patients, the AE37 dose will be de- escalated to 500 micrograms (dose level −1) to complete stage I accrual. If systemic toxicity occurs in 3 or more patients at this dose (dose level −1) accrual will be halted and the toxicity reviewed by the study team.

7.2 Study regimen

Study therapy should begin within 2 weeks following study entry. (Note: Women of child bearing potential must have a negative pregnancy test within 72 hours of each dose of study therapy.) see Section 4.1.13, Table 2 and Table 3). See Sections 7.1.1, 7.1.2, 7.1.3, 4.1.11 and Table 7 for DTH response assessment prior to beginning study therapy.) Study therapy should be given in the order outlined in Table 5 and Table 6. See Section 8 for treatment management.

Table 5: Safety Cohort Study Therapy:

Drug	Dose	Dosing Interval	Planned Duration
AE37 peptide vaccine a,b,c	1000 micrograms via intradermal injection	Day 1 of each 21 day cycle x 5 doses	15 weeks (5 cycles)
Pembrolizumabd	200 mg IV over 30 minutes	Day 1 of each 21 day cycle	Until disease progression or intolerable toxicity (Maximum 35 cycles; 2 years)
a        See Section 6.0 for required correlative study blood sample and optional tissue collection and submission instructions. Refer to the B-001 Pathology and Correlative Science Instructions. b       Patients must have negative reaction to DTH inoculation to begin study therapy. See Section 7.1 and Table 7. Patients will receive 1000 micrograms as two 500 microgram intradermal injections of approximately 5cm apart on the anterior or medial side of the same thigh. See Section 9.1.6 for AE37 administration instructions. Note: If there is a large local reaction (>100 mm) such that the reaction at the two sites begins to merge, the subsequent dose of AE37 is reduced by one half, (i.e., 500 micrograms, dose level −1). If Grade 3 systemic toxicity is observed in > 25% of patients the AE37 dose will be de-escalated to 500 micrograms (dose level 1) for subsequent patients in Stage I of the study. See Section 8.2.2 , Table 7 and Table 8. c        A 1-hour observation period is required following each AE37 vaccination, before pembrolizumab can be administered. d       Pembrolizumab should be administered intravenously over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron to 5 micron in-line or add-on filter. See Section 8.0 and Table 10 for treatment management of infusion reactions; Section 9.2 for drug information and preparation instructions. 1 cycle = 21 days

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Table 6: Expansion Cohort Study Therapy

Drug	Dose	Dosing Interval	Planned Duration
AE37 peptide vaccinea, b, c	*X micrograms via intradermal injections	Day 1 of each 21 day cycle x 5 doses	15 weeks
Pembrolizumabd	200 mg IV over 30 minutes	Day 1 of each 21 day cycle	Until disease progression or intolerable toxicity (Maximum 35 cycles; 2 years)
a        See Section 6.0 for required correlative study blood sample instructions. Refer to the B-001 Pathology and Correlative Science Instructions. b       Patients must have negative reaction to DTH inoculation to begin study therapy. See Section 7.1 and Table 7. *Note: Patients will receive the AE37 vaccine dose established during Stage I of the study [i.e., 1000 micrograms or 500 micrograms]) x on Day 1 for five cycles.. See Section 8.2.3. The dose of AE37 vaccine will be administered in two split dose intradermal injections on the anterior or medial side of the same thigh (See Section 9.1.6 for AE37 administration instructions.) Note: If the Stage II starting dose is 1000 micrograms, a patient has local toxicity the AE37 dose may be de-escalated to dose level − 1. See Table 7 and Table 8. c       A 1-hour observation period is required following the each AE37 vaccination, before pembrolizumab can be administered. d       Pembrolizumab should be administered intravenously over 30 minutes through an intravenous line containing a sterile, non-pyrogenic, low-protein binding 0.2 micron to 5 micron in-line or add-on filter. See Section 8.0 and Table 10 for treatment management of infusion reactions. See Section 9.2 for drug information and preparation instructions. 1 cycle = 21 days

7.3 Supportive therapy

7.3.1 Growth factor support

The use of growth factors (e.g., G-CSF, GM-CSF) is not permitted.

7.3.2 Erythropoietin

The use of erythropoiesis-stimulating agents is not permitted.

7.3.3 Other supportive care

Patients should receive supportive care for other treatment-related symptoms at the investigator's discretion.

7.4 Contraindications and precautions

• Study therapy is contraindicated in patients who are pregnant or lactating. See Sections 4.2.16, 7.5, and Section 10.4.

• Immunotherapy not specified in this protocol is not permitted.

• Antineoplastic systemic chemotherapy is not permitted.

• Radiation therapy is not permitted.

• The use of systemic glucocorticoids (e.g., prednisone 10 mg orally per day or equivalents) is

permitted to modulate symptoms of suspected immunologic adverse events.

− Note: Inhaled steroids are allowed for the management of asthma.

− Use of prophylactic corticosteroids to avoid allergic reactions (e.g., to IV contrast dye) is permitted.

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• Live attenuated vaccinations within 30 days prior to the first dose of study treatment and while participating in the trial. Seasonal influenza vaccines for injection are generally killed viruses and are allowed. However, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines, and are not allowed.

• Patients should not donate blood while participating in this study or for at least 120 days after the last infusion of study therapy.

• Patients should not donate eggs while participating in this study or for at least 120 days following the last infusion of study therapy.

7.5 Contraception

Study therapy may have adverse effects on a fetus in utero. It is not known if pembrolizumab has transient adverse effects on the composition of sperm. Female patients of reproductive potential must agree to use (or have their partner use) acceptable contraception during heterosexual activity to avoid becoming pregnant or impregnating a partner, respectively, while receiving study drug and for 120 days after the last dose of study drug. See Appendix B for acceptable methods of contraception.

For this trial, male partners of female patients of child bearing potential will be considered to be of non-reproductive potential if they have azoospermia (whether due to having had a vasectomy or due to an underlying medical condition).

Female patients will be considered of non-reproductive potential if they are either:

• postmenopausal (defined as at least 12 months with no menses without an alternative medical cause; in women < 45 years of age a high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. In the absence of 12 months of amenorrhea, a single FSH measurement is insufficient.); or

• have had a hysterectomy and/or bilateral oophorectomy, bilateral salpingectomy or bilateral tubal ligation/occlusion, at least 6 weeks prior to screening; or

• has a congenital or acquired condition that prevents childbearing.

7.6 Pregnancy

If a female patient should inadvertently become pregnant while on treatment with pembrolizumab, the patient will immediately be removed from the study. The site will contact the patient at least monthly and document the patient’s status until the pregnancy has been completed or terminated. See Section 10.4 for reporting requirements.

7.7 Participation in other clinical trials

If a patient enrolled on B-001 is considering participation in another clinical trial (including supportive therapy trials), contact the NSABP DSSM (see Information Resources).

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8.0 TREAMENT MANAGEMENT

8.1 General instructions

• The NCI CTCAE v4.0 must be used to Grade the severity of AEs.

• All treatment decision must be based on the AE requiring the greatest modification.

• AE37 vaccine doses that have been reduced may not be re-escalated.

• All hematologic, gastrointestinal, and genitourinary toxicities must be < Grade 2 prior to initiating Dose 1 of study therapy. Patients unable to receive Dose 1 (i.e. Day 1/ Cycle 1 dose) will be considered screen failures.

• Each study cycle is 21 days; missed cycles will not be made up.

• Pembrolizumab, unless otherwise discontinued due to toxicity, patient request or disease progression, should continue for up to 2 years after the first dose (Day 1) of the first treatment cycle regardless of any missed doses or treatment delays (maximum 35 cycles).

8.2 Treatment management for study therapy

The study treatment schedule should be maintained. If necessary, the timing of a treatment may be adjusted to 3 days earlier or 3 days later than the scheduled date of treatment. All doses administered or missed must be recorded. See Table 9 for treatment management.

8.2.1 Treatment decisions when therapy must be held

• Study therapy will be given on the same day. However if pembrolizumab is held for toxicity, AE37 should still be given. When toxicity has resolved, resume pembrolizumab on Day 1 of the next cycle. See Table 9 for treatment management.

• If a scheduled dose of study therapy is missed, the study therapy may be given within 7 days of the appointed time (which resets the date for further vaccinations) or be considered a missed dose.

• AE37 vaccine dosing:

− In order to receive a subsequent vaccination, patients who have vaccination- related toxicity must have recovered to ≤ Grade 1 toxicity for the parameters used to assess levels of organ function required for eligibility after each vaccination.

8.2.2 Dose modifications

• There are no dose reductions for pembrolizumab.

− Adverse events (both non-serious and serious) associated with pembrolizumab exposure may represent an immunologic etiology. These adverse events may occur shortly after the first dose or several months after the last dose of treatment. Pembrolizumab must be withheld for drug-related toxicities and severe or life-threatening AEs as per Table 9.

• AE37 dose modifications

− A reduction in the dose of AE37 may be required depending upon the local reaction to multiple doses (see Table 7). AE37 is given as split dose intradermal injections at two sites on the upper thigh 5 cm apart. If there is a large local reaction (>100 mm) such that the reaction at the two sites begins to merge, the subsequent dose of AE37 is reduced by one half (i.e., dose

level – 1). See Table 7 and Table 8.

− Vaccine-related toxicities requiring a ≥ 2 week delay in starting Cycle 2 or subsequent cycles will result in a dose level reduction for subsequent AE37 vaccinations. See Section 7.1.4, Table 7 and Table 8.

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Table 7. AE37 vaccine local reaction assessment

Local skin reaction at vaccination sites	Grade 1	Grade 2	Grade 3	Grade 4
	Mild erythema	Non-confluent erythema, mild tenderness at site	Confluent erythema, ulceration and/or severe pain at site	Severe ulceration, necrosis; urgent intervention necessary

Table 8. Dose levels for AE37 vaccine

AE37 Vaccine	Dose Level 0 Starting Dose	Dose Level −1	Dose Level −2	Dose Level −3	Dose Level − 4
	1000 mcg	500 mcg	250 mcg	125 mcg	Discontinue

8.2.3 Treatment decisions when therapy must be discontinued

Treatment must be permanently discontinued if:

• Pembrolizumab must be held for greater than 12 weeks study therapy.

• Greater or equal to Grade 2 toxicity attributed to the AE37 vaccine persists for

> 28 days. The patient will not receive further vaccination and will discontinue study therapy. See Table 3.

Note: Should pembrolizumab be permanently discontinued prior to Cycle 5; AE37 vaccinations should continue per study schedule unless otherwise contraindicated.

• Consent is withdrawn or patient is lost to follow-up.

• An adverse event occurs that, in the opinion of the investigator or sponsor, contradicts further dosing. See Table 9.

• The patient becomes pregnant or intends to conceive a child while actively on study.

• Grade 3 or greater infusion reaction occurs.

• If tumor progression occurs during study therapy.

8.2.4 Dose modification and toxicity management guidelines for immune-related AEs associated with pembrolizumab

AEs associated with pembrolizumab exposure may represent an immunologic etiology. These immune-related AEs (irAEs) may occur shortly after the first dose or several months after the last dose of pembrolizumab treatment and may affect more than one body system simultaneously. Therefore, early recognition and initiation of treatment is critical to reduce complications. Based on existing clinical trial data, most irAEs were reversible and could be managed with interruptions of pembrolizumab, administration of corticosteroids and/or other supportive care. For suspected irAEs, ensure adequate evaluation to confirm etiology or exclude other causes. Additional procedures or tests such as bronchoscopy, endoscopy, skin biopsy may be included as part of the evaluation. Based on the severity of irAEs, withhold or permanently discontinue pembrolizumab and administer corticosteroids. Dose modification and toxicity management guidelines for irAEs associated with pembrolizumab are provided in Table 9.

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Table 9. Dose modification and toxicity management guidelines for immune-related AEs associated with pembrolizumab

General instructions: 1.       Corticosteroid taper should be initiated upon AE improving to Grade 1 or less and continue to taper over at least 4 weeks. 2.       For situations where pembrolizumab has been withheld, pembrolizumab can be resumed after AE has been reduced to Grade 1 or 0 and corticosteroid has been tapered. Pembrolizumab should be permanently discontinued if AE does not resolve within 12 weeks of last dose or corticosteroids cannot be reduced to ≤ 10 mg prednisone or equivalent per day within 12 weeks. 3.       For severe and life-threatening irAEs, IV corticosteroid should be initiated first followed by oral steroid. Other immunosuppressive treatment should be initiated if irAEs cannot be controlled by corticosteroids.
Immune- related AEs	Toxicity grade or conditions (CTCAEv4.0)	Action taken to pembrolizumab	irAE management with corticosteroid and/or other therapies	Monitor and follow-up
Pneumonitis	Grade 2	Withhold	•     Administer corticosteroids (initial dose of 1-2mg/kg prednisone or equivalent) followed by taper	•         Monitor patients for signs and symptoms of pneumonitis •         Evaluate patients with suspected pneumonitis with radiographic imaging and initiate corticosteroid treatment •         Add prophylactic antibiotics for opportunistic infections •         Report ≥ Grade 2 events to DSSM.
	Grade 3 or 4, or recurrent Grade 2	Permanently discontinue
Diarrhea / colitis	Grade 2 or 3	Withhold	•     Administer corticosteroids (initial dose of 1-2mg/kg prednisone or equivalent) followed by taper	•        Monitor patients for signs and symptoms of enterocolitis (i.e. diarrhea, abdominal pain, blood or mucus in stool with or without fever) and of bowel perforation (i.e. peritoneal signs and ileus). •        Patients with ≥ Grade 2 diarrhea suspecting colitis should consider GI consultation and performing endoscopy to rule out colitis. •        Patients with diarrhea/colitis should be advised to drink liberal quantities of clear fluids. If sufficient oral fluid intake is not feasible, fluid and electrolytes should be substituted via IV infusion. •        Report ≥ Grade 2 events to DSSM.
	Grade 4	Permanently discontinue

Table 9 continues on next page.

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Table 9. Dose modification and toxicity management guidelines for immune-related AEs associated with pembrolizumab (continued)

Immune-related AEs	Toxicity grade or conditions (CTCAEv4.0)	Action taken to pembrolizumab	irAE management with corticosteroid and/or other therapies	Monitor and follow-up
AST / ALT elevation or Increased Bilirubin	Grade 2	Withhold	•     Administer corticosteroids (initial dose of 0.5- 1mg/kg prednisone or equivalent) followed by taper	•        Monitor with liver function tests (consider weekly or more frequently until liver enzyme value returned to baseline or is stable •        Report ≥ Grade 2 events to DSSM.
	Grade 3 or 4	Permanently discontinue	•     Administer corticosteroids (initial dose of 1-2mg/kg prednisone or equivalent) followed by taper
Type 1 diabetes mellitus (T1DM) or Hyperglycemia	Newly onset T1DM or Grade 3 or 4 hyperglycemia associated with evidence of b-cell failure	Withhold	•     Initiate insulin replacement therapy for patients with T1DM •     Administer anti-hyperglycemic in patients with hyperglycemia	•         Monitor patients for hyperglycemia or other signs and symptoms of diabetes. •         Report ≥ Grade 2 events to DSSM.
Hypophysitis	Grade 2	Withhold	•      Administer corticosteroids and initiate hormonal replacements as clinically indicated.	•         Monitor for signs and symptoms of hypophysitis (including hypopituitarism and adrenal insufficiency) •         Report ≥ Grade 2 events to DSSM.
	Grade 3 or 4	Withhold or permanently discontinue1
Hyperthyroidism	Grade 2	Continue	•     Treat with non-selective beta- blockers (e.g. propranolol) or thionamides as appropriate	•         Monitor for signs and symptoms of thyroid disorders. •         Report ≥ Grade 2 events to DSSM.
	Grade 3 or 4	Withhold or Permanently discontinue
Hypothyroidism	Grade 2-4	Continue	•      Initiate thyroid replacement hormones (e.g. levothyroxine or liothyroinine) per standard of care	•         Monitor for signs and symptoms of thyroid disorders. •         Report ≥ Grade 2 events to DSSM.

Table 9 continues on next page.

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Table 9. Dose modification and toxicity management guidelines for immune-related AEs associated with pembrolizumab (continued)

Immune-related AEs	Toxicity grade or conditions (CTCAEv4.0)	Action taken to pembrolizumab	irAE management with corticosteroid and/or other therapies	Monitor and follow-up
Nephritis and renal dysfunction	Grade 2	Withhold	•      Administer corticosteroids (prednisone 1-2mg/kg or equivalent) followed by taper.	•         Monitor changes of renal function •         Report ≥ Grade 2 events to DSSM.
	Grade 3 or 4	Permanently discontinue
All Other immune-related AEs	Grade 3, or intolerable/ persistent Grade 2	Withhold	•      Based on severity of AE administer corticosteroids	•         Ensure adequate evaluation to confirm etiology or exclude other causes •         Report ≥ Grade 2 events to DSSM.
	Grade 4 or recurrent Grade 3	Permanently discontinue
NOTES: 1.       Withhold or permanently discontinue pembrolizumab is at the discretion of the investigator or treating physician. 2.       For patients with Grade 3 or 4 immune-related endocrinopathy where withhold of pembrolizumab is required, pembrolizumab may be resumed when AE resolves to ≤ Grade 2 and is controlled with hormonal replacement therapy or achieved metabolic control (in case of T1DM).

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8.3 Supportive care guidelines for pembrolizumab

8.3.1 Supportive care measures for the management of AEs with potential immunologic etiology

Patients should receive appropriate supportive care measures as deemed necessary by the treating investigator. Suggested supportive care measures for the management of AEs with potential immunologic etiology are outlined along with the dose modification guidelines in Section8.2.4, (Table 9) and Section 8.3.2 (Table 10). Where appropriate, these guidelines include the use of oral or IV treatment with corticosteroids, as well as additional anti-inflammatory agents if symptoms do not improve with administration of corticosteroids. Note that several courses of steroid tapering may be necessary as symptoms may worsen when the steroid dose is decreased.

For each disorder, attempts should be made to rule out other causes such as metastatic disease or bacterial or viral infection, which might require additional supportive care. The treatment guidelines are intended to be applied when the Investigator determines the events to be related to pembrolizumab. Note: If after the evaluation of the event, it is determined not to be related to pembrolizumab, the Investigator does not need to follow the treatment guidance. Refer to (Table 9) in Section 8.2.4 and Section 8.3.3 for guidelines regarding dose modification and supportive care. It may be necessary to perform conditional procedures such as bronchoscopy, endoscopy, or skin photography as part of evaluation of the event.

8.3.2 Management of Infusion Reactions

Signs and symptoms usually develop during or shortly after drug infusion and generally resolve completely within 24 hours of completion of infusion. Table 10 below shows treatment guidelines for patients who experience an infusion reaction associated with administration of pembrolizumab (MK-3475).

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Table 10. Infusion Reaction Treatment Guidelines

NCI CTCAE Grade	Treatment	Premedication at subsequent dosing
Grade 1 Mild reaction; infusion interruption not indicated; intervention not indicated.	Increase monitoring of vital signs as medically indicated until the patient is deemed medically stable in the opinion of the investigator.	None
Grade 2 Requires infusion interruption but responds promptly to symptomatic treatment (e.g., antihistamines, NSAIDS, narcotics, IV fluids); prophylactic medications indicated for ≤ 24 hrs	Stop Infusion and monitor symptoms. Additional appropriate medical therapy may include but is not limited to: •         IV fluids •         Antihistamines •         NSAIDS •         Acetaminophen •         Narcotics. Increase monitoring of vital signs as medically indicated until the patient is deemed medically stable in the opinion of the investigator. If symptoms resolve within one hour of stopping drug infusion, the infusion may be restarted at 50% of the original infusion rate (e.g., from 100 mL/hr to 50 mL/hr). Otherwise dosing will be held until symptoms resolve and the patient should be premedicated for the next scheduled dose. Patients who develop Grade 2 toxicity despite adequate premedication should be permanently discontinued from further trial treatment administration.	The patient may be premedicated 1.5h (+/− 30 minutes) prior to infusion of pembrolizumab (MK-3475) with: •         Diphenhydramine 50 mg PO (or equivalent dose of antihistamine). •         Acetaminophen 500- 1000 mg PO (or equivalent dose of antipyretic).

Table 10 continues on next page.

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Table 10 Infusion Reaction Treatment Guidelines (continued)

NCI CTCAE Grade	Treatment	Premedication at subsequent dosing
Grades 3 or 4 Grade 3: Prolonged (i.e., not rapidly responsive to symptomatic medication and/or brief interruption of infusion); recurrence of symptoms following initial improvement; hospitalization indicated for other clinical sequelae (e.g., renal impairment, pulmonary infiltrates) Grade 4: Life-threatening; pressor or ventilatory support indicated	Stop Infusion. Additional appropriate medical therapy may include but is not limited to: •      IV fluids •      Antihistamines •      NSAIDS •      Acetaminophen •      Narcotics •      Oxygen •      Pressors •      Corticosteroids •      Epinephrine. Increase monitoring of vital signs as medically indicated until the patient is deemed medically stable in the opinion of the investigator. Hospitalization may be indicated. The patient is permanently discontinued from further trial treatment administration.	No subsequent dosing
Appropriate resuscitation equipment should be available in the room and a physician readily available during the period of drug administration.

8.3.3 Other allowed dose interruption for pembrolizumab

Pembrolizumab may be interrupted for situations other than treatment-related AEs such as medical / surgical events or logistical reasons not related to study therapy. Patients should be placed back on study therapy within 3 weeks of the scheduled interruption, unless otherwise discussed with DSSM. The reason for interruption should be documented in the patient's study record

8.4 Liver dysfunction (Hy's Law)

Hy’s Law is based on the observation that pure hepatocellular injury sufficient to cause hyperbilirubinemia is an ominous indicator of the potential for a drug to cause serious liver injury. A diagnosis of potential drug-induced liver injury caused by a study drug can only be determined/inferred by excluding other potential causes of liver injury (e.g., other drugs or viral hepatitis) and by ruling out an obstructive cause for the elevated bilirubin (e.g., alkaline phosphatase should not be substantially elevated) (FDA 2009; Temple 2006).

8.4.1 Definition of cases potentially meeting Hy's Law criteria

Patients who present with the following laboratory abnormalities should be evaluated further to definitively determine the etiology of the abnormal laboratory values:

• Patients with AST or ALT baseline values within the normal range who subsequently present with AST or ALT > 3 times the ULN concurrent with a total bilirubin

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> 2 times the ULN with no evidence of hemolysis and an alkaline phosphatase

< 2 times the ULN or not available.

• Patients with pre-existing AST or ALT baseline values above the normal range who subsequently present with AST or ALT > 2 times the baseline values and > 3 times the ULN, or ³ 8 times the ULN (whichever is smaller) concurrent with a total bilirubin of > 2 times the ULN and increased by one ULN over baseline or > 3 times the ULN (whichever is smaller) with no evidence of hemolysis and an alkaline phosphatase < 2 times the ULN or not available.

8.4.2 Evaluation of potential Hy's Law cases

The patient should return to the investigational site and be evaluated as soon as possible, preferably within 48 hours from awareness of the abnormal results. This evaluation should include laboratory tests, detailed history, and physical assessment. In addition to repeating AST and ALT, laboratory tests should include albumin, creatine kinase, total bilirubin, direct and indirect bilirubin, gamma-glutamyl transferase (GGT), international normalized ratio (INR) and alkaline phosphatase. A detailed history, including relevant information, such as review of ethanol, recreational drug and supplement consumption, family history, sexual history, travel history, history of contact with a jaundiced patient, surgery, blood transfusion, history of liver or allergic disease, and work exposure, should be collected. Further testing for acute hepatitis A, B, or C infection and liver imaging (e.g. biliary tract) may be warranted. The possibility of progressive disease should be considered.

Potential Hy's Law cases should be reported as serious adverse events (see Sections 10.3.3 and 10.6).

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9.0 DRUG INFORMATION

9.1 AE37 peptide vaccine

9.1.1 AE-37 Description

The AE37 peptide is a nineteen amino-acid peptide referred to as AE37 (Ii-Key/HER2 776-790 hybrid). The drug substance, AE37, is provided by PolyPeptide Laboratories San Diego. The suspended substance (lypophilized peptide suspended in sterile, normal saline) is formulated into plastic cryovials containing 1000 mcg of peptide + saline.

9.1.2 Toxicity

Refer to the current AE-37 vaccine IB for safety and toxicity information.

9.1.3 Contraindications

Patients with autoimmune diseases should not be administered the AE37 vaccine.

9.1.4 Concomitant medications and other substances

Corticosteroid use, prescription anti-inflammatory drugs, or other immunosuppressants which in the opinion of the investigator would preclude participation in this immunotherapy trial should be used sparingly and not in close proximity with the immunizations (one week before or after immunization).

9.1.5 Preparation

The suspended peptide will be formulated by [PLACEHOLDER for a company to be determined later] and shipped to the individual study site pharmacy. Per the site Standard of Practice, the site pharmacist or research nurse coordinator will remove one frozen sterile vial containing 1000 mcg peptide/1.0 mL saline from the freezer and will thaw it at room temperature.

Mixing of the 1 mL solution is accomplished by repeatedly withdrawing the fluid into the syringe and gently injecting it back into the container using aseptic technique.

9.1.6 Method of Administration

Patients will receive two intradermal injections of approximately 0.5 mL volume on the anterior or medial side of the same thigh. The general area of vaccination will be at a location midway between the inguinal ligament and the knee and will be administered in the same lymph node draining area. The vaccinations will be given every 21 days for 5 doses total.

Intradermal vaccinations should be given in a method similar to the “PPD Skin Test” through a 26- or 27-gauge needle (3/8 inch) in the anterior thigh midway between the inguinal ligament and the knee. The whole 1 mL vaccination volume will be administered in 2 different sites approximately 5 cm (about 2 inches) apart from each other, by carefully injecting 500 μL (0.5 cc) at each vaccination site by intradermal injection per the diagram shown below.

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The vaccinations will be administered using sterile technique by a well-trained research nurse or trained study staff. The patient must be monitored for 1 hour after the vaccination for signs of any adverse reaction.

• Cleanse the area by swabbing the skin (an approximately 4 to 5 inch circle) with alcohol pads.

• Hold the skin taut before injecting. Place the 2 intradermal vaccinations in 2 quadrants of the cleansed circle.

• As depicted below keep the syringe low and flat along the skin surface (inject with needle bevel side up). Inject 500 μL forming a nice “bleb” under the skin.

• Slowly retract the needle and allow the “bleb” to resorb. Repeat 1 more time to completely administer the full 1.0 mL volume. Observe the patient and injection sites for 1 hour.

• Place a 4x6 sterile gauze bandage over the site on the thigh to protect from irritation for 12 to 24 hours.

• Any leakage of the dose onto the skin or inability to deliver the full 1 mL volume to the 2 sites should be noted in the eCRF.

• Patients must be observed immediately after vaccinations for signs of an acute allergic reaction. If symptoms such as difficulty breathing, angioedema, diffuse and significant urticaria, and/or hypotension are observed, immediate emergency medical attention will be provided.

9.2 Pembrolizumab (MK-3475, KEYTRUDAÒ) (NSC-776864)

Pembrolizumab is an investigational agent in the B-001 study.

9.2.1 Description

Pembrolizumab is a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD 1) receptor, thus inhibiting its interaction with programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). Based on preclinical in vitro data, pembrolizumab has high affinity and potent receptor blocking activity for PD 1.

Pembrolizumab has an acceptable preclinical safety profile and is in clinical development as an intravenous (IV) immunotherapy for advanced malignancies.

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9.2.2 Supply

Pembrolizumab (MK-3475) Solution for Infusion is a sterile, non-pyrogenic aqueous solution supplied in single-use Type I glass vial containing 100 mg/4 mL of pembrolizumab. The product is preservative-free solution which is essentially free of extraneous particulates.

9.2.3 Toxicity

Refer to the current pembrolizumab IB for toxicity information.

9.2.4 Preparation

• Allow pembrolizumab to equilibrate to room temperature for 15 – 30 minutes.

• Pembrolizumab infusion solutions should be prepared in 0.9% Sodium Chloride Injection, USP (normal saline) with a final concentration of pembrolizumab between 1 mg/mL and 10 mg/mL.

• Pembrolizumab SHOULD NOT BE MIXED WITH OTHER DILUENTS.

• Pembrolizumab is compatible with the following infusion bag materials: PVC plasticized with DEHP, non-PVC (polyolefin), EVA, and PE lined polyolefin.

• After adding the required amount of drug into the infusion bag, gently invert the bag 10-15 times to mix the solution.

• Once a dose is prepared, pembrolizumab should be administered within 4 hours. Pembrolizumab solutions may be stored at room temperature for a cumulative time of up to 4 hours. This includes room temperature storage of admixture solutions in the IV bags and the duration of infusion.

• In addition, IV bags may be stored under refrigeration at 2 °C to 8 °C (36 °F to 46 °F) for up to 20 hours. If refrigerated, allow the IV bags to come to room temperature prior to use.

• Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Discard the drug product vial if extraneous particulate matter other than translucent to white proteinaceous particles is observed.

• Sites should follow their SOPs for drug transport and delivery, with all possible effort to minimize agitation of the drug product between the pharmacy and the clinic.

• Do not use pembrolizumab if discoloration is observed.

• Do not shake or freeze the vial(s).

• Do not administer the product as an IV push or bolus.

• Do not combine, dilute, or administer it as an infusion with other medicinal products.

9.3 Study therapy procurement

Pembrolizumab will be supplied free of charge by Merck and Company, Inc. and distributed via an external vendor. AE37 vaccine will be supplied free of charge by Antigen Express and distributed via external vender. Pembrolizumab and AE37 vaccine must be requested by the principal investigator (or his/her authorized designee) at each participating institution

(see Information Resources). The initial supply of pembrolizumab and AE37 may be requested at the time the first patient signs the B-001 consent form. Pembrolizumab and AE37 vaccine will be shipped directly to the investigator whose sites are participating in B-001.

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9.4 Study therapy storage

9.4.1 AE 37 Vaccine

The AE37 peptide suspended in sterile saline is stored at ≤ -20 ˚C. At room temperature, the AE37 suspension should be used within two hours per label instructions. However, it can be prepared 24 hours prior to injection as long as it is kept refrigerated (4°C).

9.4.2 Pembrolizumab

Pembrolizumab (MK-3475) Solution for Infusion, 100 mg/4 mL vial: Vials should be stored at refrigerated conditions (2 – 8 °C). Note: Vials should be stored in the original box to ensure the drug product is protected from light.

9.5 Transfer of study therapy

Study therapy may not be used outside the scope of B-001, nor can study therapy be transferred or licensed to any party not participating in this clinical trial.

9.6 Destruction of study therapy vials

• Pembrolizumab:

At the end of an infusion for an individual patient, any remaining or unused study drug should be destroyed at the site according to the institution’s policy for drug destruction. At the completion of the study, all unused study drugs will also be destroyed at the site as per institutional policy for drug destruction after the monitoring review is completed by DSSM.

• AE37 vaccine and DTH

All unopened, partially used, or vial bottles of study therapy shall be destroyed by study sites in accordance with the local institution standard operating procedures.

• Written documentation of destruction must contain the following:

- identity (distribution numbers) of study therapy destroyed;

- quantity of study therapy vials destroyed;

- date of destruction (date discarded in designated hazardous container for destruction);

- name and signature of the person who discarded the study therapy vials in a hazardous container for destruction.

• Maintain appropriate records of the disposal, including dates and quantities.

9.7 Drug inventory records

The investigator, or a responsible party designated by the investigator, must maintain a careful record of the receipt, return, and destruction of all study therapy vials received through the

B-001 study using an Investigational Agent Accountability Record Form.

9.8 Drug accountability

The investigator, or a responsible party designated by the investigator, must maintain a careful record of the receipt, disposition, and return of all drug received through the B-001 study using an investigational agent accountability record form.

Records or logs must comply with applicable regulations and guidelines, and should include:

• Amount received and placed in storage area,

• Amount currently in storage area,

• Label ID number or batch/lot number,

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• Dates and initials of person responsible for each study drug inventory entry/movement,

• Amount dispensed and returned for each patient, including unique patient identifiers,

• Amount transferred to another area for dispensing or storage,

• Non-study disposition (e.g., lost, wasted, broken), and

• Amount destroyed.

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10.0 ADVERSE EVENT REPORTING REQUIREMENTS

The investigator is responsible for the detection and documentation of events meeting the criteria and definition of an adverse event (AE) or a serious adverse event (SAE), as provided in this protocol. Routine, adverse events of special interest (AESI), and expedited adverse event report forms and their supporting documentation must be submitted to DSSM according to the instructions in Sections 10.3, 10.4 and 10.6.

10.1 Definition of an AE

An AE is any untoward, undesired, or unplanned event in the form of signs, symptoms, disease, laboratory findings, or other physiologic observations occurring in a patient participating in

B-001. The event does not need to be causally related to study therapy or other requirements of the B-001 trial to be considered an AE.

• Examples of an AE include, but are not limited to, the following:

- Any toxicity related to study therapy.

- Any clinically significant worsening of a pre-existing condition.

- An AE occurring from a symptomatic overdose of any study therapy, whether accidental or intentional. See Section 10.3.2.

- A symptomatic AE that has been associated with the discontinuation of the use of any of the agents included in the study therapy.

- An AE occurring during a clinical study that is not related to the study therapy, but is considered by the investigator or sponsor to be related to the study requirements, for example, an AE may be an untoward event related to a medical procedure required by the protocol.

• A laboratory test result should be reported as an AE if it meets any of the following criteria:

- Accompanied by clinical symptoms.

- Results in a change in study treatment (e.g., dosage modification, treatment interruption or treatment discontinuation).

- Results in medical intervention (e.g., potassium supplementation for hypokalemia) or treatment discontinuation.

- Clinically significant per the investigator.

• Examples of clinical events that should not be considered AEs:

- Medical or surgical procedure (e.g., endoscopy, appendectomy). Note, the condition that leads to the procedure may be an AE, but the procedure itself is not.

- Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at the start of the study that do not worsen.

- Progression of the cancer under study is not considered an adverse event unless it is considered drug-related by the investigator.

10.2 Definition of an SAE

An SAE is any untoward medical occurrence that, at any dose, causes one of the following:

• Results in death.

• Is life-threatening.

The term 'life-threatening' in the definition of 'serious' refers to an event in which the patient was at risk of death at the time of the event. It does not refer to an event, which might have caused death, if it were more severe.

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• Requires hospitalization or prolongation of existing hospitalization

Hospitalization is any inpatient admission to a health care facility even if for less than

24 hours. Hospitalization or prolongation of a hospitalization constitutes a criterion for an AE to be serious; however, it is not in itself considered an SAE. In the absence of an AE, a hospitalization or prolongation of a hospitalization should not be reported as an SAE. For example, the following hospitalizations would not require expedited reporting for an SAE:

- hospitalization or prolongation of hospitalization needed for a procedure required by the protocol or as part of another routine procedure; or

- hospitalization for a pre-existing condition that has not worsened.

• Results in persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions.

This is not intended to include experiences of relatively minor medical significance such as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (e.g., sprained ankle) which may interfere or prevent everyday life functions but do not constitute a substantial disruption.

• Is a congenital anomaly/birth defect.

Also, appropriate medical judgment should be exercised in deciding whether SAE reporting is required in other situations, such as important medical events that may not result in death, be life-threatening, or require hospitalization, but may jeopardize the patient and may require medical or surgical intervention to prevent one of the other outcomes listed in the definition of an SAE. Examples of such events are intensive treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in inpatient hospitalization, or development of drug dependency or drug abuse.

10.3 Events requiring expedited reporting

All events listed in Sections 10.3 and 10.4 must be reported in an expedited manner according to the instructions in Section 10.6.

10.3.1 SAEs

All events meeting the definition of an SAE (Section 10.2) require expedited reporting.

10.3.2 Other events requiring expedited reporting

Other events must be recorded, reported, and followed up as indicated for an SAE (see

10.3 and 10.6 for reporting procedures). This includes the following events:

• Pregnancy exposure to study therapy. (If a pregnancy is confirmed, use of study therapy must be discontinued immediately. See Section 10.4.)

• Lactation exposure to study therapy.

• Medication errors involving study therapy with or without AE symptoms, including product confusion and potential product confusion. (A medication error is any preventable event that may cause or lead to inappropriate use or harm while the study therapy is in control of the healthcare professional or patient. Examples of reportable medication error include administration of unassigned treatment and administration of expired study therapy.)

• Overdose

- In this study an overdose for pembrolizumab is defined as ≥1000 mg (5 times the dose). An overdose of vaccine is defined as a study patient receiving a dose of study therapy in excess of that specified in this protocol or the Investigator’s Brochure.

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- Any overdose of a study patient with or without associated AEs/SAEs, is required to be reported within 24 hours of knowledge of the event to DSSM. Overdose does not automatically make an AE serious, but if the consequences of the overdose are serious, for example death or hospitalization, the event is serious and must be recorded and reported as an SAE (see Section 10.3.2 and 10.6). There is currently no specific treatment in the event of an overdose of study therapy. The investigator will use clinical judgment to treat any overdose.

• Any death, excluding death due to progression of colon cancer.

• Potential Hy's Law cases (see Section 8.4 and 10.3.3).

10.3.3 Clinical laboratory abnormalities

• Abnormal laboratory findings (e.g., clinical chemistry and hematology) or other abnormal assessments (e.g., x-rays and scans) will be recorded as AEs or SAEs if they meet the definition of an AE or SAE, as defined in Sections 10.1, 10.2, respectively, and if the abnormality meets reporting requirements as described in Section 10.3.3.

• Special reporting requirements related to Hy’s Law: All cases confirmed on repeat testing as meeting one of the criteria described in Section 8.4 with no other cause for LFT abnormalities identified at the time should be considered potential Hy’s Law cases regardless of availability of all the results of the investigations performed to determine etiology of the abnormal LFTs. Such potential Hy’s Law cases should be reported as serious adverse events (see Section 10.3.3).

10.3.4 Disease-related events and/or disease-related outcomes not qualifying as SAEs

An event that is part of the natural course of breast cancer does not need to be reported as an SAE. Progression breast cancer will be reported in the appropriate eCRF.

Note: Any occurrence of secondary malignancy (leukemia secondary to oncology chemotherapy [AML], myelodysplastic syndrome [MDS]) and/or treatment-related secondary malignancy is to be reported as an SAE.

10.4 Pregnancy

• If a patient becomes pregnant while receiving study therapy, discontinue study therapy and notify DSSM (see Information Resources). The investigator will record pregnancy information on the Pregnancy eCRF and submit it as an expedited report (within 24 hours) upon learning of a patient’s pregnancy. (See separate consent for release of pregnancy outcome information.)

• Information about the use in pregnancy encompasses the entire course of pregnancy and delivery, and perinatal and neonatal outcomes even if there were no abnormal findings. Information on the status of the mother and child will be forwarded to DSSM. Generally, follow-up will be no longer than 6 to 8 weeks following the estimated delivery date. Any premature termination of the pregnancy will also be reported.

• Any pregnancy complication or elective termination of a pregnancy for medical reasons will be recorded as an AE or SAE. A spontaneous abortion is always considered to be an SAE and will be reported as such.

• Any SAE occurring in association with pregnancy brought to the investigator's attention after the patient has completed the study and considered by the investigator as possibly related to study therapy, must be reported to the DSSM.

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10.5 Grading the severity of the AE

The NCI CTCAE v4.0 must be used to determine the Grade of the AE. The CTCAE provides descriptive terminology and a grading scale for each AE listed. Information regarding the CTCAE can be found on the CTEP Web site at http://ctep.cancer.gov. If further assistance is needed, contact DSSM (see Information Resources).

10.6 Expedited reporting instructions

10.6.1 Time period for reporting SAEs and other events requiring expedited reporting

• All SAEs and other events as noted in Sections 10.2, and 10.3 regardless of relationship to study therapy will be reported in an expedited manner as described in Section 10.6. Reporting SAEs (and other applicable events) regardless of relationship to study therapy begins with the first dose of study therapy and continues until 30 days after the last dose of study therapy.

• Any SAE assessed as related to study participation (e.g., protocol-mandated procedures) will be recorded from the time a patient consents to participate in the study up to and including any follow-up contact.

• Following the AE assessment 90 days after the last dose of study therapy, only SAEs determined to be related to study therapy will be reported in an expedited manner using B-001 CRF.

• The investigator must follow up on all SAEs until the events have subsided, until values have returned to baseline, or until the condition has stabilized.

10.6.2 Reporting instructions

• All SAEs and other events requiring expedited reporting must be reported using B-001 SAE CRF and submitted to DSSM within 24 hours of the study site personnel's initial notification of the event.

• When reporting potential Hy's Law cases, the SAE CRF should include the following:

- Seriousness Criteria = Important Medical Event

- Assessment/Narrative: Include the term “Potential Hy’s Law case” in the narrative; the text should also detail what additional study results are available at the time of reporting and what other studies are planned or results pending to further investigate alternative causes of the abnormal ALT/AST or bilirubin that triggered the report. The timing of planned patient follow-up should also be noted. See Section 8.4.

• NSABP will forward expedited report forms that meet reporting requirements concurrently to the FDA and to Merck and Antigen Express pharmacovigilance divisions with the causality assessment.

• Investigators are responsible for reporting AEs that meet specific criteria to their local IRBs.

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10.7 Time period and frequency for routine reporting of AEs

• Patients will be monitored for the occurrence of AEs at each scheduled assessment and during any contact with the patient during the study.

• All AEs, including SAEs and other AEs that have been reported on B-001SAE CRF, regardless of relationship to study therapy, will be recorded on Form AE of the CRF from the first dose of study therapy until 90 days after the last dose of study therapy.

• If the patient stops study therapy and begins a new treatment prior to the last dose of study therapy, AE assessments should be collected only up to the date the new therapy begins.

• For routine reporting, all ³ Grade 1 AEs will be reported on Form AE of the CRF.

• The investigator must follow up on all AEs until the events have subsided, until values have returned to baseline, or until the condition has stabilized.

10.8 Documentation requested following death

For deaths that occur within 30 days of the last dose of study therapy:

• Autopsy reports should be secured whenever possible and should be submitted to DSSM.

• A copy of the death certificate should be forwarded to DSSM if it is readily available or if it contains important cause-of-death information that is not documented elsewhere.

• Submit the last clinic/office note made before the death or the investigator’s note summarizing events resulting in death.

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11.0 ASSESSMENT OF EFFECT

11.1 Definitions

RECIST 1.1 (Eisenhauer 2009) will be adapted to account for the unique tumor response characteristics seen with treatment of pembrolizumab. Immunotherapeutic agents such as pembrolizumab may produce antitumor effects by potentiating endogenous cancer-specific immune responses. The response patterns seen with such an approach may extend beyond the typical time course of responses seen with cytotoxic agents, and can manifest a clinical response after an initial increase in tumor burden or even the appearance of new lesions. Standard RECIST may not provide an accurate response assessment of immunotherapeutic agents such as pembrolizumab. Therefore, RECIST 1.1 will be used with the following adaptations:

• Patients with progressive radiographic metastatic disease who are clinically asymptomatic and without other significant reason to discontinue therapy (i.e., toxicity, physician's judgement or patient's decision to stop therapy) may continue to receive study therapy per protocol until the next scheduled tumor assessment (Table 3) to confirm progression.

• If progression is confirmed the date of progression will be at the time of the initial scan indicating progression.

If repeat imaging shows < 20% tumor burden compared to nadir, stable or improved previous new lesion (if identified as cause for initial progressive disease [PD]), and stable/improved non-target disease (if identified as cause for initial PD), treatment may be continued / resumed.

11.1.1 Measurable disease

Measurable lesions are defined as those that can be accurately measured in at least one dimension (longest diameter to be recorded) as ³ 20 mm with conventional techniques (PET/CT, CT scan, or MRI) or as ³ 10 mm with spiral CT scan with 5 mm cuts. All tumor measurements must be recorded in millimeters (or decimal fractions of centimeters). The same method (CT or MRI) used at baseline should be used at all other tumor measurement time points.

11.1.2 Non-measurable disease

All other lesions, including small lesions (longest diameter ≥ 20 mm with conventional techniques or < 10 mm using spiral CT scan with 5 mm cuts) are considered to be

non-measurable disease.

11.1.3 Target lesions

Up to a maximum of five measurable lesions (maximum 2 lesions/organ), should be identified as target lesions and recorded and measured at baseline. Target lesions should be selected on the basis of their size (lesions with the longest diameter) and their suitability for accurate repeated measurements by CT scan or MRI. A sum of the longest diameter (LD) for all target lesions will be calculated and reported as the baseline sum LD. The baseline sum LD will be used as reference by which to characterize the objective tumor response.

11.1.4 Non-target lesions

All sites of disease which are not used as target lesions should be identified as non-target lesions. Location of individual lesions within the liver does not have to be specifically recorded. All sites of non-target lesions must be assessed along with the target lesions.

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11.2 Response criteria

11.2.1 Evaluation of target lesions

• Complete response (CR)

Disappearance of all target lesions

• Partial response (PR)

At least a 30% decrease in the sum of the of LD of target lesions, taking as reference the baseline sum LD

• Progressive disease (PD)

At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since baseline or the appearance of one or more new lesions

• Stable disease (SD)

Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since baseline.

11.2.2 Evaluation of non-measurable/non-target lesions

• Complete response (CR): disappearance of all non-target lesions

• Incomplete response/stable disease (SD): persistence of one or more non-target lesion(s)

• Progressive disease (PD): appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions

11.3 Evaluation of best overall response

The best overall response is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started).

Refer to Table 11 for a summary of the criteria that contribute to the determination of response.

Table 11. Determination of response

Target Lesions	Non-Target Lesions	New Lesions	Overall Response
CR	CR	No	CR
CR	Incomplete response/SD	No	PR
PR	Non-PD	No	PR
SD	Non-PD	No	SD
PD	Any	Yes or No	PD
Any	PD	Yes or No	PD
Any	Any	Yes	PD

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11.4 Symptomatic deterioration

Patients with a global deterioration of health status requiring discontinuation of treatment without objective evidence of disease progression at that time should be reported as "symptomatic deterioration." This is also true for "symptomatic deterioration" after therapy is completed.

Every effort should be made to document objective progression even after discontinuation of treatment.

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12.0 PATIENT ENTRY PROCEDURES

12.1 Patient consent form

Before study entry, the consent form including any addenda, must be signed and dated by the patient and the person obtaining informed consent. In addition, before study entry, a copy of the signed and dated consent form must be forwarded to DSSM. All patient signatures (except initials of first, middle, and last names) should be expunged prior to submission.

12.2 Study entry

DSSM will verify that the institution has current IRB approval for the study. Entry will not take place if the IRB approval is not current for the institution with IRB oversight responsibility.

All patients must be enrolled through DSSM. Once the entry eCRFs have begun to be entered, submit copies of the redacted signed consent form, and supporting documents to industry.trials@nsabp.org.

The entry material must be received by DSSM no later than 4:00 p.m. Eastern Time, Monday through Friday, excluding holidays. Once received the review process will begin. When the review is complete and approved, an enrollment confirmation will be sent. This process could involve some unavoidable delays. Therefore, it is necessary to plan adequate time (at least 24 hours) between study entry and the initiation of the patient’s study therapy.

12.3 Patient study number and treatment assignment

• After all the entry materials have been reviewed and approved, the institution will receive the following via e-mail:

- confirmation of registration and study entry;

- Patient Identification number.

- Patient cohort assignment

12.4 Investigator-initiated discontinuation of study therapy

In addition to the conditions outlined in the protocol, the investigator may require a patient to discontinue study therapy if one of the following occurs:

• the patient develops a serious side effect that cannot be tolerated or that cannot be controlled with other medications,

• the patient’s health gets worse,

• the patient is unable to meet the study requirements, or

• new information about the study drugs or other treatments for colon cancer becomes available.

If study therapy is stopped, study data and other materials should be submitted according to the study schedule unless the patient withdraws from the study or until there is a diagnosis of a secondary malignancy.

12.5 Patient-initiated discontinuation of study therapy

Even after a patient agrees to take part in this study, the patient may stop study therapy at any time. If study therapy is stopped, no new therapy begins and the patient still allows the study doctor to submit information, study data and other materials should be submitted according to the study schedule (Table 3).

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12.6 Patient-initiated withdrawal from the study

If a patient chooses to have no further interaction regarding the study, the investigator must provide DSSM with written documentation of the patient’s decision to fully withdraw from the study. Any data collected up to the time of withdrawal from the study will continue to be used.

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13.0       DATA HANDLING AND RECORDKEEPING

Refer to the "B-001 eCRF Completion Guidelines" for detailed instructions regarding data collection, AE reporting, and electronic case report form completion.

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14.0 STATISTICAL CONSIDERATION

14.1 Sample size determination and protocol duration for the primary endpoint

The hypothesis tested to determine the activity of AE37 plus pembrolizumab (at the recommended biologic dose) expressed in terms of ORR:

H0: ORR <0.15

HA: ORR >0.40

With the specified null and alternative hypotheses, a type I error rate of 0.05 and power of 0.90 to reject H0 if the true response rate is 40%, a Simon two stage design consists of initially treating 13 evaluable patients (Simon 1989). Enrollment should end for an inadequate response if no more than 2 patients have an objective response. If 3 or more have an objective response, enrollment continues to a total of 29 patients. If at least 8 responses are seen (ORR > 0.276), the treatment will be considered worth testing further.

14.2 Statistical analysis plan

This trial uses a Simon two-step design. In step 1, we will evaluate the overall response rate to possibly stop for futility according to the plans described in the sample size determination. In addition, after step 1 we will also evaluate the dose of AE37. If 4 or more of the first 13 patients (> 25%) have Grade 3 or higher toxicity we will de-escalate the dose from 1000 to 500 micrograms daily.

Following step 2, we will declare the combination therapy suitable for further study if at least 8 of 29 total patients have objective response. 95% confidence intervals will be reported along with the objective response rate. All patients with a baseline tumor measurement and receiving any protocol treatment will be included in efficacy analysis.

All secondary aims will be analyzed after the end of the study, that is after step 1 if the study closes early or after step 2 otherwise. Kaplan-Meier estimates of PFS and OS will be provided. Tabulations of maximum Grade observed for each patient for each observed toxicity will be provided along with a summary of maximum Grade observed for each patient for any toxicity.

14.3 Monitoring

• A medical review team comprising of the Protocol Chair, Medical Director of DSSM, study statistician, Director of the DSSM, designated physician(s), and designated DSSM staff will formally monitor the study on a monthly basis to identify accrual, toxicity, and any endpoint problems that might be developing.

• The Protocol Officer and designated DSSM staff will participate in a weekly web-ex with investigators who have patients enrolled on the B-001 study. Investigators who have patients receiving study therapy are required to participate. All B-001 investigators and study team members are encouraged to attend.

• The maximum grade for each type of toxicity will be recorded for each patient and frequency tables will be reviewed to determine toxicity patterns.

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15.0       PUBLICATION INFORMATION

The publication or citation of study results will be made in accordance with the publication policy of the NSABP that is in effect at the time the information is to be made publicly available.

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16.0 REFERENCES

Alexandrov 2013

Alexandrov LB, Nik-Zainal S, Wedge DC, et al. Signatures of mutational processes in human cancer. Nature 2013; 500(7463):415-421.

Anastasopoulou 2015

Anastasopoulou EA, Voutsas IF, Keramitsoglou T, et al. A pilot study in prostate cancer patients treated with the AE37 Ii-key-HER-2/neu polypeptide vaccine suggests that HLA-A*24 and HLA- DRB1*11 alleles may be prognostic and predictive biomarkers for clinical benefit. Cancer Immunol Immunother 2015; 64:1123-1136.

Benavides 2009

Benavides LC, Gates JD, Carmichael MG, et al. The impact of HER2/neu expression level on response to the E75 vaccine: from U.S. Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Clin Cancer Res 2009; 15:2895-2904.

Brown 2003

Brown JA, Dorfman DM, Ma FR, et al. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J Immunol 2003; 170: 1257-1266.

Dirix 2015

Dirix LY, Ticaks I, Nikolinakos P, et al. Avelumab (MSB0010718C), an anti-PD-L1 antibody, in patients with locally advanced or metastatic breast cancer: a phase 1b JAVELIN Solid Tumor trial. 2015; Oral presentation, 38th Annual San Antonio Breast Cancer Symposium. December 8- 12, 2015.

Disis 1994

Disis ML, Calenoff E, McLaughlin G, et al. Existent T-cell and antibody immunity to HER- 2/neu protein in patients with breast cancer. Cancer Res 1994; 54: 16-20.

Disis 2010

Disis ML. Immune regulation of cancer. J Clin Oncol 2010; 28(29):4531-4538.

Disis 2015

Disis ML, Stanton SE. Triple-negative breast cancer: immune modulation as the new treatment paradigm. Am Soc Clin Oncol Educ Book 2015; e25-30.

Dong 2002

Dong H, Strome SE, Salomao DR, et al. Tumor-associated B7-H1 promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat Med 2002; 8:793-800.

FDA Guidance 2009

FDA-Guidance. Drug-Induced Liver Injury: Premarketing Clinical Evaluation; July 2009. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/U CM174090.pdf (2009).

Fourcade 2009

Fourcade J, Kudela P, Sun Z, et al. PD-1 is a regulator of NY-ESO-1specific CD8+ T cell expansion in melanoma patients. J Immunol 2009; 182:5240-5349.

Fourcade 2010

Fourcade J, Sun Z, Benallaoua M, et al. Upregulation of Tim-3 and PD-1 expression is associated with tumor antigen-specific CD8+ T cell dysfunction in melanoma patients. J Exp Med 2010; 207: 2175-2186.

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Fourcade 2012

Fourcade J, Sun Z, Pagliano O, et al. CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1. Cancer Res 2012; 72: 887-896.

Fourcade 2014

Fourcade J, Sun Z, Pagliano O, et al. PD-1 and Tim-3 Regulate the Expansion of Tumor Antigen-Specific CD8+ T Cells Induced by Melanoma Vaccines. Cancer Res 2014; 369:134- 144.

Eisenhauer 2009

Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009; 45(2): 228-247.

Francisco 2010

Francisco LM, Sage PT, Sharpe AH. The PD-1 pathway in tolerance and autoimmunity. Immunol Rev 2010; 236: 219-242.

Galon 2006

Galon J, Costes A, Sanchez-Cabo F, et al. Type, density, and location of immune cells within human colorectal tumors predict clinical outcome. Science 2006; 313(5795):1960-1964.

Gates 2010

Gates JD, Clifton, GT, Benavides LC, et al. Circulating regulatory T cells (CD4+CD25+FOXP3+) decrease in breast cancer patients after vaccination with a modified MHC class II HER2/neu (AE37) peptide. Vaccine 2010; 28:7476-7482.

Hamid 2013

Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma. N Engl J Med 2013; 369(2):134-144.

HER2 Hybrid peptide (AE37) IB

HER2 Hybrid Peptide (AE37) Investigator's Brochure v4. Antigen Express, Inc. November 11, 2013.

Irie 2005

Irie A, Yamauchi A, Kontani K, et al. Galectin-9 as a prognostic factor with antimetastatic potential in breast cancer. Clin Cancer Res 2005; 11:2962-2968.

Le 2015

Le DT, Uram JN, Wang H, et al. PD-1 Blockade in Tumors with Mismatch-Repair Deficiency. N Engl J Med 2015; 25(372):2509-2520.

Lee 2000

Lee TV, Kim DK, Peoples GE, et al. Secretion of CXC chemokine IP-10 by peripheral blood mononuclear cells from healthy donors and breast cancer patients stimulated with HER2 peptides. J Interferon Cytokine Res 2000; 20:391-401.

Llosa 2015

Llosa NJ, Cruise M, Tam A, et al. The vigorous immune microenvironment of microsatellite instable colon cancer is balanced by multiple counter-inhibitory checkpoints. Cancer Discov 2015; 5(1):43-51.

Mittendorf 2006

Mittendorf E, Storrer C, Foley R. Evaluation of the HER2/neu-derived peptide GP2 for use in peptide-based breast cancer vaccine trial. Cancer 2006; 106(11):2309-2317.

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Mittendorf 2016

Mittendorf EA, Ardavanis A, Symanowski J, et al. Primary analysis of a prospective, randomized, single-blinded phase II trial evaluating the HER2 peptide AE37 vaccine in breast cancer patients to prevent recurrence. Ann Oncol 2016; 27:1241-1248.

MK-3475 IB

MK-3475 (pembrolizumab) Investigator's Brochure; 11th edition. Merck Sharp and Dohme Corp.; Merck & Co. September 1, 2016.

Nanda 2016

Nanda R, Chow L, Dees EC, et al. Pembrolizumab in Patients with Advanced Triple-Negative Breast. Phase IbKEYNOTE-012 Study. J Clin Oncol 2016; 34(21):2460-2467.

Nitta 2016

Nitta H, Kelly BD, Allred C, Et al. The assessment of Her2 status in breast cancer: the past, the present, and the future. Pathol Int 2016; 66(6):313-324.

Pages 2005

Pages F, Berger A, Camus M, et al. Effector memory T cells, early metastasis, and survival in colorectal cancer. N Engl J Med 2005; 353(25):2654-2666.

Peoples 1995

Peoples GE, Goedegebuure PS, Smith R, et al. Breast and ovarian cancer-specific cytotoxic T lymphocytes recognize the same HER2/neu-derived peptide. Proc Natl Acad Sci USA 1995; 92:432-436.

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Perez SA, Kallinteris NL, Bisias S, et al. Results from a phase I clinical study of novel Ii- Key/HER-2/neu(776-790) hybrid peptide vaccine in patients with prostate cancer. Clin Cancer Res 2010; 16(13):3495-3506.

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Perez SA, Anastasopoulou EA, Tzonis P, et al. AE37 peptide vaccination in prostate cancer: a 4- year immunological assessment updates on a phase I trial. Cancer Immunol Immunother 2013; 62: 1599-1608.

Perez 2014

Perez SA, Anastasopoulou EA, Papamichail M, et al. AE37 peptide vaccination in prostate cancer: identification of biomarkers in the context of prognosis and prediction. Cancer Immunol Immunother 2014; 63:1141-1150.

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Rizvi 2015

Rizvi NA, Hellmann MD, Snyder A, et al. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 2015; 348(6230): 124-128.

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Simon R. Optimal two-stage designs for phase II clinical trials. Control Clin Trials 1989; 10(1):1-10.

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Sharpe AH, Freeman GJ. The B7-CD28 superfamily. Nat Rev Immunol 2002; 2:116-126.

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Slamon DJ, Godolphin W, Jones LA, et al. Studies of the HER2/neu proto-oncogene in human breast and ovarian cancer. Science 1989; 244:707-717.

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Snyder A, Makarov V, Merghoub T, et al. Genetic Basis for Clinical Response to CTLA-4 Blockade in Melanoma. N Engl J Med 2014; 371(23):2189-2199.

Sotiriadou 2007

Sotiriadou NN, Kallinteris NL, Gritzapis AD, et al. Ii-Key/HER2/neu(776-790) hybrid peptides induce more effective immunological responses over the native peptide in lymphocyte cultures from patients with HER2/neu+ tumors. Cancer Immunol Immunother 2007; 56:601-13.

Stanton 2016

Stanton SE, Adams S, Disis ML. Variation in the Incidence and Magnitude of Tumor-Infiltrating Lymphocytes in Breast Cancer Subtypes: A Systematic Review. JAMA Oncol 2016; Jun 23. doi. 10.1001/jamaonclol.2016.1061.

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Stevens PJ, Tarpey PS, Davies H, et al. The landscape of cancer genes and mutational processes in breast cancer. Nature 2012; 486(7403):400-404.

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Temple, R. Hy's law: predicting serious hepatotoxicity. Pharmacoepidemiol Drug Safety 2006; 15(4): 241-243.

Thompson 2007

Thompson RH, Dong H, Lohse CM, et al. PD-1 is expressed by tumor-infiltrating immune cells and is associated with poor outcome for patients with renal cell carcinoma. Clin Cancer Res 2007; 13:1757-1761.

Tumeh 2014

Tumeh PC, Harview CL, Yearley JH, et al. PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature 2014; 515(7528):568-571.

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Vogelstein B, Papadopoulos N, Velculescu VE, et al. Cancer genome landscapes. Science 2013; 339(6127):1546-1558.

Weidanz 2006

Weidanz JA, Nguyen T, Woodburn T, et al. Levels of specific peptide-HLA class I complex predicts tumor cell susceptibility to CTL killing. J Immunol 2006; 177(8): 5088-5097.

Yadav 2014

Yadav M, Jhunjhunwala S, Phung QT, et al. Predicting immunogenic tumour mutations by combining mass spectrometry and exome sequencing. Nature 2014; 515(7528):572-576.

Zhu 2013

Zhu J, Peng T, Johnston C, et al. Immune surveillance by CD8alpha.alpha+ skin-resident T-cells in human herpes virus infection. Nature 2013; 497:494-497.

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APPENDIX A DETERMINATION OF PERFORMANCE STATUS

ECOG or Zubrod Scale		Karnofsky Score
0	Fully active; able to carry on all pre-disease performance without restriction	90–100%
1	Restricted in physically strenuous activity but ambulatory	70–80%
2	Ambulatory and capable of self-care, but unable to carry out any work activities	50–60%
3	Capable of only limited self- care; confined to bed or chair more than 50% of waking hours	30–40%
4	Completely disabled	10–20%

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APPENDIX B CONTRACEPTION

The following are acceptable methods of contraception for patients and partners of child-bearing potential:

Single method (one of the following is acceptable):

• Female patient of child-bearing potential

− intrauterine device (IUD)

− contraceptive rod implanted into the skin

• Male partner of a female patient of child-bearing potential

− vasectomy

Combination method (requires use of two of the following):

• diaphragm with spermicide (cannot be used in conjunction with cervical cap/spermicide)

• cervical cap with spermicide (nulliparous women only)

• contraceptive sponge (nulliparous women only)

• male condom or female condom (cannot be used together)

• hormonal contraceptive: oral contraceptive pill (estrogen/progestin pill or progestin-only pill), contraceptive skin patch, vaginal contraceptive ring, or subcutaneous contraceptive injection.

If a contraceptive method listed above is restricted by local regulations/guidelines, then it does not qualify as an acceptable method of contraception for patients participating at sites in this country/region.

Note: Abstinence (relative to heterosexual activity) can be used as the sole method of contraception if it is consistently employed as the patient’s preferred and usual lifestyle and if considered acceptable by local regulatory agencies and ERCs/IRBs. Periodic abstinence

(e.g., calendar, ovulation, sympto-thermal, post-ovulation methods, etc.) and withdrawal are not acceptable methods of contraception.

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Appendix B SUPPLY OF COMPOUND

Schedule of Deliveries for AE37

Delivery Date	Quantity of Vials (Immunization) (Liquid – 0.5mL, 0.5mg vial)
November 2017	347
Total	347

Delivery Date	Quantity of Vials (DTH*) (Liquid – 0.5mL, 0.1mg vial)
November 2017	70
Total	70

*Delayed Type Hypersensitivity

Schedule of Deliveries for KEYTRUDA®

Delivery Date	Quantity of Vials (Liquid - 4mL, 100mg vial)
November 2017	525
June 2018	100
Total	625

102 

Schedule I

DATA SHARING / SAMPLE TESTING SCHEDULE

Study Procedures	Shared between the Two Parties	Not Shared	Timing to provide item (data/sample, etc.)	Party to Analyze Data/Sample
Clinical Data (includes clinical /oncologic / medication history; vital signs / weight; physical examinations; ECOG performance status; 12-lead ECG; routine laboratory tests; pregnancy test; serologic tests; endocrine function assessments; other baseline physiological measurements)	X		Within 30 days of top-line results memo (format TBD)	Antigen Express
Tumor Imaging “If warranted”: assessment to support all efficacy analyses in a format that is in compliance with SDTM 3.1.3, the raw imaging data in a DICOM format that is de-identified, and if collected, all radiologist reporting, including tumor measurements and assessment of response and progression	X		Within 30 days of top-line results memo (format TBD)	Antigen Express
All clinical safety data (line listings of adverse events / SAEs)	X		Every three  months (also reference PV agreement)	Antigen Express
Results from any additional Pharmacodynamic and Biomarker Studies specified in protocol	X		Within 30 days of top-line results memo	Antigen Express
Results from Biomarker including any other exploratory biomarkers	X		For secondary objective data (PK and specified BM) within 30 days of top-line results memo (format TBD). Same timeline planned for data related to exploratory objectives, if available	Antigen Express
*Tumor PD-L1 Biomarker Assay: categorical result (If run by Merck)	X		Quarterly based on Merck’s chosen IHC vendor. Ad hoc data transfers will be determined as needed by the JDC.	Merck
*Tumor PD-L1 Biomarker Assay: scoring and raw data (If run by Merck)		X	N/A	Merck
RNA Profiling (tissue)	X		Within 30 days of top-line results memo	Merck
DNA analysis for mutational load	X		Within 30 days of top-line results memo	Antigen Express
* Only one PD-L1 assay will be run.

103 

EX-10.2

Clinical Trial Agreement

PHASE II STUDY

between

NSABP Foundation, Inc.

and

Antigen Express, Inc.

TABLE OF CONTENTS

RECITALS		3
ARTICLE I	DEFINITIONS	3
ARTICLE II	SCOPE OF SERVICES	5
ARTICLE III	STUDY CONDUCT	6
ARTICLE IV	FINANCIAL SUPPORT	7
ARTICLE V	SUPPLY, OWNERSHIP, AND DISTRIBUTION OF STUDY DRUG	8
ARTICLE VI	BIOLOGIC RESPOSITORY AND TISSUE COLLECTION	9
ARTICLE VII	WARRANTIES AND DISCLAIMERS	10
ARTICLE VIII	AUDITS, MONITORING, SITE QUALIFICATION, AND ACCESS TO RESEARCH RECORDS	10
ARTICLE IX	RECORDS AND REPORTS	10
ARTICLE X	FINANCIAL DISCLOSURE AND CONFLICT OF INTEREST	11
ARTICLE XI	CONFIDENTIAL INFORMATION	12
ARTICLE XII	PUBLICATIONS / PRESENTATIONS AND GENERAL PUBLICITY	14
ARTICLE XIII	DATA OWNERSHIP AND INVENTIONS	15
ARTICLE XIV	NOTICE	17
ARTICLE XV	INDEMNIFICATION; INSURANCE; LIMITATIONS OF LIABILITY	18
ARTICLE XVI	HUMAN SUBJECTS	20
ARTICLE XVII	TERM AND TERMINATION	20
ARTICLE XVIII	AMENDMENTS	21
ARTICLE XIX	SEVERABILITY	21
ARTICLE XX	INTEGRATION	22
ARTICLE XXI	ASSIGNMENT	22
ARTICLE XXII	INDEPENDENT CONTRACTOR	22
ARTICLE XXIII	NO TRANSFER OF PROPRIETARY RIGHTS NOT SPECIFIED	22
ARTICLE XXIV	CONFORMANCE WITH LAW AND ACCEPTED PRACTICE	22
ARTICLE XXV	WAIVER	22
ARTICLE XXVI	FORCE MAJEURE	23
ARTICLE XXVII	DEBARMENT	23
ARTICLE XXVIII	GOVERNING LAW	23
ARTICLE XXX	ENTIRE AGREEMENT	23
ARTICLE XXXI	COUNTERPARTS	23
BINDING EXECUTION		24

1

APPENDICES

Appendix A	NSABP Protocol entitled, "A Phase II Clinical Trial of Pembrolizumab in Combination with the AE37 Peptide Vaccine in Patients with Metastatic Triple Negative Breast Cancer, (FB-14)," including the sample Informed Consent Form
Appendix B	Budget, Payment Schedule, and Task List
Appendix C	NSABP Ownership of Data/Materials Policy
Appendix D	Selected Terms of Agreement for Disclosure to Sites

2

CLINICAL TRIAL AGREEMENT

This Clinical Trial Agreement (“Agreement”) is entered into and effective as of the 20th day of November, 2018 (“Effective Date”), by and between NSABP Foundation, Inc., a 501(c)(3) non-profit Pennsylvania membership corporation with its principal office and place of business at Nova Tower 2, Two Allegheny Center, Suite 1200, Pittsburgh, Pennsylvania 15212-5234 (“NSABP”), and Antigen Express, Inc., a Delaware corporation with its principal office and place of business at 33 Redwing Road, Wellesley, MA 02481 (“Antigen Express”). NSABP and Antigen Express shall hereinafter be referred to individually as “Party,” and together as “Parties.”

RECITALS

WHEREAS, NSABP conducts research and educational activities designed to improve the outcome for cancer patients via improved therapeutic and prevention modalities. The activities contemplated by this Agreement are of interest and benefit to NSABP and Antigen Express, and such activities will further NSABP's medical research objectives in a manner consistent with its non-profit, scientific and charitable status;

WHEREAS, Antigen Express is a platform and product-based company developing proprietary immunotherapeutic vaccine formulations for large, unmet medical needs, with a focus on antigen-specific stimulation of immunological response;

WHEREAS, NSABP and Antigen Express wish to have NSABP conduct the clinical research contemplated in this Agreement on behalf of Antigen Express, using Antigen Express' immunotherapeutic vaccine, AE37 in combination with pembrolizumab (KeytrudaÒ), for the treatment of metastatic triple negative breast cancer.

NOW, THEREFORE, the Parties enter into this Agreement with the intent to be legally bound under the terms and conditions herein set forth.

ARTICLE I

DEFINITIONS

The following terms, whether used in the singular or plural, have the respective meaning as set forth hereinbelow, as follows:

1.1 “AE” or “Adverse Event” shall have the meaning given in the Protocol.

1.2 "Antigen Express Study Drug" shall mean the Antigen Express AE37 peptide immunotherapeutic vaccine.

1.3 “Applicable Law” shall have the meaning given in Section 3.2 of this Agreement.

1.4 “Claims” shall have the meaning given in Section 15.1 of this Agreement.

3

1.5 “Confidential Information” shall have the meaning given in Section 11.1 of this Agreement.

1.6 “CRFs” shall mean the case report forms for the Study and shall include electronic CRFs (“eCRFs”) and the data contained therein.

1.7 “Data” shall mean all data generated by the conduct of the Study. For purposes of clarity, Data does not include patient medical records (other than CRFs, Informed Consent Forms, and SAE filings and narratives in respect of Subjects) or other Participating Site source documentation, which shall remain the property of the Participating Site.

1.8 “Disclosing Party” shall have the meaning given in Section 11.2 of this Agreement.

1.9 “EC/IRB” shall mean the Ethics Committee/Institutional Review Board established pursuant to 21 CFR Part 56 for the purpose of reviewing clinical investigations and their equivalents in countries other than the United States.

1.10 “FDA” shall mean the United States Food and Drug Administration.

1.11 “Good Clinical Practices" or "ICH GCP” shall mean good clinical practices as adopted by the International Conference on Harmonisation (“ICH”) of Technical Requirements for Registration of Pharmaceuticals for Human Use Good Clinical Practices. For clarification for U.S. sites, ICH GCP shall mean as defined in the most recent version of any FDA rules, regulations and guidelines on good clinical practice.

1.12 “IB” shall mean the clinical investigator brochure for the Antigen Express Study Drug and/or the Merck Study Drug, to be provided by Antigen Express and Merck, as applicable, hereunder, as it may be updated and amended from time to time by Antigen Express or Merck, as the case may be.

1.13 “IND” shall mean a claimed Investigational New Drug Application under 21 CFR § 312.

1.14 “Indemnitees” shall have the meaning given in Section 15.1 of this Agreement.

1.15 “Informed Consent Form” shall mean the informed consent form that is to be signed by all Subjects enrolled in the Study, together with any amendments thereto.

1.16 “Investigator” shall mean a licensed health professional who is a qualified clinical investigator willing and able, and engaged by NSABP or Participating Sites, in accordance with this Agreement, to conduct a clinical investigation under the Protocol pursuant to 21 CFR § 312.

1.17 “Materials” shall have the meaning set forth in Article VI.

1.18 “Merck” means Merck Sharp & Dohme B.V.

1.19 “Merck Agreement” means the Clinical Trial Collaboration and Supply Agreement by and among Merck and Antigen Express made as of June 28, 2017 as the same may be amended from time to time in accordance with the terms thereof.

1.20 "Merck Study Drug" shall mean Pembrolizumab, a humanized anti-human PD-1 monoclonal antibody.

4

1.21 “NDA” shall mean a New Drug Application under the Federal Food, Drug and Cosmetic Act, as amended.

1.22 “Other Inventions” shall have the meaning given in Section 13.4 of this Agreement.

1.23 “Participating Sites” shall mean Research Collaborators and their respective Research  Site(s) that are participating in the Study

1.24 “Protocol” or “FB-14” shall mean the NSABP protocol entitled “A Phase II Clinical Trial of Pembrolizumab in Combination with the AE37 Peptide Vaccine in Patients with Metastatic Triple Negative Breast Cancer,” and will be interpreted to include all modifications and amendments made in accordance with this Agreement, as well as the original Protocol and sample patient Informed Consent Form attached hereto as Appendix A and incorporated into this Agreement by this reference, and other Protocol related documents necessary for the effective communications of the Protocol.

1.25 “Receiving Party” shall have the meaning given in Section 11.2 of this Agreement.

1.26 “Research Collaborator” shall mean an entity where a Subject is seen, consented, treated and/or data is collected and completed for the Study, which entity is the official designated lead institution of a research collaborator through a collaborative arrangement with NSABP and is participating in the Study.

1.27 “Research Site(s)” shall mean a site that is cooperating with a Research Collaborator and, through that cooperation, is participating in the Study.

1.28 “SAEs” shall have the meaning given in the Protocol.

1.29 “Sponsor” shall mean Antigen Express.

1.30 “Study” shall mean all work to be carried out pursuant to the Protocol and this Agreement.

1.31 “Study Drugs” shall mean the Antigen Express Study Drug and the Merck Study Drug.

1.32 “Study Drug Inventions” shall have the meaning given in Section 13.1.

1.33 “Study Personnel” shall mean the personnel conducting the Study at Participating Sites, including Investigators.

1.34 “Subject(s)” shall mean those individuals who provide their informed consent and participate in the Study.

All other capitalized terms used herein shall have the meaning expressly ascribed to them herein.

ARTICLE II

SCOPE OF SERVICES

2.1               NSABP will conduct the Study in accordance with (a) the Protocol; (b) this Agreement; and (c) all Applicable Law.

2.2               This Agreement is not intended to be an exclusive contract and shall not limit the freedom of the Parties or any individuals participating in this work to engage in other research or other activities. NSABP and Antigen Express both retain the right to collaborate with other entities to conduct the types of clinical trials contemplated by this Agreement.

5

2.3               Antigen Express is the holder of the IND for the Study.

2.4 Norman Wolmark, M.D., shall be the NSABP Principal Investigator.

2.5               NSABP will enter into signed, written contracts with its Research Collaborators who wish to participate in the Study to (a) require that all Study Personnel are qualified to conduct the Study; (b) require that the Study is conducted under the direction of the applicable Investigators at a Participating Site and under the direction of the NSABP Principal Investigator and with the prior approval and on-going review of all appropriate and necessary review authorities; (c) obligate Research Collaborators, who shall obligate their respective Research Sites, to terms and conditions with respect to the Study that are required pursuant to this Agreement; and (d)  comply with Applicable Law. For clarification purposes, references herein to contractual obligations of Participating Sites shall include the requirement that each Research Collaborator impose such obligations upon its Research Sites.

2.6               Antigen Express shall use commercially reasonable efforts to timely perform its obligations hereunder (a) in a good and scientific manner; (b) in accordance with all standard laboratory and clinical practices; and (c) in compliance with all Applicable Law.

2.7               The Parties acknowledge and agree that Pembrolizumab is to be provided free of charge by Merck for purposes of the Study. NSABP acknowledges and agrees that Antigen Express has entered into the Merck Agreement for the supply of Pembrolizumab. Antigen Express will direct Merck to deliver the Merck Study Drug to NSABP’s designated drug distributor. The Parties agree that, if for any reason, the Merck Study Drug is not available for the Study, the Study will not be conducted and either Party may terminate this Agreement in accordance with Article XVIII.

ARTICLE III

STUDY CONDUCT

3.1 Antigen Express’s willingness to provide the Study funding and supply the Antigen Express Study Drug pursuant to this Agreement is predicated upon (a) its review of, and the mutual agreement of the Parties with respect to, the Protocol; (b) Subject enrollment and Study progress in accordance with Appendix B, and (c) the terms and conditions of this Agreement.

3.2 The Study will be performed in accordance with the terms and conditions contained herein, the terms and conditions of the Protocol, and all applicable laws, rules, regulations, and guidelines including but not limited to those regulations promulgated by the FDA including 21 CFR 312, as applicable, federal and state privacy and patient confidentiality laws, and ICH Good Clinical Practices (collectively, “Applicable Law”).

3.3 Antigen Express acknowledges that NSABP does not consider itself a HIPAA-covered entity; however, NSABP shall collect, use, store, access, and disclose personal health information (as that term is defined in HIPAA) (“PHI”) collected from Subjects only as permitted by the IRB approved Informed Consent Form or HIPAA authorization form obtained from a Subject. Antigen Express agrees that, to the extent Antigen Express and any Antigen Express designee has access to PHI, Antigen Express and such Antigen Express designee shall collect, use, store, access, and disclose PHI collected from Subjects only as permitted by the IRB approved Informed Consent Form or HIPAA authorization form obtained from a Subject. Any IRB approved Informed Consent Form or any HIPAA authorization form shall expressly permit Antigen Express to share Data with Merck. In order for Antigen Express to share or provide any Data that includes PHI with Merck, Antigen Express shall first obligate Merck to store, use, process, and handle any such Data with PHI only as permitted by the IRB approved Informed Consent Form or HIPAA authorization form.

6

3.4 NSABP or Antigen Express may at any time suggest amendments to the Protocol as may appear desirable; such amendments shall be discussed between Antigen Express and NSABP and (except as set forth below) such amendments may be made binding only upon mutual, signed written amendment to the Protocol. If such amendments are requested by Antigen Express and have been agreed to by NSABP, and such amendments increase or decrease the costs of the Study, NSABP will submit to Antigen Express a written estimate of the difference in costs arising from the amendments requested by Antigen Express and Antigen Express, at its discretion, shall decide whether NSABP shall implement such amendments. If such amendments are requested by NSABP, NSABP will submit to Antigen Express a written estimate of the difference in costs arising from the amendments requested by NSABP and Antigen Express, at its sole discretion, shall decide whether it will pay any increased costs. Notwithstanding anything to the contrary, if NSABP reasonably believes that generally accepted standards of clinical research and/or medical practice, or other appropriate concerns, justify an amendment to the Protocol such amendment shall become effective thirty (30) days after Antigen Express’s receipt of notice thereof from NSABP. Amendments to the Protocol shall result in a description of the impact the amendment will have on the schedule of financial support, if any. NSABP shall require that the Protocol and Informed Consent Form, and amendments thereto, be submitted to the appropriate EC/IRBs. NSABP will make all required submissions to the IND in connection with any amendment to the Protocol made pursuant to this Section 3.4.

3.5 Antigen Express shall sponsor an IND application with the FDA and will cross-reference appropriate INDs held by Merck and Antigen Express. The Parties acknowledge and agree that this is a combo-IND as the Antigen Express Study Drug is an immunotherapeutic vaccine, which falls under the Center for Biologics Evaluation and Research ("CBER"), while the Merck Study Drug is a drug that falls under the Center for Drug Evaluation and Research ("CDER"). NSABP shall perform the regulatory required filings on behalf of Antigen Express. NSABP shall copy Antigen Express on all regulatory filings and communications in respect of the IND. Antigen Express shall provide to, and shall require Merck to provide to, NSABP all necessary documentation and information required in support of such IND filings and reporting. Antigen Express shall approve any IND filings and reporting prior to NSABP submitting such documents, with the exception of SAEs due to the required timing of filings. NSABP will provide Antigen Express any SAEs filings promptly after submission to the FDA. NSABP shall provide Antigen Express with a copy of the IND application and the letter issued by the FDA, which references the IND application number, and other communications regarding the IND. Without limitation, Article XI shall apply to any Confidential Information Antigen Express supplies directly to NSABP in support of the IND.

ARTICLE IV

FINANCIAL SUPPORT

4.1 In consideration for NSABP’s activities pursuant to this Agreement, including those obligations specifically undertaken by NSABP as shown in the Task List attached hereto as Appendix B (“Budget, Payment Schedule, and Task List”), Antigen Express agrees to pay to NSABP a total sum as set forth in Appendix B in accordance with the terms and conditions set forth in Appendix B.

7

4.1.1 The total amount payable, as set forth in Appendix B. assumes completed enrollment in the Study and 12-month accrual of not less than 29 evaluable Subjects, or such greater number ultimately determined appropriate to reach the Study endpoints using an intent to treat analysis at a level of statistical significance.

4.1.2 Antigen Express shall not be obligated to make any payments to NSABP in excess of the amount set forth in Appendix B unless Antigen Express and NSABP agree to such excess amount in writing.

4.2 If Antigen Express requests the attendance of NSABP staff and/or Study Personnel at any meeting necessary to provide information regarding the Study or one or both of the Study Drugs, Antigen Express shall reimburse NSABP for reasonable and necessary travel and lodging expenses incurred by such personnel to attend such meeting(s) and that have been specifically approved in advance in writing by Antigen Express. Antigen Express shall make such reimbursements within thirty (30) days of receiving acceptable detailed documentation of such expenses.

4.3 The Parties agree that the compensation being paid to NSABP under this Agreement constitutes the fair market value for the activities to be conducted hereunder. No amounts paid under this Agreement are intended to be for, nor shall they be construed as an offer or payment made in exchange for any explicit or implicit agreement to purchase, prescribe, recommend, or provide a favorable formulary status for any Antigen Express product or service.

4.4 It is expected that for all items required under the Protocol for which Antigen Express has agreed to provide compensation, Antigen Express will be the sole source of monetary compensation. Accordingly, NSABP shall inform its Research Collaborators that they shall not charge any Subject nor submit claims to, or otherwise seek reimbursement from, third party payers or any federal healthcare program for the Study Drugs or any examinations, tests or procedures paid by Antigen Express under the Protocol, nor shall they include the cost of the Study Drugs in any cost report to third party payers.

ARTICLE V

SUPPLY, OWNERSHIP AND DISTRIBUTION OF STUDY DRUG

5.1 Study Drug Supply. Without charge to NSABP, Antigen Express shall, and shall require Merck to, use commercially reasonable efforts to ensure timely, safe, and accurate shipment of the Antigen Express Study Drug and the Merck Study Drug, respectively, for use solely in the Study and in accordance with the Protocol, in quantities sufficient to meet the requirements of the Study. For clarification purposes, references in this Article V to contractual obligations of Antigen Express shall include the requirement that Antigen Express imposes such obligations upon Merck.

5.1.1 Antigen Express (including, as applicable, through Antigen Express' drug distributor vendor), at its expense, shall take commercially reasonable steps to assure appropriate supply, handling and storage up to the point of delivery to NSABP’s contracted drug distributor of the Study Drugs, in accordance with the terms of this Agreement, the Protocol, and any Applicable Law relating thereto.

8

5.1.2 Antigen Express represents and warrants to NSABP that the Study Drugs are manufactured under Good Manufacturing Practices.

5.1.3 Antigen Express will provide Certificates of Analysis to NSABP for each lot of finished Study Drugs provided. Upon request of NSABP copies of documentation of shipment of the Study Drugs to NSABP’s drug distributor will be provided to NSABP by Antigen Express.

5.1.4 NSABP shall obligate all Participating Sites to maintain accurate records of all Study Drugs received, dispensed, and destroyed in accordance with the Protocol and to store all Study Drugs in accordance with labeled conditions in a secure and locked location to prevent theft or misuse.

5.1.5 Title to and ownership of all Antigen Express Study Drug and Merck Study Drug provided hereunder shall remain with Antigen Express and Merck, respectively.

5.1.6 In the event that Antigen Express or any regulatory agency orders a recall or withdrawal of the Study Drugs (a “Recall”), Antigen Express agrees to reimburse NSABP all reasonable fees that NSABP is obligated to pay NSABP’s drug distributor to the extent related to such Recall. The Parties agree to cooperate fully with each other in effecting any Recall.

5.2 Study Drug Distribution.

5.2.1 Antigen Express will ship, or have shipped, the Study Drugs to NSABP’s drug distributor in appropriately marked containers in accordance with 21 CFR § 312.6. NSABP will contract with its drug distributor for the redistribution of the Study Drugs to Participating Sites in accordance with Applicable Law. NSABP will obligate its drug distributor to (a) store and distribute the Study Drugs according to the labeled conditions, (b) distribute the Study Drugs only to Participating Sites in countries where the Study is approved in accordance with Applicable Law, and (c) to maintain complete and accurate records of the Study Drugs shipment, receipt, disposition, return and destruction, as applicable.

5.3 Disposition of Unused Supplies. Following termination or completion of the Study, any unused Study Drugs shall be handled as described in the Protocol and NSABP's written instructions.

5.4 Continued Supply. If medically appropriate, at the time the Protocol closes early to accrual, Study Drugs shall continue to be supplied in accordance with this Article V to Subjects receiving the Study Drugs, until completion of treatment as prescribed in the Protocol.

ARTICLE VI

BIOLOGIC REPOSITORY AND BIOSPECIMEN COLLECTION

Under the terms and conditions set forth in this Article VI, Antigen Express and/or NSABP may agree to design specific research projects in the Study, which require the collection of all serum, blood, tissue or other biospecimen samples obtained in connection with the Study ("the Materials"). Such research projects shall be expressly set forth in specific prospective clinical research designs in the Protocol, included in the Informed Consent Form for the Study, and addressed in this Agreement. In addition, if agreed to by the Parties, and to the extent expressly set forth in the Protocol, and in conformance with Applicable Law, NSABP will make its Biologic Repository available for storage of such Materials. Nothing in this Agreement obligates either Party to do anything with respect to any such research projects.

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ARTICLE VII

WARRANTIES AND DISCLAIMERS

EXCEPT AS EXPRESSLY SET FORTH IN THIS AGREEMENT, NEITHER OF THE PARTIES MAKES ANY, AND EACH HEREBY DISCLAIMS AND NEGATES ANY AND ALL REPRESENTATIONS AND WARRANTIES (EXPRESS, IMPLIED, STATUTORY, OR OTHERWISE), WHETHER WRITTEN OR ORAL, EXPRESSED OR IMPLIED, WITH RESPECT TO THE SUBJECT MATTER OF THIS AGREEMENT, INCLUDING ANY AND ALL IMPLIED WARRANTIES OF QUALITY, PERFORMANCE, MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE OR USE, THE PATENTABILITY, VALIDITY, SCOPE, OR ENFORCEABILITY OF THE RIGHTS GRANTED HEREIN, AND/OR THE NON-INFRINGEMENT OF THIRD PARTY INTELLECTUAL PROPERTY RIGHTS.

ARTICLE VIII

AUDITS
AND ACCESS TO RESEARCH RECORDS

8.1 At mutually agreeable times NSABP will give Antigen Express, Merck, and their designees access to all records and documentation maintained by NSABP (however stored) relating to the Study for audit purposes. NSABP will also make those records available for the purposes of any audit by a regulatory authority.

8.2 Antigen Express may arrange in advance with the NSABP Principal Investigator and NSABP to conduct co-audits of Participating Sites during normal business hours. Antigen Express and NSABP agree to use commercially reasonable efforts to limit such audits to one day or less in length. Notwithstanding the above, NSABP or Antigen Express may conduct for cause audits where the immediate need to assure Subject safety, data integrity, or regulatory compliance exists or as required to address FDA or other government requests with as little as forty-eight (48) hours' notice. Notwithstanding anything to the contrary, the Parties agree and acknowledge that any visit to a Participating Site may be subject to that Participating Site’s policies and procedures, such as those for patient confidentiality and privacy, security, safety, and the like. The Parties agree to comply with any such policies and procedures of any such Participating Site while at such Participating Site’s facilities of which a Party is informed.

8.3 NSABP will obligate Research Collaborators to make their records or documents available for the purposes of any audit by a regulatory authority.

8.4 The Parties agree to treat any information obtained in any audit or during any visit as Confidential Information subject to Article 11 hereunder.

ARTICLE IX

RECORDS AND REPORTS

9.1 NSABP, or its designated representative shall perform the following recordkeeping and reporting obligations in a timely and accurate fashion in accordance with NSABP's standard procedures and Applicable Law, as follows:

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(a) preparation and maintenance of complete and accurate written records, accounts, notes, reports, and data of the Study; and

(b) preparation and submission to Antigen Express of CRFs for each Subject.

9.2 Each Party will provide to the other Party copies of all Study communications exchanged by the Party and the FDA, the Office for Human Research Protection (“OHRP”), or other regulatory agency, including any that characterize any analyses or conclusions of Study Data or which otherwise cite an opinion about the Study rendered by NSABP.

9.3 Adverse Reactions and SAEs.

9.3.1 Antigen Express shall, and shall require Merck to, promptly provide NSABP with relevant IB updates, significant safety information, including without limitation those serious and unexpected suspected adverse reactions (as defined by FDA regulations) for the Antigen Express Study Drug and the Merck Study Drug, respectively, (from any source) and other relevant information upon which the Parties may mutually agree.

9.3.2 As related to the Antigen Express Study Drug, NSABP agrees to report all serious and unexpected suspected adverse reactions that emerge during the Study to the FDA according to 21 CFR § 312.32, to other regulatory agencies and the appropriate EC/IRB as required by Applicable Law within the requisite applicable timeframes and will concurrently forward all such reports to Antigen Express.

9.3.3 As related to the Merck Study Drug, the IND will be filed with a request for a waiver that exempts Merck from any requirement to notify the FDA of any suspected unexpected serious adverse reactions related to the administration of the Merck Study Drug in any clinical study other than as part of the Study. In the event such waiver is not granted, Antigen Express will sponsor the Study under its extant IND for the Antigen Express Drug (with a right of reference to the IND for the Merck Study Drug).

9.4 NSABP agrees to maintain adequate and accurate records as required under 21 CFR § 312.62 relating to the disposition of the Investigational New Drug and the treatment of Subjects in the Study, if applicable. Prior to discarding such records, NSABP will notify Antigen Express of pending destruction, at which time Antigen Express may elect, at its own expense, to maintain the records until the requirements of marketing applications in other territories have been met. NSABP shall provide Antigen Express with interim Study status reports (e.g., toxicity reports, monthly accrual reports, site status information) in accordance with Appendix B.

9.5 NSABP shall register the Study with www.ClinicalTrials.gov.

ARTICLE X

FINANCIAL DISCLOSURE AND CONFLICT OF INTEREST

NSABP shall collect financial disclosure statements from each Investigator sufficient to allow Antigen Express to submit complete and accurate certification or disclosure statements required under 21 CFR Part 54. In the event Antigen Express decides to file the results and Antigen Express Study Data with the FDA and/or another health authority in support of a marketing authorization, NSABP will reasonably assist Antigen Express in meeting its certification and disclosure obligations including, without limitation, by providing Antigen Express with the financial disclosure statements and assisting Antigen Express in collecting any missing information from Investigators.

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ARTICLE XI

CONFIDENTIAL INFORMATION

11.1 “Confidential Information” shall mean all information and materials related to the Study (whether owned by a Disclosing Party or by a third party to whom such Disclosing Party owes an obligation of confidence) disclosed by a Disclosing Party to a Receiving Party, including (without limitation) the Study Protocol, case report forms, the IB, proprietary technology, procedures, formulations, protocols, patient information or identifiers, know-how, clinical data, specifications, documents and related Study materials, techniques, processes, biospecimens, products samples, apparatus, research plans, business plans, or identity of potential collaborators.

11.2 The Parties may disclose to each other (including their respective agents and representatives and to Participating Sites and their respective agents and representatives) Confidential Information to aid in effecting or completing performance of the Study under this Agreement. Confidential Information, whether written, electronic, or verbal, disclosed by either Party hereunder (the “Disclosing Party”) to the other (the “Receiving Party”) shall be treated as confidential by the Receiving Party for a period of five (5) years following completion or closure of the Study to accrual. All such disclosures of Confidential Information shall be in writing or other tangible form and shall be prominently marked with the legend “CONFIDENTIAL” or “CONFIDENTIAL INFORMATION” or the like. If disclosed orally or in other than documentary or electronic form, Confidential Information shall be reduced to a tangible form within thirty (30) days thereafter and a copy of such tangible form, bearing the foregoing confidentiality legend, shall be provided to the designated representative of the Receiving Party. Notwithstanding the foregoing, failure by a Party to mark any item "Confidential" or reduce an item to writing does not constitute a designation of non-confidentiality when the confidential nature is readily apparent to a reasonable observer from context and subject matter. The Receiving Party further agrees not to disclose to others or use for any purpose, other than as reasonably necessary for performance of the Study or exercise of rights under this Agreement, Confidential Information disclosed pursuant to this Agreement. These obligations of non-disclosure and non-use shall not apply to information:

(a) that is or becomes publicly available through no fault of the Receiving Party;

(b) that is already independently known to the Receiving Party hereunder prior to receipt from the Disclosing Party hereunder, as shown by its prior written records or is independently developed by the Receiving Party without use of any Confidential Information received from the Disclosing Party; or

(c) that subsequent to its disclosure hereunder, is disclosed to the Receiving Party on a non-confidential basis by a third party with the legal right to do so.

11.3 In the event Antigen Express, or its designees, or Merck, or its designees shall come into contact with a Subject’s Study records, Antigen Express, or its designees, shall, and Antigen Express will require Merck, or its designees to, hold in confidence the identity of the Subject, and shall comply with Applicable Law regarding the confidentiality of such records as if these records were patient medical records.

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11.4 Confidential Information shall not be disclosed by the Receiving Party without prior written approval of the Disclosing Party to any third party, which approval shall not be unreasonably withheld or delayed, except as set forth in this Article XI or, if required by the FDA or any other applicable governmental or regulatory agency having the authority to make such a demand or to any court of law pursuant to a subpoena, or a judicial order, or as permitted by Applicable Law. NSABP and Antigen Express agree to contact the other Party prior to the release of any Confidential Information pursuant to this Section 11.3 and allow the other Party to exhaust any legal action it may take to prevent or limit the disclosure and, at Disclosing Party's request, shall cooperate with the Disclosing Party to seek a protective order or other appropriate remedy. In the event the Receiving Party hereunder finds it necessary to disclose Confidential Information of the Disclosing Party to a proper governmental authority, if permitted by Applicable Law, it shall first notify the Disclosing Party hereunder and the Parties shall endeavor to agree upon a mutually satisfactory way to disclose such Confidential Information as is necessary for this limited purpose and required by Applicable Law. Nothing herein shall prevent a Party from complying with a legal obligation to disclose Confidential Information of the other Party so long as the Receiving Party:

(a) to the extent practicable, provides the Disclosing Party prompt notice of the Receiving Party’s perceived obligation of disclosure and intent to disclose (or to resist disclosure);

(b) cooperates with the Disclosing Party's lawful attempts to prevent or limit the disclosure or obtain protection for such Confidential Information; and;

(c) only disclosing that portion of Confidential Information that is legally required to disclose.

11.5 Receiving Party must within thirty (30) days, upon written request of a Disclosing Party (a) return all Confidential Information in its possession or control to the Disclosing Party; or (b) destroy or delete all Confidential Information in its possession or control. Notwithstanding the foregoing, the Receiving Party may retain one (1) physical copy of such Confidential Information for archival and legal purposes and electronic back-up and/or archival storage copies made in accordance with the Receiving Party’s standard document retention procedures solely for purposes of disaster recovery and compliance with such policies. When Receiving Party has complied with its obligations described above, upon request by Disclosing Party, it shall confirm to Disclosing Party, in writing that it has returned, destroyed or deleted all Confidential Information.

11.6 Permitted Disclosures.

11.6.1 Receiving Party may provide Disclosing Party’s Confidential Information to its directors, employees, consultants, contractors and agents. NSABP may provide, or permit Participating Sites to provide, Confidential Information to (a) Research Collaborators and their Research Sites, (b) EC/IRBs and Study Personnel, and (c) applicable accreditation organizations (including their respective agents and representatives). In each case, Confidential Information may (i) be provided on a need-to-know basis, and (ii) provided that the Receiving Parties thereof are subject to written obligations, or bound by institutional policies, of confidentiality and non-use with regard to such Confidential Information that are the same or substantially the same as those contained hereunder.

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11.6.2 Notwithstanding the foregoing, Participating Sites may disclose Confidential Information: (a) to the applicable EC/IRB(s) or other necessary oversight or governmental or regulatory authority as required by Applicable Law, and (b) to obtain informed consent from patients who may wish to enroll in a Study, provided, however, that such Confidential Information shall only be disclosed to the extent necessary and will not be provided in response to unsolicited inquiries by telephone or to individuals who are not eligible Study candidates.

11.6.3 A Participating Site may disclose Confidential Information to the extent such disclosure is necessary for the medical treatment of a Subject in an emergency and is unable to provide prior notice of the disclosure, so long as NSABP provides notice to Antigen Express of such disclosure promptly after NSABP becomes aware of such disclosure, and such disclosure only includes such Confidential Information as is medically necessary for such medical treatment.

11.7 The terms and conditions of this Agreement shall be deemed the Confidential Information of NSABP, subject to this Article XI. Notwithstanding the foregoing, Antigen Express acknowledges that pass-through provisions for NSABP contracts with its Research Collaborators may allow disclosure of the terms and conditions of such contracts pursuant to institutional policies or Applicable Law.

ARTICLE XII

PUBLICATIONS / PRESENTATIONS AND GENERAL PUBLICITY

12.1 Notwithstanding the obligations of confidentiality and non-use set forth below, NSABP will be free to publish and present the results of the Study subject to the following conditions: Antigen Express will be furnished with a copy of any proposed publication, presentation, or abstract of previously unpublished Data relating to the Study conducted under this Agreement for review and comment, thirty (30) days prior to such submission for publication or presentation (collectively, "Review Period"). Such Review Period does not begin until receipt of the proposed publication, presentation, or abstract by Antigen Express. Antigen Express shall have the Review Period to respond with any requested revisions, including without limitation the deletion of Antigen Express Confidential Information (which shall be deemed to include Merck's Confidential Information), other than the results of the Study, and revisions to protect any existing or future patents. NSABP shall act in good faith upon such requested revisions, except NSABP shall delete any Antigen Express Confidential Information (which shall be deemed to include Merck Confidential Information), other than the results of the Study, from such proposed publication. At the expiration of such Review Period, NSABP may proceed with the submission for publication, presentation, or abstract; provided, however, that in the event Antigen Express has notified NSABP in writing during the Review Period that Antigen Express reasonably believes that prior to such publication, presentation, or abstract it must take action to protect its intellectual property interests, such as the filing of a patent application claiming an invention or a trademark registration application, NSABP shall either (1) delay such publication, presentation, or abstract for an additional seventy-five (75) days or until the foregoing action(s) have been taken, whichever shall first occur; or (2) if NSABP is unwilling to delay the publication, presentation, or abstract, NSABP will remove from the publication, presentation, or abstract the information which Antigen Express has specified it reasonably believes would jeopardize its intellectual property interests. Under certain circumstances, a shorter review period may be granted in writing by Antigen Express.

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12.2 Notwithstanding anything to the contrary in this Agreement, in the event that neither NSABP nor Antigen Express publishes a manuscript on the primary endpoint of the Study within eighteen (18) months after the occurrence of the Study primary endpoint events or after the early termination of the Study, whichever occurs first, Participating Sites, or multiple Participating Sites, will have the right to publish or present with respect to the applicable Participating Sites’ own Study-related data provided that any such Participating Sites first comply with the strictures applicable to NSABP in section 12.1 above.

12.3 Neither Party shall mention or otherwise use (nor authorize others to use) the name, trademark, trade name, logo or names of the employees of the other Party in any publication, press release or promotional material without the prior written approval of the other Party; provided, however, that Antigen Express shall have the right to identify NSABP as the group responsible for conducting the Study. Antigen Express agrees that its use of the name, symbols, and/or marks of NSABP, or names of NSABP’s employees, shall be limited to identification of NSABP and its Research Collaborators and subcontractor's staff as collaborators with NSABP. Antigen Express will not use, nor authorize others to use, the name, symbols, or marks of NSABP in any advertising or publicity material or make any form of representation or statement, which would constitute an express or implied endorsement by NSABP of the Antigen Express Study Drug without prior written approval from NSABP. Likewise, NSABP shall not use the name of Antigen Express or the marks of Antigen Express in such a manner without the written permission of Antigen Express. Antigen Express agrees to allow the following information to appear on NSABP’s and/or Participating Site’s Clinical Trials Directory website: the identification of Antigen Express, as the Sponsor of the Study, Study title, Study status, trial type, Study phase, Study category and subcategory, Study objectives and designs, conditions treated, treatment(s) or intervention(s), key eligibility criteria and exclusion criteria; provided, however, that such information includes no additional information beyond the information Antigen Express posts on its own website or on www.clinicaltrials.gov.

ARTICLE XIII

DATA OWNERSHIP AND INVENTIONS

13.1 NSABP shall not acquire, as a result of the Study, and nothing transfers by operation of this Agreement, any proprietary rights in the Study Drugs or any patent right, copyright or other proprietary right that Antigen Express or Merck owns as of the Effective Date. Any inventions or discoveries (whether patentable or not) relating to the Antigen Express Study Drug ("AE Study Drug Invention(s)") or the Merck Study Drug ("Merck Study Drug Invention(s)") and conceived or made during the performance of the Study (collectively, hereinafter “Study Drug Invention(s)”), by NSABP, Participating Sites or Study Personnel, alone or jointly with others, shall be solely owned by Antigen Express or Merck, respectively.

13.2 NSABP shall, and will contractually obligate Participating Sites and Study Personnel to (through NSABP), promptly notify Antigen Express of any Study Drug Inventions. “Contractually obligate,” as used in Article XIII, means that NSABP will include contractual provisions with its Research Collaborators requiring them to obligate Participating Sites and Study Personnel to perform the specified action(s). NSABP hereby assigns and will assign, and will contractually obligate Participating Sites and Study Personnel to, assign and agree to assign, any and all of their rights, title and interest in Study Drug Inventions to Antigen Express or Merck, as applicable. Upon Antigen Express’ request, NSABP shall take, and shall contractually obligate Participating Sites and Study Personnel to take, at Antigen Express’ or Merck's expense, such actions as Antigen Express or Merck reasonably deems necessary or appropriate to obtain patent or other proprietary protection in Antigen Express’ or Merck's name, as applicable, with respect to the applicable Study Drug Inventions, and shall execute and deliver, and shall contractually obligate Participating Sites and Study Personnel to execute and deliver, all reasonably requested applications, assignments, and other documents and take such other measures as Antigen Express or Merck reasonably requests, in order to record Antigen Express’ or Merck's rights, as applicable, in the applicable Study Drug Inventions.

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13.3 All Data generated or obtained in connection with the Study, and all proprietary rights to the foregoing, shall be owned by Antigen Express and/or Merck. All Materials generated or obtained in connection with the Study, and all proprietary rights to the foregoing, shall be owned by NSABP and be subject to the NSABP Ownership of Data/Materials Policy attached as Appendix C except to the extent such policy conflicts with the terms of this Agreement. NSABP agrees to treat such Data as Confidential Information of Antigen Express pursuant to Article XI prior to public release of the Data in accordance with the terms of this Agreement. Antigen Express agrees to treat the Materials as Confidential Information of NSABP pursuant to Article XI. Antigen Express hereby grants to Subject to Article XI, NSABP (and NSABP may grant to Participating Sites) a perpetual, irrevocable, world-wide, royalty-free, non-exclusive right and license to use the Data for non-commercial research, scientific, and educational purposes. Subject to Article XI, NSABP hereby grants to Antigen Express a royalty-free, non-exclusive right and license to use the Materials to perform the Study. Notwithstanding Article XI, Antigen Express shall have the right to use the Data for regulatory purposes in its sole discretion. NSABP agrees not to use the Data for an NDA, supplemental NDA, or any other regulatory submission relating to a regulatory approval for the Study Drugs by others.

13.4 With respect to any inventions or discoveries (whether patentable or not) (i) conceived or made in the performance of the Study, or (ii) from the use of Data or Materials (or data or materials derived therefrom), by NSABP, Participating Sites or Study Personnel, alone or jointly with others, that are not conceived in the course of NSABP’s performance of the Study that do not constitute Study Drug Inventions (“Other Inventions”) shall have the determination of the ownership of such Other Inventions by inventorship (as determined by U.S. patent law)., even if they arise from research using Data and/or Materials, or data and/or materials derived therefrom, obtained in connection with the Study. The Parties agree that for purposes of this Article XIII, performance of sub-studies conducted by NSABP and/or Antigen Express with such Data and/or Materials shall not be deemed performance of the Study, unless any such sub-study is expressly and specifically defined in the Protocol as a sub-study within the Study.

13.5 NSABP shall promptly notify Antigen Express of any Other Inventions, and will contractually obligate its Participating Sites and Study Personnel to, promptly notify NSABP of any Other Inventions.

13.6 Antigen Express agrees to, and has obtained from Merck the agreement to, grant to NSABP, NSABP Principal Investigator, Participating Sites, Investigators and/or Study Personnel who conceived or actually reduced to practice the Study Drug Invention(s) or Joint Study Drug Invention(s) the right to use such Study Drug Invention or Joint Study Drug Invention for internal non-commercial academic/educational clinical, and research purposes of NSABP and/or the Participating Site.

13.7 NSABP hereby grants, and will obligate its Participating Sites and Study Personnel (for this Section 13.7, each an "Institution") to grant, to Antigen Express:

13.7.1 a royalty-free, perpetual license to use Other Inventions solely for Antigen Express’ internal research purposes, provided that the license granted under this Section does not include the right to use Other Inventions to make, have made, sell, offer for sale, import or export any products or services, and

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13.7.2 an option to negotiate to obtain an exclusive royalty-bearing, worldwide license, including the right to sublicense, to Institution’s interest in Other Inventions. Antigen Express’ option under this section may be exercised at any time during a period of 180 days (the “Option Period”) after the written submission to Antigen Express of each such Other Invention by notice in writing from Antigen Express to Institution. Upon Antigen Express’ exercise of its option with regard to any particular Other Invention, Institution and Antigen Express will negotiate in good faith in an attempt to reach a license agreement satisfactory to all interested parties (the “Negotiation Period”). Unless extended by the written mutual consent of the interested parties, the Option Period and the Negotiation Period shall not exceed twelve (12) months in the aggregate. If Antigen Express fails to exercise an option during an Option Period or the interested parties fail to conclude an exclusive license to any Other Invention within the applicable Negotiation Period, Institution shall have no further obligation to Antigen Express hereunder with regard to Institution’s interest in such Other Inventions.

ARTICLE XIV

NOTICE

Any notice required or permitted hereunder related to this Agreement shall be in writing and shall be deemed given as of the date it is: (a) delivered by hand; (b) by overnight courier; (c) delivered by facsimile (with transmission confirmed); or (d) received by the Party to receive such notice by registered or certified mail, postage prepaid, return receipt requested, and addressed as set forth below, or to such other address as is subsequently specified in writing.

If to NSABP:	With a copy to:
Joan Beyer Goldberg, MPH	Norman Wolmark, M.D.
Chief Executive Officer	Chairman
NSABP Foundation, Inc.	NSABP Foundation, Inc
Nova Tower 2	Nova Tower 2
Two Allegheny Center, Suite 1200	Two Allegheny Center, Suite 1200
Pittsburgh, PA 15212-5234	Pittsburgh, PA 15212-5234
If to Antigen Express:	With a copy to:
Antigen Express, Inc.
33 Redwing Road	Generex Biotechnology Corporation
Wellesley, MA 02481	4145 North Service Road, Suite 200
	Burlington, Ontario, Canada L7L 6A3
	Attention:	Mark Fletcher
		Executive Vice-President & General Counsel

Any change(s) to the list in this Article XIV will be communicated in writing to the other Party, pursuant to the terms of this Article XIV.

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ARTICLE XV

INDEMNIFICATION; INSURANCE; LIMITATIONS OF LIABILITY

15.1 Antigen Express Indemnification. Antigen Express shall defend, indemnify, and hold harmless the NSABP Principal Investigator, NSABP, Participating Sites, and their respective officers, employees, IRBs, contractors, and agents (collectively the “NSABP Indemnitees”), from any and all liabilities, expenses including attorneys' fees, claims, actions, or suits, including (without limitation) those for personal injury or death (the “Claims”):

(a) related to the use of the Antigen Express Study Drug used in accordance with the Study and written instructions/information provided by Antigen Express to NSABP or through NSABP to any third party including participants in connection with the Study;

(b) related to the use of the Antigen Express Study Drug in accordance with the Protocol and/or written instructions/information supplied or distributed to third parties (including the general public) by Antigen Express in connection with the Antigen Express Study Drug;

(c) related to any claimed design defect, manufacturing defect, contamination or adulteration, or failure to warn relating to the Antigen Express Study Drug.

REGARDLESS OF WHETHER THE SAME ARE CAUSED, IN WHOLE OR IN PART, BY THE CONCURRENT NEGILGENCE OF THE INDEMNITEES; PROVIDED, HOWEVER:

(i) that NSABP Indemnitees conduct the Study in accordance with Protocol requirements and written instructions delivered by Antigen Express concerning administration of the Antigen Express Study Drug and the Merck Study Drug and applicable ICH GCP guidelines;

(ii) that such loss does not arise out of, in the case of NSABP, the breach of this Agreement by the NSABP or, in the case of the Participating Site Indemnitees, the negligence or willful malfeasance of any Indemnitees;

(iii) that Antigen Express is promptly notified in writing of any written complaint or claim, or any serious injury relating to any loss subject to this indemnification; and,

(iv) that Antigen Express shall have the right to select defense counsel and to direct the defense or settlement of any such claim or suit. Notwithstanding the foregoing, this Section 15.1(iv) shall apply to state universities or institutions only to the extent allowed under applicable state law.

15.2 Merck Indemnification. Antigen Express represents and warrants that under the terms of the Merck Agreement, Merck has agreed to defend, indemnify and hold harmless Antigen Express, its affiliates, and its and their employees, directors, subcontractors and agents from and against any liability to the extent such liability was directly caused by:

(a) negligence or willful misconduct on the part of Merck (or any of its affiliates, or its and their employees, directors, subcontractors or agents;

(b) a breach on the part of Merck of any of its representations and warranties or any other covenants or obligations of Merck under the Merck Agreement; or

(c)       a breach of Applicable Law by Merck.

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15.3 Antigen Express shall provide diligent defense against or settlement of any Claims, whether such Claims are rightfully or wrongfully brought or filed.

15.4 Any Claim, to the extent found by a court of competent jurisdiction to have resulted from the negligence or willful malfeasance of an Indemnitee, is excluded from the Antigen Express indemnity obligations under this Agreement to such extent. Deviations, defined as single event variations from the terms of Protocol which would not have a significant deleterious effect on the research or on the participant that may arise out of necessity, do not constitute negligence or willful malfeasance or a violation of the requirements of Section 15.1(i) and/or Section 15.1(ii) above.

15.5 The NSABP Indemnitee(s) shall reasonably cooperate with Antigen Express and its legal representatives in the investigation and defense of any Claim covered under this Agreement. In the event a Claim is or may be asserted, NSABP shall have the right to select and to obtain representation by separate legal counsel. Legal counsel selected by NSABP may participate in any settlement negotiations or legal proceedings subject to Article XV, but Indemnitor(s) shall retain the right to direct the settlement or defense of any Claim, subject to the NSABP Indemnitee’s consent and to the extent allowed under state law for Participating Sites that are state universities and institutions, which consent shall not be unreasonably withheld or delayed. If NSABP, or Participating Sites that are state universities and institutions, exercises such right, all costs and expenses incurred by NSABP, or such Participating Sites, for such separate counsel shall be borne by NSABP, or such Participating Site.

15.6 Selected Terms of Agreement for Disclosure to Sites. Attached as Appendix C to this Agreement is a listing of Selected Terms of Agreement for Disclosure to Sites. NSABP may provide a copy of Appendix D to Research Collaborators and/or subcontractors as reasonably deemed necessary or helpful by NSABP in connection with negotiating the terms of agreements with Research Collaborators and/or subcontractors for performance of the Study.

15.7 Antigen Express warrants that it maintains a policy or program of insurance or self-insurance at levels sufficient to support the indemnification obligation assumed herein. Upon request, Antigen Express will provide evidence of its insurance.

15.8 Each of the Participating Sites is responsible for maintaining, at its own expense and throughout the term of this Agreement, insurance as it deems appropriate to protect its liabilities and contractual obligations. However, failure of any Participating Site to have insurance coverage, ability to obtain insurance coverage or any inadequacy of insurance coverage shall not relieve or decrease liabilities, if any, of the Parties or that Participating Site under this Agreement. It is understood that NSABP, including its agents, Participating Sites, and subcontractors, is not responsible for the acts or omissions of Antigen Express. A program of self-insurance will suffice for compliance with this provision.

15.9 NSABP SHALL NOT BE LIABLE BEFORE OR AFTER TERMINATION OF THIS AGREEMENT UNDER ANY CONTRACT, STRICT LIABILITY, NEGLIGENCE, STATUTORY, OR OTHER LEGAL OR EQUITABLE THEORY:

15.9.1 FOR ANY DIRECT, SPECIAL INCIDENTAL, CONSEQUENTIAL, OR OTHER DAMAGES RELATED TO ANY PRODUCT, MATERIAL, EQUIPMENT, DATA, SERVICE, OR OTHER ITEM, IF ANY, PROVIDED HEREUNDER, OR ANY PRODUCT, MATERIAL, EQUIPMENT, SERVICE, OR ITEM, IF ANY, SUPPLIED TO THIRD PARTIES BY ANTIGEN EXPRESS AS A RESULT OF THE RESEARCH CONDUCTED UNDER STUDY; OR

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15.9.2 FOR COST OF PROCUREMENT OF SUBSTITUTE SERVICES OR ANY SPECIAL, INCIDENTAL, OR CONSEQUENTIAL DAMAGES RELATED TO ANY OBLIGATIONS UNDER THIS AGREEMENT.

ARTICLE XVI

HUMAN SUBJECTS

16.1 Informed consent of the Subjects shall be obtained in accordance with 45 CFR Part 46. Related EC/IRB review and approval of Protocol, including the Informed Consent Form, shall be obtained in accordance with 21 CFR Part 56. The patient consent and/or HIPAA authorization form(s) as approved by the EC/IRB shall disclose that documentation may be provided to representatives of Antigen Express, the FDA, or other regulatory agencies and that patient identifying information will be removed prior to submission thereto. Subject to Applicable Law, during audits of the Study at NSABP, Participating Sites, or their designated agents and representatives, Antigen Express shall have the right to review informed consent forms to assure that they conform to Applicable Law.

16.2 If a Subject suffers an adverse reaction, illness, or injury which was directly caused by the Antigen Express Study Drug, Antigen Express will reimburse for the reasonable and necessary costs of diagnosis and treatment of any Subject’s injury, including hospitalization, but only to the extent such expenses are not attributable to (a) the negligence, recklessness, or willful misconduct of a participating Investigator, a Participating Site or its officers, agents, consultants, contractors, or employees; (b) a material failure to follow Protocol not required for medical treatment of a Subject; or (c) the natural progression of an underlying or pre-existing condition or events, unless exacerbated by participating in the Study.

ARTICLE XVII

TERM AND TERMINATION

17.1           This Agreement shall be effective upon the Effective Date and shall continue until the completion of the obligations of this Agreement.

17.2 This Agreement may be terminated by either Party, immediately upon prior written notice to the other Party, if any of the following conditions occur.

17.2.1 Immediately upon written notice to the other Party:

17.2.1.1 if the authorization and approval to perform the Study in the United States is withdrawn by the FDA;

17.2.1.2 if human and/or toxicology test results, in the reasonable opinion of either Antigen Express or NSABP, are of such magnitude and/or frequency of incidence as to support termination of the Study;

17.2.1.3 if the emergence of any adverse reaction or side-effect of any drug administered in the Study or a modification to the Protocol raises safety issues of such magnitude and/or incidence in the reasonable opinion of either Antigen Express or NSABP to support termination of the Study;

20

17.2.1.4 If the manufacture of the Antigen Express Study Drug or Merck Study Drug ceases and/or the supply of the Antigen Express Study Drug or Merck Study Drug has been exhausted.

17.2.2 Either Party shall have the right to terminate this Agreement in the event the other Party remains in material breach of any Section of this Agreement after thirty (30) days to cure any such material breach after its receipt of notice of same in writing from the other Party.

17.3 NSABP shall have the right to terminate this Agreement in the event Antigen Express fails to pay an undisputed amount due to NSABP hereunder within forty-five (45) days after being notified by NSABP that it is in arrears of payments due hereunder; or

17.4 Obligations Upon Termination. If this Agreement is terminated for any reason, the Study shall be discontinued in accordance with the provisions of the Protocol, this Agreement, and in a manner designed to preserve Subject safety and data integrity. Both Parties shall take all reasonable steps to cooperate with the other to wind-down the Study in an efficient, safe, and cost-effective manner. The need for any continued Subject safety monitoring and the appropriate manner to cease conducting Study procedures will be reasonably determined by NSABP in accordance with Applicable Law. In addition, payments will be made to NSABP by Antigen Express for reasonable costs incurred for all NSABP services performed up to the time of termination in accordance with this Agreement, and for any reasonable, non-cancelable expenses related to the Study. Such amounts shall take into account any payments previously made to NSABP hereunder.

17.5 Survival. No expiration or termination of this Agreement will release the Parties from their rights or obligations accrued prior to expiration or the effective date of termination. The rights and duties under (a) Sections 2.6, 4.1, 4.2, 4.3, 4.4, 5.1; (b) Articles VIII, IX, XI, XII, XIII, XV, XVI, XXIV, XXV, and XXVII; and (c) Appendix B will survive the expiration or termination of this Agreement.

ARTICLE XVIII

AMENDMENTS

This Agreement may be extended, renewed, or otherwise amended at any time only by the mutual prior written consent of Parties hereto.

ARTICLE XIX

SEVERABILITY

If any provision(s) of this Agreement is or becomes invalid, is ruled illegal by any court of competent jurisdiction, or is held unenforceable, the unenforceability thereof shall not affect the remainder of this Agreement which shall remain in full force and effect and enforceable in accordance with its terms. Further, it is the intention of the Parties that in lieu of each such provision, which is invalid, illegal, or unenforceable, there shall be a new provision as similar as possible in economic and business objective intended by the Parties for such invalid, illegal, or unenforceable provision, but which substituted provision shall be valid, legal, and enforceable.

21

ARTICLE XX

INTEGRATION

Appendices identified within this Agreement are incorporated in this Agreement by reference.

ARTICLE XXI

ASSIGNMENT

21.1 Neither Party hereto may assign, cede, or otherwise transfer any of its rights or obligations under this Agreement without the prior written consent of the other Party; which consent may not be unreasonably withheld; provided, however, that without such consent either Party may freely assign this Agreement in connection with the transfer or sale of all, or substantially all, of its assets or business, or its merger or consolidation with another company. Notwithstanding the above, either Party may assign this Agreement in whole or in part to any wholly-owned subsidiary or its affiliate without consent of the other Party.

21.2 This Agreement shall inure to the benefit of, and be binding upon, each Party signatory hereto, its successors, and permitted assigns. No assignment shall relieve either Party of the performance of any accrued obligation, which such Party may then have under this Agreement. Any permitted assignee will assume the rights and obligations of its assignor under this Agreement.

ARTICLE XXII

INDEPENDENT CONTRACTOR

The relationship of the Parties to this Agreement is that of independent contractors. Neither Party is authorized or empowered to act as an agent for the other for any purpose save and except as expressly provided for in this Agreement, and shall not on behalf of the other enter into any contract, warranty, or representation as to any matter. Neither Party shall be bound by the acts or conduct of the other, except as provided by the terms of this Agreement.

ARTICLE XXIII

NO TRANSFER OF PROPRIETARY RIGHTS NOT SPECIFIED

It is agreed that neither Antigen Express nor NSABP transfers to the other by operation of this Agreement any patent right, copyright, or other proprietary right of either Party, except to the extent expressly set forth herein.

ARTICLE XXIV

CONFORMANCE WITH LAW AND ACCEPTED PRACTICE

In performing their respective obligations hereunder, the Parties shall comply, as applicable, with generally accepted standards of clinical practice, with the Protocol, and with all Applicable Law governing the performance of clinical investigations as applicable to the Study.

ARTICLE XXV

WAIVER

No waiver of any term, provision, or condition of this Agreement whether by conduct or otherwise in any one or more instances shall be deemed to be or construed as a further or continuing waiver of any such term, provision or condition, or of any other term, provision or condition of this Agreement.

22

ARTICLE XXVI

FORCE MAJEURE

Neither Party shall be liable for any failure to perform as required by this Agreement, to the extent such failure to perform is due to circumstances reasonably beyond either Party's control, such as labor disturbances or labor disputes of any kind, accidents, failure of utilities, mechanical breakdowns, material shortages, hurricanes, tornadoes, blizzards, electrical outages, disease, or other such occurrences.

ARTICLE XXVII

DEBARMENT

NSABP certifies that as of the Effective Date, neither NSABP nor any person engaged or employed thereby directly in the performance of or providing services for the Study is (i) currently debarred under Section 306(a) or (b) of the Federal Food, Drug and Cosmetic Act; or (ii) disqualified. NSABP shall obligate its Research Collaborators to certify that (i) none of its Investigators or Participating Sites, nor any of their respective Study Personnel, are currently debarred; or disqualified; and (ii) will notify NSABP immediately of any such occurrence. If at any time after execution of this Agreement, NSABP becomes aware of any such debarment or disqualification, NSABP hereby certifies that NSABP will promptly notify Antigen Express.

ARTICLE XXVIII

GOVERNING LAW

This Agreement and the rights and obligations of the Parties hereunder shall be governed by and construed under the laws of the Commonwealth of Pennsylvania without reference to principles of conflicts of laws. The Parties hereby agree that any and all disputes or controversies arising out of or related to this Agreement shall be subject to venue and jurisdiction in the state and federal courts situated in Pittsburgh, Allegheny County, Pennsylvania. Notwithstanding the foregoing, this Article XXIX shall not apply to Participating Sites that are state universities or institutions, and contracts with such Research Collaborators will be silent on choice of law.

ARTICLE XXX

ENTIRE AGREEMENT

This Agreement and the Appendices hereto, represent the entire understanding and agreement of the Parties with respect to the subject matter herein, and supersedes all prior discussions, agreements, and understanding entered into orally or otherwise between the Parties in connection with the subject matter herein. Each Party confirms that it is not relying on any representations or warranties of any other Party except as specifically set forth in this Agreement. To the extent of any conflict or inconsistency between the terms of this Agreement, Appendices or the Protocol, the terms of this Agreement will control, except that the terms of the Protocol will nonetheless control with respect to scientific and medical issues in connection with any such conflict or inconsistency. This Agreement may only be modified by a writing duly executed by both Parties.

ARTICLE XXXI

COUNTERPARTS

This Agreement and any amendments may be executed in any number of counterparts, each of which shall be an original and all of which together shall constitute one and the same document, binding on all Parties notwithstanding that each of the Parties may have signed different counterparts. Facsimiles or scanned copies of signatures or electronic images of signatures shall be considered original signatures unless prohibited by Applicable Law.

[The remainder of this page intentionally left blank.]

23

BINDING EXECUTION

IN WITNESS WHEREOF, the Parties hereto have executed this Agreement in duplicate by the proper persons thereunto duly authorized.

NSABP FOUNDATION, INC. ANTIGEN EXPRESS, INC.

By:	By:
Joan Beyer Goldberg, MPH
Printed Name	Printed Name
Chief Executive Officer
Title	Title
Date	Date

24

Appendix A

PROTOCOL

A Phase II Clinical Trial of Pembrolizumab in Combination with the AE37 Peptide Vaccine in Patients with Metastatic Triple Negative Breast Cancer (FB-14)

[Appendix A is set out on the following pages]

A-1

Appendix B

BUDGET, PAYMENT SCHEDULE, AND TASK LIST

1. Antigen Express agrees to pay NSABP an amount not to exceed $2,118,461 as set forth in this Appendix B to perform the work under the terms of this Agreement. Such payments assumes (a) an actual enrollment of twenty-nine (29) evaluable patients, (b) five (5) sites, (c) twelve (12) months accrual, (d) six (6) months average treatment, and (d) at least one (1) patient receives treatment for 24 months.

2. Antigen Express will make payments to NSABP in the increments and at the times indicated on the Payment Schedule in this Appendix B. Payments to NSABP shall be made in four phases as follows – Start-Up Activities, Accrual and Treatment Period, Follow-Up Period and Primary Endpoint. Antigen Express shall pay NSABP invoices not later than thirty (30) days after receipt of an invoice.

3. Start-Up Activities – $340,000 – Within thirty days after receipt of a fully executed Agreement, Antigen Express will make an initial payment (“Initial Payment”) to NSABP in the amount of $340,000. The Initial Payment shall become nonrefundable upon execution of this Agreement to the extent it has been expended for costs actually reasonably incurred or committed pursuant to this Agreement. The Initial Payment supports: pre-study activities, site start-up costs, drug distributor, central lab, and database start-up costs, and other initiation and administration functions, and protocol education and awareness building.

4. Accrual and Treatment Period – $1,458,461 – Antigen Express will pay NSABP $1,458,461 during the Accrual and Treatment Period commencing with the enrollment of the first (1) Subject randomized to FB-14 and in increments as indicated on the Payment Schedule contained in this Appendix B. These payments support the costs of regulatory, administrative, and other services as anticipated in the performance of FB-14. In addition, payments include support for activities performed and costs incurred at Participating Sites, such as: patient screening, eligibility assessment and recruitment activities, patient instruction, incidental supplies and materials, tissue acquisition and storage, other unfunded costs related to the study, and the cost of patient care procedures that are considered non-routine care.

5. Follow-Up Period - $240,000 – Antigen Express shall pay an amount up to $240,000 in three (3) annual payments of $80,000 each. Invoices for annual payments will be submitted at the beginning of the calendar years for which the payments are related.

6. Primary Endpoint - $80,000 – Antigen Express will make a final payment of $80,000 upon completion of the primary endpoint analysis and submission of the primary endpoint manuscript to Antigen Express.

7. Antigen Express shall not be obligated to make any payments to NSABP in excess of the amounts provided herein, unless such excess amounts have been agreed upon in advance and in writing by NSABP and Antigen Express.

8. In the event Antigen Express disputes any portion of an invoice, Antigen Express shall pay NSABP the undisputed amount of the invoice within thirty (30) days after Antigen Express' receipt of the invoice and notify NSABP in writing within fifteen (15) days after Antigen Express' receipt of the invoice of the amount of the invoice that is disputed and the reason for the dispute, after which each of Antigen Express and NSABP shall endeavor to resolve the disputed portion of the invoice.

B-1

9. If, for any reason, FB-14 is terminated, or FB-14 is closed to accrual prior to completion, or FB-14 is not completed with final analysis, in accordance with Article XVIII herein, Antigen Express agrees to pay NSABP for services rendered and commitments for services rendered through the termination date. Payment of the outstanding amount due determined by the final accounting analysis and will be made by Antigen Express after Antigen Express has received a final report and accounting for the FB-14 and all queries are resolved.

10. NSABP shall invoice Antigen Express referring to this Agreement and any appropriate invoice number provided by Antigen Express. Invoices shall be payable by Antigen Express forty-five (45) days from Antigen Express’s receipt of invoice.

Generex Biotechnology Corporation

4145 North Service Road, Suite 200

Burlington, Ontario, Canada L7L 6A3

Attention: Mark Fletcher, Executive Vice-President & General Counsel

mfletcher@generex.com

416-364-2551, ext 235

11. Checks shall be made payable to “NSABP Foundation, Inc.”, (Tax Identification Number 25-1781357) and sent to:

Accounts Receivables

NSABP Foundation, Inc.

Nova Tower 2

Two Allegheny Center, Suite 1200

Pittsburgh, PA 15212

B-2

B-3

Appendix B

FB-14

Task List

Compound:	Pembrolizumab and AE37 Peptide Vaccine  (collectively, "Study Drugs")
Protocol:	FB-14
SOP Accountability:	NSABP
IND Holder:	Antigen Express
Version Date:	02/06/2018

Key: E = Execute; R = Review; S = Support A = Approve; AC = Accept	Antigen express	NSABP	merck
1.       Protocol Preparation
Approve / Accept final Study proposal	AC	E	AC
Write draft Protocol (consultants, literature review, background research)		E
Review draft Protocol	R		R
Write final Protocol	A	E	AC
Write Protocol amendments	A	E	AC
Provide copies of Protocol		E
2.       Informed Consent Document Preparation
Prepare informed consent template		E
Assist sites with informed consent modification(s)		E
Prepare and review translations		E
3.       eCRF Development & eCRF Completion Guide
Design eCRF		E
Write eCRF Completion Guidelines		E
eCRF Distribution		E
4.       Design Systems Required for Data Management
IT Set-Up, System Administration and Maintenance		E
5.       Design & Implement Patient Registration
Develop registration mechanism		E
6.       Database Design & Implementation
Design clinical database		E
Programming and mapping of SAS datasets		E
7.       Distribution of Study Documents
Distribute Protocol to Sites		E
Distribute amendments to Sites		E
Distribution of IB to NSABP	E		E
Distribution of IB to Sites		E
8.       Site Qualifications
Develop list of Sites for qualification	R, A	E
Site qualification		E
Site selection	R, A	E
9.       Investigator Site Contracts & Budgets
Negotiate and finalize Site-specific CDAs		E
Negotiate and finalize Site-specific Study Agreements		E
10.   Site Regulatory Documents
Collect the following regulatory documents for Sites:
Ø  FDA Form 1572		E
Ø  CVs for Investigators and Subinvestigators		E
Ø  Medical licenses for Investigators and Subinvestigators		E
Ø  Financial Disclosure for Investigators and Subinvestigators		E
Ø  Protocol Signature Page signed by Investigator		E
Ø  IB Acknowledgement Page signed by Investigator		E
Ø  IRB-approved Institution Informed Consent Form		E
Ø  IRB approval documents		E
Ø  OHRP IRB registration		E
11.   Agency Regulatory Documents
IND-related filings with the FDA	S/A	E	S
clinicaltrials.gov registration		E
12.   Study Initiation Visits (SIV)
Plan, organize, manage webcast SIV		E
Record and post SIV content		E
Present Science / Protocol / Safety Profile		E
Present regulatory topics		E
Present AE / SAE reporting		E
Present monitoring information		E
Present eCRFs		E
Present Biologic Repository lab procedures / information	E	E	E
Present Study Drugs Ordering Process to Sites		E
13.   Site Monitoring
Develop and Implement monitoring plan		E
Conduct monitoring (Source document verification, drug accountability, regulatory document review, eCRF review, supply inventory, etc.)		E
Identify and report non-compliance		E
Provide written monitoring reports		E
Conduct Site close-out procedure (final source document verification, drug accountability, regulatory document review, eCRF review, study supply disposition, etc.)		E
14.   Quality Control & Quality Assurance Audits
Develop Protocol-specific Audit Plan		E
Perform QC review of Study Data and TMF		E
Perform QA audits according to Audit Plan		E
Perform audits of vendors		E
15.   Operational Issues
Provide on-going Site support		E
16.   Serious Adverse Event Management
Receive SAE report from Sites and review		E
Write Protocol-specific SAE Reporting Work Instruction		E
Maintain a tracking log of all SAE reports from Sites		E
Write SAE Narrative		E
SAE follow-up and resolution		E
SAE reporting to FDA	R/A	E
SAE reporting to Antigen Express/Merck (as applicable)		E
Distribution of IND Safety Reports (expedited reports) to Investigators		E
SAE reconciliation		E
Global SUSARS reporting	S	E	S
17.   Sample Management
Tumor Samples		E
Blood Samples		E
18.   Project Management
Process and provide payments to Sites		E
Organize and participate in periodic conference calls with Antigen Express/Merck (agenda, logistics, etc.)	S	E	S
Prepare meeting and conference call minutes following meeting/call completion and distribute to project team		E
Manage project management issues		E
19.   Management of Study Kits
Supply Study Kits		E
Process Study Kit orders and reorders		E
Distribute Study Kits to Sites		E
Coordinate post-Study disposition of Study Kits		E
Manage general Study Kit issues		E
20.   Management of Study Drugs
Manufacture of the Study Drugs	E		E
Labeling (investigational use)	E (both study drugs)		E
Distribute to the designated NSABP drug distributor	E
Receipt of the Study Drugs from the manufacturer		E
Process Site Study orders and reorders		E
Coordinate post-Study disposition of Study Drugs		E
Provide post-Study accountability of Study Drugs		E
Manage general Study Drugs issues		E
21.   Data Management
Write data validation plan		E
Write data management plan		E
Write statistical analysis plan	R	E
Provide Electronic Data Capture System		E
Validate EDC System		E
Resolve queries		E
Perform QC review of eCRFs		E
Code terms		E
Approve coding		E
22.   Tables, Listings & Figurines
Define safety listings and tables		E
Define efficacy listings and tables		E
Produce safety listings and tables		E
Produce efficacy listings and tables		E
Validate safety listings and tables		E
Validate efficacy listings and tables		E
23.   Study Reports
Provide final statistical report	R/AC	E
Prepare primary publication	R	E
Prepare subsequent publications / abstracts	R	E

B-4

Appendix C

NSABP’s Ownership of Data and Materials Ownership Policy

[Appendix C is set out on the following pages]

C-1

Appendix D

SELECTED TERMS OF AGREEMENT FOR DISCLOSURE TO SITES

Indemnification

This is to confirm that Antigen Express and NSABP have agreed to the following for the FB-14 trial:

1. Antigen Express (Indemnitor) shall defend, indemnify, and hold harmless the NSABP Principal Investigator, NSABP, Participating Sites, and their respective officers, employees, IRBs, contractors, and agents (collectively the “NSABP Indemnitees”), from any and all liabilities, expenses including attorneys' fees, claims, actions, or suits, including (without limitation) those for personal injury or death (the “Claims”):

(a) related to the use of the Antigen Express Study Drug used in accordance with the Study and written instructions/information provided by Antigen Express to NSABP or through NSABP to any third party including participants in connection with the Study;

(b) related to the use of the Antigen Express Study Drug in accordance with the Protocol and/or written instructions/information supplied or distributed to third parties (including the general public) by Antigen Express in connection with the Antigen Express Study Drug;

(c) related to any claimed design defect, manufacturing defect, contamination or adulteration, or failure to warn relating to the Antigen Express Study Drug.

REGARDLESS OF WHETHER THE SAME ARE CAUSED, IN WHOLE OR IN PART, BY THE CONCURRENT NEGILGENCE OF THE INDEMNITEES; PROVIDED, HOWEVER:

(i) that NSABP Indemnitees conduct the Study in accordance with Protocol requirements and written instructions delivered by Antigen Express concerning administration of the Antigen Express Study Drug and applicable ICH GCP guidelines;

(ii) that such loss does not arise out of, in the case of NSABP, the breach of the Clinical Trial Agreement by NSABP or, in the case of the Participating Site Indemnitees, the negligence or willful malfeasance of any Indemnitees;

(iii) that Antigen Express is promptly notified in writing of any written complaint or claim, or any serious injury relating to any loss subject to this indemnification; and,

(iv) that Antigen Express shall have the right to select defense counsel and to direct the defense or settlement of any such claim or suit. Notwithstanding the foregoing, this Section 15.1(iv) shall apply to state universities or institutions only to the extent allowed under applicable state law.

D-1

2. Antigen Express represents and warrants that under the terms of the agreement between Merck and Antigen Express, Merck ("Indemnitor") has agreed to defend, indemnify and hold harmless Antigen Express, its affiliates, and its and their employees, directors, subcontractors and agents from and against any liability to the extent such liability was directly caused by:

(a) negligence or willful misconduct on the part of Merck (or any of its affiliates, or its and their employees, directors, subcontractors or agents;

(b) a breach on the part of Merck of any of its representations and warranties or any other covenants or obligations of Merck under this Agreement; or

(c) a breach of Applicable Law by Merck.

3. Indemnitor(s) shall provide diligent defense against or settlement of any Claims, whether such Claims are rightfully or wrongfully brought or filed.

3. Any Claim, to the extent found by a court of competent jurisdiction to have resulted from the negligence or willful malfeasance of an Indemnitee, is excluded from the Indemnitor(s)' indemnity obligations under this Agreement to such extent. Deviations, defined as single event variations from the terms of Protocol which would not have a significant deleterious effect on the research or on the participant that may arise out of necessity, do not constitute negligence or willful malfeasance or a violation of the requirements of Section 15.1(i) and/or Section 15.1(ii) above.

4. The NSABP Indemnitee(s) shall reasonably cooperate with Indemnitor(s) and its legal representatives in the investigation and defense of any Claim covered under this Agreement. In the event a Claim is or may be asserted, NSABP shall have the right to select and to obtain representation by separate legal counsel. Legal counsel selected by NSABP may participate in any settlement negotiations or legal proceedings subject to Article XV, but Antigen Express shall retain the right to direct the settlement or defense of any Claim, subject to the NSABP Indemnitee’s consent and to the extent allowed under state law for Participating Sites that are state universities and institutions, which consent shall not be unreasonably withheld or delayed. If NSABP, or Participating Sites that are state universities and institutions, exercises such right, all costs and expenses incurred by NSABP, or such Participating Sites, for such separate counsel shall be borne by NSABP, or such Participating Site.

Antigen Express, Inc.:

__________________________________

Name

__________________________________

Title

__________________________________

Signature

D-2

EX-10.3

LICENSE AND RESEARCH AGREEMENT

BETWEEN 

ANTIGEN EXPRESS, INC.

(A WHOLLY-OWNED SUBSIDIARY OF

GENEREX BIOTECHNOLOGY CORPORATION)

AND

SHENZHEN BIOSCIEN PHARMACEUTICALS CO. LTD.

November 29th, 2017

1

TABLE OF CONTENTS

 

2

3

 

4

LICENSE AND RESEARCH AGREEMENT

This License and Research Agreement (the "Agreement"), effective as of the day of November, 2017 (the "Effective Date"), is by and between Antigen Express, Inc., a wholly-owned subsidiary of Generex Biotechnology Corporation, a Delaware corporation, with an address of 4145 North Service Road, Suite 200, Burlington, Ontario, Canada L7L 6A3 (hereinafter referred as "Licensor"), and Shenzhen BioScien Pharmaceuticals Co., Ltd., located at Room 311, First Building, Shenzhen Overseas Venture Park (Longgang), Shenzhen 518116, Guangdong, China (hereinafter referred to as "Licensee"). Licensor and Licensee may each be referred to herein individually as a "Party" and collectively

RECITALS

WHEREAS, Licensor is a publicly-traded biotechnology company (OTCPink:GNBT) managed by an executive management team and governed by the Board of Directors (the

“Board”);

WHEREAS, the executive management team is responsible for all matters relating to patent administration and technology transfer applicable to Licensor, and is expressly authorized to negotiate and execute this Agreement;

WHEREAS, Licensor is (or in the future, may be) the owner of certain patent rights, other intellectual property rights, know-how and other proprietary rights in the Territory relating to Licensed Compounds and/or Research Information (as each of these capitalized terms is defined herein);

WHEREAS, Licensor desires to grant to Licensee an exclusive license in the Field (as defined below) in the Territory (as defined below) related to the Licensed Compounds and Research Information;

WHEREAS, Licensee desires to research and develop Licensed Compounds, Research Information and Licensed Products, and to commercialize Licensed Products, in the Field in the Territory;

WHEREAS, Licensor and Licensee wish to enter into this Agreement to enable Licensee to further develop and commercialize Licensed Products that incorporate or use one or more compounds within the Licensed Compounds and/or the Research Information, and to enable Licensee to use and exploit in the Field in the Territory any information, technology or intellectual property that relates to Licensed Compounds or Research Information, or that covers Research Inventions.

NOW THEREFORE, in consideration of the premises and mutual covenants set forth below and other good and valuable consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties hereby agree as follows:

1. DEFINITIONS

For the purposes of this Agreement, except as otherwise expressly provided herein or unless the context otherwise requires: (a) references to "Articles," "Sections" and other subdivisions, and to "Exhibits," shall refer to articles, sections, subdivisions and exhibits of this Agreement, unless specified to be referring to another agreement between the Parties; (b) the use of the term "including" shall mean "including without limitation"; (c) the words "herein," "hereof," "hereunder" and other words of similar import refer to this Agreement as a whole, and not to any particular provision; (d) the use of the phrase "by Licensor," "by Licensee" or "by a Party" shall mean "by such Party (and/or on behalf of such Party)"; and (e) the following initially capitalized terms in this Agreement, whether used in the singular or plural, shall have the following meanings:

1.1 Affiliate

Any Person that directly, or indirectly through one or more intermediaries, controls, is controlled by, or is under common control with the designated Party, but only for so long as such relationship exists. For the purposes of this definition, "control" means (a) in the case of corporate entities, ownership of fifty percent (50%) or more of the outstanding shares of stock entitled to vote for directors of such corporation, or (b) in the case of non-corporate entities, direct or indirect ownership of fifty percent (50%) or more of the equity interest with the power to direct the management and policies of such non-corporate entities, or (c) the possession, directly or indirectly, of such other power to direct or cause the direction of the management and policies of any Person, whether through the ownership of voting securities, by contract, or otherwise.

1.3 Approved Sale

The sale of a Licensed Product for human pharmaceutical use in the Territorys.

1.4 AE37

Peptide name: AE37 (li-Key/HER2/neu776-790)

Trade name: AE37

Appearance: White lyophilized powder 91'1

Peptide sequence: AC-LRMKGVGSPYVSRLLGICL-NH2

Molecular Weight: 1052.6 daltons

Peptide counter ion: Acetate

AE37 means the hybrid HER2/neu peptide AE37 (li-Key/HER2/neu776-790), a fifteen amino-acid peptide to which the four amino-acid sequence LRMK has been added and it is produced by solid-phase peptide synthesis. The AE37 peptide is manufactured, purified by High Performance Liquid Chromatography (HPLC), and lyophilized in an acetic acid and acetonitrile solution. The drug substance is stored as a lyophilized powder as per Good Manufacturing Practices (GMP) including in-process, drug substance and finished drug substance testing of AE37; testing includes appearance, purity by HPLC and mass spectral analysis, identification by amino acid content and sequence, and quality by bioburden, sterility USP and endotoxin. The peptide is purified to ¥95 0,/0 purity. Residual organic volatiles, counter ion content, water content and non-peptide content (by AA) are also routinely determined. The drug substance is lyophilized and frozen at -20 oc and the bulk drug substance is provided as per clinical protocol requirements.

Manufacturer (Drug Substance and Drug Product) of AE37 AE37

PolyPeptide Laboratories San Diego

9395 Cabot Drive

San Diego, CA 92126 USA

1.5 Change of Control

With respect to a Party, a "Change of Control" of such Party shall mean (a) a sale or conveyance of all or substantially all of the assets of such Party to which this Agreement relates; (b) a consolidation, merger or reorganization of such Party with or into any other company, limited liability company or other entity (other than a wholly-owned subsidiary of such Party) or other transaction or series of transactions in which the stockholders of such Party immediately prior to the transaction fail to own fifty percent (50%) or more of the voting stock of the surviving company following the transaction (taking into account only stock of the company held by such stockholders prior to the transaction); or (c) an acquisition of shares from such Party or an Affiliate or from the stockholders of such Party or an Affiliate immediately prior to such acquisition as a result of which a third party or group of third parties acquires control, directly or indirectly, of fifty percent (50%) or more of the voting stock of such Party following such acquisition.

1.6 China

The People's Republic of China (PRC), including the Hong Kong Special Administrative Region of the PRC, Taiwan and the Macau Special Administrative Region of the PRC.

1.7 Collaboration

Two or more affiliates (including Licensor and Licensee) work together to realize or achieve the drug development and commercialization successfully. For example, the collaboration will be established with a major pharmaceutical company to perform the combination therapeutic clinical trials.

1.8 Combination Therapy

Two or more medications combined and used to treat one disease. For example, AE37 combined with a checkpoint inhibitor for the treatment of prostate cancer.

1.9 Confidential Information

Any and all non-public information that is disclosed by a Party (the "Disclosing Party") to the other Party (the "Receiving Party") is in connection with this Agreement. For the sake of clarity, the Parties acknowledge that a Disclosing Party may or may not be the c».mer of such disclosed information (for example, if one Party discloses to the other Party any Confidential Information that is jointly owned hereunder, such disclosure does not render such Confidential Information solely owned by the Disclosing Party, but such information remains Confidential Information). Disclosures by a Party's Affiliate shall be deemed disclosures by that Party, and disclosures to a Party's Affiliate shall be deemed disclosures to that Party. Notwithstanding the foregoing, Confidential Information shall not include any part of such information that:

1.9.1 Was already known to the Receiving Party without access to or use of Confidential Information of the Disclosing Party, as evidenced by the Receiving Party's written records;

1.9.2 Was generally available to the public or was otherwise part of the public domain at the time of disclosure hereunder to the Receiving Party;

1.9.3 Became generally available to the public or otherwise becomes part of the public domain after disclosure hereunder to the Receiving Party, and other than through any act or omission of the Receiving Party in breach of this Agreement;

1.9.4 Was subsequently lawfully disclosed to the Receiving Party by a third party on a non-confidential basis, other than in breach of a confidentiality obligation of such third party to the Disclosing Party or any other third party; or

1.9.5 Was developed or discovered by the Receiving Party or its Affiliates without access to or use of Confidential Information of the Disclosing Party, as evidenced by the written records or communications of either Party.

1.10 Control(s) or Controlled

With respect to any (a) item of information, including Research Information and Technical Information, or (b) intellectual property right, the possession (whether by ownership, license or otherwise, but other than pursuant to this Agreement) by a Party of the lawful and contractual ability to disclose to the other Party, or to grant to the other Party access and/or a license to or under, such item of information or intellectual property right within the scope of this Agreement, without the obligation to pay' royalties or other consideration to any third party.

1.11 Dollars

United States Dollars, or the lawful currency of the United States of America.

1.12 Field

The Field is restricted to preventative, palliative and other therapeutic uses and applications of the Licensed Compound, the Research Information, and the Licensed Product for the immunotherapeutic treatment of prostate cancer.

1.13 Government Authorization

Any consent, license, registration or permit issued, granted, given or otherwise made available by or under the authority of any Governmental Body or pursuant to any law, regulation, or ordinance.

1.14 Governmental Body

1.14.1 nation, state, county, city, town, borough, village, district or other jurisdiction;

1.14.2 federal, state, local, municipal, foreign or other government;

1.14.3 governmental or quasi-governmental authority of any nature (including any agency, branch, department, board, commission, court, tribunal or other entity exercising governmental or quasi-governmental powers);

1.14.4 multi-national organization or body

1.14.5 body exercising, or entitled or purporting to exercise, any administrative, executive, judicial, legislative, police, regulatory or taxing authority or power; or

1.14.6 official of any of the foregoing

1.16 Licensed Compounds

AE37 and all its associated compounds in the patent, as immunotherapy for prostate cancer, that are owned or controlled by Licensor.

1.17 Licensed Know-How

Any and all know-how, trade secret or other intellectual property rights (including rights in Research Information and Technical Information, but excluding Licensed Patent Rights and other rights to patents or patent applications) owned or Controlled by Licensor, as of the Effective Date or at any time during the term of this Agreement, and relating to the use and/or exploitation of Licensed Compounds, Research Information and/or Licensed Products in the Field; provided that the term "Licensed Know-How" shall expressly exclude: a) know-how, trade secret and other intellectual property rights related to any active pharmaceutical ingredient in a Combination Product that is not itself a Licensed Product; b) know-how, trade secret and other intellectual property rights related to AE37 that are outside the Field.

1.18 Licensed Patent Rights

(a) Any and all patents and pro、'isional and non-provisional patent applications set forth in Exhibit A attached hereto; and (b) any and all other patents and patent applications owned or Controlled by Licensor anywhere in the Territory, as Ofthe Effective Date or at any time during the term Of this Agreement, containing one or more Claims to, or otherwise covenng, any Licensed Compound or Research Information; including any and all renewals, divisions, continuations and continuations-in-part Of any Of the foregoing，any and all patents issumg thereon, and any reissues, reexamination, extensions, substitutions, confirmations, registrations, revalidations, revisions and additions Of or to such patents, and any and all foreign counterparts anywhere in the TetTitory Of any Of the foregoing.

1.19 Licensed Product

Any formulations Of a final Drug Product, as defined by the U•S• FDA, Of AE37 immunotherapy for prostate cancer that is manufactured under standards established by Regulatory Authorities for commercialsale in the Territory in the Field.

1.20 NDA

New Drug Application filed with the Food and Drug Administration Of the United States or any successor agency thereto (“FDA") and the Chinese Food and Drug Administration (“CFDA').

1.21 Net sales

With respect to a Licensed product, the aggregate gross invoice prices charged for sales Of such Licensed Product to third parties by Licensee and its Affiliates and Sub-licensees after deducting, if not previously deducted from the amount invoiced or received for sales Of Licensed Products:

1.21.1 reasonable and customary trade, quantity, and cash discounts actually given, as well as discounts, rebates or governmentally mandated payments, to the extent actually allowed and taken;

1.21.2 returns, rebates, chargebacks and other allowances actually given; iß*h,

1.21.3 retroactive price reductions that are actually granted;

1.21.4 to the extent separately stated on the relevant invoices, actual transportation and insurance costs incidental to sales of Licensed Products; and

1.21.5 taxes, tariffs, customs duties and surcharges and other governmental charges (other than income taxes) incurred in connection with the sale, exportation, or importation of Licensed Products.

In the event that a Licensed Product is sold in the form of a combination product containing one or more active pharmaceutical ingredients which are themselves not Licensed Products (a "Combination Product"), the Net Sales attributable to the Licensed Product portion of such Combination Product, for the purposes of determining royalty payments hereunder, shall be determined by multiplying the Net Sales of the Combination Product, during the applicable Royalty Reporting Period, by the fraction A/(A+B), where A is the average sales price of the Licensed Product when sold separately in finished form, and B is the sum of the average sales prices of each of the other active pharmaceutical ingredients included in the Combination Product when sold separately in finished form, in each case during the applicable Royalty Reporting Period or, if sales of both the Licensed Product and the other active pharmaceutical ingredients included in the Combination Product did not occur in such period, then in the most recent Royalty Reporting Period in which sales of both occurred. In the event that such average sales price cannot be determined for both the Licensed Product and all other active pharmaceutical ingredients included in the Combination Product, Net Sales attributable to the Licensed Product portion of such Combination Product for the purposes of determining royalty payments hereunder shall be calculated by multiplying the Net Sales of the Combination Product by the fraction C/(C+D), where C is the fully absorbed cost of the Licensed Product (exclusive of royalties, milestone payments or similar costs and payments to a third party(ies)), and D is the sum of the fully absorbed cost of each other active pharmaceutical ingredient(s)included in the Combination Product (which fully absorbed cost of the other active pharmaceutical ingredient(s) included in the Combination Product shall exclude any royalties, milestone payments, and similar costs and payments to a third party(ies)).

Sales Of Licensed Product among Licensee, its Affiliates and Sub-licensees for resale by Licensee, its Affiliate(s) or Sub-licensee(s) shall not be considered a sale of Licensed product, but the resale by Licensee or such Affiliate(s) or Sub-licensee(s) to a third party shall be a sale of Licensed Product.

Licensee shall have the right to distribute or make available commercially reasonable quantities Of Licensed Products free of charge for use in clinical studies, for charitable purposes, and for use as commercial samples.

1.22 Non-Affiliate Acquirer

Any Person that is not an Affiliate of Licensee and that no officer, director or stockholder of Licensee or group thereof Controls (where "Control" is defined as in the definition of "Affiliate' except that the relevant percentage shall be five percent（5％）instead of percent（50％).

1.23 Person

An individual, partnership, corporation, business trust, limited liability company, limited liability partnership, joint stock company, trust, unincorporated association, joint、venture or other entity or a Governmental Body.

1.24 Phase I Clinical Study 第 I 期临床研宄

A controlled clinical study in humans of a Licensed Product that is conducted in accordance with FDA guidelines for conduct ofa Phase I clinical study to evaluate the safety (dose range) of the Licensed Product, and to determine the dose range of the Licensed Product, which clinical study is typically well controlled and closely monitored and intended to obtain statistical significance.

1.25 Phase II Clinical Study

A controlled clinical study in humans of a Licensed Product that is conducted in accordance with FDA guidelines for conduct of a Phase Il clinical study to evaluate the effectiveness of the Licensed Product for a particular indication or indications in patients with the disease or condition under study, and to determine the common short-term side effects and risks associated with the Licensed Product, which clinical study is typically well controlled and closely monitored and intended to obtain statistical significance.

1.26 Phase II Clinical Study

An expanded controlled and/or uncontrolled clinical study in humans of a Licensed Product that is performed after preliminary evidence from Phase Il studies suggesting effectiveness of the Licensed Product has been obtained, which study is intended to gather additional information about Licensed Product effectiveness and safety that is needed to evaluate the overall benefit-risk relationship of the Licensed Product, and to provide an adequate basis for physician labeling. Phase Ill Clinical Studies are used to support an application for Regulatory Approval submitted to a Regulatory Authority in the Territory.

1.27 Regulatory Approval

The approval or authorization (including the approval of an NDA, where applicable) by any Regulatory Authority in the Territory that is necessary for the import, manufacturing, distribution, marketing, promotion, and sale of Licensed Product(s) in the Territory.

1.28 Regulatory Authority

China Food and Drug Administration (CFDA).

1.29 Research Inormation

All information developed or generated by Licensor in respect of the Licensed Compounds, including Research Inventions, technical information and data, pre-clinical and clinical information and data, process and product information, formulas, formulations, compositions, materials (including biological and chemical materials), devices, research information and data, manufacturing information and data, computer programs, test results, business plans, accounting records, research and development reports, supplier information, marketing and sales information, other business and financial information, trade secrets and know-how, and any record of the above, including writings, computer records and programs, photographic films, drawings, illustrations, pictures, video recordings, audio recordings, models and samples.

1.30 Research Inventions

Any inventions or improvements (whether or not patentable) conceived, reduced to practice, made, developed or generated by Licensor others working under Licensor's direction or control.

1.31 Sub-license Agreement

An agreement between Licensee and a Sub-licensee that complies with the provisions and requirements of Section 3.3 below.

1.32 Sub-licensee

Any Person to which Licensee shall have granted a sublicense of the rights granted to Licensee by Licensor hereunder.

1.33 Technical Information

All information (including all Confidential Information of Licensor, data, materials, devices, research reagents and results, formulas, drawings, samples, processes, designs, submitted manuscripts, draft manuscripts, information contained in laboratory notebooks and records, process information, clinical protocols and results, and other information and know-how) pertaining to the isolation, identification, synthesis, manufacture or use of a Licensed Compound, a Research Invention and/or a Licensed Product (but expressly excluding information related to any active pharmaceutical ingredient in a Combination Product that is not itself a Licensed Product) in the Field (a) that is owned or Controlled by Licensor as of the Effective Date; or (b) that Licensor comes to own or Control at any time during the term of this Agreeme0nt independent from, and not in connection with or in the course of performing under, this Agreement. The term "Technical Information" shall expressly exclude Research Information.

1.34 Territory

China (including mainland, Taiwan, Hong Kong and Macau.

1.35 Additional Definitions

Defined Term	Section in which Defined
Antigen Express	Preamble
Agreement	Preamble
CDA	5.1
Combination product	1.23.5
Board	Recitals
Common Stock
Competitive Product	4.2.4(a)
Disclosing Party	1.9
Effective Date	Preamble
FDA	1.22
Heads	14.10.2
Licensee	Preamble
Licensee Indemnitee	10.2
Licensor	Preamble
Licensor Indemnitee	10.1
Losses	10.1
Note
Panel	14.10.3
Party/Parties	Preamble
Proposed Public Disclosure	5.6
Purchase Agreement	Recitals
Receiving Party	1.9
Research Term
Royalty Reporting Period	4.2.6
Securities
Shortfall Payment	3.4
Third-Party Claim	7.3

2. RIGHTS AND RESPONSIBILITIES

2.1 Licensee

The Licensee and its Sub-licensee have the same rights that are granted by the Licensor described in this Agreement in performing the research, development, production of the Licensed Compounds for product, product commercialization and distribution in the Field in the Territory. In order to accelerate the process of drug development, the Licensee and its Sub-licensee can chose the best suitable country or area outside of the Territory to conduct the clinical trials including establishment of global multi-center clinic trial. The Licensee will provide 100% of the funding to support the clinical development and commercialization of Licensed Compounds, alone and in combination therapy, in the Territory, including, without limitation, funding of the Phase I Clinical Study, the Phase Il Clinical Study and the Phase Ill Clinical Study for the treatment of prostate cancer, which will be conducted in compliance with ICH guidelines. The Licensee is responsible for obtaining the Regulatory Approval from the Chinese Food and Drug Administration ("CFDA") for the Licensed Compounds as monotherapy and/or combination therapy for the immunotherapeutic treatment of prostate cancer in the Territory. The Licensee agrees to provide 100% of the funding required to manufacture, market, sell, and distribute the Licensed Compounds for the Field in the Territory. The Licensee has the right to file New Drug Applications (NDA) and to file Marketing Authorization Applications (MAA) with the CFDA and has the right to produce the product in the Territory.

2.2 Licensor

Subject to compliance by the Licensee with its funding and other obligations under this Agreement, the Licensor shall support the research, development and commercialization of the Licensed Compounds to be performed by Licensee in the Territory. The support from the Licensor includes, but is not limited to, sharing study data and information and providing various consulting, operational and management strategies. The Licensor shall ensure compliance by Antigen Express, Inc. with its obligations under the Clinical Trial Collaboration and Supply Agreement with Merck Sharp & Dohme B.V. dated June 28, 2017 in respect of a combination therapy (AE37+check point inhibitor) for breast cancer.

The Licensor will provide the Licensee with all documentations, materials, and files to support the applications for certificates for all clinical trials and New Drug Application (NDA) and to file Marketing Authorization Application (MAA) in the Territory, all as contemplated by this Agreement. The Licensor shall provide reasonable cooperation to the Licensee in respect of the clinical studies in the Territory required by this Agreement.

3. LICENSE AND SUB-LICENSES

3.1 Exclusive License Granted to Licensee

Subject to the terms and conditions of this Agreement, Licensor hereby grants to Licensee, and Licensee accepts, an exclusive (even as to Licensor and its Affiliates), royalty-bearing license, including the right to grant sub-licenses through multiple tiers of sub-licensing (subject to Section 3.3 below), under Licensed Know-How and Licensed Patent Rights, to make, have made, use and import Licensed Compounds, Research Information and Licensed Products, and to produce, distribute, promote, market, sell and offer for sale Licensed Products, in the Field in the Territory.

3.2 Retained Rights of Licensor

Notwithstanding anything to the contrary in Section 3.1, Licensor and its Affiliates retain the right to use and practice the Licensed Know-How and Licensed Patent Rights: (a) for development and commercialization of Licensed Compounds, Research Information and/or Licensed Products in the Field, either themselves, or with or for the benefit of a third party, globally, except in the Territory; and (b) for research, teaching and educational purposes (excluding research and/or development of Licensed Compounds, Research Information and Licensed Products for use and/or exploitation in the Field in the Territory on behalf of any Person other than Licensee or its Affiliates). Licensee shall not utilize the Licensed Compounds, Licensed Know-How, Licensed Patent Rights, Research Information, Research Inventions, or Technical Information for any purpose other than the production, distribution, and sale of Licensed Products in the Field in the Territory in accordance with this Agreement.

3.3 Sub-licenses Granted by Licensee

Each Sub-license Agreement executed by Licensee or any Sub-licensee shall be subject and subordinate to the terms and conditions of this Agreement, and shall contain terms and conditions consistent with those in this Agreement, sufficient to enable Licensee to comply with this Agreement and requiring the Sub-licensee to comply with the relevant terms and conditions of this Agreement, including this Section 3.3 and Sections 4.22, 4.2.5, 4.2.6, 9.1 and 10.5, and Article 5. Subject to Licensor's obligations set forth in Article 5, Licensee shall provide Licensor with an accurate and complete copy of any Sub-license Agreement within seven (7) days of entering into such Sub-license Agreement. Unless otherwise agreed in writing by Licensor, any sub-license of the rights granted under Section 2.1 shall terminate on any termination or expiration of this Agreement.

3.4 Diligence Obligations

During the term of this Agreement, Licensee shall use commercially reasonable efforts to develop and commercialize Licensed Products in the Territory, either itself or through its Affiliates and Sub-licensees. To that end, Licensee agrees to provide Licensor with a detailed time & events schedule (the "Timeline") for the commercial development of the Licensed Products in the Field in the Territory. Licensor reserves the right to review and approve the Timeline to ensure the global regulatory and commercial integrity of the development program. Without limiting the generality of the foregoing, beginning eighteen (18) months from the Effective Date, Licensee (itself or through its Affiliates and/or Sub-licensees) shall initiate the Phase Il Clinical Study in the Field. Licensee agrees to expend a minimum of Five Hundred Thousand United States Dollars ($500,000 USD) during this 18 month period to complete the regulatory requirements for chemistry, manufacturing & control (CMC), toxicology, and a Phase I Clinical Study necessary to initiate the Phase Il Clinical Study. From the initiation of a Phase Il Clinical Study, and for three (3) years thereafter, Licensee agrees to expend a minimum of Five Hundred Thousand United States Dollars ($500,000 USD) annually toward the clinical development of the Licensed Products in the Field in the Territory, with an understanding that a Phase Ill Clinical Study will be initiated at the end of this 3-year period. Thereafter, and until the commercial launch of Licensed Products in the Field in the Territory, Licensee agrees to expend a minimum of One Million United States Dollars ($1,000,000 USD) annually to complete the Phase Ill Clinical Study, regulatory submissions, and other product development activities required by the CFDA for regulatory approval and commercialization of the Licensed Products in the Field in the Territory.

Each six (6) months, Licensee shall provide Licensor with a comprehensive and detailed written report summarizing its efforts under this Section 3.4 in the prior six (6) month period, comprising of a listing of research and development activities. The report will include a progress report, with any updates to the Timeline for key events in the research and development of Licensed Products in the Field in the Territory.

Licensee agrees to share all clinical data and reports with Licensor to support the submission of global regulatory filings regarding the safety and efficacy of the Licensed Products.

In the event that Licensee fails to expend the monetary amount set forth in this Section 3.4 in any given 12-month period, Licensee may cure such default by paying to Licensee the difference between the agreed-upon amount, and the amount actually expended by Licensee in that 12-month period ("Shortfall Payment"); provided that such Shortfall Payment shall be delivered within thirty (30) days after Licensee is required to deliver the WTitten report evidencing such default. If Licensee fails to cure such default by making such Shortfall Payment, Licensor shall have the right to either terminate this Agreement, including the licenses granted hereunder, or convert the exclusive licenses granted in Section 3.1 to non-exclusive licenses, by written notice to Licensee. In the event that any dispute arises under this Section

3.4, such dispute shall be resolved in accordance with Section 14.10.

3.5 Reservation of Rights

Licensor reserves all rights not expressly granted in this Agreement, and no rights or licenses are granted in this Agreement except as expressly set forth herein, whether by implication, estoppel or otherwise.

4. PAYMENTS, ROYALTIES AND STOCK

In consideration for the license rights and other rights granted by Licensor to Licensee under this Agreement, on the date of execution of this Agreement, Licensee shall pay to Licensor a non-refundable, non-creditable upfront payment of Seven Hundred Thousand United States Dollars ($700,000 USD), by wire transfer to the Licensor account designated in Exhibit B annexed hereto. In addition, in consideration for the license rights and other rights granted by Licensor to Licensee under this Agreement, Licensee shall pay the following milestone payments to Licensor, upon achievement of the corresponding milestone events:

4.1 Milestone Payments

4.1.1 Upon achievement of the recited milestone events by the Licensee, Licensee shall pay the following milestone payments to Licensor:

(a) One Million United States Dollars ($1,000,000) USD, upon completion of the Phase Il Clinical Study of a Licensed Product in the Territory as defined by locking of the applicable clinical study database;

(b) One Million United States Dollars ($1,000,000 USD), upon completion of the Phase Ill Clinical Study of a Licensed Product in the Territory as defined by locking of the applicable clinical study database;

(c) Two Million United States Dollars ($2,000,000 USD), upon first NDA or MAA (or equivalent) approval in the Territory in respect of a Licensed Product.

4.1.2 Licensor shall be notified by the Licensee promptly upon achievement any of the above-specified milestone events, and Licensee shall pay Licensor the specified corresponding milestone payment within thirty (30) days after achieving the applicable milestone event.

4.2 Royalties

4.2. I Subject to Sections 4.2.2, 4.2.3 and 4.2.4, as further consideration for the license rights granted to Licensee under this Agreement, and in addition to any milestone payments payable to Licensor pursuant to Section 4.1, during the term of this Agreement Licensee shall pay to Licensor an intellectual property royalty payment in an amount equal to Ten Percent (10%) of Net Sales within the Territory of Licensed Products. The Parties acknowledge and agree that the royalty rates and structure set forth in this Section 4.2 (including the reduction in royalty rates provided for herein) (a) have been adopted after good faith negotiation and for the convenience of the Parties; and (b) are payable whether or not a Licensed Product is covered by Licensed Patent Rights.

4.2.2 Notwithstanding anything to the contrary in this Section 4.2, Licensee shall have no obligation to pay royalties to Licensor on sales of Licensed Products between Licensee and its Affiliates or Sub-licensees, where such Licensed Products will be resold to an unrelated third party; provided that, in such instances, the obligation to pay royalties hereunder shall arise upon the sale (or resale) of Licensed Products by Licensee's Affiliate or Sub-licensee to unrelated third parties. If, however, Licensee's Affiliate or Sub-licensee is the commercial end user of such Licensed Products (for uses other than research, development or testing purposes), then royalties shall be due hereunder on the greater of (a) Licensee's Net Sales resulting from Licensee's sale of such Licensed Products to such

Affiliate or Sub-licensee, and (b) Net Sales determined using the average sales price of Licensed Products in arms' length sales to unrelated third parties during the current Royalty Reporting Period or, if there were no such sales during such Royalty Reporting Period, during the most recent Royalty Reporting Period when there were such sales.

4.2.3 In the event that Licensee is obligated to pay a royalty under one or more third-party license agreements with respect to a Licensed Compound component of a Licensed Product, then Licensee may reduce the royalty rate payable to Licensor (as set forth in Section 4.2.1) by an amount equal to one-half the total royalties payable to such third-party licensors; provided, however, that application of this Section 4.2.3 shall not reduce the royalty rate payable by Licensee to less than Four Percent (4.0%).

4.2.4 Upon:

(a)      the date of first Approved Sale in the Territory of a Competitive Product (wherein the term "Competitive Product" is defined as any product containing as an active pharmaceutical ingredient one or more Licensed Compounds, which product is has the same pharmaceutical purpose as a Licensed Product) or a generic version of a Licensed Product, if a Licensed Product was covered by Licensed Patent Rights in the Territory at or prior to the time of such Competitive Product Approved Sale, but is no longer covered by Licensed Patent Rights (whether due to expiration, abandonment, a final, Lin-appealable adjudication of invalidity or otherwise); or

(b)     the date of first Approved Sale of a Competitive Product in the Territory, if a Licensed Product was not covered by Licensed Patent Rights in such country at or prior to the time of such sale;

the royalty rate payable by Licensee with respect to such Licensed Product shall be reduced to Four Percent (4.0%), unless and until such Licensed Product shall subsequently be covered by Licensed Patent Rights in the Territory.

4.2.5 Licensee shall keep, and shall obligate each of its Affiliates and Sub-licensees, if any, to keep, full and accurate books of account containing all particulars that are reasonably necessary for the purpose of calculating the royalties and other amounts payable by Licensee to Licensor hereunder. Without limiting the foregoing sentence, Licensee shall keep full and accurate records of gross sales revenues from and Net Sales of Licensed Products. Such books, records and pertinent supporting data of Licensee, its Affiliates and Sub-licensees that are necessary to verify the payment of royalties and other amounts in compliance with this Agreement shall be available for inspection by Licensor during normal business hours of Licensee, for three (3) years following the end of the calendar half year to which they pertain (but Licensor may not perform such inspection more than once per twelve (12)-month period). Any such inspection shall be performed by an independent certified public accountant retained by Licensor (and reasonably acceptable to Licensee) for the sole purpose of verifying reports and payments by Licensee hereunder.

4.2.6 Within six (6) months after the first day of January and July of each year during the term of this Agreement (including the first day of the half year following the expiration or termination of this Agreement), and beginning after the first commercial sale of a Licensed Product in the Territory, Licensee shall deliver to Licensor a true and accurate reports of any royalty amounts payable to Licensor under this Agreement in relation to Net Sales made by or reported to Licensee in the preceding calendar half year (the "Royalty Reporting Period"), as well as other information that is pertinent to calculation of such royalties (e.g., a report due on May 31 shall pertain to the preceding period January I through March 31). Licensee shall require its Affiliates and Sub-licensee to report to Licensee information as reasonably necessary to comply with Licensee's obligations under this Agreement. These reports shall include at least the following:

(a)      the calendar half year period covered by the report;

(b)     a description of each Licensed Product sold by Licensee, and each Licensed Product sale reported to Licensee by its Affiliates and Sub-licensees, during such calendar half year;

(c)      the total quantity of each Licensed Product sold by Licensee, and each Licensed Product sale reported to Licensee by its Affiliates and Sub-licensees, during such calendar half year, by country (or by region, but only if regional reporting is consistent with the Net Sales information kept by Licensee in its normal course of business);

(d)     gross sales revenues, deductions from gross sales and Net Sales made or reported during such calendar half year, by Licensed Product and by country (or by region, but only if regional reporting is consistent with the Net Sales information kept by Licensee in its normal course of business);

(e)      names and addresses of all Affiliates and Sub-licensees of Licensee involved in the distribution or sale of Licensed Products in such calendar half year, if Licensee has not previously provided such information to Licensor; and

(f)       total royalties payable to Licensor for such calendar half year.

4.2.7 Simultaneously with the delivery of each half year royalty report, Licensee shall pay to Licensor the royalty calculated for the Royalty Reporting Period covered by such report. If no royalties are due, it shall be so reported by Licensee. Each such royalty payment shall be made in Dollars by wire transfer of immediately available funds to the Licensor account designated Exhibit B annexed hereto (or such other account as may be designed in writing by the Licensor from time-to-time). In the event that conversion from any foreign currency shall be required, such conversion shall be at the average rate of exchange published in The Wall Street Journal for the calendar half year to which the payment pertains. Any amount not paid when due hereunder shall accrue interest at the lesser of one and one-half percent (l .5%) or the maximum rate allowed by law.

4.3 Withholding of Taxes

Each Party shall comply with applicable tax authority guidelines regarding filing and reporting for income tax purposes. Neither Party shall treat their relationship under this Agreement as a partnership or as a pass-through entity for tax purposes. Licensee shall be responsible for and shall collect all governmental and regulatory sales and other taxes, charges, duties and fees that are due and owing upon sales of Licensed Products by Licensee and its Affiliates and Sub-licensees to third parties, excluding taxes on Licensor's net income. Any withholding taxes shall be paid by Licensee at the rate(s) required by applicable law, and shall be paid to the appropriate fiscal or tax authorities on behalf of Licensor. Licensee shall promptly provide to Licensor receipts from the government or taxing authority evidencing payment of such taxes, if available, or other proof of payment if official receipts are not available, and shall provide reasonable assistance to Licensor to obtain tax credits therefor. To the extent Licensor actually uses any such tax credits for withholding taxes, as determined by it in its reasonable discretion, Licensor shall refund to Licensee the amount of such credits used; provided that Licensor shall not be required to refund any payment of such withholding tax to Licensee to the extent such payment would result in Licensor being in a worse after-tax economic position (as determined by Licensor in its reasonable judgment) than if such withholding tax had never been imposed.

5. CONFIDENTIALITY; PUBLICATION

Licensee shall ensure that its employees and those of its Affiliates and Sub-licensees who have access to any Technical Information of Licensor agree in writing to be bound by appropriate confidentiality and non-use obligations which are no less stringent than those imposed on Licensee hereunder.

5.1 Confidential Information

Except to the extent expressly authorized by this Agreement or otherwise agreed by the Parties in writing, each Party shall treat Confidential Information of the other Party in accordance with that certain Confidential Disclosure Agreement by and among the Parties (the "CDA") dated as of the I st day of September, 2016.

5.2 Permitted Disclosures

Notwithstanding the foregoing Section 5.1, the Receiving Party may disclose Confidential Information of the Disclosing Party, and Licensee may disclose Technical Information to the extent such disclosure is reasonably necessary to:

5.2.1 file or prosecute patent applications, or in connection with patent interferences or patent oppositions, as contemplated by this Agreement;

5.2.2 prosecute or defend litigation, as contemplated by this Agreement;

5.2.3 file documents required by applicable law, including filings with the U.S. Securities and Exchange Commission and comparable governmental agencies applicable to the Parties, with tax authorities, and with Regulatory Authorities as contemplated by this Agreement;

5.2.4 exercise rights granted hereunder to the Receiving Party and perform obligations of the Receiving Party hereunder; and

5.2.5 otherwise comply with applicable governmental laws and regulations, court orders and legal requirements.

5.3 Obligations of the Receiving Party

In the event that a Receiving Party is required to, or shall deem it necessary to, disclose Confidential Information of the Disclosing Party pursuant to Section 5.2, then except as otherwise expressly set forth herein, the Receiving Party (a) shall, to the extent practicable, give reasonable advance notice to the Disclosing Party of such disclosure, and (b) if requested by the Disclosing Party, use reasonable efforts to cooperate with the Disclosing Party's efforts to secure confidential treatment of such information. In any event, Licensee and Licensor shall take all reasonable precautions to avoid any unauthorized use or disclosure of Confidential Information or materials of the other Party, and Research Information, Licensed Know-How or confidential Licensed Patent Rights.

5.4 Permitted Disclosure by Licensee

Notwithstanding the foregoing Sections 5.2 and 5.3, Licensee may disclose the existence (if not publicly disclosed previously in accordance with this Article 5 or Section 14.5) and/or the terms of this Agreement (a) in confidence, to its lenders, investment bankers, investors and potential investors, attorneys, financial advisors and other financial institutions of its choice for purposes of financing the business operations of Licensee, and (b) subject to appropriate written obligations of confidentiality and non-use, to a potential acquirer of all or substantially all of the assets of Licensee related to the subject matter of this Agreement. Notwithstanding the foregoing Sections 5.2 and 5.3, Licensee may disclose any and all Licensed Know-How and Licensed Patent Rights (y) to Licensee's Affiliates; its actual and potential Sublicensees; and its actual and potential business partners (and any of the directors, officers, employees, advisors, consultants, distributors and agents of the foregoing recipients set forth in this clause (y)); provided, however, that Licensee shall impose upon such recipients described in clause (y) appropriate written obligations of confidentiality and non-use; and (z) to Regulatory Authorities in the Territory. Licensee may publicize and/or disclose the execution of this Agreement and further information and developments regarding this Agreement (including in a press release(s)), subject to Section 14.5.

5.5 Survival

The foregoing restrictions and obligations imposed by this Section 5 shall survive expiration or termination of this Agreement for whatever reason.

5.6 Publication

Licensor and Licensee recognize the importance to scientists of the ability to publish and present clinical trial results, and agree that subject to the terms of this Section 5.6, Licensee shall have the right to do so. Licensor and Licensee also recognize that patent rights in and outside the Territory can be jeopardized by submission of a manuscript or by public disclosure (including a presentation at a scientific conference) in or outside of the Territory prior to the filing of suitable patent applications. Therefore, Licensee agrees that, before submission to a publisher or disclosure to any other third party (including a presentation at a scientific conference), each proposed publication or public presentation containing any Licensed Know-How pertaining to Licensed Compounds, Research Information and/or Licensed Products (a "Proposed Public Disclosure") shall be submitted to Licensor for review in connection with preservation of patent rights, to ensure (a) that none of Licensor's Confidential Information or Research Information is included in the Proposed Public Disclosure, and (b) that such Proposed Public Disclosures and submissions to publishers containing such Licensed Know-How are consistent with Licensor's intellectual property, development and commercialization plans and objectives in the Territory. Licensor shall have sixty (60) days from receipt of such Proposed Public Disclosure to review it, which review period may be extended for an additional thirty (30) days in the event that Licensee provides substantial and reasonable need for such extension. During such period, as extended, Licensor may request the removal of any of its Confidential Information or any Research Information that is contained in the Proposed Public Disclosure and, in the event Licensor determines a need to delay the Proposed Public Disclosure to protect or preserve patent rights, Licensor shall request such delay in writing within such review period (as extended), and Licensee will delay such Proposed Public Disclosure for an additional period of up to one hundred twenty (120) days to permit Licensor to file a patent application(s). If requested by Licensor, Licensee shall remove from such Proposed Public Disclosure any of Licensor's Confidential Information and/or or Research Information (as applicable). Scientists employed by Licensor or Licensee will be expected to treat matters of authorship in a proper, collaborative spirit, giving credit where it is due and proceeding in a manner that complies with this Section 5.6 and fosters cooperation and communication.

6. INTELLECTUAL PROPERTY RIGHTS; OWNERSHIP

6.1 Ownership

Licensor owns all patents and other intellectual properties licensed to Licensee pursuant to this Agreement. Any extant intellectual property rights in respect of the Licensed Compounds, Research Information, the Licensed Know-How, the Licensed Patent Rights, and any intellectual property rights that may be discovered, identified, developed, generated, modified, obtained or derived by Licensor or Licensee in future activities pertaining to the Licensed Compounds, Research Information, the Licensed Know-How, the Licensed Patent Rights and Licensed Products will be solely and exclusively owned by Licensor.

6.2 Patent Prosecution

Licensee shall have the full right and authority to, and shall use commercially reasonable efforts to, prepare, file, prosecute and maintain all Licensed Patent Rights in the Field in the Territory (which Licensed Patent Rights shall, for greater certainty, be the sole and exclusive property of Licensor), in consultation with Licensor, using counsel of its choice reasonably acceptable to Licensor. To the extent practicable, Licensee shall provide Licensor with drafts of substantive prosecution papers to be submitted to patent offices in the Territory (with reasonable advance notice, so that Licensor may have an opportunity to comment in a timely fashion), and Licensee shall give suggestions from Licensor reasonable consideration (but without any obligation to incorporate or accept such suggestions). Licensee shall provide Licensor with copies of all substantive prosecution papers submitted to or received from patent offices in the Territory, including patent applications and amendments thereto, relating to the Licensed Patent Rights. Licensor shall cooperate with and assist Licensee in connection with such preparation, filing, prosecution and maintenance of Licensed Patent Rights, at no charge to Licensee for the time of Licensor's employees; provided that Licensee shall reimburse Licensor for its reasonable out-of-pocket expenses incurred in connection therewith. Licensee shall not abandon or discontinue prosecution of any patent application or patent within the Licensed Patent Rights without giving Licensor at least ninety (90) days' written notice prior to any applicable deadline; provided, however, Licensee may take ministerial and non-material procedural actions regarding the Licensed Patent Rights without providing prior written notice to Licensor. If Licensee provides such notice, Licensor may continue prosecution and/or maintenance of such abandoned or discontinued patent application or patent within the Licensed Patent Rights at its sole discretion and expense, and such thereafter such patent application or patent within the Licensed Patent Rights shall no longer be included in the Licensed Patent Rights hereunder.

6.3 Expenses

6.3.1 Patent Expenses. All costs incurred by Licensee for patent and patent application preparation, filing, prosecution, issuance and maintenance in connection with patent applications and patents within the Licensed Patent Rights in the Territory shall be borne solely by Licensee.

6.3.2 Technology Transfer Expenses. To the extent that members of the Licensor's executive management team, including, without limitation, Dr. Eric von Hofe, PhD, the President of Antigen Express, Inc., are required to travel to the Territory from time-to-time in order to facilitate the performance of this Agreement by the Parties, the Licensee shall reimburse the Licensor for any and all customary and reasonable travel expenses incurred in that respect.

7. INTELLECTUAL PROPERTY PROTECTION

7.1 Notice of Suspected Infringement of Licensed Patent Rights

Each Party shall inform the other Party of any threatened or suspected infringement of any Licensed Patent Right in the Field in the Territory coming to its attention, or of the institution of any third-party action or proceeding that may adversely impact any Licensed Patent Right in the Field in the Territory.

7.2 Control of Infringement Actions

7.2.1 Licensee shall have the first right, but not the obligation, at its sole expense, to take action in its own name, and in Licensor's name as a nominal party if reasonably necessary, against any such alleged infringer, or in any such third-party action or proceeding. In such event, after each Party has recovered all of its costs and expenses from such action or proceeding, Licensee shall be entitled to all remaining recoveries in any such action or proceeding; provided that any such remaining recoveries shall be deemed to be Net Sales, and Licensee shall pay Licensor royalties on such Net Sales at the rates provided in this Agreement. Licensor will assist Licensee, at Licensee's expense, in such actions or proceedings, if reasonably requested by Licensee or required by law. Licensor shall have the right to participate and to be represented in any such action or proceeding by its own counsel, at its own expense. In the event that any Licensed Patent Rights that are the subject of such action or proceeding have been sublicensed by Licensee hereunder, any such Sub-licensee shall also have the right to participate in such prosecution or defense. Licensee shall not settle any such action or proceeding without Licensor's written consent, not to be unreasonably withheld or delayed, if such settlement would, in Licensor's reasonable judgment, adversely affect the scope or validity of the Licensed Patent Rights.

7.2.2 If Licensee, its Affiliate or Sub-licensee elects not to take action within six (6) months after being informed of such alleged infringement or such third-party action or proceeding (or, if shorter, within thirty (30) days before any applicable deadline), Licensor may take action, at its sole expense, and shall be entitled to all damages assessed in any such action or proceeding.

7.2.3 The Party undertaking action under either Section 7.2.1 or 7.22 shall keep the other Party informed of the status of the matter on an ongoing basis.

7.3 Notice of a Claim of Infringement by a Third Party

In the event that a third party at any time threatens to or brings suit against Licensee, Licensor, or Licensee's Affiliate(s) or Sub-licensee(s) alleging infringement of any third-party patent or other intellectual property right due to the research, development, manufacture, use, sale, offer for sale or importation of any Licensed Compound or Licensed Product in the Field in the Territory (a "Third-Party Claim"), the Party receiving notification of the Third-Party Claim shall promptly notify the other Party, enclosing a copy of all pleadings served, if any.

7.4 Defense of a Third-Party Claim

Licensee shall have the right, in its discretion, to control the defense of such Third-Party Claim in its own name (and in Licensor's name as a nominal party, if reasonably necessary), provided that Licensee shall not settle such matter in any way that imposes an unreimbursed obligation on Licensor without Licensor's consent, not to be unreasonably withheld or delayed, and such defense, including settlement of the matter (which settlement may, in Licensee's discretion, include obtaining a license from such third party), shall be at Licensee's own expense and under its direction and control. Licensor, at Licensee's expense, will reasonably assist Licensee in such defense, if so requested. In addition, Licensor shall have the right to participate and be represented in any defense of such Third-Party Claim by its own counsel, at its own expense. Any judgments, settlements or damages payable with respect to a Third-Party Claim shall be paid by Licensee, subject to any claims against the other Party for breach of or for indemnification under this Agreement, or any other remedies that are otherwise available at law or in equity.

8. REPRESENTATIONS AND WARRANTIES

8.1 Representations and Warranties of Licensee

Licensee hereby represents and warrants to Licensor, as of the Effective Date, that:

8.1.1 It has the right, power and authority to enter into this Agreement and to perform its obligations hereunder.

8.1.2 This Agreement has been duly executed and delivered by Licensee, and is a legal, valid and binding obligation enforceable against Licensee in accordance with its terms, subject to applicable bankruptcy, insolvency, reorganization, arrangement, moratorium and other laws relating to or affecting creditors' rights generally and equitable principles.

8.1.3 The execution, delivery and performance of this Agreement, and the rights and licenses granted hereunder, do not conflict with, violate or breach any agreement to which Licensee is a party, and there are no agreements, assignments or encumbrances of Licensee that are inconsistent with the provisions of this Agreement.

8.1.4 The execution and delivery by Licensee of this Agreement and the performance by Licensee of the obligations under this Agreement require no governmental or regulatory approvals to be obtained on the part of Licensee, or, if required, Licensee has obtained or will have obtained such approvals.

8.2 Representations, Warranties and Covenants of Licensor

Licensor hereby represents, warrants and covenants to Licensee, as of the Effective Date, that:

8.2.1 The Board has granted Licensor all requisite right, power and authority to enter into this Agreement and to perform Licensor's obligations hereunder and Licensor is fully and lawfully empowered to grant the rights and licenses granted to Licensee herein.

8.2.2 This Agreement has been duly executed and delivered by Licensor, and is a legal, valid and binding obligation enforceable against Licensor in accordance with its terms, subject to applicable bankruptcy, insolvency, reorganization, arrangement, moratorium and other laws relating to or affecting creditors' rights generally and equitable principles.

8.2.3 The execution, delivery and performance of this Agreement, and the rights and licenses granted to Licensee hereunder, do not conflict with, violate or breach any agreement to which Licensor is a party, and there are no agreements, assignments or encumbrances in existence to which Licensor is a party that are inconsistent with the provisions of this Agreement. Licensor has not granted, and will not grant, any license or other right in any of the Licensed Compounds, Licensed Patent Rights, Research Inventions, or Licensed Know-How that conflicts with any of the licenses or rights granted to Licensee under this Agreement.

8.2.4 Exhibit A sets forth a true and complete list of all patents and patent applications filed on or before the Effective Date in the Territory that are Licensed Patent Rights, and all such patents and patent applications are owned and Controlled by Licensor.

8.2.5 To the best of the Licensor' s knowledge, Information, and belief, no patents within the Licensed Patent Rights are being infringed by a third party.

8.2.6 The Licensor has not recei、red any written notice from any third party, including any Governmental Body, claiming any ownership interest in the Licensed patent Rights or the Licensed Compounds (whether by inventorship, assignment or otherwise).

8.2.7 (a) No lawsuit has been filed against Licensor, nor has any third party threatened writing to file a lawsuit against Licensor, with respect to the Licensed Compounds, Licensed Products or Licensed Patent Rights; and (b) no patent or patent application within the Licensed Patent Rights is or has been involved in any reissue, reexamination, interference, opposition or equivalent or similar proceeding to which Licensor is a party and (c) the Licensed Patent Rights are not subject to any judgments or settlements against or owed by Licensor.

8.2.8 The execution and delivery by Licensor of this Agreement, and the performance by Licensor Of the obligations under this Agreement, require no governmental or regulatory approvals to be obtained on the part Of Licensor, or, if required, Licensor has obtained or will obtain such approvals.

8.2.9 Licensor has not knowingly failed to disclose to Licensee any material adverse facts regarding (a) communications to or from any pertinent Regulatory Authority with respect to the Licensed Compounds or Licensed Products; and/or (b) any adverse events or product recalls or withdrawals with respect to the Licensed Compounds or Licensed Products.

8.3 Disclaimer ofWarranties

Except as otherwise expressly set forth in this Article 8, and without affecting either party's obligations under this agreement, neither licensor nor licensee makes any representation or extends any warranty of any kind, either express or implied, to the other party with respect to any patent rights, know-how, materials, rights, clinical data or any other subject matter of this agreement, and each party hereby disclaims all implied warranties, including implied warranties of merchantability, fitness for a particular purpose and non-infringement, with respect to any and all of the foregoing. Each party hereby disclaims any representation or warranty that the development, manufacture of commercialization of any licensed product pursuant to this agreement will be successful or that any particular sales level with respect to the licensed products will be achieved.

9. REGULATORY MATTERS    

9.1 Export Controls

Licensee and its Affiliates and Sub-licensees shall comply with all applicable laws, rules and regulations of any relevant Governmental Body in the Territory in the exercise of their rights and discharge of their responsibilities under this Agreement, including export laws, restrictions and regulations of any United States or foreign agency or authority in the Territory, and will not export or re-export, or allow or authorize the export or re-export, of any Licensed Compound, Licensed Products, Technical Information, material, technology or other information it obtains or learns pursuant to this Agreement in violation of this Agreement or of any such laws, restrictions or regulations in the Territory.

10. INDEMNIFICATION, INSURANCE AND LIMITATION OF LIABILITY

10.1 Indemnification by Licensee

Licensee shall indemnify, defend and hold harmless Licensor and its Affiliates, and each of their respective employees, officers, directors, and agents (each, a "Licensor Indemnitee") from and against any and all liability, loss, damage, penalty, expense (including reasonable attorneys' fees and expenses) and cost (collectively, "Losses") resulting from, arising out of, or relating to:

10.1.1 Licensee's failure to perform its obligations under this Agreement or Licensee's or its Affiliates' or Sub-licensees' negligence or willful misconduct in the course of such performance;

10.1.2 any and all claims arising from the research, development, use, manufacture, sale, offer for sale, importation, distribution, marketing and promotion of the Licensed Products in the Territory by Licensee or any of its Affiliates or Sub-licensees; or

10.1.3 a breach by Licensee of its representations and warranties under this Agreement;

provided that Licensee's obligations under this Section 10.1 shall not apply to the extent such claims, actions or suits result from the gross negligence or willful misconduct of any Licensor Indemnitee.

10.2 Indemnification by Licensor

Licensor shall indemnify, defend and hold harmless Licensee and its Affiliates and Sub-licensees, and each of their respective employees, members, officers, directors and agents (each, a "Licensee Indemnitee") from and against any and all Losses resulting from, arising out of, or relating to:

10.2.1 claims for death of or injury to any person(s) resulting directly from Licensor's negligence or willful misconduct;

or

10.2.3 a breach by Licensor of its representations and warranties under this Agreement;

provided that Licensor's obligations under this Section 10.2 shall not apply to the extent such claims, actions or suits result from the gross negligence or willful misconduct of any Licensee Indemnitee.

10.3 Other Remedies

The foregoing indemnification provisions shall not be exclusive, and shall be in addition to any other remedies available to the Parties hereunder.

10.4 Insurance

On a date that is no later than Licensee's initiation of the first human clinical study of a Licensed Product in the Field in the Territory, Licensee shall, at its own cost, obtain and carry in full force and effect, during the remainder of the term of this Agreement and thereafter as provided below, insurance, including comprehensive commercial general liability insurance (including contractual liability and product liability insurance), in amounts and subject to deductibles customary in the pharmaceutical industry and sufficient to cover its obligations under this Agreement. Upon the request of Licensor, Licensee shall provide Licensor with Certificates of Insurance evidencing compliance with this Section 10.4.Licensee shall continue to maintain such insurance for so long as it, or any Affiliate or Sub-licensee, continues to develop, manufacture or sell Licensed Products in the Field in the Territory, and thereafter as may be required to cover manufacture or sales of distributed Licensed Products in the Field in the Territory.

10.5 Limitation of Liability

In no event will Licensor or any Licensor Indemintees be liable to any Licensee Indemnitees for any indirect, incidental, special, exemplary of consequential damages, including lost profits or revenues, arising out of or in connection with this agreement or any breach thereof whether based in contract, tort (including negligence and strict liability) or otherwise, to the maximum extent allowed by law.

11. TERM AND TERMINATION

11.1 Term

Unless sooner terminated in accordance with this Agreement, the term of this Agreement shall commence on the Effective Date and shall continue, in the territory, until the later of: (a) expiration of the last-to-expire patent within the Licensed Patent Rights in such country, or (b) the fifteenth (15th) anniversary of the first Approved Sale of a Licensed Product in such country. Following such expiration, Licensee shall have a fully paid-up license that corresponds to the license granted to Licensee in Section 3.1.

11.2 Termination

11.2.1 In the event that Licensee or Licensor breaches a material undertaking or obligation hereunder, the other Party shall have the right, without limitation of any other right it has under this Agreement on account of such breach, to terminate this Agreement on ninety (90) days (or, in the case of breach of an obligation to pay money, thirty (30) days) prior written notice specifying such breach and demanding its cure; provided, however, that if the alleged breaching Party shall cure such breach during such ninety (90)-day (or thirty (30)-day, if applicable) period, then such notice of termination shall be null and void; otherwise, this Agreement shall be terminated on and after the expiration of said ninety (90)-day (or thirty (30)-day, if applicable) period.

11.2.2 This Agreement may be terminated at any time by a Party upon the filing or institution of bankruptcy, reorganization, liquidation or receivership proceedings by or against the other Party, or upon an assignment of a substantial portion of its assets for the benefit of creditors by such other Party; provided, however, that in the event of any involuntary bankruptcy or receivership proceeding, such right to terminate shall only become effective if the proceeding is not dismissed within sixty (60) days after the filing thereof.

11.2.3 At any time after eighteen (18) months following the Effective Date, this Agreement may be terminated in Licensee's sole discretion on sixty (60) days prior written notice to Licensor.

11.3 Effect of Termination or Expiration

11.3.1 Termination of this Agreement under any provision herein shall not affect the obligation of Licensee to pay Licensor any royalty or other payments which have accrued and are unpaid as of the date of termination, nor shall the same prejudice any other accrued right of Licensor or Licensee under this Agreement. For the sake of clarity, if a payment obligation has not accrued as of the effective date of termination of this Agreement, then, except as expressly set forth herein, any subsequent event or achievement that would have resulted in accrual of such payment obligation — if the Agreement had not been terminated — shall have no effect on any payment(s) hereunder. Within ninety (90) days after termination, Licensee shall render to Licensor a written statement of the kind required by Section 4.2.6 hereof with respect to any due and unpaid royalties, and shall accompany such a statement with payment to cover same.

11.3.2 In the event of termination of this Agreement, other than a termination of this Agreement by Licensee pursuant to Section 11.2.3 or a termination of this Agreement by Licensor pursuant to Section 11.2.1 or Section 11.2.2, Licensee, its Affiliates and Sublicensees shall be entitled, for a period of twelve (12) months thereafter, to sell Licensed Products existing or being manufactured on the date of termination; provided that Net Sales from sales of such Licensed Products shall be subject to royalty payments under Section

4.2.

11.3.3 If either party has a right to terminate this Agreement pursuant to Section I I .2.1 or 11.2.2, then such party may elect (in its sole discretion) to do one of the following: (a) terminate this Agreement and retain its right to pursue any and all remedies permitted at law or in equity (including contract damage remedies), or (b) continue the Agreement while simultaneously pursuing any and all remedies permitted at law or in equity (including contract damage remedies). Maybe we could suspend payments until adjudication.

11.4 Survival

Expiration or termination of this Agreement, whether in whole or in part, shall not relieve the Parties of any obligation accruing prior to such expiration or termination. Any expiration or termination of this Agreement shall be without prejudice to the rights and the legal and equitable remedies of the Parties accrued or accruing under this Agreement prior to expiration or termination, subject to the terms and conditions of this Agreement (including, for the avoidance of doubt, the right to enforce the terms and conditions set forth herein without terminating this Agreement, and further including any obligations of a Party that are expressly identified in this Agreement as surviving, or that by their nature or context logically survive, termination, relinquishment or expiration of this Agreement). Without limiting the foregoing sentence, the provisions of Article 1 (to the extent definitions are embodied in the following listed Articles and Sections of this Agreement) and Articles 5, 10 and 13, and Sections 6.1, 11.3, 14.5, 14.6, 14.9, 14.10 shall survive any expiration or termination of this Agreement. Except as set forth in this Article I l, upon termination or expiration of this Agreement all other rights, licenses and obligations of the Parties shall cease.

12. ASSIGNMENT

Neither Party shall have any right or ability to assign or transfer this Agreement or any obligations or benefit under this Agreement (whether by operation of law or otherwise) without the written consent of the other Party (and any unauthorized purported assignment will be void). Any Change of Control of Licensee shall be deemed an assignment of this Agreement for purposes of this Section. Notwithstanding the foregoing Licensee may assign this Agreement, without the consent of Licensor, to an Non-Afflliate Acquirer in connection with the transfer or sale of all or substantially all of its assets or business to which this Agreement relates to such Non-Affiliate Acquirer, or in the event of its merger or consolidation with, acquisition by, or sale to such a Non-Affiliate Acquirer; provided that such Non-Affiliate Acquirer (a) agrees in writing to be bound by the terms and conditions of this Agreement; and (b) has the financial and other resources to perform its obligations under this Agreement. Subject to the foregoing, this Agreement will be binding upon and inure to the benefit of the Parties and the successors and permitted assigns of Licensee and/or Licensor.

13. NOTICES AND ADDRESSES

13.1 Delivery of Notices

Any written communication, notice, report or payment shall be deemed to be sufficiently given when delivered in person, or sent by confirmed facsimile, or two (2) days after being sent by internationally recognized overnight courier (e.g., FedEx, DHL, etc.), if addressed and sent to a Party at its address set forth below.

If to Licensor:
Generex Biotechnology Corporation
4145 North Service Road
Suite 200
Burlington, Ontario, Canada L7L 6A3
Attentions	Mark A. Fletcher
	Executive Vice-President & General Counsel
	mfletcher@generex.com
If to Licensee:
Shenzhen BioScien Pharmaceuticals CO. LTD.
NAME ADDRESS: Room 311, First Building, Shenzhen Overseas Venture Park (Longgang), Shenzhen 518116, China
Email:	2575962704@qq.com

13.2 Change of Address

Either Party may change its mailing address for the purpose of this Agreement by giving the other Party notice of such change in accordance with Section 13.1 at least fifteen (15) days prior to the date upon which the change is to become effective.

14. MISCELLANEOUS

Agreement  

14.1 Entire Agreement

This Agreement constitutes the entire understanding between the Parties with respect to the subject matter hereof, and except for the CDA, which shall continue in full force and effect with respect to any disclosures by a Party made prior to the Effective Date, the Option Agreement, and the Purchase Agreement, this Agreement shall supersede and replace all prior agreements, understandings, writings and discussions between the Parties relating to said subject matter.

14.2 Amendment; Waiver

This Agreement may be amended, and any of its terms or conditions may be waived, only by a written instrument executed by Licensor and Licensee or, in the case of a waiver, by the Party waiving compliance. The failure of either Licensor or Licensee at any time or times to require performance of any provision hereof shall in no manner affect its rights to enforce the same at a later time. No waiver by either Party of any condition or term in any one or more instances shall be construed as a further or continuing waiver of such condition or term or any other condition or term.

14.3 Titles; Captions

All titles and captions in this Agreement are for convenience only, and shall not be interpreted as having any substantive meaning.

14.4 Independent Contractors

Except as set forth in Article 8, nothing in this Agreement authorizes Licensee or Licensor to act as agent for the other Party as to any matter. Licensee and Licensor are not Affiliates of one another; and their relationship is that of independent contractors. Nothing in this Agreement will be deemed to create an agency, joint venture, amalgamation, partnership, employment, franchise, fiduciary of similar relationship between them.

14.5 Publicity and Disclosure

Except as set forth in Article 5, neither Licensor nor any of its Affiliates shall use the name of Licensee or any Affiliate or Sub-licensee of Licensee, or any director, employee, officer, or representative of Licensee, in any advertising, press release, promotion or sales literature without the prior written approval of Licensee, which shall not be unreasonably withheld or delayed. Except as set forth in Article 5, neither Licensee nor any of its Affiliates or Sub-licensees shall use the name of Licensor or any Affiliate of Licensor, or any director, employee, officer, or representative of Licensor, in any advertising, press release, promotion or sales literature without the prior written approval of Licensor, which shall not be unreasonably withheld or delayed.

14.6 Use of Trademarks

Licensee and its Affiliates and Sub-licensees may use any trademark(s) owned or Controlled by Licensee or any of its Affiliates or Sub-licensees in connection with the Licensed Products to be made, used, sold, offered for sale, imported or distributed in the Territory. Licensor shall have no ownership or other right in or to such trademark(s) of Licensee, its Affiliates or its Sub-licensees.

14.7 Marking

All Licensed Products shall be marked with the patent numbers of issued patents within the Licensed Patent Rights that cover such Licensed Products, to the extent practicable and permitted by law in countries in which such markings have notice value against infringers of patents.

14.8 Severability

If any provision of this Agreement is or becomes invalid, is ruled illegal by any court of competent jurisdiction or is deemed unenforceable under the current applicable law from time to time in effect during the term hereof, it is the intention of the Parties that the remainder of this Agreement shall not be affected thereby. It is further the intention of the Parties that, in lieu of each such provision, there shall be substituted or added as part of this Agreement a provision which shall be as similar as possible in economic business objectives, as intended by the Parties, to such invalid, illegal or unenforceable provision, but which shall be valid, legal and enforceable.

14.9 Governing Law & Language

The construction and performance of this Agreement shall be governed by the laws of the State of New York, USA without regard to conflicts of laws principles that would require the application of any other law. In the event of any discrepancies between the English language version of this Agreement and any other version, the English language version shall be the original and shall control in the event of any question concerning the meaning or import of its terms. The English language shall be the official language of all correspondence, meetings and arbitration between the Parties.

14.10 Dispute Resolution

14.10.1 Disputes. The Parties recognize that disputes as to certain matters may arise from time-to-time during the term of the Agreement. It is the objective of the Parties to establish procedures to facilitate the resolution of disputes arising under this Agreement in an expedient manner and without resort to litigation. The Parties shall attempt to settle any such dispute through good faith negotiations in the spirit of mutual cooperation between business executives with authority to resolve the dispute. To accomplish this objective, and with respect to all disputes hereunder, the Parties agree to follow the procedures set forth in this Section 14.10 if and when a dispute between the Parties arises under this Agreement.

14.10.2 Escalation. Prior to taking action as provided in Section 14.10.3 of this Agreement, the Parties shall first submit such dispute to Licensee's Chief Executive Officer and to the President & Chief Executive Officer of Licensor (the Heads" ) for resolution. The Heads to whom any dispute is submitted shall attempt to resolve the dispute through good faith negotiations over a reasonable period, not to exceed forty-five (45) calendar days following one Party's receipt of a notice of dispute from the other Party, unless the Heads mutually agree in writing to extend such period of negotiation. Such 45-day period shall be deemed to commence on the date the dispute was submitted to the Heads. All negotiations pursuant to this Section 14.10.2 shall be confidential, "without prejudice", and shall be treated as compromise and settlement negotiations for purposes of applicable rules of evidence.

14.10.3 Arbitration. Any dispute that is not resolved by negotiation and/or escalation pursuant to Sections 14.10.1 and/or 14.10.2 shall, upon the submission of a written request of either Party to the other Party, be submitted to China International Economic and Trade Arbitration Commission (CIETAC) for arbitration in Beijing, China, which shall be conducted in accordance with CIETAC's arbitration rules in effect at the time of applying for arbitration. The presiding arbitrator shall not be a Chinese national or a citizen of the United States. The arbitral award is final and binding upon both Parties, shall be the sole and exclusive remedy of the Parties, and shall be enforceable in any court of competent jurisdiction. The English language shall be used throughout the arbitral proceedings. Relevant documents in other languages shall be translated into English if the arbitrators so direct. The Parties agree that they shall share equally the cost of the arbitration filing and hearing fees. Each Party shall bear its own attorneys' and expert fees and all associated costs and expenses.

14.11 Counterparts

This Agreement may be executed by original or facsimile signature in several counterparts, all of which shall be deemed to be originals, and all of which shall constitute one and the same Agreement. Notwithstanding the foregoing, the parties shall deliver original execution copies of this Agreement to one another as soon as practicable following execution thereof.

[The remainder of this page intentionally left blank.]

5

IN WITNESS WHEREOF, the Parties hereto have executed this Agreement by and through their duly authorized representatives as of the Effective Date.

	Antigen Express, Inc.
	by its parent company,
	Generex Biotechnology Corporation
By:	/s/ Joseph Moscato
Name:
Title:
Date:	November 13th, 2017
	Shenzhen BioScien Pharmaceuticals Co., Ltd.
By:
Title:
	I am a legal representative of the Licensee and have authority to legally bind the Licensee.
Date:	November 29th, 2017

6

Exhibit A

LICENSED PATENT RIGHTS

Hybrid Peptides Modulate the Immune Response

REH-2007 PCT Granted 00812837.5 25-Aug-2000

China (People's Republic) ZL 00 8 12837.5 11-Nov-2009

7

EX-23.1

Exhibit 23.1

Consent of Independent Registered Public Accounting Firm

We hereby consent to the use in this Registration Statement on Form 10 of our report dated March 12, 2020, related to the financial statements of NuGenerex Immuno-Oncology, Inc. as of July 31, 2019 and 2018 and for the fiscal years then ended, which appears in this Registration Statement of NuGenerex Immuno-Oncology, Inc. The report for NuGenerex Immuno-Oncology, Inc. includes an explanatory paragraph about the existence of substantial doubt about its ability to continue as a going concern.

/s/ Mazars USA LLP

Edison, New Jersey

June 12, 2020