10-K 1 a13-26710_110k.htm 10-K

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UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

 

FORM 10-K

 

x      ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

 

For the fiscal year ended December 31, 2013

 

OR

 

o         TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934

 

For the transition period from                 to                 

 

Commission file number 000-50549

 

GTx, Inc.

(Exact name of registrant as specified in its charter)

 

Delaware

 

62-1715807

(State or other jurisdiction of

incorporation or organization)

 

(I.R.S. Employer Identification No.)

 

 

 

175 Toyota Plaza

7th Floor

Memphis, Tennessee

 

38103

(Address of principal executive offices)

 

(Zip Code)

 

(901) 523-9700

(Registrant’s telephone number, including area code)

 

Securities registered pursuant to Section 12(b) of the Act:

 

Title of Each Class

 

Name of Each Exchange on Which Registered

Common Stock, par value $0.001 per share

 

The NASDAQ Stock Market, LLC

 

Securities registered pursuant to Section 12(g) of the Act:  None

 

Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act.  Yes  o No  x

 

Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act.  Yes  o  No  x

 

Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes  x    No  o

 

Indicate by check mark whether the registrant has submitted electronically and posted on its corporate Web site, if any, every Interactive Data File required to be submitted and posted pursuant to Rule 405 of Regulation S-T during the preceding 12 months (or for such shorter period that the registrant was required to submit and post such files).  Yes  x    No  o

 

Indicate by check mark if disclosure of delinquent filers pursuant to Item 405 of Regulation S-K is not contained herein, and will not be contained, to the best of registrant’s knowledge, in definitive proxy or information statements incorporated by reference in Part III of this Form 10-K or any amendment to this Form 10-K.  x

 

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

 

Large accelerated filer o

 

Accelerated filer x

 

 

 

Non-accelerated filer o

 

Smaller reporting company o

(Do not check if a smaller reporting company)

 

 

 

Indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the Act).   Yes o  No  x

 

The aggregate market value of common stock held by non-affiliates of the registrant based on the closing sales price of the registrant’s common stock on June 28, 2013 as reported on The NASDAQ Global Market was $181,397,363.

 

There were 75,161,437 shares of registrant’s common stock issued and outstanding as of March 10, 2014.

 

 

 



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DOCUMENTS INCORPORATED BY REFERENCE

 

Certain portions of the registrant’s definitive proxy statement to be filed with the Securities and Exchange Commission pursuant to Regulation 14A, not later than 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K, in connection with the Registrant’s 2014 Annual Meeting of Stockholders are incorporated by reference into Part III of this Annual Report on Form 10-K.

 



Table of Contents

 

TABLE OF CONTENTS

 

 

 

Page

Special Note Regarding Forward-Looking Statements

 

1

 

 

 

Part I

 

 

Item 1.

Business

 

2

Item 1A.

Risk Factors

 

22

Item 1B.

Unresolved Staff Comments

 

38

Item 2.

Properties

 

38

Item 3.

Legal Proceedings

 

38

Item 4.

Mine Safety Disclosures

 

39

 

 

 

Part II

 

 

Item 5.

Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities

 

39

Item 6.

Selected Financial Data

 

41

Item 7.

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

 

42

Item 7A.

Quantitative and Qualitative Disclosures About Market Risk

 

53

Item 8.

Financial Statements and Supplementary Data

 

54

Item 9.

Changes in and Disagreements With Accountants on Accounting and Financial Disclosure

 

54

Item 9A.

Controls and Procedures

 

54

Item 9B.

Other Information

 

55

 

 

 

Part III

 

 

Item 10.

Directors, Executive Officers and Corporate Governance

 

55

Item 11.

Executive Compensation

 

55

Item 12.

Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters

 

55

Item 13.

Certain Relationships and Related Transactions, and Director Independence

 

56

Item 14.

Principal Accounting Fees and Services

 

56

 

 

 

Part IV

 

 

Item 15.

Exhibits and Financial Statement Schedules

 

56

 

 

 

Signatures

 

60

 

 

 

Index to Financial Statements

 

F-1

 



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SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

 

This Annual Report on Form 10-K contains forward-looking statements. The forward-looking statements are contained principally in the sections entitled “Risk Factors,” “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and “Business.” These statements involve known and unknown risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performances or achievements expressed or implied by the forward-looking statements. Forward-looking statements include statements about:

 

·                  the implementation of our business strategies, including our ability to preserve or realize any significant value from our enobosarm (GTx-024) and GTx-758 (Capesaris®) programs;

 

·                  the therapeutic and commercial potential of our product candidates;

 

·                  the timing of regulatory discussions and submissions, and the anticipated timing, scope and outcome of related regulatory actions or guidance;

 

·                  our ability to establish and maintain potential new collaborative, partnering or other strategic arrangements for the development and commercialization of our product candidates;

 

·                  the anticipated progress of our clinical programs, including whether our ongoing and planned clinical trials will achieve clinically relevant results;

 

·                  the timing, scope and anticipated initiation, enrollment and completion of our ongoing and planned clinical trials and any other future clinical trials that we may conduct;

 

·                  our ability to obtain and maintain regulatory approvals of our product candidates and any related restrictions, limitations, and/or warnings in the label of an approved product candidate;

 

·                  our ability to market, commercialize and achieve market acceptance for our product candidates;

 

·                  our ability to protect our intellectual property and operate our business without infringing upon the intellectual property rights of others; and

 

·                  our estimates regarding the sufficiency of our cash resources, expenses, capital requirements and needs for additional financing, and our ability to obtain additional financing.

 

In some cases, you can identify forward-looking statements by terms such as “anticipates,” “believes,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “should,” “will,” “would,” and similar expressions intended to identify forward-looking statements. Forward-looking statements reflect our current views with respect to future events, are based on assumptions, and are subject to risks, uncertainties and other important factors.  We discuss many of these risks in this Annual Report on Form 10-K in greater detail in the section entitled “Risk Factors” under Part I, Item 1A below. Given these risks, uncertainties and other important factors, you should not place undue reliance on these forward-looking statements. Also, forward-looking statements represent our estimates and assumptions only as of the date of this Annual Report on Form 10-K. You should read this Annual Report on Form 10-K and the documents that we incorporate by reference in and have filed as exhibits to this Annual Report on Form 10-K, completely and with the understanding that our actual future results may be materially different from what we expect.

 

Except as required by law, we assume no obligation to update any forward-looking statements publicly, or to update the reasons actual results could differ materially from those anticipated in any forward-looking statements, even if new information becomes available in the future.

 

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PART I

 

ITEM 1.                                                BUSINESS

 

Overview

 

GTx, Inc., a Delaware corporation incorporated on September 24, 1997 and headquartered in Memphis, Tennessee, is a biopharmaceutical company dedicated to the discovery, development and commercialization of small molecules for the treatment of cancer, including treatments for prostate and breast cancer, cancer supportive care, including prevention and treatment of cancer-related muscle wasting or cachexia, and other serious medical conditions.

 

We are developing selective androgen receptor modulators, or SARMs, a new class of drugs with the potential to prevent and treat muscle wasting in patients with cancer and other musculoskeletal wasting or muscle loss conditions, including chronic sarcopenia (age related muscle loss), as well as the potential to be used as a hormonal therapy for the treatment of metastatic breast cancer.  Our lead SARM product candidate, enobosarm (GTx-024), has to date been evaluated in fourteen completed or ongoing clinical trials enrolling approximately 1,320 subjects, including in three Phase 2 and two Phase 3 clinical trials.  Enobosarm is the generic name given to the compound by the USAN Council and the World Health Organization and is the first compound to receive the SARM stem in its name, recognizing enobosarm as the first in this new class of compounds.

 

We announced in August 2013 that the POWER 1 (platinum plus taxane chemotherapy) and POWER 2 (platinum plus non-taxane chemotherapy) (Prevention and treatment Of muscle Wasting in patients with cancER) Phase 3 clinical trials evaluating enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced non-small cell lung cancer, or NSCLC, failed to meet the primary statistical criterion for the co-primary endpoints of lean body mass and physical function that were assessed statistically using responder analyses as pre-specified for the United States Food and Drug Administration, or FDA.  However, efficacy data from the studies demonstrated enobosarm’s consistent effect on maintaining or improving lean body mass compared to placebo and that maintenance or improvement in lean body mass is potentially associated with longer survival in patients, regardless of treatment.  As for safety, enobosarm was generally well tolerated, with the occurrence of serious adverse events similar across the placebo and treated groups.

 

Enobosarm 3 mg demonstrated a statistically significant effect versus placebo on the primary endpoint of physical function through Day 84 in the POWER 1 Phase 3 clinical trial as assessed by continuous variable analysis, as pre-specified in our statistical analysis plan for the European Medicines Agency, or EMA.  Therefore, we met with representatives from two member countries to the EMA in January of 2014 to review and discuss the results of the POWER trials to determine an appropriate path forward for submitting a marketing authorization application, or MAA, in the European Union for enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced NSCLC.  Based on input from the two member countries, we believe data from the POWER 1 trial, as well as supporting data from the POWER 2 trial, are sufficient to support the submission of a MAA to the EMA seeking marketing authorization for enobosarm 3 mg in the more narrow indication of the prevention and treatment of muscle wasting in patients with advanced NSCLC treated with platinum plus taxane chemotherapy.  We plan to initiate seven Phase 1 clinical studies that are typically required for registration purposes and develop a pediatric investigational plan, or PIP, necessary for submission of the MAA.  We currently expect to submit the MAA to the EMA for enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced NSCLC treated with platinum plus taxane chemotherapy by the first quarter of 2015, after completion of the Phase 1 studies and acceptance of the PIP by the EMA’s Pediatric Committee.

 

In our meeting with the FDA in February 2014 to review and discuss the results of the POWER clinical trials, we learned that since data from the two POWER trials failed to meet the primary statistical criterion pre-specified for the co-primary endpoints of lean body mass and physical function, the FDA was not willing to accept a new drug application, or NDA, for enobosarm 3 mg. However, based on input from the FDA meeting, we believe there is a regulatory path forward for enobosarm 3 mg in the United States, and we plan to meet again with the FDA to discuss a potential Phase 3 clinical program evaluating enobosarm 3 mg for an indication of muscle wasting or cachexia in patients with NSCLC.  Any such Phase 3 clinical trial program would be subject to our ability to obtain additional funding and would be required to be successfully completed prior to any NDA submission to the FDA for enobosarm 3 mg.

 

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SARMs also have the potential to be used as a novel hormonal therapy for the treatment of metastatic breast cancer.  Nonselective steroidal androgens have been used to treat breast cancer; however, the unwanted virilizing side effects have limited their widespread clinical use. We believe that enobosarm, by targeting the androgen receptor, or AR, in estrogen receptor, or ER, positive breast cancer, has the potential to provide clinical benefit to women with metastatic breast cancer by treating their disease while minimizing the unwanted masculinizing side effects associated with steroidal androgens, and unlike androgens, cannot be converted into an estrogen.  In the second quarter of 2013, we initiated a Phase 2 open label study evaluating enobosarm 9 mg for the treatment of AR positive and ER positive metastatic breast cancer in women who have previously responded to hormonal therapy for the treatment of their metastatic breast cancer.   Nine clinical study sites in the U.S. have fully enrolled the study with 22 postmenopausal women with metastatic breast cancer to assess clinical benefit response after six months of enobosarm 9 mg treatment, which is defined as either those women receiving treatment who have demonstrated a complete response (disappearance of all targeted lesions), a partial response (at least a 30 percent decrease in the sum of the diameters of the targeted lesions) or stable disease (no disease progression from baseline).  In February 2014, we reported that enobosarm 9 mg continues to be well tolerated by patients in the study, and that we expect to meet the pre-specified goal of demonstrating, after six months of treatment, at least three clinical benefit responses in at least 14 patients with AR positive and ER positive metastatic breast cancer. The study is ongoing and data from all patients in the study is expected late in the second quarter of 2014.

 

Additionally, we are developing GTx-758 (Capesaris®), an oral nonsteroidal selective ER alpha agonist, for secondary hormonal therapy in men with metastatic and nonmetastatic castration resistant prostate cancer, or CRPC, and, potentially, as a secondary hormonal treatment for advanced prostate cancer used in combination with androgen deprivation therapy, or ADT.  We believe GTx-758 has the potential to reduce free testosterone without also causing certain estrogen deficiency side effects, such as bone loss and hot flashes, which are common with current androgen deprivation therapies for prostate cancer.  We also believe that GTx-758 may be effective, in combination with ADT, as a secondary hormonal treatment of advanced prostate cancer by reducing free testosterone to levels lower than those attainable with ADT alone and potentially reducing the estrogen deficiency side effects caused by the use of ADT.

 

In May 2012, we announced that the FDA had removed its full clinical hold on our Investigational New Drug, or IND, application for GTx-758.  The full clinical hold was placed on our three then ongoing Phase 2 clinical trials evaluating GTx-758 to treat men with advanced prostate cancer in February 2012 and resulted in the discontinuation of these trials.  The full clinical hold followed our reports to the FDA of venous thromboembolic events (blood clots), or VTEs, in subjects treated with GTx-758 at the doses being studied in those trials (1000 mg and higher per day).  Based upon feedback from the FDA in connection with the removal of the full clinical hold, we initiated in the third quarter of 2012 a Phase 2 clinical trial to evaluate the safety and efficacy of lower doses of GTx-758 as secondary hormonal therapy in men with metastatic CRPC.

 

GTx is currently conducting a Phase 2 open-label clinical trial in men who have developed metastatic or nonmetastatic CRPC while on ADT.  GTx-758 has previously demonstrated the ability to increase the production of a protein called sex hormone binding globulin, or SHBG, that binds testosterone and thereby reduces free testosterone.  By reducing free testosterone, we believe serum prostate specific antigen, or PSA, will be reduced in men with CRPC.  The primary endpoint of the current Phase 2 clinical trial is the proportion of subjects with a > 50% decline from baseline in serum PSA by Day 90. Other key endpoints include serum SHBG and total and free testosterone levels, as well as prostate cancer progression, in the study subjects.   In addition, the clinical study will evaluate the ability of GTx-758 to treat certain estrogen deficiency side effects associated with luteinizing hormone releasing hormone, or LHRH, agonists such as hot flashes and bone loss.  The Phase 2 clinical trial allows us to assess the safety and tolerability of GTx-758 in these subjects, including the incidence of VTEs.  The original trial design provided for 75 total subjects to be enrolled in three sequential dosing arms, with the first 25 subjects in the study being enrolled in the GTx-758 125 mg dosing arm.  Assuming that an acceptable incidence of VTEs was observed when the last subject enrolled in the GTx-758 125 mg dosing arm completed one 30 day cycle of therapy, enrollment of the next 25 subjects would commence in the GTx-758 250 mg dosing arm.  Similarly, the GTx-758 500 mg dosing arm was to have commenced enrollment of the final 25 subjects when the last subject enrolled in the 250 mg dose arm completed one 30 day cycle of therapy, assuming an acceptable incidence of VTEs has been observed in both of the lower dosage arms and management had decided to continue testing at the next higher dose.  After reviewing data collected from the GTx-758 125 mg dosing arm indicating the ability of the drug to substantially increase SHBG and lower free testosterone without any unexpected side effects occurring, the clinical trial protocol was amended in the third quarter of 2013 to eliminate the 500 mg dosing arm and to increase the number of subjects to be enrolled in the 125 mg and the 250 mg dosing arms to 38 patients per arm. Enrollment in the 125 mg cohort has been completed without any occurrence of VTEs, and after a pre-specified safety review by the independent Data Safety Monitoring Board, we are now enrolling subjects in the 250 mg arm.  Depending upon

 

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the safety and efficacy data observed in the 125 mg cohort and assuming no safety issues are observed in the first ten metastatic patients enrolled in the 250 mg cohort, enrollment of the 250 mg cohort will be opened to individuals with metastatic or nonmetastatic CRPC.  The study is ongoing and data from all patients in the study is expected late in the second half of 2014.

 

At December 31, 2013, we had cash, cash equivalents and short-term investments of $14.7 million compared to $56.1 million at December 31, 2012.  On March 6, 2014, we completed a private placement of units consisting of 11,976,048 shares of common stock and warrants to purchase 10,179,642 shares of our common stock for gross proceeds of approximately $21.3 million.  If exercised in full, the warrants could result in additional gross proceeds of approximately $17.0 million.

 

In October 2013, we announced and implemented a plan to reduce our operating expenses, including a significant reduction in our workforce, in order to preserve capital while we evaluate feasible regulatory pathways for enobosarm 3 mg, conduct our two ongoing Phase 2 clinical trials of enobosarm 9 mg and GTx-758, and pursue discussions with potential partners.  Therefore, we are no longer conducting drug discovery activities and are focusing our research and development activities on the ongoing clinical development of our current product candidates.

 

Scientific Background on Estrogen and Androgen Hormones and

Selective Hormone Receptor Modulators

 

Estrogens and androgens are hormones that play critical roles in regulating the reproductive system and contributing to the homeostasis of the muscular, skeletal, cardiovascular, metabolic and central nervous systems.

 

Testosterone, the predominant androgen, is important for masculine physical characteristics, such as muscle size and strength and bone strength, as well as for mental well-being.  Male reproductive health is dependent on testosterone for sexual interest, fertility, erectile function and normal prostate function.  Testosterone is converted into a more potent androgen, dihydrotestosterone, or DHT, which acts as the primary androgen in the prostate, sebaceous glands and hair follicles, and may cause unwanted effects like benign prostatic hyperplasia, or BPH, acne and hair loss.  In aging men, there is a gradual decline in testosterone levels, which contributes to a loss of muscle mass and strength, erectile dysfunction, decreased sexual interest, depression and mood changes.  Moreover, in men, testosterone is converted to estradiol, the primary estrogen in men and women.  Estrogens improve bone quality and reduce the risk of hot flashes and skeletal fractures.

 

Estrogens and androgens perform their physiologic functions by binding to and activating their respective hormone receptors located in various tissues.  Once a hormone binds with its receptor, this activates a series of cellular events that results in the hormone specific tissue effects.

 

Pharmaceuticals that target estrogen or androgen receptors have been used medically for over 50 years.  The drugs that have been used to stimulate androgen receptors are either natural or synthetic hormones, known as anabolic/androgenic steroids.  Steroids are generally believed to activate hormone receptors in all tissue types in a non-selective manner resulting in not only beneficial effects but also in unwanted clinical effects.  In men, the lack of selectivity of testosterone and its conversion to DHT may result in unwanted side effects, such as the potential stimulation of latent into clinical prostate cancer, worsening of BPH, development or worsening of acne, or loss of hair in men.  Hair growth, acne and masculinization are also of concern in women who are exposed to exogenous testosterone.  To date, no orally available testosterone products have been approved for use in the United States.  Those testosterone products that are available must be administered by intramuscular injections or by transdermal patches or gels that may not be convenient for patients and, in some cases, can result in inconsistent blood levels of testosterone.

 

There are also classes of small molecules that are not steroids that can bind to the same hormone receptors. These nonsteroidal small molecules may either stimulate or block hormone receptors depending on the type of tissue in which the receptor is found and the interaction of the small molecule with the receptor.  A drug that has the ability to either block or stimulate the hormone receptor in this manner is called a selective hormone receptor modulator.  A selective hormone receptor modulator may be able to mimic the beneficial, while minimizing the unwanted, effects of natural or synthetic steroid hormones.

 

A SARM is a small molecule that binds to and selectively modulates androgen receptors, the primary receptor to which testosterone binds.  SARMs potentially have beneficial effects in muscle and bone while avoiding testosterone’s unwanted effects in the prostate in men or skin and hair in men and women.  Although no SARMs

 

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have been commercialized to date, we believe that SARMs, without the harmful side effects of testosterone or other exogenous anabolic steroid therapies, can potentially be developed to treat a range of medical conditions, including:

 

·                  muscle loss conditions of chronic diseases, such as cancer, AIDS, chronic kidney disease, end-stage renal disease, and neurodegenerative disorders;

·                  muscle loss of acute conditions such as trauma, burns, and rehabilitation;

·                  muscle loss conditions associated with aging such as frailty and chronic sarcopenia;

·                  the prevention and/or treatment of osteoporosis;

·                  disorders of the central nervous system, such as low libido, depression and other mood disorders;

·                  low testosterone conditions, such as primary and secondary hypogonadism;

·                  disorders of male reproductive functions, such as infertility and erectile dysfunction;

·                  androgen receptor positive breast cancer; and

·                  other conditions, such as anemia.

 

A selective ER alpha agonist is a nonsteroidal compound with the ability to preferentially bind and activate estrogen receptor alpha as compared to estrogen receptor beta.  GTx-758, a selective ER alpha agonist, has previously demonstrated the ability to increase serum concentrations of SHBG, an important serum protein that tightly binds to testosterone and regulates serum concentrations of unbound (free) testosterone. Free testosterone is the functionally active form of the hormone and is capable of passively diffusing into prostate cancer cells or is available to target tissues for androgen action.  We believe that GTx-758 may have the ability to treat men with advanced prostate cancer and men with metastatic and nonmetastatic CRPC by lowering serum free testosterone concentrations and lowering the incidences of hot flashes, bone loss or other side effects related to LHRH agonists and antagonists.

 

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Product Candidates

 

The following table identifies the development phase and status for each of our clinical product candidates:

 

Product Candidate/ Proposed Indication

 

Program

 

Clinical
Development
Phase

 

Status

Enobosarm

 

 

 

 

 

 

3 mg

 

 

 

 

 

 

Prevention and treatment of muscle wasting in patients with advanced NSCLC

 

SARM

 

Phase 3

 

Pursuing a potential MAA submission in the EU for the more narrow indication of advanced NSCLC patients treated with platinum plus taxane chemotherapy and planning to meet again with FDA to discuss a potential Phase 3 program.

 

 

 

 

 

 

 

Enobosarm

 

 

 

 

 

 

9 mg

 

 

 

 

 

 

Treatment of women with androgen receptor positive and estrogen receptor positive metastatic breast cancer

 

SARM

 

Phase 2

 

Completed enrollment of the Phase 2, open-label clinical trial. Data is expected late in the second quarter of 2014.

 

 

 

 

 

 

 

GTx-758

 

 

 

 

 

 

Secondary hormonal therapy in men with metastatic or nonmetastatic CRPC

 

Selective ER alpha agonist

 

Phase 2

 

Completed enrollment of the 125 mg cohort of the Phase 2 clinical trial for secondary hormonal therapy in men with metastatic CRPC and are currently enrolling the 250 mg cohort in both metastatic and nonmetastatic CRPC.

 

SARMs

 

SARMs are a new class of drugs with the potential to prevent and treat muscle wasting in patients with cancer and other musculoskeletal wasting or muscle loss conditions, including chronic sarcopenia, as well as the potential to be used as a novel hormonal therapy for the treatment of metastatic breast cancer.  Enobosarm has been evaluated in fourteen completed or ongoing clinical trials enrolling approximately 1,320 subjects, including in three Phase 2 and two Phase 3 clinical trials.

 

Enobosarm for the Prevention and Treatment of Muscle Wasting in Patients with Advanced NSCLC

 

Scientific Overview.  Muscle wasting, a cancer related symptom, can begin early in the course of cancer and frequently leads to cancer cachexia, a complex metabolic condition characterized by accelerated loss of skeletal muscle and severe weight loss.  Cancer cachexia is usually viewed as an end of life condition in patients with advanced or incurable malignancies.  The common clinical symptoms attributed to muscle wasting include decline in physical function and impaired immune function which contribute to increased disability, fatigue, diminished quality of life, and reduced survival.

 

Although muscle wasting associated with cancer can be partially attributed to poor nutrition, treatment with appetite stimulants and nutritional intervention alone is not effective, likely because they do not address the underlying catabolic processes responsible for muscle wasting.  Additionally, patients with severe weight loss, poor performance status, and metastatic cancer that is no longer responding to cancer treatment may be less likely to respond to single therapies designed to increase muscle mass and improve physical function.  Because muscle wasting, which often leads to refractory cancer cachexia, has a significant negative impact on the patient and their family, early prevention and treatment of muscle wasting are critical.

 

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Enobosarm is an oral nonsteroidal SARM which means that it is similar to testosterone in activating androgen receptors in muscle, thereby potentially promoting lean body mass (muscle) and improving physical function, while avoiding other effects which have been observed with testosterone such as hair growth, stimulation of sebaceous glands, the cause of acne, or enhanced growth of the prostate, which may exacerbate BPH or stimulate prostate cancer.

 

Potential Market.  Lung cancer accounts for more deaths than any other cancer in both men and women.  Worldwide, there are an estimated 1.5 million new cases and approximately 1.3 million deaths annually.  In the United States, there are approximately 225,000 new cases and 160,000 deaths attributed to lung cancer each year.  Approximately 85% of all newly diagnosed lung cancers are NSCLC.  Approximately 186,000 new cases of NSCLC are diagnosed each year in the top five markets of the European Union and up to 30% of these patients will be treated with a taxane as first line chemotherapy.  Up to 50% of NSCLC patients have severe muscle wasting at diagnosis with the majority developing severe wasting throughout the course of their disease.  Body functional limitations, such as the inability to walk up or down steps without rest, or the inability to lift 10 pounds, are present in almost 90% of lung cancer survivors.

 

There are currently no drugs approved for the prevention or treatment of muscle wasting in patients with advanced NSCLC.  Supplemental nutritional support alone has little or no benefit in counteracting muscle wasting in cancer patients.  Although there are two commercially available steroids, nandrolone and oxandrolone, that are sometimes prescribed off-label for the treatment of weight loss in cancer patients, chronic use of these drugs may result in liver toxicity or other adverse events and has limited their use.  Appetite stimulants such as Megace® (megestrol acetate) and dronabinol are also used off-label for weight loss and loss of appetite in patients with cancer.  Additionally, there are other companies developing drugs for the treatment of muscle wasting, appetite stimulation and cachexia.  These compounds may compete with enobosarm if approved for commercial sale.

 

Clinical Trials.  In July 2007, we initiated a Phase 2b randomized, double blind, placebo-controlled clinical trial evaluating enobosarm for the treatment of muscle wasting in 159 patients diagnosed with NSCLC, colorectal cancer, non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, or breast cancer.   In October 2008, we announced top line results of this clinical trial.  The study met its primary endpoint of absolute change in total lean body mass compared to placebo and the secondary endpoint of physical function, measured by stair climb, after 16 weeks of treatment.

 

We held End of Phase 2 meetings with the FDA prior to initiating our Phase 3 clinical development of enobosarm for the prevention and treatment of muscle wasting in patients with advanced NSCLC. Based upon data from our Phase 2 clinical trials and with feedback from the FDA, we designed the POWER 1 and POWER 2 Phase 3 clinical trials evaluating enobosarm for this indication.  We also met with representatives from two member countries to the EMA, who confirmed that the design of the POWER 1 and POWER 2 clinical trials should be sufficient for the EMA to support registration in Europe.  We conducted the POWER trials at sites in the United States, Europe, Russia and South America.  Each of the placebo-controlled, double-blind clinical trials was fully enrolled during the fourth quarter of 2012, with approximately 325 patients in each clinical trial.  In each of these clinical trials, patients with Stage III or IV NSCLC were randomized to placebo or enobosarm 3 mg at the time they began first line standard platinum doublet chemotherapy.  The only difference in the two clinical trials was that patients enrolled in the POWER 1 trial received a platinum plus taxane chemotherapy while patients enrolled in the POWER 2 trial were treated with platinum plus non-taxane chemotherapy. The last patients completed the Phase 3 clinical trials in May 2013.  The vital status (survival) of patients participating in the trials is continuing to be periodically monitored in accordance with the clinical trial protocols to assess whether the survival of enobosarm treated patients is adversely affected.  This assessment will continue until there are 450 deaths among all patients participating in the two clinical trials.  To date, there has been no detrimental effect on survival of enobosarm treated patients as evidenced by the trials.

 

The POWER trials evaluated the effect of enobosarm versus placebo on the co-primary endpoints of total lean body mass (muscle) assessed by dual x-ray absorptiometry, or DXA, and of physical function assessed by the Stair Climb Test at three months of treatment. Durability of effect of enobosarm was assessed as a secondary endpoint at five months in those patients who demonstrated a lean body mass, or LBM, response at Day 84.  In the POWER trials, we failed to meet the primary statistical criterion for the co-primary endpoints of LBM and physical function assessed by responder analysis as agreed upon by the FDA.  The responder analysis of the co-primary endpoints showed mixed results (for POWER 1 and POWER 2, p values at Day 84 for LBM were 0.036 and 0.113, respectively, and p values at Day 84 for stair climb power, or SCP, were 0.315 and 0.289, respectively).  However, when the same endpoints were assessed using another statistical test, the continuous variable analysis, which was

 

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pre-specified in our statistical analysis plan for the EMA, enobosarm 3 mg demonstrated significant improvement in the primary endpoint of SCP, compared to placebo, in the POWER 1 trial (p value of 0.0147) but did not show statistically significant improvement in SCP in the POWER 2 trial (p value of 0.7923).  The continuous variable analysis of LBM was pre-specified as a key secondary endpoint.  Enobosarm had a statistically significant improvement in LBM, compared to placebo, in both POWER trials (p values were 0.0002 and 0.0227 at Day 84 for POWER 1 and POWER 2, respectively).  Across both clinical trials, enobosarm was generally well tolerated, with the occurrence of serious adverse events and overall incidence of adverse events similar across placebo and treatment groups.  In POWER 1, the four most common adverse events reported (in decreasing order of incidence) were nausea, alopecia, anemia and vomiting.  In POWER 2, the four most common adverse events reported were anemia, nausea, neutropenia and vomiting.  In the safety analysis of survival, there has been no evidence that the survival of enobosarm treated patients had been adversely affected by the drug candidate.

 

Regulatory Initiatives.  Based on agreement with the FDA, we pre-specified the statistical test of a responder analysis of the co-primary endpoints of LBM and SCP at Day 84.  A responder analysis categorizes each subject as either a success or failure, where subjects who did not remain on the trial through the Day 84 visit are labeled as a non-responder, regardless of their reason for discontinuation, including death.  However for EMA regulatory purposes, we pre-specified in our statistical analysis plan that the primary endpoint would be SCP through Day 84, with LBM through Day 84 being the key secondary endpoint, and the data would be analyzed by a statistical test called continuous variable analysis.  A continuous variable analysis utilizes all available data for each subject from their previous clinical visits, so subjects without Day 84 data can still contribute to the analysis via their Day 42 assessment.  Since enobosarm 3 mg demonstrated a statistically significant effect versus placebo on the primary endpoint of physical function through Day 84 in the POWER 1 trial, assessed by continuous variable analysis, as pre-specified in our statistical analysis plan for the EMA, we met with representatives from two member countries to the EMA in January of 2014 to review and discuss the results of the POWER trials to determine an appropriate path forward for submitting a MAA in the European Union for enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced NSCLC.  We believe data from the POWER 1 trial (platinum plus taxane chemotherapy) is sufficient to support the submission of a MAA for the more narrow indication of the prevention and treatment of muscle wasting in patients with advanced NSCLC treated with platinum plus taxane chemotherapy, and that the confounding results in SCP from the POWER 2 trial can be explained by the effects of the chemotherapy toxicity on the patients receiving platinum plus non-taxane chemotherapy.  We plan to initiate seven Phase 1 clinical studies that are typically required for registration purposes and develop a PIP necessary for submission of the MAA.  We currently expect to submit the MAA to the EMA for enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced NSCLC treated with platinum plus taxane chemotherapy by the first quarter of 2015, after completion of the Phase 1 studies and acceptance of the PIP by the EMA’s Pediatric Committee.

 

In our meeting with the FDA in February 2014 to review and discuss the results of the POWER clinical trials, we learned that since data from the two POWER trials failed to meet the primary statistical criterion pre-specified for the co-primary endpoints of lean body mass and physical function, the FDA was not willing to accept a NDA for enobosarm 3 mg. However, based on input from the FDA meeting, we believe there is a regulatory path forward for enobosarm 3 mg in the United States, and we plan to meet again with the FDA to discuss a potential Phase 3 clinical program evaluating enobosarm 3 mg for an indication of muscle wasting or cachexia in patients with NSCLC.  Any such Phase 3 clinical trial program would be subject to our ability to obtain additional funding and would be required to be successfully completed prior to any NDA submission to the FDA for enobosarm 3 mg.

 

Enobosarm for the Treatment of AR Positive and

ER Positive Metastatic Breast Cancer

 

Scientific Overview.  Clinical assessment of breast cancer includes routine characterization of receptor status including the presence or absence of ER, progesterone receptor, and human epidermal growth factor receptor 2 in the tumor tissue.  Receptor status is used to guide treatment decisions.  Hormonal manipulation with selective ER modulators, ER antagonists, or aromatase inhibitors is the standard treatment given to patients with tumors that are positive for the ER.

 

The AR is the most commonly expressed steroid receptor in breast cancer with approximately 75-90% of ER positive and approximately 50% of ER negative breast cancers expressing AR. Prior studies have shown that women with metastatic breast cancer, treated with tamoxifen who then progress, subsequently respond to steroidal androgens. Although steroidal androgens have been used to treat breast cancer, unwanted virilizing side

 

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effects such as body and facial hair growth, acne and deepening of voice, have limited their widespread clinical use. Enobosarm may provide a targeted approach by exploiting the therapeutic benefits of a selective nonsteroidal androgen therapy without concerns of masculinization or conversion to estrogen.

 

Potential Market.  Breast cancer is the most commonly diagnosed cancer in women with one in eight women developing invasive breast cancer during their lifetime.  In 2011, 2.9 million women with a history of breast cancer were living in the United States.  An estimated 20-30% of women diagnosed with invasive breast cancer will have a recurrence or metastasis. In 2014, an estimated 230,000 new cases of breast cancer will be diagnosed in women in the United States.  Approximately 6% of these women will already have metastatic disease at time of diagnosis.

 

Currently, treatment approaches to postmenopausal hormonally sensitive breast cancer include antiestrogens (tamoxifen, toremifene) and aromatase inhibitors (letrozole, anastrazole, exemestane).  Fulvestrant, an injectable ER antagonist, is indicated for the treatment of hormone receptor positive metastatic breast cancer in postmenopausal women after progression on antiestrogen therapy. Enobosarm may represent a novel therapeutic option for the treatment of postmenopausal metastatic breast cancer in women who have progressed on previous hormonal therapy.

 

Clinical Trial.  In the second quarter of 2013, we initiated a Phase 2 open label study evaluating enobosarm 9 mg for the treatment of AR positive and ER positive metastatic breast cancer in women who have previously responded to hormonal therapy for the treatment of their metastatic breast cancer.  Nine clinical study sites in the U.S. have fully enrolled the study with 22 postmenopausal women with metastatic breast cancer to assess clinical benefit response after six months of enobosarm 9 mg treatment, which is defined as either those women receiving treatment who have demonstrated a complete response (disappearance of all targeted lesions), a partial response (at least a 30 percent decrease in the sum of the diameters of the targeted lesions) or stable disease (no disease progression from baseline).  In February 2014, we reported that enobosarm 9 mg continues to be well tolerated by patients in the study, and that we expect to meet the pre-specified goal of demonstrating, after six months of treatment, at least three clinical benefit responses in at least 14 patients with AR positive and ER positive breast cancer. The study is ongoing and data from all patients in the study is expected late in the second quarter of 2014.

 

Selective ER Alpha Agonist

 

GTx-758 for the secondary hormonal treatment of CRPC

 

Scientific Overview.  ADT is the most common treatment for patients who have advanced prostate cancer.  ADT reduces testosterone, a primary growth factor for prostate cancer, to castrate levels.  ADT is currently accomplished either surgically by removal of the testes or chemically by injection with LHRH agonists or antagonists.  These LHRH agents work by shutting off LH secretion by the pituitary gland thereby stopping testosterone production by the testes. The reduction in testosterone by ADT also results in very low estrogen levels in men because estrogen is derived from testosterone.  Estrogen deficiency side effects associated with LHRH therapies may include bone loss and fractures, adverse lipid changes, hot flashes, gynecomastia, decreased libido, impaired cognitive function, increase in body fat composition, metabolic syndrome, diabetes and cardiovascular disease.  We believe GTx-758 has the potential to reduce free testosterone without also causing certain estrogen deficiency side effects, such as bone loss and hot flashes, which are common with current androgen deprivation therapies for prostate cancer.

 

Potential Market.  We are developing GTx-758 for secondary hormonal therapy in men with metastatic and nonmetastatic CRPC, and, potentially, as a secondary hormonal treatment for advanced prostate cancer used in combination with ADT.  We believe that GTx-758 may be effective, in combination with ADT, as a secondary hormonal treatment of advanced prostate cancer by reducing free testosterone, the unbound biologically active form of testosterone, to levels lower than those attainable with ADT alone and potentially reducing the estrogen deficiency side effects caused by the use of ADT.

 

In the United States alone, we believe there are approximately 80,000 men who have developed resistance to LHRH therapies and therefore have CRPC but who have not received chemotherapy. We believe there are approximately 36,000 men diagnosed each year with metastatic hormone sensitive prostate cancer.  Zytiga® is currently the only drug approved for the treatment of metastatic CRPC in patients who have not yet received chemotherapy, although several other drugs are in clinical development for this indication.  We believe new hormonal therapies in development, if approved, will be used prior to chemotherapy as physicians and patients look for treatment options capable of delaying cancer progression and possibly prolonging survival prior to

 

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chemotherapy.

 

In the United States, there are currently approximately 750,000 men with nonmetastatic hormone sensitive prostate cancer and approximately 60,000 new cases are diagnosed each year.  For hormone sensitive advanced prostate cancer, ADT is the most common treatment.  There are no approved androgen deprivation therapies designed to significantly minimize estrogen deficiency side effects, including bone loss, fractures, insulin resistance and hot flashes.  For many men on ADT, physicians are currently prescribing certain drugs, some of them on an off-label basis, to help ameliorate some of the specific estrogen deficiency related side effects of ADT.  These drugs include the use of estrogen patches and compounds, as well as, off-label use of bisphosphonates for osteoporosis and Megace® (megestrol acetate) for hot flashes.

 

Our ability to develop GTx-758 as an effective secondary hormonal therapy for men with metastatic and nonmetastatic CRPC or potentially, as a secondary hormonal treatment for advanced prostate cancer used in combination with ADT, is dependent on our ability to find an appropriate dose that is both effective and safe for these patient populations.

 

Clinical Trials.  In 2009, we evaluated GTx-758 in healthy male volunteers in two Phase 1 clinical trials, including a ten day multiple ascending dose study in 61 subjects where GTx-758 demonstrated the ability to increase serum SHBG and to reduce serum total and free testosterone.  In September 2010, we announced that in a Phase 2, open label, pharmacokinetic and pharmacodynamic clinical trial in young healthy male volunteers, GTx-758 suppressed serum total testosterone to castrate levels (levels of serum total testosterone less than 50ng/dL), increased serum SHBG, and reduced serum free testosterone, the form of testosterone which is available to prostate cancer cells for growth.  The percentage of treatment compliant subjects receiving 1500 mg of GTx-758 who achieved medical castration was comparable to rates of castration observed with LHRH agonists or antagonists therapies.  In May 2011, we completed a Phase 1 clinical trial of GTx-758 using a tablet formulation in older healthy male volunteers.  In this trial, reductions in testosterone to medical castration levels, increases in SHBG and decreases in free testosterone were observed in GTx-758 doses given orally each day.

 

We designed two Phase 2 clinical trials to identify an appropriate dose of GTx-758 to achieve and maintain medical castration (less than 50ng/dL) from Day 28 to Day 364 in men with advanced prostate cancer.  In June 2011, we initiated the Phase 2 maintenance dose finding clinical trial evaluating GTx-758 1000 mg and 2000 mg once-a-day doses compared to Lupron Depot® (leuprolide acetate for depot suspension) in 164 men with advanced prostate cancer.  We also initiated the Phase 2 loading dose finding clinical trial evaluating 1000 mg and 1500 mg doses twice-a-day to medically castrate men by Day 28 in 104 men with advanced prostate cancer. After Day 28, castrate patients were to continue treatment on one of two once-a-day doses of GTx-758, 2000 mg or 1000 mg, until Day 360.  We were also conducting a second line hormonal therapy Phase 2 clinical trial evaluating GTx-758 2000 mg once-a-day dose in 25 men with CRPC.  The objective of this trial was to determine the ability of GTx-758 to reduce serum PSA and the duration of this PSA reduction in men with CRPC who are currently receiving ADT.  On February 21, 2012, we announced that the FDA had placed a full clinical hold on our IND application for GTx-758, effective February 17, 2012, causing us to stop all three of these clinical trials.  The full clinical hold followed our reports to the FDA of VTEs (blood clots) in subjects treated with GTx-758 at the doses being studied in the trials (1000 mg and higher per day).  There were two deaths in subjects treated with GTx-758 and two deaths in subjects treated with Lupron Depot®.  As a result of the full clinical hold, we suspended further enrollment into these three trials and notified clinical sites to discontinue treatment of subjects with GTx-758.

 

In May 2012, we announced that the FDA had removed its full clinical hold on our IND for GTx-758.  Based upon feedback from the FDA in connection with the removal of the full clinical hold, in the third quarter of 2012 we initiated a Phase 2 clinical trial to evaluate the safety and efficacy of three lower doses of GTx-758 as secondary hormonal therapy in men with metastatic CRPC.

 

GTx is currently conducting a Phase 2 open-label clinical trial in men who have developed metastatic or nonmetastatic CRPC while on ADT.  GTx-758 has previously demonstrated the ability to increase the production of a protein called SHBG that binds testosterone and thereby reduces free testosterone.  By reducing free testosterone, we believe serum PSA will be reduced in men with CRPC.  The primary endpoint of the current Phase 2 open-label clinical trial is the proportion of subjects with a > 50% decline from baseline in serum PSA by Day 90. Other key endpoints include serum SHBG and total and free testosterone levels, as well as prostate cancer progression, in the study subjects.   In addition, the clinical study will evaluate the ability of GTx-758 to treat certain estrogen deficiency side effects associated with currently available ADT agents such as hot flashes and bone loss.  The Phase 2 clinical trial will allow us to assess the safety and tolerability of GTx-758 in these subjects, including the incidence of VTEs.  The original trial design provided for 75 total subjects to be enrolled in three sequential dosing arms, with

 

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the first 25 subjects in the study being enrolled in the GTx-758 125 mg dosing arm.  Assuming that an acceptable incidence of VTEs was observed when the last subject enrolled in the GTx-758 125 mg dosing arm completed one 30 day cycle of therapy, enrollment of the next 25 subjects would commence in the GTx-758 250 mg dosing arm.  Similarly, the GTx-758 500 mg dosing arm was to have commenced enrollment of the final 25 subjects when the last subject enrolled in the 250 mg dose arm completed one 30 day cycle of therapy, assuming an acceptable incidence of VTEs has been observed in both of the lower dosage arms and management had decided to continue testing at the next higher dose.  After reviewing data collected from the GTx-758 125 mg dosing arm indicating the ability of the drug to substantially increase SHBG and lower free testosterone without any unexpected side effects occurring, the clinical trial protocol was amended in the third quarter of 2013 to eliminate the 500 mg dosing arm and to increase the number of subjects to be enrolled in the 125 mg and the 250 mg dosing arms to 38 patients per arm.  Enrollment in the 125 mg cohort has been completed without any occurrence of VTEs, and after a pre-specified safety review by the independent Data Safety Monitoring Board, we are now enrolling subjects in the 250 mg arm.  Depending upon the safety and efficacy data observed in the 125 mg cohort and assuming no safety issues are observed in the first ten metastatic patients enrolled in the 250 mg cohort, enrollment of the 250 mg cohort will be opened to individuals with metastatic or nonmetastatic CRPC.  The study is ongoing and data from all patients in the study is expected late in the second half of 2014.

 

Our Strategy

 

Our objective is to discover, develop and commercialize small molecules for the treatment of cancer, including treatments for prostate and breast cancer, cancer supportive care, prevention and treatment of cancer-related muscle wasting or cachexia, and other serious medical conditions.  Key elements of our strategy to achieve these objectives are to:

 

Pursue Clinical Development of Enobosarm and Related Regulatory Initiatives.  Based upon the results of our POWER 1 clinical trial, as well as supporting data from the POWER 2 clinical trial, we plan to submit a MAA by the first quarter of 2015 to the EMA for enobosarm 3 mg for the more narrow indication of the prevention and treatment of muscle wasting in patients with advanced NSCLC treated with platinum plus taxane chemotherapy. We also plan to meet again later this year with the FDA to discuss a potential Phase 3 program for enobosarm 3 mg to prevent and treat muscle wasting or cachexia in patients with NSCLC. We will continue to evaluate whether to enter into strategic partnerships or collaborations for the development and commercialization of this product candidate or to continue to pursue development efforts in the European Union, and potentially in the United States, on our own.  In any event, significant additional funding would be required for us to conduct and complete any additional Phase 3 clinical trials of enobosarm.  We are also developing enobosarm for the treatment of AR positive and ER positive metastatic breast cancer in women who have previously responded to hormonal therapy for the treatment of their metastatic breast cancer.  Assuming positive results are achieved from our ongoing Phase 2 clinical study, we will meet with members of our enobosarm breast cancer steering committee to seek input on the design and implementation for additional clinical studies for this product candidate, the conduct and completion of which would be subject to our ability to obtain additional funding. Additionally, subject to additional funding, we may develop enobosarm for other indications in patients who could benefit from the treatment of enobosarm.

 

Pursue Clinical Development of GTx-758.  Assuming the receipt of positive data from our ongoing Phase 2 clinical trial to evaluate the safety and efficacy of lower doses of GTx-758 as secondary hormonal therapy in men with metastatic and nonmetastatic CRPC, we plan to initiate additional clinical trials in order to seek marketing authorization for this product candidate.

 

Licenses and Collaborative Relationships

 

In addition to our internally-developed and discovered small molecules, we have established and intend to continue to pursue licenses from and collaborative relationships with pharmaceutical companies and academic institutions to further the development and potential commercialization of our product candidates.  While we currently have no ongoing collaborations for the development and commercialization of our product candidates, our strategy includes selectively partnering or collaborating with leading pharmaceutical and biotechnology companies to assist us in furthering the development and potential commercialization of our product candidates.

 

In July 2007, we and the University of Tennessee Research Foundation, or UTRF, entered into a consolidated, amended and restated license agreement, or the SARM License Agreement, to consolidate and replace our two previously existing SARM license agreements with UTRF and to modify and expand certain rights and obligations

 

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of each of the parties under both license agreements.  Pursuant to the SARM License Agreement, we were granted exclusive worldwide rights in all existing SARM technologies owned or controlled by UTRF, including enobosarm, and certain improvements thereto, and exclusive rights to certain future SARM technology that may be developed by certain scientists at the University of Tennessee or subsequently licensed to UTRF under certain existing inter-institutional agreements with The Ohio State University. Unless terminated earlier, the term of the SARM License Agreement will continue, on a country-by-country basis, for the longer of 20 years or until the expiration of the last valid claim of any licensed patent in the particular country in which a licensed product is being sold. UTRF may terminate the SARM License Agreement for our uncured breach or upon our bankruptcy.

 

Under the SARM License Agreement, we paid UTRF a one-time, upfront fee of $290,000 as consideration for entering into the SARM License Agreement.  We are also obligated to pay UTRF annual license maintenance fees, low single-digit royalties on net sales of products and mid-single-digit royalties on sublicense revenues. During the year ended December 31, 2007, we paid UTRF a sublicense royalty of approximately $1.9 million as a result of our previous collaboration with Merck & Co., Inc.  We also agreed to pay all expenses to file, prosecute and maintain the patents relating to the licensed SARM technologies, and are obligated to use commercially reasonable efforts to develop and commercialize products based on the licensed SARM technologies. In December 2008, we and UTRF amended the SARM License Agreement, or the SARM License Amendment, to, among other things, clarify the treatment of certain payments that we may receive from our current and future sublicensees for purposes of determining sublicense fees payable to UTRF, including the treatment of payments made to us in exchange for the sale of our securities in connection with sublicensing arrangements. In consideration for the execution of the SARM License Amendment, we paid UTRF $494,000.

 

Manufacturing

 

We do not currently own or operate manufacturing facilities, and we rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our product candidates.

 

There are no complicated chemistries or unusual equipment required in the manufacturing process for enobosarm.  The active ingredient in enobosarm is manufactured using a five-step synthetic process that uses commercially available starting materials for each step.  Enobosarm drug product is manufactured using conventional manufacturing technology without the use of novel excipients.  We rely on third-party vendors for drug substance and drug product manufacturing.

 

There are no complicated chemistries or unusual equipment required in the manufacturing process for GTx-758.  The active ingredient in GTx-758 is manufactured using a three-step synthetic process that uses commercially available starting materials for each step.  GTx-758 drug product is manufactured using conventional manufacturing technology without the use of novel excipients.  We rely on third-party vendors for the manufacture of GTx-758 drug substance and drug product.

 

Competition

 

The biotechnology and biopharmaceutical industries are characterized by rapidly advancing technologies, intense competition and a strong emphasis on proprietary products.  We face competition from many different sources, including commercial pharmaceutical and biotechnology enterprises, academic institutions, government agencies and private and public research institutions.

 

Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing approved products than we do.  Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies.  Our commercial opportunities will be reduced or eliminated if our competitors develop and commercialize similar products that are safer, more effective, have fewer side effects or are less expensive than any products that we and/or our collaborators may develop.

 

Enobosarm for the Prevention and Treatment of Muscle Wasting in Patients with Advanced NSCLC

 

There are currently no drugs approved for the prevention or treatment of muscle wasting in patients with advanced NSCLC. Although there are two commercially available steroids, nandrolone and oxandrolone, that

 

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are sometimes prescribed off-label for the treatment of weight loss in cancer patients, chronic use of these drugs may result in liver toxicity or other adverse events and has limited their use.  For example, oxandrolone has a black box warning for liver toxicity as well as warnings and precautions related to increased risk for prostate cancer in men and virilization in women.  Oxandrolone is indicated as an adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections and severe trauma, and in some patients who without pathophysiologic reasons fail to maintain normal weight and to offset the protein catabolism associated with prolonged administration of corticosteroids.

 

Testosterone products have been used off-label to treat secondary hypogonadism.  Owing to their potentially unwanted effects and inconvenient dosing, we believe that testosterone products have had a limited impact on the market for muscle wasting.  There are other SARM product candidates in development that may compete with our SARM product candidates if approved, including SARMs in development from Ligand Pharmaceuticals, Inc. and GlaxoSmithKline plc.  Pfizer, Inc., Eli Lilly and Company, and Amgen Inc. have previously reported myostatin inhibitors in development that may compete with enobosarm if approved for commercial sale. In addition, Cytokinetics, Inc. is developing a troponin activator with a muscle specific mechanism in Phase 2 studies with a focus on neurological muscle diseases (amyotrophic lateral sclerosis and myasthenia gravis) and Novartis AG is developing a human monoclonal antibody for various muscle indications.  Moreover, there are other categories of drugs in development, including ghrelin receptor agonists, growth hormone, secretagogues, inflammatory modulators, and other agents, that may have some muscle activity. Helsinn Group is developing anamorelin, a ghrelin receptor agonist, in Phase 3 clinical trials for the treatment of cancer cachexia in patients with NSCLC.  Appetite stimulants such as Megace® (megestrol acetate) and dronabinol are also used off-label for weight loss and loss of appetite in patients with cancer.

 

GTx-758 for the Secondary Hormonal Treatment of CRPC

 

There are various products approved or under clinical development to treat men with advanced prostate cancer who have metastatic CRPC which may compete with GTx-758.  Dendreon Corporation markets and sells Provenge®, an autologous cellular immunotherapy, for the treatment of asymptomatic or minimally symptomatic metastatic CRPC.  Zytiga®, sold by Johnson & Johnson, has been approved for the treatment of metastatic CRPC in both patients who have and have not received prior chemotherapy.  Medivation, Inc. has received approval for Xtandi®, an oral androgen receptor antagonist, for the treatment of metastatic CRPC in men previously treated with docetaxel.  Medivation continues to develop Xtandi® for men with metastatic CRPC prior to receiving chemotherapy.  Johnson & Johnson acquired Aragon Pharmaceuticals, Inc., which developed a second generation anti-androgen (ARN-509) that is currently being evaluated in Phase 2 studies in men with progressive, advanced prostate cancer.  Millennium: The Takeda Oncology Company is developing TAK-700 for the treatment of men with metastatic CRPC prior to chemotherapy.  GTx-758 is being developed as a treatment for this same patient population prior to the initiation of chemotherapy.

 

Intellectual Property

 

We will be able to protect our technology from unauthorized use by third parties only to the extent it is covered by valid and enforceable patents or is effectively maintained as trade secrets. Patents and other proprietary rights are an essential element of our business.

 

For enobosarm and our other SARM compounds, we have an exclusive license from UTRF under its issued patents and pending patent applications in the United States, Canada, Australia, Japan, China and other countries in Asia, before the European Patent Office designating Germany, Great Britain, Spain, France, Italy, and other European Union countries, as well as in certain other countries outside those regions, covering the composition of matter of the active pharmaceutical ingredient for pharmaceutical products, pharmaceutical compositions and methods of synthesizing the active pharmaceutical ingredients. We have also exclusively licensed from UTRF issued and pending patent applications in the United States, Canada, Australia, Japan, China and other countries in Asia, before the European Patent Office designating Germany, Great Britain, Spain, France, Italy and other European Union countries, as well as in certain other countries outside those regions, related to methods for treating muscle wasting disorders, including cancer cachexia, and for treating sarcopenia and increasing muscle performance, muscle size and muscle strength and increasing the strength of or mass of a bone and for treating bone related disorders, including bone frailty and osteoporosis.  The patents we licensed from UTRF and issued in the United States for enobosarm expire in 2024.  Issued patents for our other SARM compounds in the United States will expire between 2021 and 2029, depending on the specific SARM compound.  The patents we licensed from UTRF and issued outside of the United States for enobosarm expire in 2025, and with respect to other SARM

 

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compounds, expire in 2021, 2023, and 2027, depending on the specific SARM compound.  We have pending patent applications for enobosarm and our other SARM compounds that, if issued, would expire in the United States and in countries outside the United States in 2025 and 2027, depending on the specific SARM compound. We have pending patent applications for SARMs in combination with anti-cancer agents that, if issued, would expire in the United States in 2024 and in countries outside the United States in 2028.

 

We have our own issued and pending patent applications in the United States, Canada, Australia, Europe, Japan, China and other countries in Asia, as well as in certain other countries outside those regions, related to solid forms of enobosarm. Issued patents covering solid forms of enobosarm in the United States will expire in 2028.  Pending patent applications in countries outside of the United States will expire in 2028.  We have our own pending patent applications in the United States and as an International Application related to methods of treating breast cancer using our SARM compounds. Such patent applications, if issued, would expire in 2033 in the United States and outside of the United States. We also have an allowed United States Application directed to methods of treating eye disorders using our SARM compounds and pending applications in Canada, Australia, Europe,  Japan, China and other countries in Asia, as well as in certain other countries outside those regions. The issued patent in the United States related to eye disorders will expire in 2031 and patent applications outside the United States, if issued, would expire in 2031.

 

We have our own pending patent applications in the United States, Australia, Canada, before the European Patent office designating Germany, Great Britain, Spain, France, Italy and other European Union countries, Japan, and other jurisdictions internationally covering GTx-758 as the composition of matter of the active pharmaceutical ingredient for products developed with this compound and for pharmaceutical compositions and/or methods of treating advanced prostate cancer and treating bone loss, bone fractures, bone mineral density and osteoporosis in male subjects with prostate cancer having undergone androgen deprivation therapy.  Issued patents covering composition of matter for GTx-758 in the United States will expire in 2029, and pending patent applications in the United Sates covering GTx-758 method of use will expire in 2029 and 2030.  Pending patent applications in countries outside of the United States will expire between 2026 and 2030.

 

We cannot be certain that any of our patent applications, or those of our licensors, will result in issued patents. In addition, because the patent positions of biopharmaceutical companies are highly uncertain and involve complex legal and factual questions, the patents we own and license, or any further patents we may own or license, may not prevent other companies from developing similar or therapeutically equivalent products.  Patents also will not protect our product candidates if competitors devise ways of making or using these product candidates without legally infringing our patents.  In recent years, several companies have been extremely aggressive in challenging patents covering pharmaceutical products, and the challenges have often been successful. We cannot be assured that our patents will not be challenged by third parties or that we will be successful in any defense we undertake. Failure to successfully defend a patent challenge could materially and adversely affect our business.

 

In addition, changes in either patent laws or in interpretations of patent laws in the United States and other countries may materially diminish the value of our intellectual property or narrow the scope of our patent protection.  On September 16, 2011, the Leahy-Smith America Invents Act, or the Leahy-Smith Act, was signed into law. The Leahy-Smith Act includes a number of significant changes to United States patent law. These include provisions that affect the way patent applications will be prosecuted and may also affect patent defense and enforcement.  Accordingly, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material adverse effect on our business and financial condition.

 

We also rely on trade secrets, technical know-how and continuing innovation to develop and maintain our competitive position. We seek to protect our proprietary information by requiring our employees, consultants, contractors, outside scientific collaborators and other advisors to execute non-disclosure and confidentiality agreements and our employees to execute assignment of invention agreements to us on commencement of their employment. Agreements with our employees also prevent them from bringing any proprietary rights of third parties to us. We also require confidentiality or material transfer agreements from third parties that receive our confidential data or materials.

 

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Government Regulation

 

New Drug Development and Approval Process

 

Numerous governmental authorities in the United States and other countries extensively regulate the testing, clinical development, manufacturing and marketing of pharmaceutical products and ongoing research and development activities. In the United States, the FDA rigorously reviews pharmaceutical products under the Federal Food, Drug, and Cosmetic Act and applicable regulations. Non-compliance with FDA regulations can result in administrative and judicial sanctions, including warning letters, clinical holds, fines, recall or seizure of products, injunctions, total or partial suspension of production, refusal of the government to approve marketing applications or allow entry into supply contracts, refusal to permit import or export of products, civil penalties, criminal prosecution and other actions affecting a company and its products. The FDA also has the authority to revoke previously granted marketing authorizations.

 

To secure FDA approval, an applicant must submit extensive preclinical and clinical data, as well as information about product manufacturing processes and facilities and other supporting information to the FDA for each indication to establish a product candidate’s safety and efficacy. The development and approval process takes many years, requires the expenditure of substantial resources and may be subject to delays or limitations of approval or rejection of an applicant’s new drug application, or NDA. Even if the FDA approves a product, the approval is subject to post-marketing surveillance, adverse drug experience and other recordkeeping and reporting obligations, and may involve ongoing requirements for post-marketing studies. The FDA also has authority to place conditions on any approvals that could restrict the commercial applications, advertising, promotion or distribution of these products. Product approvals may be withdrawn if compliance with regulatory standards is not maintained or if problems occur following initial marketing.

 

Preclinical and Clinical Testing

 

Preclinical studies involve laboratory evaluation of product characteristics and animal studies to assess the biological activity and safety of the product. In some cases, long-term preclinical studies are conducted while clinical studies are ongoing. The FDA, under its Good Laboratory Practices regulations, regulates preclinical studies. Violations of these regulations can, in some cases, lead to invalidation of the studies, requiring these studies to be replicated. When the preclinical testing is considered adequate by the sponsor to demonstrate the safety and scientific rationale for initial human studies, the results of the preclinical tests, together with manufacturing information and analytical data, are submitted to the FDA as part of an IND. The IND becomes effective, if not rejected by the FDA, within 30 days after the FDA receives the IND. The FDA may, either during the 30-day period after filing of an IND or at any future time, impose a clinical hold on proposed or ongoing clinical trials on various grounds, including that the study subjects are or would be exposed to an unreasonable and significant health risk. If the FDA imposes a clinical hold, clinical trials cannot commence or recommence without FDA authorization and then only under terms authorized by the FDA.

 

Clinical trials involve the administration of the investigational product candidates to humans under the supervision of a qualified principal investigator. Clinical trials must be conducted in accordance with Good Clinical Practices under protocols submitted to the FDA as part of the IND. In addition, each clinical trial must be approved and conducted under the auspices of an Investigational Review Board, or IRB, and with patient informed consent. The IRB typically considers, among other things, ethical factors and the safety of human subjects.

 

Clinical trials are conducted in three sequential phases, but the phases may overlap. Phase 1 clinical trials usually involve healthy human subjects. The goal of a Phase I clinical trial is to establish initial data about the safety, tolerability and pharmacokinetic properties of the product candidates in humans. In Phase 2 clinical trials, controlled studies are conducted on an expanded population of patients with the targeted disease. The primary purpose of these tests is to evaluate the effectiveness of the drug candidate on the patients to determine if there are any side effects or other risks associated with the drug and to determine the optimal dose of the drug from the safety and efficacy profile developed from the clinical study. Phase 3 trials involve even larger patient populations, often with several hundred or even several thousand patients, depending on the use for which the drug is being studied. Phase 3 trials are intended to establish the overall risk-benefit ratio of the drug and provide, if appropriate, an adequate basis for product labeling. During all clinical trials, physicians monitor the patients to determine effectiveness and to observe and report any reactions or other safety risks that may result from use of the drug candidate.

 

Product Formulation and Manufacture

 

Concurrent with clinical trials and preclinical studies, companies must develop information about the chemistry and physical characteristics of the drug and finalize a process for manufacturing the product. In addition, manufacturers, including contract manufacturers, are required to comply with current applicable FDA Good

 

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Manufacturing Practice regulations. The current Good Manufacturing Practice regulations include requirements relating to quality control and quality assurance, as well as the corresponding maintenance of records and documentation. The manufacturing process must be capable of consistently producing quality batches of the product and the manufacturer must develop methods for testing the quality, purity and potency of the final drugs. Additionally, appropriate packaging must be selected and tested and chemistry stability studies must be conducted to demonstrate that the product does not undergo unacceptable deterioration over its shelf-life.

 

Compliance with current Good Manufacturing Practice regulations also is a condition of new drug application approval. The FDA must approve manufacturing facilities before they can be used in the commercial manufacture of drug products. In addition, manufacturing establishments are subject to pre-approval inspections and unannounced periodic inspections.

 

New Drug Application Process

 

After the completion of the clinical trial phases of development, if the sponsor concludes that there is substantial evidence that the drug candidate is safe and effective for its intended use, the sponsor may submit a NDA to the FDA. The application must contain all of the information on the drug candidate gathered to that date, including data from the clinical trials, and be accompanied by a user fee.

 

Under the Prescription Drug User Fee Act, or PDUFA, submission of a NDA with clinical data requires payment of a fee, with some exceptions. In return, the FDA assigns a goal of six or ten months from filing of the application to return of a first “complete response,” in which the FDA may approve the product or request additional information. There can be no assurance that an application will be approved within the performance goal timeframe established under PDUFA.  The FDA initially determines whether a NDA as submitted is acceptable for filing. The FDA may refuse to file an application, in which case the FDA retains one-half of the user fees. If the submission is accepted for filing, the FDA begins an in-depth review of the application. As part of this review, the FDA may refer the application to an appropriate advisory committee, typically a panel of clinicians, for review, evaluation and a recommendation. The FDA is not bound by the recommendation of an advisory committee.

 

If the FDA evaluations of the NDA and the manufacturing facilities are favorable, the FDA may issue an approval letter authorizing commercial marketing of the drug candidate for specified indications. The FDA could also issue a “complete response” letter at the end of the review period.  A “complete response” letter will be issued to let a company know that the review period for a drug is complete and that the application is not yet ready for approval. The letter will describe specific deficiencies and, when possible, will outline recommended actions the applicant might take to get the application ready for approval.

 

Marketing Approval and Post-Marketing Obligations

 

If the FDA approves an application, the drug becomes available for physicians to prescribe. Periodic reports must be submitted to the FDA, including descriptions of any adverse reactions reported. The FDA may require post-marketing studies, also known as Phase IV studies, as a condition of approval. In addition to studies required by the FDA after approval, trials and studies are often conducted to explore new indications for the drug. The purpose of these trials and studies and related publications is to develop data to support additional indications for the drug, which must be approved by the FDA, and to increase its acceptance in the medical community. In addition, some post-marketing studies are done at the request of the FDA to develop additional information regarding the safety of a product.

 

The FDA may impose risk evaluation mitigation strategies, or REMS, on a product if the FDA believes there is a reason to monitor the safety of the drug in the marketplace.  REMS could add training requirements for healthcare professionals, safety communications efforts, and limits on channels of distribution, among other things.  The sponsor would be required to evaluate and monitor the various REMS activities and adjust them if need be.  Whether a REMS would be imposed on a product and any resulting financial impact is uncertain at this time.

 

Any products manufactured or distributed pursuant to FDA approvals are subject to continuing regulation by the FDA, including record keeping requirements, reporting of adverse experiences with the drug, drug sampling and distribution requirements, notifying the FDA and gaining its approval of certain manufacturing or labeling changes, complying with certain electronic records and signature requirements, and complying with FDA promotion and advertising requirements. Drug manufacturers and their subcontractors are required to register their establishments and are subject to periodic unannounced inspections for compliance with Good Manufacturing Practice requirements. Also, newly discovered or developed safety or effectiveness data may require changes to a product’s

 

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approved labeling, including the addition of new warnings and contraindications, or even in some instances revocation or withdrawal of the product’s approval.

 

Approval Outside of the United States

 

In order to market any product outside of the United States, we must comply with numerous and varying regulatory requirements of other countries regarding safety and efficacy and governing, among other things, clinical trials and commercial sales and distribution of our products, which broadly reflect the issues addressed by the FDA above. Approval procedures vary among countries and can involve additional product testing and additional administrative review periods. The time required to obtain approval in other countries might differ from and be longer than that required to obtain FDA approval. Marketing approval in one country does not ensure marketing approval in another, but a failure or delay in obtaining marketing approval in one country may negatively impact the regulatory process in other countries.

 

As in the United States, the marketing approval process in Europe and in other countries is a lengthy, challenging and inherently uncertain process.  If we fail to comply with applicable foreign regulatory requirements, we may be subject to fines, suspension or withdrawal of marketing approvals, product recalls, seizure of products, operating restrictions and criminal prosecution. Generally the development and approval procedures are harmonized throughout the European Union: however, there is limited harmonization in relation to national pricing and reimbursement practices.

 

Under European Union regulatory systems, a company may not market a medicinal product without marketing authorization. There are three procedures for submitting a MAA in the EU: (1) the mutual recognition procedure (MRP); (2) the decentralized procedure (DCP) and (3) the centralized procedure (CP). The submission strategy for a given product will depend on the nature of the product, the target indication(s), the history of the product, and the marketing plan. The centralized procedure is compulsory for medicinal products which are produced by biotechnology processes, advanced therapy medicinal products and orphan drugs. Besides the products falling under the mandatory scope, the centralized procedure is also open for other innovative products that are new active substances or other medicinal products that constitute a significant therapeutic, scientific or technical innovation.

 

The centralized procedure leads to approval of the product in all 27 EU member states and in Norway, Iceland and Liechtenstein. Submission of one MAA thus leads to one assessment process and one authorization that allows access to all applicable markets within the entire EU. The process of the centralized procedure is triggered when the applicant sends the letter announcing the intent to submit a MAA (letter of intent). The letter of intent also initiates the assignment of the Rapporteur and Co-Rapporteur, who are the two appointed members of the Committee for Human Medicinal Products, or CHMP, representing two EU member states.

 

When using the MRP or DCP, the applicant must select which and how many EU member states in which to seek approval. In the case of an MRP, the applicant must initially receive national approval in one EU member state. This will be the so-called reference member state (RMS) for the MRP. Then, the applicant seeks approval for the product in other EU member states, the so-called concerned member states (CMS) in a second step: the mutual recognition process. For the DCP, the applicant will approach all chosen member states at the same time. To do so, the applicant will identify the RMS that will assess the submitted MAA and provide the other selected member states with the conclusions and results of the assessment.

 

When the application for marketing authorization is made, the competent authority responsible for granting a marketing authorization must verify whether the application complies with the relevant requirements, including compliance with the agreed PIP.  Assuming it does, the marketing authorization may be granted and the relevant results are included in the summary of product characteristics (SmPC) for the product, along with a statement indicating compliance with the agreed PIP. It is not necessary for the product actually to be indicated for use in the pediatric population (for example, if the results show that that would not be appropriate).

 

Drug Price Competition and Patent Term Restoration Act of 1984

 

Under the Drug Price Competition and Patent Term Restoration Act of 1984, known as the Hatch-Waxman Act, a portion of a product’s patent term that was lost during clinical development and application review by the FDA may be restored. The Hatch-Waxman Act also provides for a statutory protection, known as exclusivity, against the FDA’s acceptance or approval of certain competitor applications. The Hatch-Waxman Act also provides the legal

 

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basis for the approval of abbreviated new drug applications, or ANDAs.

 

Patent term extension can compensate for time lost during product development and the regulatory review process by returning up to five years of patent life for a patent that covers a new product or its use. This period is generally one-half the time between the effective date of an IND and the submission date of a NDA, plus the time between the submission date of a NDA and the approval of that application. Patent term extensions, however, are subject to a maximum extension of five years, and the patent term extension cannot extend the remaining term of a patent beyond a total of 14 years. The application for patent term extension is subject to approval by the United States Patent and Trademark Office in conjunction with the FDA. It generally takes at least six months to obtain approval of the application for patent term extension.

 

The Hatch-Waxman Act also provides for a period of statutory protection for new drugs that receive NDA approval from the FDA. If a new drug receives NDA approval as a new chemical entity, meaning that the FDA has not previously approved any other new drug containing the same active entity, then the Hatch-Waxman Act prohibits an ANDA or a NDA submitted pursuant to section 505(b)(2) of the Federal Food, Drug, and Cosmetics Act, where the applicant does not own or have a legal right of reference to all of the data required for approval to be submitted by another company for a generic version of such drug (505(b)(2) NDA), with some exceptions, for a period of five years from the date of approval of the NDA. The statutory protection provided pursuant to the Hatch-Waxman Act will not prevent the filing or approval of a full NDA, as opposed to an ANDA or 505(b)(2) NDA, for any drug, including, for example, a drug with the same active ingredient, dosage form, route of administration, strength and conditions of use. In order to obtain a NDA, however, a competitor would be required to conduct its own clinical trials, and any use of the drug for which marketing approval is sought could not violate another NDA holder’s patent claims.

 

If NDA approval is received for a new drug containing an active ingredient that was previously approved by the FDA but the NDA is for a drug that includes an innovation over the previously approved drug, for example, a NDA approval for a new indication or formulation of the drug with the same active ingredient, and if such NDA approval was dependent upon the submission to the FDA of new clinical investigations, other than bioavailability studies, then the Hatch-Waxman Act prohibits the FDA from making effective the approval of an ANDA or 505(b)(2) NDA for a generic version of such drug for a period of three years from the date of the NDA approval. This three year exclusivity, however, only covers the innovation associated with the NDA to which it attaches. Thus, the three year exclusivity does not prohibit the FDA, with limited exceptions, from approving ANDAs or 505(b)(2) NDAs for drugs containing the same active ingredient but without the new innovation.

 

While the Hatch-Waxman Act provides certain patent restoration and exclusivity protections to innovator drug manufacturers, it also permits the FDA to approve ANDAs for generic versions of their drugs assuming the approval would not violate another NDA holder’s patent claims. The ANDA process permits competitor companies to obtain marketing approval for a drug with the same active ingredient for the same uses but does not require the conduct and submission of clinical studies demonstrating safety and effectiveness for that product. Instead of safety and effectiveness data, an ANDA applicant needs only to submit data demonstrating that its product is bioequivalent to the innovator product as well as relevant chemistry, manufacturing and product data. The Hatch-Waxman Act also instituted a third type of drug application that requires the same information as a NDA, including full reports of clinical and preclinical studies, except that some of the information from the reports required for marketing approval comes from studies which the applicant does not own or have a legal right of reference. This type of application, a 505(b)(2) NDA, permits a manufacturer to obtain marketing approval for a drug without needing to conduct or obtain a right of reference for all of the required studies.

 

If a competitor submits an ANDA or 505(b)(2) NDA for a compound or use of any compound covered by another NDA holder’s patent claims, the Hatch-Waxman Act requires, in some circumstances, the applicant to notify the patent owner and the holder of the approved NDA of the factual and legal basis of the applicant’s opinion that the patent is not valid or will not be infringed. Upon receipt of this notice, the patent owner and the NDA holder have 45 days to bring a patent infringement suit in federal district court and obtain a 30-month stay against the company seeking to reference the NDA. The NDA holder could still file a patent suit after the 45 days, but if they miss the 45-day deadline, they would not have the benefit of the 30-month stay. Alternatively, after this 45-day period, the applicant may file a declaratory judgment action, seeking a determination that the patent is invalid or will not be infringed. Depending on the circumstances, however, the applicant may not be able to demonstrate a controversy sufficient to confer jurisdiction on the court. The discovery, trial and appeals process in such suits can take several years. If such a suit is commenced, the Hatch-Waxman Act provides a 30-month stay on the approval of the competitor’s ANDA or 505(b)(2) NDA. If the litigation is resolved in favor of the competitor or the challenged patent expires during the 30-month period, unless otherwise extended by court order, the stay is lifted and the FDA

 

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may approve the application. Under regulations issued by the FDA, and essentially codified under the Medicare prescription drug legislation, the patent owner and the NDA holder have the opportunity to trigger only a single 30-month stay per ANDA or 505(b)(2) NDA. Once the applicant of the ANDA or 505(b)(2) NDA has notified the patent owner and the NDA holder of the infringement, the applicant cannot be subjected to another 30-month stay, even if the applicant becomes aware of additional patents that may be infringed by its product.

 

Pharmaceutical Pricing and Reimbursement

 

We currently have no marketed products.  In both domestic and foreign markets, sales of any products for which we receive regulatory approval for commercial sale will depend in part on the availability of reimbursement from third-party payors. Third-party payors include government health administrative authorities, managed care providers, private health insurers and other organizations. These third-party payors are increasingly challenging the price and examining the cost-effectiveness of medical products and services. In addition, significant uncertainty exists as to the reimbursement status of newly approved healthcare products. We may need to conduct expensive pharmacoeconomic studies in order to demonstrate the cost-effectiveness of our products. Our product candidates may not be considered cost-effective. Adequate third-party reimbursement may not be available to enable us to maintain price levels sufficient to realize an appropriate return on our investment in product development.

 

If we obtain appropriate approval in the future to market any of our oral drug product candidates, those products could potentially be covered by various government health benefit programs as well as purchased by federal agencies.  The participation in such programs or the sale of products to such agencies is subject to regulation.  The marketability of any products for which we receive regulatory approval for commercial sale may suffer if the government and third-party payors fail to provide adequate coverage and reimbursement.

 

Medicaid is a joint federal and state program that is administered by the states for low income and disabled beneficiaries. Under the Medicaid Drug Rebate Program, manufacturers are required to pay a rebate for each unit of product reimbursed by the state Medicaid programs. The amount of the rebate for each product is set by law and may be subject to an additional discount if certain pricing increases more than inflation.

 

Medicare is a federal program that is administered by the federal government that covers individuals age 65 and over as well as those with certain disabilities.  Oral drugs may be covered under Medicare Part D.  Medicare Part D provides coverage to enrolled Medicare patients for self-administered drugs (i.e., drugs that do not need to be injected or otherwise administered by a physician). Medicare Part D is administered by private prescription drug plans approved by the U.S. government and each drug plan establishes its own Medicare Part D formulary for prescription drug coverage and pricing, which the drug plan may modify from time-to-time. The prescription drug plans negotiate pricing with manufacturers and may condition formulary placement on the availability of manufacturer discounts.  Since 2011, manufacturers with marketed brand name drugs have been required to provide a 50% discount on brand name prescription drugs utilized by Medicare Part D beneficiaries when those beneficiaries reach the coverage gap in their drug benefits.

 

Drug products are subject to discounted pricing when purchased by federal agencies via the Federal Supply Schedule (FSS). FSS participation is required for a drug product to be covered and reimbursed by certain federal agencies and for coverage under Medicaid, Medicare Part B and the PHS pharmaceutical pricing program. FSS pricing is negotiated periodically with the Department of Veterans Affairs.  FSS pricing is intended not to exceed the price that a manufacturer charges its most-favored non-federal customer for its product. In addition, prices for drugs purchased by the Veterans Administration, Department of Defense (including drugs purchased by military personnel and dependents through the TRICARE retail pharmacy program), Coast Guard, and PHS are subject to a cap on pricing (known as the “federal ceiling price”) and may be subject to an additional discount if pricing increases more than the rate of inflation.

 

To maintain coverage of drugs under the Medicaid Drug Rebate Program, manufacturers are required to extend discounts to certain purchasers under the Public Health Service (PHS) pharmaceutical pricing program.  Purchasers eligible for discounts include hospitals that serve a disproportionate share of financially needy patients, community health clinics and other entities that receive health services grants from the PHS.

 

The United States and state governments continue to propose and pass legislation designed to reduce the cost of healthcare.  In March 2010, the United States Congress enacted the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act which includes changes to the coverage and reimbursement of drug products under government health care programs.  Adoption of other new legislation at the federal or state level could further limit reimbursement for pharmaceuticals.

 

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Although we currently have no products approved for commercial sale, we marketed FARESTON® through September 30, 2012 and the product was covered under various government health benefit programs as well as purchased by federal agencies.  We could be subject to liability under federal laws regulating our participation in such programs or the sale of our product to such agencies if we failed to comply with applicable requirements, including reporting prices for our products or offering products for sale at certain prices.

 

Regulations Pertaining to Sales and Marketing

 

Although we currently have no products approved for commercial sale, we may be subject to various federal and state laws pertaining to health care “fraud and abuse,” including anti-kickback laws and false claims laws for activities related to our previous sales of FARESTON®, which we sold to a third party in 2012, or to future sales of any of our product candidates that may in the future receive regulatory and marketing approval.  Anti-kickback laws generally prohibit a prescription drug manufacturer from soliciting, offering, receiving, or paying any remuneration to generate business, including the purchase or prescription of a particular drug.  Although the specific provisions of these laws vary, their scope is generally broad and there may not be regulations, guidance or court decisions that apply the laws to particular industry practices.  There is therefore a possibility that our practices might be challenged under such anti-kickback laws. False claims laws prohibit anyone from knowingly and willingly presenting, or causing to be presented, any claims for payment for reimbursed drugs or services to third party payors (including Medicare and Medicaid) that are false or fraudulent.  Violations of fraud and abuse laws may be punishable by criminal or civil sanctions, including fines and civil monetary penalties, and/or exclusion from federal health care programs (including Medicare and Medicaid).

 

Laws and regulations have been enacted by the federal government and various states to regulate the sales and marketing practices of pharmaceutical manufacturers with marketed products.  The laws and regulations generally limit financial interactions between manufacturers and health care providers and/or require disclosure to the government and public of such interactions. Many of these laws and regulations contain ambiguous requirements or require administrative guidance for implementation. Given the lack of clarity in laws and their implementation, our prior reporting (when we marketed FARESTON®) or any future reporting (if we obtain approval and/or reimbursement from federal healthcare programs for our product candidates) could be subject to the penalty provisions of the pertinent laws and regulations.

 

Research and Development

 

Since our inception in 1997, we have been focused on drug discovery and development programs.  Research and development expenses include, but are not limited to, our expenses for personnel associated with our research activities, screening and identification of product candidates, formulation and synthesis activities, manufacturing, preclinical studies, toxicology studies, clinical trials, regulatory and medical affairs activities, quality assurance activities and license fees.  Our research and development expenses were $32.3 million for the year ended December 31, 2013, $38.9 million for the year ended December 31, 2012, and $31.9 million for the year ended December 31, 2011. As a result of the October 2013 reduction in our workforce, we are no longer conducting drug discovery activities and are focusing our research and development activities on the ongoing clinical development of our current product candidates.

 

 Employees

 

As of December 31, 2013, we had 32 employees, 8 of whom were M.D.s and/or Ph.D.s.  None of our employees are subject to a collective bargaining agreement. We believe that we have good relations with our employees.

 

Available Information

 

We file electronically with the U.S. Securities and Exchange Commission, or SEC, our annual reports on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K and amendments to those reports filed or furnished pursuant to Section 13(a) or 15(d) of the Securities Exchange Act of 1934.  We make available on our Web site at www.gtxinc.com, free of charge, copies of these reports as soon as reasonably practicable after we electronically file such material with, or furnish it to, the SEC.  Further, copies of these reports are located at the

 

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SEC’s Public Reference Room at 100 F Street, NE, Washington, D.C. 20549. Information on the operation of the Public Reference Room can be obtained by calling the SEC at 1-800-SEC-0330.  The SEC maintains a Web site that contains reports, proxy statements, and other information regarding our filings at www.sec.gov.  The information provided on our Web site is not part of this report, and is therefore not incorporated by reference unless such information is otherwise specifically referenced elsewhere in this report.

 

Management

 

The following table sets forth information about our executive officers and other key medical, clinical and regulatory officers as of February 26, 2014.

 

Name

 

Age

 

Position(s)

Executive Officers

 

 

 

 

Mitchell S. Steiner, M.D., F.A.C.S.

 

53

 

Chief Executive Officer and Vice Chairman of the Board of Directors

Marc S. Hanover

 

51

 

President, Chief Operating Officer and Acting Principal Financial Officer

James T. Dalton, Ph.D.

 

51

 

Vice President, Chief Scientific Officer

Henry P. Doggrell

 

65

 

Vice President, Chief Legal Officer and Secretary

 

 

 

 

 

Other Key Medical, Clinical and Regulatory Officers

 

 

 

 

Jeffrey G. Hesselberg

 

55

 

Vice President, Regulatory Affairs

Mary Ann Johnston, PharmD

 

42

 

Vice President, Medical Affairs and Clinical Operations

 

Executive Officers of the Registrant

 

Mitchell S. Steiner, M.D., F.A.C.S., a co-founder of GTx, has served as our Chief Executive Officer and Vice Chairman of our Board of Directors since our inception in September 1997. From 1995 to 2003, Dr. Steiner held numerous academic appointments, including Chairman and Professor of Urology, Director of Urologic Oncology and Research and the Chair of Excellence in Urologic Oncology at the University of Tennessee.  Dr. Steiner holds a B.A. in Molecular Biology from Vanderbilt University and an M.D. from the University of Tennessee, and performed his surgery and urologic training at The Johns Hopkins Hospital.

 

Marc S. Hanover, a co-founder of GTx, has served as our President and Chief Operating Officer since our inception in September 1997, and has served as our acting principal financial officer since December 31, 2013.  Mr. Hanover also served as a member of our Board of Directors until August 2011.  Prior to joining GTx, Mr. Hanover was a founder of Equity Partners International, Inc., a private equity firm in Memphis, Tennessee, and participated as a founder and investor in three healthcare companies.  From 1985 to 1997, Mr. Hanover was a Senior Vice President and a member of the Executive Management Committee of National Bank of Commerce in Memphis, Tennessee.  Mr. Hanover holds a B.S. in Biology from the University of Memphis and a MBA in Finance from the University of Memphis.

 

James T. Dalton, Ph.D., was appointed Vice President, Chief Scientific Officer on January 1, 2011, and prior to that he served as Vice President, Preclinical Research and Development since January 2005.  Dr. Dalton served as a scientific consultant to GTx from 1999 to 2005.  Prior to joining GTx, Dr. Dalton held several academic appointments including Assistant and Associate Professor of Pharmaceutical Sciences in the College of Pharmacy at the University of Tennessee, Memphis (1992-2000) and Professor in the Division of Pharmaceutics, College of Pharmacy at The Ohio State University (2000-2007).   SARMs were first discovered in Dr. Dalton’s research laboratories, and he is co-inventor on all SARM and GTx-758 patents.  Dr. Dalton holds a B.S. in Pharmacy from the University of Cincinnati and a Ph.D. in Pharmaceutics and Pharmaceutical Chemistry from The Ohio State University.

 

Henry P. Doggrell currently serves as our Vice President, Chief Legal Officer and Secretary, after joining GTx in October 2001 as General Counsel and Secretary.  From April 1998 to August 2001, Mr. Doggrell was Senior Vice President, Corporate Affairs at Buckeye Technologies, Inc., a specialty cellulose company, where he was responsible for matters including corporate finance, investor relations, mergers and acquisitions, intellectual property and licensing and strategic development.  From 1996 to 1998, Mr. Doggrell served as General Counsel and

 

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Secretary of Buckeye Technologies.  Prior to joining Buckeye Technologies, Mr. Doggrell was a partner of the Baker, Donelson, Bearman, Caldwell and Berkowitz law firm from 1988 to 1996, where he served as a member of the law firm management committee and Chair of the firm’s Corporate Securities department.  Mr. Doggrell holds a B.S. in Commerce from the University of Virginia and a JD from Vanderbilt University.

 

Other Key Medical, Clinical and Regulatory Officers of the Registrant

 

Jeffrey G. Hesselberg was appointed Vice President, Regulatory Affairs in May 2007.  He joined GTx from ICOS Corporation, where from 1996 to May 2007 he served as Manager, Associate Director, and then Director of Regulatory Affairs.  Most recently, Mr. Hesselberg worked on the successful development, launch and commercialization of Cialis® (tadalafil) for the treatment of erectile dysfunction.  From 1984 to 1996, Mr. Hesselberg worked for Immunex Corporation and the Puget Sound Blood Center. Mr. Hesselberg holds a B.S. in Molecular Biology from the University of Wisconsin—Madison and a MBA from the University of Washington.

 

Mary Ann Johnston, PharmD, was appointed Vice President, Medical Affairs and Clinical Operations in January 2014.  Previously, she served as the Vice President, Medical Affairs since November 2012.  Before that, she served as Director, Medical Affairs and Team Leader, Medical Science Liaisons, heading up the field-based medical organization since 2009.  Prior to joining GTx, Dr. Johnston was Director, Medical Science Liaisons and Managed Markets at Actelion Pharmaceuticals specializing in pulmonary arterial hypertension. Before joining the pharmaceutical industry, Dr. Johnston practiced as a clinical specialist at the University of Texas Medical Branch in Galveston where she served as an adjunct professor for the University of Houston and University of Texas schools of pharmacy with a clinical practice focused in cardiology and critical care. Dr. Johnston holds a Doctor of Pharmacy degree from Samford University McWhorter School of Pharmacy and completed a postdoctoral residency at the Department of Veterans Affairs Medical Center in Tuscaloosa, Alabama.

 

ITEM 1A.                                       RISK FACTORS

 

We have identified the following additional risks and uncertainties that may have a material adverse effect on our business, financial condition or results of operations.  Investors should carefully consider the risks described below before making an investment decision.  Our business faces significant risks and the risks described below may not be the only risks we face.  Additional risks not presently known to us or that we currently believe are immaterial may also significantly impair our business operations.  If any of these risks occur, our business, results of operations or financial condition could suffer, the market price of our common stock could decline and you could lose all or part of your investment in our common stock.

 

Risks Related to Our Financial Condition and Need for Additional Financing

 

We have incurred losses since inception, and we anticipate that we will incur continued losses for the foreseeable future.

 

As of December 31, 2013, we had an accumulated deficit of $455.4 million. Our net loss for the year ended December 31, 2013 was $42.1 million. We expect to incur significant operating losses for the foreseeable future as we continue our clinical development activities and potentially seek regulatory approval of our product candidates. These losses, among other things, have had and will continue to have an adverse effect on our stockholders’ equity and working capital.

 

Our current product candidates, enobosarm (GTx-024) and GTx-758 (Capesaris®), will require significant additional clinical development and financial resources in order to obtain necessary regulatory approvals for these product candidates and to develop them into commercially viable products.  A substantial portion of our efforts and expenditures have been devoted to enobosarm 3 mg, which was the subject of our POWER 1 and POWER 2 Phase 3 clinical trials for the prevention and treatment of muscle wasting in patients with advanced non-small cell lung cancer, or NSCLC, and we are substantially dependent on the successful development, regulatory approval and commercialization of enobosarm 3 mg. The failure of the POWER trials to meet the primary statistical criterion for the co-primary endpoints agreed upon with the FDA significantly depressed our stock price and harmed our future prospects. While we expect to submit a marketing authorization application, or MAA, to the European Medicines Agency, or EMA, by the first quarter of 2015 seeking marketing approval of enobosarm 3 mg in the European Union for the more narrow indication of the prevention and treatment of muscle wasting in patients with advanced

 

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NSCLC treated with platinum plus taxane chemotherapy, the EMA must determine that the safety and efficacy data from the POWER 1 trial are sufficient to support approval of the MAA.  However, the EMA may determine that the safety and efficacy data from the POWER 1 trial, as supported by data from the POWER 2 trial, are insufficient to support approval of the planned MAA submission and that one or more additional Phase 3 clinical trials of enobosarm 3 mg would be required to be successfully conducted by us in order to support any such approval.  If we are required to successfully conduct and complete any additional Phase 3 clinical trials of enobosarm 3 mg in order to support potential approval of enobosarm 3 mg in the European Union, we would be required to obtain substantial additional capital, and given the uncertainties inherent in the clinical development process, there can be no assurances that we would be successful in obtaining the additional funding necessary to support additional Phase 3 clinical trials of enobosarm 3 mg.  In such event, we may be required to cease further development of our enobosarm program and forego any return on our investment from our enobosarm program. Based on recent input from the United States Food and Drug Administration, or FDA, we plan to meet again with the FDA later in the year to discuss a potential Phase 3 clinical program for enobosarm 3 mg for the prevention and treatment of muscle wasting or cachexia in patients with NSCLC. There can be no assurance that we will reach agreement with the FDA on any Phase 3 program for enobosarm 3 mg.  In addition, we would be required to obtain substantial additional capital in order to conduct any Phase 3 clinical trials of enobosarm 3 mg to support potential approval in the United States and there can be no assurances that we would be successful in obtaining the additional funding necessary to support additional Phase 3 clinical trials of enobosarm 3 mg.  In any event, we do not expect to obtain FDA or EMA approval, or any other regulatory approvals, to market any of our product candidates, including enobosarm, for the foreseeable future, and it is possible that none of our product candidates will ever receive any regulatory approvals.

 

Because of the numerous risks and uncertainties associated with developing and commercializing small molecule drugs, we are unable to predict the extent of any future losses or when we will become profitable, if at all. We have funded our operations primarily through public offerings and private placement of our common stock, as well as payments from our former collaborators.  We also previously recognized product revenue from the sale of FARESTON®, the rights to which we sold to a third party in the third quarter of 2012.  Currently, we have no ongoing collaborations for the development and commercialization of our product candidates, and as a result of the sale of our rights and certain assets related to FARESTON®, we also currently have no sources of revenue.

 

If we and/or any potential collaborators are unable to develop and commercialize enobosarm or GTx-758, if development is further delayed or is eliminated, or if sales revenue from enobosarm or GTx-758 upon receiving marketing approval, if ever, is insufficient, we may never become profitable and we will not be successful.

 

We will need to raise substantial additional capital and may be unable to raise capital when needed, which would force us to delay, reduce or eliminate our product development programs or commercialization efforts.

 

We will need to raise substantial additional capital to:

 

·                  fund our operations and conduct clinical trials, including to conduct and complete any additional Phase 3 clinical trials of enobosarm 3 mg that may be required to support approval of enobosarm 3 mg in the European Union or to pursue regulatory approval of enobosarm 3 mg in the United States;

 

·                  continue our research and development;

 

·                  seek regulatory approval for our product candidates; and

 

·                  commercialize our product candidates, if any such product candidates receive regulatory approval for commercial sale.

 

As of the date of this Annual Report on Form 10-K, we estimate that  our current cash, cash equivalents and short-term investments, together with interest thereon, will be sufficient to meet our projected operating requirements for at least the next twelve months. We have based this estimate on our current business plan and assumptions that may prove to be wrong.  We could utilize our available capital resources sooner than we currently expect, and we could need additional funding sooner than currently anticipated.  In any event, to complete the development of and seek regulatory approval for enobosarm and GTx-758, we will need to obtain substantial additional funding.  Based on our current business plan and assumptions, we will need to obtain substantial additional funding to conduct any additional clinical development of our product candidates beyond the Phase 2 clinical trials we are currently conducting, the Phase 1 clinical trials we plan to conduct to support a potential MAA submission to the EMA for enobosarm 3 mg or any additional Phase 3 clinical trial we may have to conduct to seek approval from any regulatory authorities for enobosarm 3 mg.  Our future funding requirements will depend on many factors, including:

 

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·                  the scope, rate of progress and cost of our clinical development programs, including our ongoing and any future clinical trials of enobosarm and GTx-758;

 

·                  the terms and timing of any potential collaborative, licensing and other strategic arrangements that we may establish;

 

·                  the amount and timing of any licensing fees, milestone payments and royalty payments from potential collaborators, if any;

 

·                  future clinical trial results;

 

·                  the cost and timing of regulatory filings and/or approvals to commercialize our product candidates and any related restrictions, limitations, and/or warnings in the label of an approved product candidate;

 

·                  the effect of competing technological and market developments; and

 

·                  the cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights, and the cost of defending any other litigation claims.

 

We do not currently have any commitments for future external funding nor do we currently have any sources of revenue.  Until we can generate a sufficient amount of product revenue, which we may never do, we expect to finance future cash needs through public or private equity offerings, debt financings, or collaboration and licensing arrangements, or a combination of the above, as well as through interest income earned on the investment of our cash balances and short-term investments.  In October 2013, following our announcement that the POWER trials failed to achieve the results required by the FDA for us to file a new drug application, or NDA, for enobosarm 3 mg, we announced a workforce reduction of approximately 60%.  If we are unable to raise additional funds when needed, we may need to further reduce our expenditures, perhaps significantly, to preserve our cash.  Cost-cutting measures that we may take in the future may not be sufficient to enable use to meet our cash requirements, and they may negatively affect our business and growth prospects.

 

To the extent that we raise additional funds through potential collaboration, partnering or other strategic arrangements, it may be necessary to relinquish rights to some of our technologies or product candidates, or grant licenses on terms that are not favorable to us, any of which could result in the stockholders of GTx having little or no continuing interest in our enobosarm and/or GTx-758 programs as stockholders or otherwise.  To the extent we raise additional funds by issuing equity securities, our stockholders may experience significant dilution, particularly given our currently depressed stock price, and debt financing, if available, may involve restrictive covenants. For example, we announced in March 2014 that we completed a private placement of common stock and warrants to purchase additional common stock for gross proceeds of approximately $21.3 million, which financing was substantially dilutive, and our stockholders may experience additional, perhaps substantial, dilution should we again raise additional funds by issuing equity securities.  Any debt financing or additional equity that we raise may contain terms that are not favorable to us or our stockholders. Our ability to raise additional funds and the terms upon which we are able to raise such funds have been severely harmed by the failure of the two enobosarm 3 mg Phase 3 clinical trials to meet both of the co-primary endpoints agreed upon with the FDA, and may in the future be adversely impacted if we are unable to obtain approval of enobosarm 3 mg in the European Union or if we are required to conduct additional Phase 3 development of enobosarm 3 mg to obtain any such approval.  As a result of these and other factors, we cannot be certain that additional funding will be available on acceptable terms, or at all.  If adequate funds are not available when we need them, we may be required to delay, reduce the scope of or eliminate one or more of our research or development programs, including our enobosarm and GTx-758 programs, or conduct additional workforce or other expense reductions, any of which could have a material adverse effect on our business and our prospects.

 

Risks Related to Development of Product Candidates

 

We are substantially dependent on the success of enobosarm and our failure to obtain regulatory approval of our product candidates from the EMA or FDA may harm our prospects.

 

A substantial portion of our efforts and expenditures have been devoted to enobosarm 3 mg, which was the subject of our POWER 1 and POWER 2 Phase 3 clinical trials evaluating enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced NSCLC, and we are substantially dependent on the successful development, regulatory approval and commercialization of enobosarm 3 mg.  We announced in August 2013 that these two Phase 3 clinical trials failed to meet the co-primary endpoints of lean body mass and physical function that

 

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were assessed statistically using responder analyses as required by the FDA.  The failure of the POWER trials to meet each of the co-primary endpoints significantly depressed our stock price and harmed our future prospects.  While we expect to submit a MAA to the EMA for the marketing approval of enobosarm 3 mg in the European Union for the more narrow indication of the prevention and treatment of muscle wasting in patients with advanced NSCLC treated with platinum plus taxane chemotherapy by the first quarter of 2015, the EMA may determine that the safety and efficacy data from the POWER 1 trial are insufficient to support approval of the planned MAA submission and that one or more additional Phase 3 clinical trials of enobosarm 3 mg would be required to be successfully conducted by us in order to support any such approval, which would require us to obtain substantial additional funding to conduct and complete any additional Phase 3 clinical trials of enobosarm 3 mg.  Given the uncertainties inherent in the clinical development process, there can be no assurances that we would be successful in obtaining the additional funding necessary to support additional Phase 3 clinical trials of enobosarm 3 mg.  In such event, we may be required to cease further development of our enobosarm program and forego any return on our investment from our enobosarm program and we could be required to cease operations.  Based on recent input from the FDA, we plan to meet again with the FDA later in the year to discuss a potential Phase 3 clinical program for enobosarm 3 mg for the prevention and treatment of muscle wasting or cachexia in patients with NSCLC. There can be no assurance that we will reach agreement with the FDA on any Phase 3 program for enobosarm 3 mg.  In addition, we would be required to obtain substantial additional capital in order to conduct any Phase 3 clinical trials of enobosarm 3 mg to support potential approval in the United States and there can be no assurances that we would be successful in obtaining the additional funding necessary to support additional Phase 3 clinical trials of enobosarm 3 mg.

 

We and any potential collaborators will not be able to commercialize our product candidates if our preclinical studies do not produce successful results or if our clinical trials do not adequately demonstrate safety and efficacy in humans.

 

Significant additional clinical development and financial resources will be required to obtain necessary regulatory approvals for our product candidates and to develop them into commercially viable products.  Preclinical and clinical testing is expensive, can take many years to complete and has an uncertain outcome. Success in preclinical testing and early clinical trials does not ensure that later clinical trials will be successful, and interim results of a clinical trial do not necessarily predict final results.  Typically, the failure rate for development candidates is high.  If a product candidate fails at any stage of development, we will not have the anticipated revenues from that product candidate to fund our operations, and we will not receive any return on our investment in that product candidate.  For example, we announced in August 2013 that our POWER 1 and POWER 2 Phase 3 clinical trials evaluating enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced NSCLC failed to meet the co-primary endpoints of lean body mass and physical function that were assessed statistically using responder analyses as agreed upon with the FDA.  Although, based on our recent meetings with European regulators, we believe we expect to submit a MAA to the EMA for the more narrow indication of enobosarm 3 mg to prevent and treat muscle wasting in advanced NSCLC patients treated with platinum plus taxane chemotherapy, there is no guarantee that the EMA will approve our MAA, which could result in the requirement that we conduct additional clinical studies or our ceasing further development of enobosarm program.  Based on recent input from the United States Food and Drug Administration, or FDA, we plan to meet again with the FDA later in the year to discuss a potential Phase 3 clinical program for enobosarm 3 mg for the prevention and treatment of muscle wasting or cachexia in patients with NSCLC.  There can be no assurance that we and the FDA will agree on a Phase 3 clinical program for enobosarm 3 mg for the prevention and treatment of muscle wasting or cachexia in patients with NSCLC.  Even if we reach agreement with the FDA to conduct additional Phase 3 clinical trials of enobosarm 3 mg and we believe the results from any trial we conduct to be positive, the efficacy and/or safety results from the trials still may be found to be insufficient to support the submission of a NDA to the FDA or if submitted, the approval of the NDA by the FDA. For example, we received a Complete Response Letter in October 2009 from the FDA regarding our NDA for toremifene 80 mg to reduce fractures in men with prostate cancer on androgen deprivation therapy, or ADT, notifying us that the FDA would not approve the NDA.  We have since discontinued our toremifene development programs.

 

Significant delays in clinical testing could materially impact our product development costs.  We do not know whether potential clinical trials will begin on time, or whether ongoing clinical trials will need to be restructured or will be completed on schedule, if at all.  We or any potential collaborators may experience numerous unforeseen and/or adverse events during, or as a result of, preclinical testing and the clinical trial process that could delay or prevent our or our potential collaborators’ ability to commercialize our product candidates, including:

 

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·                  regulators or institutional review boards may not authorize us or any potential collaborators to commence a clinical trial or conduct a clinical trial at a prospective trial site, or we may experience substantial delays in obtaining these authorizations;

 

·                  preclinical or clinical trials may produce negative or inconclusive results, which may require us or any potential collaborators to conduct additional preclinical or clinical testing or to abandon projects that we expect to be promising;

 

·                  even if preclinical or clinical trial results are positive, the FDA or foreign regulatory authorities could nonetheless require us to conduct unanticipated additional clinical trials;

 

·                  registration or enrollment in clinical trials may be slower than we anticipate, resulting in significant delays or study terminations;

 

·                  we or any potential collaborators may suspend or terminate clinical trials if the participating patients are being exposed to unacceptable health risks;

 

·                  regulators or institutional review boards may suspend or terminate clinical research for various reasons, including noncompliance with regulatory requirements; and

 

·                  our product candidates may not have the desired effects or may include undesirable side effects.

 

If any of these events were to occur and, as a result, we or any potential collaborators have significant delays in or termination of clinical trials, our costs could increase and our ability to generate revenue could be impaired, which would materially and adversely impact our business, financial condition and growth prospects.

 

If we or any potential collaborators observe serious or other adverse events during the time our product candidates are in development or after our products are approved and on the market, we or any potential collaborators may be required to perform lengthy additional clinical trials, may be required to cease further development of such product candidates, may be denied regulatory approval of such products, may be forced to change the labeling of such products or may be required to withdraw any such products from the market, any of which would hinder or preclude our ability to generate revenues.

 

In three Phase 2 clinical trials of GTx-758, which we discontinued in February 2012, we observed venous thromboembolic events, or blood clots, in subjects treated with GTx-758 at the doses then being studied in these clinical trials (1000 mg and higher per day) and reported those events to the FDA. There were two deaths in subjects treated with GTx-758 and two deaths in subjects treated with Lupron Depot®.  In February 2012, the FDA placed all of our then ongoing clinical studies of GTx-758 on full clinical hold, and we suspended further enrollment into these studies and notified clinical sites to discontinue treatment of subjects with GTx-758.  In May 2012, the FDA notified us that it had removed the full clinical hold on GTx-758.  In the third quarter of 2012, we initiated a Phase 2 clinical trial to evaluate GTx-758, at doses lower than those which were previously being tested in our discontinued Phase 2 clinical trials, as secondary hormonal therapy in men with metastatic castration resistant prostate cancer, or CRPC.  Although our current Phase 2 clinical trial is evaluating GTx-758 at doses lower than those which were previously being tested in our discontinued Phase 2 clinical trials, we cannot be confident that we will not observe an unacceptable incidence of venous thromboembolic events or other adverse events in the current Phase 2 clinical trial. Our ability to develop GTx-758 as an effective secondary hormonal therapy for men with metastatic CRPC or, potentially, as a secondary hormonal treatment for advanced prostate cancer used in combination with ADT, is dependent on our ability to find an appropriate dose that is both effective and safe for these patient populations.  If an unacceptable incidence of venous thromboembolic events or other adverse events are observed in our current Phase 2 clinical trial of GTx-758, we may be required to abandon our development of GTx-758, in which case, we would not receive any return on our investment in that product candidate.

 

In our Phase 2 clinical trials for enobosarm for the treatment of muscle wasting in patients with cancer and healthy older males and postmenopausal females, we observed mild elevations of hepatic enzymes, which in certain circumstances may lead to liver failure, in a few patients in both the placebo and enobosarm treated groups.  Reductions in high-density lipoproteins have also been observed in subjects treated with enobosarm.  Lower levels of high-density lipoproteins could lead to increased risk of adverse cardiovascular events.

 

If the incidence of serious or other adverse events related to our product candidates increases in number or severity, if a regulatory authority believes that these or other events constitute an adverse effect caused by the drug, or if other effects are identified during clinical trials that we or any potential collaborators may conduct in the future or after any of our product candidates are approved and marketed:

 

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·                  we or any potential collaborators may be required to conduct additional preclinical or clinical trials, make changes in the labeling of any such approved products, reformulate any such products, or implement changes to or obtain new approvals of our contractors’ manufacturing facilities;

 

·                  regulatory authorities may be unwilling to approve our product candidates or may withdraw approval of our products;

 

·                  we may experience a significant drop in the sales of the affected products;

 

·                  our reputation in the marketplace may suffer; and

 

·                  we may become the target of lawsuits, including class action suits.

 

Any of these events could prevent approval or harm sales of the affected product candidates or products, or could substantially increase the costs and expenses of commercializing and marketing any such products.

 

Risks Related to Our Dependence on Third Parties

 

If we do not establish collaborations for our product candidates or otherwise raise substantial additional capital, we will likely need to alter, delay or abandon our development and any commercialization plans.

 

Our strategy includes selectively partnering or collaborating with leading pharmaceutical and biotechnology companies to assist us in furthering development and potential commercialization of our product candidates.  We face significant competition in seeking appropriate collaborators, and collaborations are complex and time consuming to negotiate and document. We may not be successful in entering into new collaborations with third parties on acceptable terms, or at all. In addition, we are unable to predict when, if ever, we will enter into any additional collaborative arrangements because of the numerous risks and uncertainties associated with establishing such arrangements. If we are unable to negotiate new collaborations, we may have to curtail the development of a particular product candidate, reduce, delay, or terminate its development or one or more of our other development programs, delay its potential commercialization or reduce the scope of our sales or marketing activities or increase our expenditures and undertake development or commercialization activities at our own expense. For example, we may have to cease further development of our enobosarm program if we are unable to raise sufficient funding for any additional clinical development of enobosarm through a new partnership, collaboration or financing.  In this regard, we do not have sufficient funds to conduct any additional clinical development of our product candidates beyond the Phase 2 clinical trials we are currently conducting, the Phase 1 clinical trials we plan to conduct to support a potential MAA submission for enobosarm 3 mg, and any additional Phase 3 clinical trial we may have to conduct to seek approval from any regulatory authority for enobosarm 3 mg is subject to our ability to raise additional funds.  There can be no assurances that we will be successful in obtaining additional funding in any event.  If we do not have sufficient funds, we will not be able to bring our product candidates to market and generate product revenues.

 

Any collaborative arrangements that we establish in the future may not be successful or we may otherwise not realize the anticipated benefits from these collaborations.  In addition, any future collaboration arrangements may place the development and commercialization of our product candidates outside our control, may require us to relinquish important rights or may otherwise be on terms unfavorable to us.

 

We have in the past established and intend to continue to establish collaborations with third parties to develop and commercialize some of our current and future product candidates, and these collaborations may not be successful or we may otherwise not realize the anticipated benefits from these collaborations. For example, in March 2011, we and Ipsen Biopharm Limited, or Ipsen, mutually agreed to terminate our collaboration for the development and commercialization of our toremifene-based product candidate, and, as a result, we will not receive any additional milestone payments from Ipsen on account of our collaboration with Ipsen. As of the date of this report, we have no ongoing collaborations for the development and commercialization of our product candidates.  We may not be able to locate third-party collaborators to develop and market our product candidates, and we lack the capital and resources necessary to develop our product candidates alone.

 

Dependence on collaborative arrangements subjects us to a number of risks, including:

 

·                  we may not be able to control the amount and timing of resources that our potential collaborators may devote to our product candidates;

 

·                  potential collaborations may experience financial difficulties or changes in business focus;

 

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·                  we may be required to relinquish important rights such as marketing and distribution rights;

 

·                  should a collaborator fail to develop or commercialize one of our compounds or product candidates, we may not receive any future milestone payments and will not receive any royalties for the compound or product candidate;

 

·                  business combinations or significant changes in a collaborator’s business strategy may also adversely affect a collaborator’s willingness or ability to complete its obligations under any arrangement;

 

·                  under certain circumstances, a collaborator could move forward with a competing product candidate developed either independently or in collaboration with others, including our competitors; and

 

·                  collaborative arrangements are often terminated or allowed to expire, which could delay the development and may increase the cost of developing our product candidates.

 

If third parties do not manufacture our product candidates in sufficient quantities, in the required timeframe, at an acceptable cost, and with appropriate quality control, clinical development and commercialization of our product candidates would be delayed.

 

We do not currently own or operate manufacturing facilities, and we rely, and expect to continue to rely, on third parties for the production of clinical and commercial quantities of our product candidates. Our current and anticipated future dependence upon others for the manufacture of our product candidates may adversely affect our future profit margins, if any, and our ability to develop product candidates and commercialize any product candidates on a timely and competitive basis.

 

We rely on third-party vendors for the manufacture of enobosarm drug substance.  If the contract manufacturers that we are currently utilizing to meet our supply needs for enobosarm or any future SARM product candidates prove incapable or unwilling to continue to meet our supply needs, we could experience a delay in conducting any additional clinical trials of enobosarm or any future SARM product candidates. In addition, we rely on third-party contractors for the manufacture of GTx-758 drug substance. We may not be able to maintain or renew our existing or any other third-party manufacturing arrangements on acceptable terms, if at all. If our suppliers fail to meet our requirements for GTx-758, enobosarm or any future product candidates for any reason, we would be required to obtain alternate suppliers. Any inability to obtain alternate suppliers, including an inability to obtain approval from the FDA of an alternate supplier, would delay or prevent the clinical development and commercialization of these product candidates.

 

Use of third-party manufacturers may increase the risk that we will not have adequate supplies of our product candidates or products.

 

Reliance on third-party manufacturers entails risks, to which we would not be subject if we manufactured product candidates or products ourselves, including:

 

·                  reliance on the third party for regulatory compliance and quality assurance;

 

·                  the possible breach of the manufacturing agreement by the third party because of factors beyond our control;

 

·                  the possible termination or non-renewal of the agreement by the third party, based on its own business priorities, at a time that is costly or inconvenient for us; and

 

·                  drug product supplies not meeting the requisite requirements for clinical trial use.

 

If we are not able to obtain adequate supplies of our product candidates, it will be more difficult for us to develop our product candidates and compete effectively. Our product candidates and any products that we and/or our potential collaborators may develop may compete with other product candidates and products for access to manufacturing facilities.

 

Our present or future manufacturing partners may not be able to comply with FDA-mandated current Good Manufacturing Practice regulations, other FDA regulatory requirements or similar regulatory requirements outside the United States. Failure of our third-party manufacturers or us to comply with applicable regulations could result in sanctions being imposed on us, including fines, injunctions, civil penalties, failure of regulatory authorities to grant marketing approval of our product candidates, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely affect supplies of our product candidates.

 

If third parties on whom we rely do not perform as contractually required or expected, we may not be able to

 

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obtain regulatory approval for or successfully commercialize our product candidates.

 

We do not have the ability to independently conduct clinical trials for our product candidates, and we must rely on third parties, such as contract research organizations, medical institutions, clinical investigators and contract laboratories to conduct our clinical trials. In addition, we rely on third parties to assist with our preclinical development of product candidates. If these third parties do not successfully carry out their contractual duties or regulatory obligations or meet expected deadlines, if the third parties need to be replaced, or if the quality or accuracy of the data they obtain is compromised due to the failure to adhere to our clinical protocols or regulatory requirements or for other reasons, our preclinical development activities or clinical trials may be extended, delayed, suspended or terminated, and we may not be able to obtain regulatory approval for or successfully commercialize our product candidates.

 

Risks Related to Our Intellectual Property

 

If we lose our license from the University of Tennessee Research Foundation, or UTRF, we may be unable to continue a substantial part of our business.

 

We have licensed intellectual property rights and technology from UTRF used in a substantial part of our business. This license agreement, under which we were granted rights to SARM compounds and technologies, including enobosarm, may be terminated by UTRF if we are in breach of our obligations under, or fail to perform any terms of, the agreement and fail to cure that breach. If this agreement is terminated, then we may lose our rights to utilize the SARM technology and intellectual property covered by that agreement to market, distribute and sell licensed products, including enobosarm, which may prevent us from continuing a substantial part of our business and may result in a material and serious adverse effect on our financial condition, results of operations and any prospects for growth.

 

If some or all of our or our licensors’ patents expire or are invalidated or are found to be unenforceable, or if some or all of our patent applications do not result in issued patents or result in patents with narrow, overbroad, or unenforceable claims, or claims that are not supported in regard to written description or enablement by the specification, or if we are prevented from asserting that the claims of an issued patent cover a product of a third party, we may be subject to competition from third parties with products in the same class of products as our product candidates or products with the same active pharmaceutical ingredients as our product candidates, including in those jurisdictions in which we have no patent protection.

 

Our commercial success will depend in part on obtaining and maintaining patent and trade secret protection for our product candidates, as well as the methods for treating patients in the product indications using these product candidates. We will be able to protect our product candidates and the methods for treating patients in the product indications using these product candidates from unauthorized use by third parties only to the extent that we or our exclusive licensors own or control such valid and enforceable patents or trade secrets.

 

Our rights to certain patents and patent applications relating to SARM compounds that we have licensed from UTRF are subject to the terms of UTRF’s inter-institutional agreements with The Ohio State University, or OSU, and our rights to future related improvements in some instances are subject to UTRF’s exercise of exclusive options under its agreements with OSU for such improvements.

 

Even if our product candidates and the methods for treating patients for prescribed indications using these product candidates are covered by valid and enforceable patents and have claims with sufficient scope, disclosure and support in the specification, the patents will provide protection only for a limited amount of time. Our and our licensors’ ability to obtain patents can be highly uncertain and involve complex and in some cases unsettled legal issues and factual questions. Furthermore, different countries have different procedures for obtaining patents, and patents issued in different countries provide different degrees of protection against the use of a patented invention by others. Therefore, if the issuance to us or our licensors, in a given country, of a patent covering an invention is not followed by the issuance, in other countries, of patents covering the same invention, or if any judicial interpretation of the validity, enforceability, or scope of the claims in, or the written description or enablement in, a patent issued in one country is not similar to the interpretation given to the corresponding patent issued in another country, our ability to protect our intellectual property in those countries may be limited. Changes in either patent laws or in interpretations of patent laws in the United States and other countries may materially diminish the value of our intellectual property or narrow the scope of our patent protection.

 

We may be subject to competition from third parties with products in the same class of products as our product candidates or products with the same active pharmaceutical ingredients as our product candidates in those jurisdictions in which we have no patent protection.  Even if patents are issued to us or our licensors regarding our

 

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product candidates or methods of using them, those patents can be challenged by our competitors who can argue such patents are invalid or unenforceable, lack of utility, lack sufficient written description or enablement, or that the claims of the issued patents should be limited or narrowly construed. Patents also will not protect our product candidates if competitors devise ways of making or using these product candidates without legally infringing our patents. The Federal Food, Drug, and Cosmetic Act and FDA regulations and policies create a regulatory environment that encourages companies to challenge branded drug patents or to create non-infringing versions of a patented product in order to facilitate the approval of abbreviated new drug applications for generic substitutes. These same types of incentives encourage competitors to submit new drug applications that rely on literature and clinical data not prepared for or by the drug sponsor, providing another less burdensome pathway to approval.

 

We also rely on trade secrets to protect our technology, especially where we do not believe that patent protection is appropriate or obtainable. However, trade secrets are difficult to protect. Our employees, consultants, contractors, outside scientific collaborators and other advisors may unintentionally or willfully disclose our confidential information to competitors, and confidentiality agreements may not provide an adequate remedy in the event of unauthorized disclosure of confidential information. Enforcing a claim that a third party illegally obtained and is using our trade secrets is expensive and time-consuming, and the outcome is unpredictable. Moreover, our competitors may independently develop equivalent knowledge, methods and know-how. Failure to obtain or maintain trade secret protection could adversely affect our competitive business position.

 

If we infringe intellectual property rights of third parties, it may increase our costs or prevent us from being able to commercialize our product candidates.

 

There is a risk that we are infringing the proprietary rights of third parties because numerous United States and foreign issued patents and pending patent applications, which are owned by third parties, exist in the fields that are the focus of our development and manufacturing efforts. Others might have been the first to make the inventions covered by each of our or our licensors’ pending patent applications and issued patents and/or might have been the first to file patent applications for these inventions. In addition, because patent applications can take many years to issue, there may be currently pending applications, unknown to us or our licensors, which may later result in issued patents that cover the production, manufacture, synthesis, commercialization, formulation or use of our product candidates. In addition, the production, manufacture, synthesis, commercialization, formulation or use of our product candidates may infringe existing patents of which we are not aware. Defending ourselves against third-party claims, including litigation in particular, would be costly and time consuming and would divert management’s attention from our business, which could lead to delays in our development or commercialization efforts. If third parties are successful in their claims, we might have to pay substantial damages or take other actions that are adverse to our business.

 

As a result of intellectual property infringement claims, or to avoid potential claims, we might:

 

·                  be prohibited from selling or licensing any product that we and/or any potential collaborators may develop unless the patent holder licenses the patent to us, which the patent holder is not required to do;

 

·                  be required to pay substantial royalties or other amounts, or grant a cross license to our patents to another patent holder; or

 

·                  be required to redesign the formulation of a product candidate so that it does not infringe, which may not be possible or could require substantial funds and time.

 

Risks Related to Regulatory Approval of Our Product Candidates

 

If we or any potential collaborators are not able to obtain required regulatory approvals, we or such collaborators will not be able to commercialize our product candidates, and our ability to generate revenue will be materially impaired.

 

Our product candidates and the activities associated with their development and commercialization are subject to comprehensive regulation by the FDA, other regulatory agencies in the United States and by comparable authorities in other countries, including the EMA. Failure to obtain regulatory approval for a product candidate will prevent us or any potential collaborator from commercializing the product candidate. We have not received regulatory approval to market any of our product candidates in any jurisdiction, and we do not expect to obtain FDA, EMA or any other regulatory approvals to market any of our product candidates for the foreseeable future, if at all.  The process of obtaining regulatory approvals is expensive, often takes many years, if approval is obtained at all, and can vary substantially based upon the type, complexity and novelty of the product candidates involved.

 

Changes in the regulatory approval policy during the development period, changes in or the enactment of

 

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additional regulations or statutes, or changes in regulatory review for each submitted product application may cause delays in the approval or rejection of an application. Even if the FDA or the EMA approves a product candidate, the approval may impose significant restrictions on the indicated uses, conditions for use, labeling, advertising, promotion, marketing and/or production of such product, and may impose ongoing requirements for post-approval studies, including additional research and development and clinical trials. Any FDA approval may also impose risk evaluation mitigation strategies, or REMS, on a product if the FDA believes there is a reason to monitor the safety of the drug in the market place. REMS may include requirements for additional training for health care professionals, safety communication efforts and limits on channels of distribution, among other things. The sponsor would be required to evaluate and monitor the various REMS activities and adjust them if need be. The FDA and EMA also may impose various civil or criminal sanctions for failure to comply with regulatory requirements, including withdrawal of product approval.

 

Furthermore, the approval procedure and the time required to obtain approval varies among countries and can involve additional testing beyond that required by the FDA. Approval by one regulatory authority does not ensure approval by regulatory authorities in other jurisdictions.

 

The FDA, the EMA and other foreign regulatory authorities have substantial discretion in the approval process and may refuse to accept any application or may decide that our data are insufficient for approval and require additional preclinical, clinical or other studies. For example, in October 2009, we received a Complete Response Letter from the FDA regarding our NDA for toremifene 80 mg to reduce fractures in men with prostate cancer on ADT notifying us that the FDA would not approve our NDA as a result of certain clinical deficiencies identified in the Complete Response Letter. We have since discontinued our toremifene 80 mg development program, as well as our other toremifene-based products and terminated our license and supply agreement with Orion for toremifene products. While we expect to submit a MAA to the EMA for the marketing approval of enobosarm 3 mg in the European Union for the more narrow indication of the prevention and treatment of muscle wasting in patients with advanced NSCLC treated with platinum plus taxane chemotherapy by the first quarter of 2015, the EMA may determine that the safety and efficacy data from the POWER 1 trial are insufficient to support approval of the planned MAA submission and that one or more additional Phase 3 clinical trials of enobosarm 3 mg would be required to be successfully conducted by us in order to support any such approval.  Based on recent input from the FDA, we plan to meet again with the FDA later in the year to discuss a potential Phase 3 clinical program for enobosarm 3 mg for the prevention and treatment of muscle wasting or cachexia in patients with NSCLC. There can be no assurance that we will reach agreement with the FDA on any Phase 3 program for enobosarm 3 mg.  Additionally, there can be no assurance that the FDA will determine that the data from our ongoing clinical trial or future clinical trials of GTx-758 will be sufficient for approval of this product candidate in any indication.  For example, we may observe an unacceptable incidence of adverse events in our ongoing, planned or potential clinical trials of enobosarm or GTx-758, which could require us to abandon the development of the affected product candidate.

 

In addition, varying interpretations of the data obtained from preclinical and clinical testing could delay, limit, or prevent regulatory approval of a product candidate.  Even if we submit an application to the FDA, the EMA and other foreign regulatory authorities for marketing approval of a product candidate, it may not result in any marketing approval.

 

We do not expect to receive regulatory approval for the commercial sale of any of our product candidates that are in development for the foreseeable future, if at all. The inability to obtain approval from the FDA, the EMA and other foreign regulatory authorities for our product candidates would prevent us or any potential collaborators from commercializing these product candidates in the United States, the European Union, or other countries. See the section entitled “Business — Government Regulation” under Part 1, Item 1 of this Annual Report on Form 10-K for additional information regarding risks associated with marketing approval, as well as risks related to potential post-approval requirements.

 

Risks Related to Commercialization

 

The commercial success of any products that we and/or any potential collaborators may develop will depend upon the market and the degree of market acceptance among physicians, patients, health care payors and the medical community.

 

Based upon our recent meetings with European regulators, we expect to submit a MAA to the EMA by the first quarter of 2015 for the more narrow indication of the prevention and treatment of muscle wasting in patients with advanced NSCLC treated with platinum plus taxane chemotherapy.  We anticipate that the commercial prospects for the drug product candidate could be diminished as a result of this more limited product indication.  Additionally, any

 

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products that we and/or any potential collaborators may develop, including enobosarm 3 mg, may not gain market acceptance for its stated indication among physicians, patients, health care payors and the medical community. If these products do not achieve an adequate level of acceptance, we may not generate material product revenues or receive royalties to the extent we currently anticipate, and we may not become profitable. The degree of market acceptance of our product candidates, if approved for commercial sale, will depend on a number of factors, including:

 

·                  efficacy and safety results in clinical trials;

 

·                  the prevalence and severity of any side effects;

 

·                  potential advantages over alternative treatments;

 

·                  whether the products we commercialize remain a preferred course of treatment;

 

·                  the ability to offer our product candidates for sale at competitive prices;

 

·                  relative convenience and ease of administration;

 

·                  the strength of marketing and distribution support; and

 

·                  sufficient third-party coverage or reimbursement.

 

If we are unable to establish sales and marketing capabilities or establish and maintain agreements with third parties to market and sell our product candidates, we may be unable to generate product revenue from such candidates.

 

We have limited experience as a company in the sales, marketing and distribution of pharmaceutical products.  In the event one of our product candidates is approved, we will need to establish sales and marketing capabilities or establish and maintain agreements with third parties to market and sell our product candidates. We may be unable to build our own sales and marketing capabilities, and there are risks involved with entering into arrangements with third parties to perform these services, which could delay the commercialization of any of our product candidates if approved for commercial sale. In addition, to the extent that we enter into arrangements with third parties to perform sales, marketing and distribution services, our product revenues are likely to be lower than if we market and sell any products that we develop ourselves.

 

If we and/or any potential collaborators are unable to obtain reimbursement or experience a reduction in reimbursement from third-party payors for products we sell, our revenues and prospects for profitability will suffer.

 

Sales of products developed by us and/or any potential collaborators are dependent on the availability and extent of reimbursement from third-party payors. Changes in the reimbursement policies of these third-party payors that reduce reimbursements for any products that we and/or any potential collaborators may develop and sell could negatively impact our future operating and financial results.

 

Medicare coverage and reimbursement of prescription drugs exists under Medicare Part D for oral drug products capable of self-administration by patients.  Our oral drug product candidates would likely be covered by Medicare Part D (if covered by Medicare at all).  In March 2010, the United States Congress enacted the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act. This health care reform legislation will increase the number of individuals who receive health insurance coverage and will close a gap in drug coverage under Medicare Part D. The legislation, however, also implemented cost containment and other measures that could adversely affect revenues from sales of product candidates, including an increase in drug rebates manufacturers must pay under Medicaid for brand name prescription drugs and extension of these rebates to Medicaid managed care.

 

Pharmaceutical manufacturers and importers of brand name prescription drugs are assessed a fee based on our proportionate share of sales of brand name prescription drugs to certain government programs, including Medicare and Medicaid, made in the preceding year if such sales exceed a defined threshold.  Since 2011, manufacturers have been required to provide a 50% discount on brand name prescription drugs sold to beneficiaries who fall within a gap that exists in the Medicare Part D prescription drug program (commonly known as the “donut hole”).

 

The health care reform legislation has been subject to political and judicial challenge.  In 2012, the Supreme Court considered the constitutionality of certain provisions of the law.  The court upheld as constitutional the mandate for individuals to obtain health insurance but held that the provision allowing the federal government to withhold certain Medicaid funds to states that do not expand state Medicaid programs was unconstitutional.  The

 

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impact of the court’s ruling remains uncertain.  Political and judicial challenges to the law may continue in the wake of the court’s ruling.

 

Economic pressure on state budgets may result in states increasingly seeking to achieve budget savings through mechanisms that limit coverage or payment for drugs.  State Medicaid programs are increasingly requesting manufacturers to pay supplemental rebates and requiring prior authorization for use of drugs where supplemental rebates are not provided.  Private health insurers and managed care plans are likely to continue challenging the prices charged for medical products and services, and many of these third-party payors may limit reimbursement for newly-approved health care products. In particular, third-party payors may limit the indications for which they will reimburse patients who use any products that we and/or any potential collaborators may develop or sell. These cost-control initiatives could decrease the price we might establish for products that we or any potential collaborators may develop or sell, which would result in lower product revenues or royalties payable to us.

 

Similar cost containment initiatives exist in countries outside of the United States, particularly in the countries of the European Union, where the pricing of prescription pharmaceuticals is subject to governmental control. In these countries, pricing negotiations with governmental authorities can extend well beyond the receipt of regulatory marketing approval for a product and may require us or any potential collaborators to conduct a clinical trial that compares the cost effectiveness of our product candidates or products to other available therapies. The conduct of such a clinical trial could be expensive and result in delays in our or a potential collaborators’ commercialization efforts. Third-party payors are challenging the prices charged for medical products and services, and many third-party payors limit reimbursement for newly-approved health care products. Recently budgetary pressures in many European Union countries are also causing governments to consider or implement various cost-containment measures, such as price freezes, increased price cuts and rebates.  If budget pressures continue, governments may implement additional cost containment measures.  Cost-control initiatives could decrease the price we might establish for products that we or any potential collaborators may develop or sell, which would result in lower product revenues or royalties payable to us.

 

Another development that could affect the pricing of drugs would be if the Secretary of Health and Human Services allowed drug reimportation into the United States. The Medicare Prescription Drug, Improvement and Modernization Act of 2003 gives discretion to the Secretary of Health and Human Services to allow drug reimportation into the United States under some circumstances from foreign countries, including from countries where the drugs are sold at a lower price than in the United States. If the circumstances were met and the Secretary exercised the discretion to allow for the direct reimportation of drugs, it could decrease the price we or any potential collaborators receive for any products that we and/or any potential collaborators may develop, negatively affecting our revenues and prospects for profitability.

 

Health care reform measures could hinder or prevent our product candidates’ commercial success.

 

Among policy makers and payors in the United States and elsewhere, there is significant interest in promoting health care reform, as evidenced by the enactment in the United States of the Patient Protection and Affordable Care Act and the Health Care and Education Reconciliation Act in 2010. Federal and state legislatures within the United States and foreign governments will likely continue to consider changes to existing health care legislation. These changes adopted by governments may adversely impact our business by lowering the price of health care products in the United States and elsewhere.

 

We operate in a highly regulated industry and new laws, regulations or judicial decisions, or new interpretations of existing laws, regulations or decisions, related to health care availability, method of delivery or payment for health care products and services, or sales, marketing and pricing practices could negatively impact our business, operations and financial condition.

 

If product liability lawsuits are brought against us, we may incur substantial liabilities and may be required to limit commercialization of any products that we may develop.

 

We face an inherent risk of product liability exposure related to our prior commercial sales of FARESTON® and the testing of our product candidates in human clinical trials, and we will face an even greater risk if we commercially sell any product that we may develop. If we cannot successfully defend ourselves against claims that our product candidates or products caused injuries, we will incur substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:

 

·                  decreased demand for any product candidates or products;

 

·                  injury to our reputation;

 

·                  withdrawal of clinical trial participants;

 

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·                  costs to defend the related litigation;

 

·                  substantial monetary awards to trial participants or patients;

 

·                  loss of revenue; and

 

·                  the inability to commercialize any products for which we obtain or hold marketing approvals.

 

We have product liability insurance that covers our clinical trials and any commercial products up to a $20 million annual aggregate limit. Insurance coverage is increasingly expensive. We may not be able to maintain insurance coverage at a reasonable cost, and we may not be able to obtain insurance coverage that will be adequate to satisfy any liability that may arise.

 

If our competitors are better able to develop and market products than any products that we and/or any potential collaborators may develop, our commercial opportunity will be reduced or eliminated.

 

We face competition from commercial pharmaceutical and biotechnology enterprises, as well as from academic institutions, government agencies and private and public research institutions. Our commercial opportunities will be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer side effects or are less expensive than any products that we and/or any potential collaborators may develop. Competition could result in reduced sales and pricing pressure on our product candidates, if approved, which in turn would reduce our ability to generate meaningful revenue and have a negative impact on our results of operations. In addition, significant delays in the development of our product candidates could allow our competitors to bring products to market before us and impair any ability to commercialize our product candidates.

 

Various products are currently marketed or used off-label for some of the diseases and conditions that we are targeting in our pipeline, and a number of companies are or may be developing new treatments. These product uses, as well as promotional efforts by competitors and/or clinical trial results of competitive products, could significantly diminish any ability to market and sell any products that we and/or any potential collaborators may develop.

 

With respect to our SARM program, there are other SARM product candidates in development that may compete with enobosarm and any future SARM product candidates, if approved for commercial sale, including SARMs in development from Ligand Pharmaceuticals Inc. and GlaxoSmithKline plc.  Pfizer Inc., Eli Lilly and Company and Amgen Inc. have myostatin inhibitors in development that may compete with enobosarm if approved for commercial sale. In addition, Cytokinetics, Inc. is developing a troponin activator with a muscle specific mechanism in Phase 2 studies, with a focus on neurological muscle diseases (amyotrophic lateral sclerosis and myasthenia gravis) and Novartis AG is developing a human monoclonal antibody for various muscle indications.  Moreover, there are other categories of drugs in development, including ghrelin receptor agonists, growth hormone, secretagogues, inflammatory modulators and other agents, that may have some muscle activity.  Helsinn Group is developing anamorelin, a ghrelin receptor agonist, in Phase 3 clinical trials for treatment of cancer cachexia in patients with NSCLC.  Appetite stimulants such as Megace® (megestrol acetate) and dronabinol are used off-label for the treatment of weight loss and the treatment of loss of appetite in patients with cancer.

 

We are developing GTx-758 for secondary hormonal therapy in men with metastatic and nonmetastatic CRPC, and, potentially, as a secondary hormonal treatment for advanced prostate cancer used in combination with androgen deprivation therapy.  There are various products approved or under clinical development to treat men with advanced prostate cancer who have metastatic CRPC which may compete with GTx-758.  Dendreon Corporation markets and sells Provenge®, an autologous cellular immunotherapy, for the treatment of asymptomatic or minimally symptomatic metastatic castrate resistant prostate cancer.  Medivation, Inc. has received approval for Xtandi®, an oral androgen receptor antagonist, for the treatment of metastatic castration-resistant prostate cancer in men previously treated with docetaxel. Medivation continues to develop Xtandi® for men with metastatic CRPC prior to receiving chemotherapy.  Zytiga®, sold by Johnson & Johnson, has been approved for the treatment of metastatic CRPC prior in patients who have received prior chemotherapy and recently received approval for the treatment of metastatic castrate resistant prostate cancer prior to chemotherapy.  Johnson & Johnson acquired Aragon Pharmaceuticals, Inc., which developed a second generation anti-androgen (ARN-509) that is currently being evaluated in Phase 2 studies in men with progressive, advanced prostate cancer.  Millennium: The Takeda Oncology Company is developing TAK-700 for the treatment of men with metastatic castrate resistant prostate cancer prior to chemotherapy.  GTx-758 is being developed as a treatment for this same patient population prior to the initiation of chemotherapy.

 

Many of our competitors have significantly greater financial resources and expertise in research and development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and

 

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marketing approved products than we do. Smaller or early-stage companies may also prove to be significant competitors, particularly through collaborative arrangements with large and established companies. These third parties compete with us in recruiting and retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring technologies and technology licenses complementary to our programs or advantageous to our business.

 

Risks Related to Employees and Growth

 

If we fail to attract and keep senior management and key scientific personnel, we may be unable to successfully develop or commercialize our product candidates.

 

Our success depends on our continued ability to attract, retain and motivate highly qualified management, clinical and scientific personnel and on our ability to develop and maintain important relationships with leading academic institutions, clinicians and scientists. If we are not able to attract and keep senior management and key scientific personnel, particularly Dr. Mitchell S. Steiner, we may not be able to successfully develop or commercialize our product candidates. All of our employees are at-will employees and can terminate their employment at any time. We do not carry “key person” insurance covering members of senior management, other than $22.5 million of insurance covering Dr. Steiner.

 

In October 2013, we announced a reduction of approximately 60% of our workforce following our announcement that our POWER trials failed to achieve the results required by the FDA to file a NDA for enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced NSCLC.  Our former Chief Financial Officer also resigned from GTx, effective December 31, 2013.  Primarily as a result of our October 2013 workforce reduction, only 32 employees remained as employees of GTx as of December 31, 2013.  Accordingly, we have been and are operating with a shortage of resources and may not be able to effectively conduct our operations with this limited number of employees.  In addition, we announced past workforce reductions in each of December 2009 and June 2011, and our history of implementing workforce reductions, along with the potential for future workforce reductions, may negatively affect our ability to retain or attract talented employees.

 

We will need to hire additional employees in order to grow our business.  Any inability to manage future growth could harm our ability to develop and commercialize our product candidates, increase our costs and adversely impact our ability to compete effectively.

 

As of December 31, 2013, we had only 32 employees, and we will need to hire experienced personnel to develop and commercialize our product candidates and to otherwise grow our business, and we will need to expand the number of our managerial, operational, financial and other employees to support that growth. Competition exists for qualified personnel in the biotechnology field.

 

Future growth, if any, will impose significant added responsibilities on members of management, including the need to identify, recruit, maintain and integrate additional employees. Our future financial performance and our ability to develop and commercialize our product candidates and to compete effectively will depend, in part, on our ability to manage any future growth effectively.

 

Risks Related to Our Common Stock

 

Market volatility may cause our stock price and the value of your investment to decline.

 

The market prices for securities of biotechnology companies in general have been highly volatile and may continue to be so in the future. The following factors, in addition to other risk factors described in this section, may have a significant impact on the market price of our common stock:

 

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·                  announcements regarding our ability to complete the prerequisites for and submit a MAA to the EMA seeking marketing approval for enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced NSCLC treated with platinum plus taxane chemotherapy;

 

·                  announcements regarding our ability to determine, in consultation with the FDA, a feasible pathway forward to seek marketing approval for enobosarm 3 mg for the prevention and treatment of muscle wasting or cachexia in patients with NSCLC;

 

·                  our ability to raise additional capital to carry through with our clinical development plans and current and future operations and the terms of any related financing arrangements;

 

·                  delays in the initiation, enrollment and/or completion of our ongoing and planned clinical trials of enobosarm and GTx-758, or negative, inconclusive or mixed results reported in any of our ongoing clinical trials of enobosarm and GTx-758;

 

·                  reports of unacceptable incidences of adverse events observed in any of our ongoing clinical trials of enobosarm and GTx-758;

 

·                  announcements regarding further cost-cutting initiatives or restructurings;

 

·                  our ability to enter into new collaborative, licensing or other strategic arrangements with respect to our product candidates;

 

·                  the terms and timing of any future collaborative, licensing or other arrangements that we may establish;

 

·                  the timing of achievement of, or failure to achieve, our and any potential collaborators’ clinical, regulatory and other milestones, such as the commencement of clinical development, the completion of a clinical trial or the receipt of regulatory approval;

 

·                  announcement of FDA approval or non-approval of our product candidates or delays in or adverse events during the FDA review process;

 

·                  actions taken by regulatory agencies with respect to our product candidates or products, our clinical trials or our sales and marketing activities, including regulatory actions requiring or leading to restrictions, limitations and/or warnings in the label of an approved product candidate;

 

·                  the commercial success of any product approved by the FDA or its foreign counterparts;

 

·                  introductions or announcements of technological innovations or new products by us, our potential collaborators, or our competitors, and the timing of these introductions or announcements;

 

·                  market conditions for equity investments in general, or the biotechnology or pharmaceutical industries in particular;

 

·                  announcements regarding our ability to comply with the minimum listing requirements of The NASDAQ Stock Market LLC;

 

·                  regulatory developments in the United States and foreign countries;

 

·                  changes in the structure or reimbursement policies of health care payment systems;

 

·                  any intellectual property infringement lawsuit involving us;

 

·                  actual or anticipated fluctuations in our results of operations;

 

·                  changes in financial estimates or recommendations by securities analysts;

 

·                  hedging or arbitrage trading activity that may develop regarding our common stock;

 

·                  sales of large blocks of our common stock;

 

·                  sales of our common stock by our executive officers, directors and significant stockholders;

 

·                  changes in accounting principles; and

 

·                  the loss of any of our key scientific or management personnel.

 

The stock markets in general, and the markets for biotechnology stocks in particular, have experienced significant volatility that has often been unrelated to the operating performance of particular companies. The financial markets continue to face significant uncertainty, resulting in a decline in investor confidence and concerns

 

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about the proper functioning of the securities markets, which decline in general investor confidence has resulted in depressed stock prices for many companies notwithstanding the lack of a fundamental change in their underlying business models or prospects. These broad market fluctuations may adversely affect the trading price of our common stock.

 

In the past, class action litigation has often been instituted against companies whose securities have experienced periods of volatility in market price. Any such litigation brought against us could result in substantial costs, which would hurt our financial condition and results of operations and divert management’s attention and resources, which could result in delays of our clinical trials or commercialization efforts.

 

Our executive officers, directors and largest stockholders have the ability to control all matters submitted to stockholders for approval.

 

As of March 10, 2014, our executive officers, directors and holders of 5% or more of our outstanding common stock, including their affiliated or associated entities, held approximately 65.9% of our outstanding common stock, and our executive officers and directors alone, including their affiliated or associated entities, held approximately 39.8% of our outstanding common stock. As a result, these stockholders, acting together, have the ability to control all matters requiring approval by our stockholders, including the election of directors and the approval of mergers or other business combination transactions. The interests of this group of stockholders may not always coincide with our interests or the interests of other stockholders.

 

If we fail to meet continued listing standards of The NASDAQ Stock Market LLC, our common stock may be delisted. Delisting could adversely affect the liquidity of our common stock and the market price of our common stock could decrease, and our ability to obtain sufficient additional capital to fund our operations and to continue as a going concern would be substantially impaired.

 

Our common stock is currently listed on The NASDAQ Global Market. The NASDAQ Stock Market LLC, or NASDAQ, has minimum requirements that a company must meet in order to remain listed on The NASDAQ Global Market. These requirements include maintaining a minimum closing bid price of $1.00 per share, and the closing bid price of our common stock on March 7, 2014 was $1.70 share. If the closing bid price of our common stock were to fall below $1.00 per share for 30 consecutive trading days or we do not meet other applicable listing requirements, we would fail to be in compliance with NASDAQ’s listing standards. There can be no assurance that we will continue to meet the minimum bid price requirement, or any other NASDAQ continued listing requirement, in the future. If we fail to meet these requirements, including the minimum bid price requirement, NASDAQ may notify us that we have failed to meet the minimum listing requirements and initiate the delisting process. If our common stock is delisted, the liquidity of our common stock would be adversely affected and the market price of our common stock could decrease, and our ability to obtain sufficient additional capital to fund our operations and to continue as a going concern would be substantially impaired.

 

Our ability to use our net operating loss carryforwards and certain other tax attributes may be limited.

 

Under Section 382 of the Internal Revenue Code of 1986, as amended, if a corporation undergoes an “ownership change,” generally defined as a greater than 50% change (by value) in its equity ownership over a three-year period, the corporation’s ability to use its pre-change net operating loss carryforwards and other pre-change tax attributes (such as research tax credits) to offset its post-change taxable income or taxes may be limited.  Although we have recently completed a study to determine whether any Section 382 limitations existed through December 31, 2013 and we do not believe that any Section 382 limitations existed at that time, Section 382 of the Internal Revenue Code is an extremely complex provision with respect to which there are many uncertainties and we have not established whether the IRS agrees with our determination.  In any event, changes in our stock ownership, some of which are outside of our control, could in the future result in an ownership change and an accompanying Section 382 limitation.  If a limitation were to apply, utilization of a portion of our domestic net operating loss and tax credit carryforwards could be limited in future periods and a portion of the carryforwards could expire before being available to reduce future income tax liabilities.

 

Anti-takeover provisions in our charter documents and under Delaware law could make an acquisition of us, which may be beneficial to our stockholders, more difficult and may prevent attempts by our stockholders to replace or remove our current management.

 

Provisions in our certificate of incorporation and our bylaws may delay or prevent an acquisition of us or a change in our management. In addition, these provisions may frustrate or prevent any attempts by our stockholders to replace or remove our current management by making it more difficult for stockholders to replace members of our Board of Directors. Because our Board of Directors is responsible for appointing the members of our management team, these provisions could in turn affect any attempt by our stockholders to replace current members of our management team. These provisions include:

 

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·                  a classified Board of Directors;

 

·                  a prohibition on actions by our stockholders by written consent;

 

·                  the ability of our Board of Directors to issue preferred stock without stockholder approval, which could be used to institute a “poison pill” that would work to dilute the stock ownership of a potential hostile acquirer, effectively preventing acquisitions that have not been approved by our Board of Directors; and

 

·                  limitations on the removal of directors.

 

Moreover, because we are incorporated in Delaware, we are governed by the provisions of Section 203 of the Delaware General Corporation Law, which prohibits a person who owns in excess of 15% of our outstanding voting stock from merging or combining with us for a period of three years after the date of the transaction in which the person acquired in excess of 15% of our outstanding voting stock, unless the merger or combination is approved in a prescribed manner. Finally, these provisions establish advance notice requirements for nominations for election to our Board of Directors or for proposing matters that can be acted upon at stockholder meetings. These provisions would apply even if the offer may be considered beneficial by some stockholders.

 

If there are substantial sales of our common stock, the market price of our common stock could drop substantially, even if our business is doing well.

 

For the 12-month period ended December 31, 2013, the average daily trading volume of our common stock on The NASDAQ Global Market was 696,413 shares. As a result, future sales of a substantial number of shares of our common stock in the public market, or the perception that such sales may occur, could adversely affect the then-prevailing market price of our common stock. As of December 31, 2013, we had 63,185,389 shares of common stock outstanding.

 

In March 2014, we completed a private placement of 11,976,048 shares of our common stock and warrants to purchase 10,179,642 shares of our common stock.  Pursuant to the terms of a registration rights agreement we entered into in connection with the private placement, we agreed to file a registration statement under the Securities Act registering the resale of the 11,976,048 shares of common stock we issued to the investors in the private placement, which include J.R. Hyde, III, our largest stockholder, as well as the 10,179,642 shares of common stock underlying the warrants we issued to those investors.  In addition, if we propose to register any of our securities under the Securities Act, either for our own account or for the account of others, the investors in the private placement are entitled to notice of the registration and are entitled to include, at our expense, their shares of common stock in the registration and any related underwriting, provided, among other conditions, that the underwriters may limit the number of shares to be included in the registration.  Moreover, J.R. Hyde, III and certain of his affiliates, have rights under a separate registration rights agreement with us to require us to file resale registration statements covering an additional 7.9 million shares of common stock held in the aggregate or to include these shares in registration statements that we may file for ourselves or other stockholders. If Mr. Hyde or his affiliates or any of our other significant stockholders, including the other investor in our March 2014 private placement, were to sell large blocks of shares in a short period of time, the market price of our common stock could drop substantially.

 

ITEM 1B.                                       UNRESOLVED STAFF COMMENTS

 

None.

 

ITEM 2.                                                PROPERTIES

 

We sublease approximately 31,000 square feet of office space located at 175 Toyota Plaza, Memphis, Tennessee, under an operating lease which expires on April 30, 2015.  Subsequent to the reduction in force implemented in October 2013, we cancelled our sublease of approximately 31,000 square feet of laboratory and office space located at 3 North Dunlap Street, Memphis, Tennessee from the University of Tennessee Research Foundation, effective December 31, 2013.

 

ITEM 3.                                                LEGAL PROCEEDINGS

 

We are not currently involved in any material legal proceedings.

 

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ITEM 4.                                                MINE SAFETY DISCLOSURES

 

Not applicable.

 

PART II

 

ITEM 5.                                                MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND ISSUER PURCHASES OF EQUITY SECURITIES

 

Market for Registrant’s Common Equity

 

Our common stock began trading on The NASDAQ Global Market under the symbol “GTXI” on February 3, 2004.  The following table presents, for the periods indicated, the high and low intraday sales prices per share of our common stock as reported on The NASDAQ Global Market.

 

 

 

2013

 

2012

 

 

 

High

 

Low

 

High

 

Low

 

First Quarter

 

$

5.41

 

$

4.15

 

$

6.55

 

$

3.15

 

Second Quarter

 

7.24

 

3.85

 

3.92

 

2.62

 

Third Quarter

 

7.14

 

1.31

 

5.35

 

3.29

 

Fourth Quarter

 

2.09

 

1.41

 

4.92

 

3.39

 

 

On March 7, 2014, the closing price of our common stock as reported on The NASDAQ Global Market was $1.70 per share and there were approximately 76 holders of record of our common stock.

 

Performance Graph(1)

 

The rules of the SEC require that we include in our annual report to stockholders a line-graph presentation comparing cumulative stockholder returns on our common stock with a broad equity market index that includes companies whose equity securities are traded on the NASDAQ and either a published industry or line-of-business standard index or an index of peer companies selected by us.  We have elected to use The NASDAQ Composite Index (which tracks the aggregate price performance of equity securities of companies traded on NASDAQ Stock Market) and The NASDAQ Biotechnology Index (consisting of a group of approximately 122 companies in the biotechnology sector) for purposes of the performance comparison that appears below.

 

The following graph shows the cumulative total stockholder return assuming the investment of $100.00 at the closing prices on December 31, 2008 on The NASDAQ Global Market for:  (1) our common stock; (2) The NASDAQ Composite Index and (3) The NASDAQ Biotechnology Index.  All values assume reinvestment of the full amounts of all dividends.  No dividends have been declared on our common stock.  The closing sale price of our common stock on December 31, 2013 as reported on The NASDAQ Global Market was $1.65.

 

The stockholder return shown on the graph below is not necessarily indicative of future performance, and we do not make or endorse any predictions as to future stockholder returns.

 

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COMPARISON OF 5 YEAR CUMULATIVE TOTAL RETURN*

Among GTx Inc., the NASDAQ Composite Index, and the NASDAQ Biotechnology Index

 

GRAPHIC

 


*$100 invested on 12/31/08 in stock or index, including reinvestment of dividends.

Fiscal year ending December 31.

 

(1) The material in this section is not “soliciting material,” is not deemed filed with the SEC and is not to be incorporated by reference in any filing of GTx, Inc. under the Securities Act of 1933 or the Securities Exchange Act of 1934 whether made before or after the date hereof and irrespective of any general incorporation language in such filing.

 

Dividend Policy

 

We have never declared or paid any cash dividends on our capital stock. We currently intend to retain any future earnings to fund the development and expansion of our business, and therefore we do not anticipate paying cash dividends on our common stock in the foreseeable future.  Any future determination to pay dividends will be at the discretion of our Board of Directors.

 

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ITEM 6.                                                SELECTED FINANCIAL DATA

 

You should read the selected financial data below in conjunction with “Management’s Discussion and Analysis of Financial Condition and Results of Operations” and the audited financial statements, notes thereto and other financial information included elsewhere in this Annual Report on Form 10-K. The following selected financial data have been derived from our audited historical financial statements, certain of which are included elsewhere in the Annual Report on Form 10-K.  Historical results are not indicative of the results to be expected in the future.

 

 

 

Years Ended December 31,

 

 

 

2013

 

2012

 

2011

 

2010

 

2009

 

 

 

(in thousands, except per share data)

 

Statement of Operations Data:

 

 

 

 

 

 

 

 

 

 

 

Revenues:

 

 

 

 

 

 

 

 

 

 

 

Collaboration revenue

 

$

 

$

 

$

8,066

 

$

56,786

 

$

11,441

 

 

 

 

 

 

 

 

 

 

 

 

 

Expenses:

 

 

 

 

 

 

 

 

 

 

 

Research and development expenses

 

32,318

 

38,887

 

31,938

 

28,495

 

32,344

 

General and administrative expenses

 

11,281

 

10,845

 

12,027

 

13,194

 

27,165

 

Total expenses

 

43,599

 

49,732

 

43,965

 

41,689

 

59,509

 

(Loss) income from operations

 

(43,599

)

(49,732

)

(35,899

)

15,097

 

(48,068

)

Other (expense) income, net

 

1,488

 

(19

)

398

 

1,363

 

188

 

(Loss) income from operations before income taxes

 

(42,111

)

(49,751

)

(35,501

)

16,460

 

(47,880

)

Income tax benefit

 

 

8,821

 

886

 

 

770

 

Net (loss) income from continuing operations

 

(42,111

)

(40,930

)

(34,615

)

16,460

 

(47,110

)

Income (loss) from discontinued operations before income taxes

 

 

22,676

 

2,207

 

(1,166

)

1,386

 

Income tax expense

 

 

(8,821

)

(886

)

 

(532

)

Net (loss) income from discontinued operations

 

 

13,855

 

1,321

 

(1,166

)

854

 

Net (loss) income

 

$

(42,111

)

$

(27,075

)

$

(33,294

)

$

15,294

 

$

(46,256

)

 

 

 

 

 

 

 

 

 

 

 

 

Net (loss) income per share — basic and diluted:

 

 

 

 

 

 

 

 

 

 

 

Net (loss) income from continuing operations

 

$

(0.67

)

$

(0.65

)

$

(0.60

)

$

0.42

 

$

(1.29

)

Net (loss) income from discontinued operations

 

 

0.22

 

0.02

 

(0.03

)

0.02

 

Net (loss) income per share

 

$

(0.67

)

$

(0.43

)

$

(0.58

)

$

0.39

 

$

(1.27

)

 

 

 

 

 

 

 

 

 

 

 

 

 

 

As of December 31,

 

 

 

2013

 

2012

 

2011

 

2010

 

2009

 

 

 

(in thousands)

 

Balance Sheet Data:

 

 

 

 

 

 

 

 

 

 

 

Cash, cash equivalents and short-term investments

 

$

14,729

 

$

56,089

 

$

74,440

 

$

58,631

 

$

49,044

 

Working capital

 

10,604

 

47,320

 

71,015

 

55,149

 

34,876

 

Total assets

 

15,605

 

57,774

 

78,656

 

64,583

 

56,034

 

Accumulated deficit

 

(455,360

)

(413,249

)

(386,174

)

(352,880

)

(368,174

)

Total stockholders’ equity (deficit)

 

10,684

 

47,701

 

71,874

 

51,727

 

(8,750

)

 

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ITEM 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF OPERATIONS

 

The following discussion and analysis should be read in conjunction with our financial statements and related notes included elsewhere in this Annual Report on Form 10-K. This discussion contains forward-looking statements based upon current expectations that involve risks and uncertainties. Our actual results and the timing of selected events could differ materially from those anticipated in these forward-looking statements as a result of several factors, including those set forth under Part I,  Item 1A “Risk Factors” and elsewhere in this Annual Report on Form 10-K.  See “Special Note Regarding Forward-Looking Statements” in this Annual Report on Form 10-K.

 

Overview

 

Business Overview

 

We are a biopharmaceutical company dedicated to the discovery, development and commercialization of small molecules for the treatment of cancer, including treatments for prostate and breast cancer, cancer supportive care, including prevention and treatment of cancer-related muscle wasting, and other serious medical conditions.

 

Business Highlights

 

We are developing selective androgen receptor modulators, or SARMs, a new class of drugs with the potential to prevent and treat muscle wasting in patients with cancer and other musculoskeletal wasting or muscle loss conditions, including chronic sarcopenia (age related muscle loss), as well as the potential to be used as a hormonal therapy for the treatment of metastatic breast cancer.  Our lead SARM product candidate, enobosarm (GTx-024), has to date been evaluated in fourteen completed or ongoing clinical trials enrolling approximately 1,320 subjects, including in three Phase 2 and two Phase 3 clinical trials.  Enobosarm is the generic name given to the compound by the USAN Council and the World Health Organization and is the first compound to receive the SARM stem in its name, recognizing enobosarm as the first in this new class of compounds.

 

We announced in August 2013 that the POWER 1 (platinum plus taxane chemotherapy) and POWER 2 (platinum plus non-taxane chemotherapy) (Prevention and treatment Of muscle Wasting in patients with cancER) Phase 3 clinical trials evaluating enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced non-small cell lung cancer, or NSCLC, failed to meet the primary statistical criterion for the co-primary endpoints of lean body mass and physical function that were assessed statistically using responder analyses as pre-specified for the United States Food and Drug Administration, or FDA.  However, efficacy data from the studies demonstrated enobosarm’s consistent effect on maintaining or improving lean body mass compared to placebo and that maintenance or improvement in lean body mass is potentially associated with longer survival in patients, regardless of treatment.  As for safety, enobosarm was generally well tolerated, with the occurrence of serious adverse events similar across the placebo and treated groups.

 

Enobosarm 3 mg demonstrated a statistically significant effect versus placebo on the primary endpoint of physical function through Day 84 in the POWER 1 clinical trial as assessed by continuous variable analysis, as pre-specified in our statistical analysis plan for the European Medicines Agency, or EMA.  Therefore, we met with representatives from two member countries to the EMA in January of 2014 to review and discuss the results of the POWER trials to determine an appropriate path forward for submitting a marketing authorization application, or MAA, in the European Union for enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced NSCLC.  Based on input from the two member countries, we believe data from the POWER 1 trial, as well as supporting data from the POWER 2 trial, are sufficient to support the submission of a MAA to the EMA seeking marketing authorization for enobosarm 3 mg in the more narrow indication of the prevention and treatment of muscle wasting in patients with advanced NSCLC treated with platinum plus taxane chemotherapy. We plan to initiate seven Phase 1 clinical studies that are typically required for registration purposes and develop a pediatric investigational plan, or PIP, necessary for submission of the MAA.  We currently expect to submit the MAA to the EMA for enobosarm 3 mg for the prevention and treatment of muscle wasting in patients with advanced NSCLC treated with platinum plus taxane chemotherapy by the first quarter of 2015, after completion of the Phase 1 studies and acceptance of the PIP by the EMA’s Pediatric Committee.

 

In our meeting with the FDA in February 2014 to review and discuss the results of the POWER clinical trials, we learned that since data from the two POWER trials failed to meet the primary statistical criterion pre-specified for the co-primary endpoints of lean body mass and physical function, the FDA was not willing to accept a new drug

 

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application, or NDA, for enobosarm 3 mg. However, based on input from the FDA meeting, we believe there is a regulatory path forward for enobosarm 3 mg in the United States, and we plan to meet again with the FDA to discuss a potential Phase 3 clinical program evaluating enobosarm 3 mg for an indication of muscle wasting or cachexia in patients with NSCLC.  Any such Phase 3 clinical program would be subject to our ability to obtain additional funding and would be required to be successfully completed prior to any NDA submission to the FDA for enobosarm 3 mg.

 

We conducted the POWER 1 and POWER 2 clinical trials of enobosarm at sites in the United States, Europe, Russia and South America.  Each of the placebo-controlled, double-blind clinical trials was fully enrolled during the fourth quarter of 2012, with approximately 325 patients in each clinical trial.  In each of these clinical trials, patients with Stage III or IV NSCLC were randomized to placebo or enobosarm 3 mg at the time they began first line chemotherapy.  The last patients completed the Phase 3 clinical trials in May 2013.  The vital status (survival) of patients participating in the trials will continue to be periodically monitored in accordance with the clinical trial protocols and is still ongoing.  The trials evaluated as co-primary endpoints the effect of enobosarm versus placebo on total lean body mass (muscle) assessed by dual x-ray absorptiometry, or DXA, and on physical function assessed by the Stair Climb Test at three months. Durability of effect was assessed as a secondary endpoint at five months in those patients who responded at Day 84.

 

SARMs also have the potential to be used as a novel hormonal therapy for the treatment of metastatic breast cancer.  Nonselective steroidal androgens have been used to treat breast cancer; however, the unwanted virilizing side effects have limited their widespread clinical use. We believe that enobosarm, by targeting the androgen receptor, or AR, in estrogen receptor, or ER, positive breast cancer, has the potential to provide clinical benefit to women with metastatic breast cancer by treating their disease while minimizing the unwanted masculinizing side effects associated with steroidal androgens, and unlike androgens, cannot be converted into an estrogen.  In the second quarter of 2013, we initiated a Phase 2 open label study evaluating enobosarm 9 mg for the treatment of AR positive and ER positive metastatic breast cancer in women who have previously responded to hormonal therapy for the treatment of their metastatic breast cancer.  Nine clinical study sites in the U.S. have fully enrolled the study with 22 postmenopausal women with metastatic breast cancer to assess clinical benefit response after six months of enobosarm 9 mg treatment, which is defined as either those women receiving treatment who have demonstrated a complete response (disappearance of all targeted lesions), a partial response (at least a 30 percent decrease in the sum of the diameters of the targeted lesions) or stable disease (no disease progression from baseline).  In February 2014, we reported that enobosarm 9 mg continues to be well tolerated by patients in the study, and that we expect to meet the pre-specified goal of demonstrating, after six months of treatment, at least three clinical benefit responses in at least 14 patients with AR positive and ER positive breast cancer. The study is ongoing and data from all patients in the study is expected late in the second quarter of 2014.

 

Additionally, we are developing GTx-758 (Capesaris®), an oral nonsteroidal selective estrogen receptor alpha agonist, for secondary hormonal therapy in men with metastatic and nonmetastatic castration resistant prostate cancer, or CRPC, and, potentially, as a secondary hormonal treatment for advanced prostate cancer used in combination with androgen deprivation therapy, or ADT.  We believe GTx-758 has the potential to reduce free testosterone without also causing certain estrogen deficiency side effects, such as bone loss and hot flashes, which are common with current androgen deprivation therapies for prostate cancer.  We also believe that GTx-758 may be effective, in combination with ADT, as a secondary hormonal treatment of advanced prostate cancer by reducing free testosterone to levels lower than those attainable with ADT alone and potentially reducing the estrogen deficiency side effects caused by the use of ADT.

 

In May 2012, we announced that the FDA had removed its full clinical hold on our Investigational New Drug, or IND, application for GTx-758.  The full clinical hold was placed on our three then ongoing Phase 2 clinical trials evaluating GTx-758 to treat men with advanced prostate cancer in February 2012 and resulted in the discontinuation of these trials.  The full clinical hold followed our reports to the FDA of venous thromboembolic events (blood clots), or VTEs, in subjects treated with GTx-758 at the doses being studied in those trials (1000 mg and higher per day).  Based upon feedback from the FDA in connection with the removal of the full clinical hold, we initiated in the third quarter of 2012 a Phase 2 clinical trial to evaluate the safety and efficacy of lower doses of GTx-758 as secondary hormonal therapy in men with metastatic CRPC.

 

GTx is currently conducting a Phase 2 open-label clinical trial in men who have developed metastatic or nonmetastatic CRPC while on ADT.  GTx-758 has previously demonstrated the ability to increase the production of a protein called sex hormone binding globulin, or SHBG, that binds testosterone and thereby reduces free testosterone.  By reducing free testosterone, we believe serum prostate specific antigen, or PSA, will be reduced in men with CRPC.  The primary endpoint of the current Phase 2 clinical trial is the proportion of subjects with a >

 

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50% decline from baseline in serum PSA by Day 90. Other key endpoints include serum SHBG and total and free testosterone levels, as well as prostate cancer progression, in the study subjects.   In addition, the clinical study will evaluate the ability of GTx-758 to treat certain estrogen deficiency side effects associated with luteinizing hormone releasing hormone agonists such as hot flashes and bone loss.  The Phase 2 clinical trial allows us to assess the safety and tolerability of GTx-758 in these subjects, including the incidence of VTEs.  The original trial design provided for 75 total subjects to be enrolled in three sequential dosing arms, with the first 25 subjects in the study being enrolled in the GTx-758 125 mg dosing arm.  Assuming that an acceptable incidence of VTEs was observed when the last subject enrolled in the GTx-758 125 mg dosing arm completed one 30 day cycle of therapy, enrollment of the next 25 subjects would commence in the GTx-758 250 mg dosing arm.  Similarly, the GTx-758 500 mg dosing arm was to have commenced enrollment of the final 25 subjects when the last subject enrolled in the 250 mg dose arm completed one 30 day cycle of therapy, assuming an acceptable incidence of VTEs has been observed in both of the lower dosage arms and management had decided to continue testing at the next higher dose.  After reviewing data collected from the GTx-758 125 mg dosing arm indicating the ability of the drug to substantially increase SHBG and lower free testosterone without any unexpected side effects occurring, the clinical trial protocol was amended in the third quarter of 2013 to eliminate the 500 mg dosing arm and to increase the number of subjects to be enrolled in the 125 mg and the 250 mg dosing arms to 38 patients per arm. Enrollment in the 125 mg cohort has been completed without any occurrence of VTEs, and after a pre-specified safety review by the independent Data Safety Monitoring Board, we are now enrolling subjects in the 250 mg arm.  Depending upon the safety and efficacy data observed in the 125 mg cohort and assuming no safety issues are observed in the first ten metastatic patients enrolled in the 250 mg cohort, enrollment of the 250 mg cohort will be opened to individuals with metastatic or nonmetastatic CRPC.  The study is ongoing and data from all patients in the study is expected late in the second half of 2014.

 

Financial Highlights

 

Our net loss for the year ended December 31, 2013 was $42.1 million.  We expect to incur significant operating losses for the foreseeable future as we continue our clinical development activities and potentially seek regulatory approval of our product candidates.  We have funded our operations primarily through the sale of equity securities, collaboration and license agreements, and prior to September 2012, product revenue from sales of FARESTON®, the rights to which we sold to a third party in the third quarter of 2012.  We currently have no ongoing collaborations for the development and commercialization of our product candidates and no source of revenue, nor do we expect to generate revenue for the foreseeable future.  We do not expect to obtain FDA or EMA approval, or any other regulatory approvals, to market any of our product candidates, including enobosarm, for the foreseeable future, and it is possible that none of our product candidates will ever receive any regulatory approvals.

 

At December 31, 2013, we had cash, cash equivalents and short-term investments of $14.7 million compared to $56.1 million at December 31, 2012.  On March 6, 2014, we completed a private placement of units consisting of 11,976,048 shares of common stock and warrants to purchase 10,179,642 shares of our common stock for gross proceeds of approximately $21.3 million.  The warrants, which have a one year term, have a per share exercise price of $1.67 that is payable only in cash.  If exercised in full, the warrants could result in additional gross proceeds of approximately $17.0 million.  As of the date of this Annual Report on Form 10-K, we estimate that our current cash, cash equivalents and short-term investments, together with interest thereon, will be sufficient to meet our projected operating requirements for at least the next twelve months.  We have based this estimate on our current business plan and assumptions that may prove to be wrong.  We could utilize our available capital resources sooner than we currently expect, and we could need additional funding sooner than currently anticipated.  In any event, to complete the development and seek regulatory approval for any of our product candidates, we will need to obtain substantial additional funding.  Based on our current business plan and assumptions, we will need to obtain substantial additional funding to conduct any additional clinical development of our product candidates beyond the Phase 2 clinical trials we are currently conducting and the Phase 1 clinical trials we plan to conduct to support a potential MAA submission to the EMA for enobosarm 3 mg.

 

While we have been able to fund our operations to date, we do not currently have any commitments for future external funding and we would need to obtain substantial additional funding to conduct and complete any additional Phase 3 clinical trials of enobosarm 3 mg. Until we can generate a sufficient amount of product revenue, which we may never do, we expect to finance future cash needs through public or private equity offerings, debt financings or collaboration and licensing arrangements, or a combination of the above, as well as through interest income earned on the investment of our cash balances and short-term investments.  In October 2013, following our receipt of the negative results in our POWER 1 and POWER 2 Phase 3 clinical trials evaluating enobosarm 3 mg, we announced and implemented a workforce reduction of approximately 60%.  If we are unable to raise additional funds when needed, we may need to further reduce our expenditures, perhaps significantly, to preserve our cash. Cost-cutting measures that we may take

 

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in the future may not be sufficient to enable us to meet our cash requirements, and they may negatively affect our business and growth prospects.

 

Research and Development

 

Since our inception in 1997, we have been focused on drug discovery and development programs.  Research and development expenses include, but are not limited to, our expenses for personnel and supplies associated with our research activities, screening and identification of product candidates, formulation and synthesis activities, manufacturing, preclinical studies, toxicology studies, clinical trials, regulatory and medical affairs activities, quality assurance activities and license fees.  As a result of the October 2013 reduction in our workforce, we are no longer conducting drug discovery activities and we are focusing our research and development activities on the ongoing clinical development of our current product candidates.

 

We expect that our research and development expenses for fiscal year 2014 will decrease as compared to fiscal year 2013 due to the completion of the POWER 1 and POWER 2 clinical trials in 2013.

 

There is a substantial risk that any development program may not produce revenue. Moreover, because of uncertainties inherent in drug development, including those factors described in Part I, Item 1A “Risk Factors” of this Annual Report on Form 10-K, we may not be able to successfully develop and commercialize any of our product candidates.

 

The successful development and commercialization of our product candidates is highly uncertain.  We cannot reasonably estimate or know the nature, timing and estimated costs of the efforts necessary to complete the development and commercialization of, or the period in which material net cash inflows are expected to commence from, any of our product candidates due to the numerous risks and uncertainties associated with developing and commercializing drugs, including the uncertainty of:

 

·                  the scope, rate of progress and cost of our clinical development programs, including our ongoing and any future clinical trials of enobosarm and GTx-758;

 

·                  the terms and timing of any potential collaborative, licensing and other strategic arrangements that we may establish;

 

·                  the amount and timing of any licensing fees, milestone payments and royalty payments from potential collaborators, if any;

 

·                  future clinical trial results;

 

·                  the cost and timing of regulatory filings and/or approvals to commercialize our product candidates and any related restrictions, limitations, and/or warnings in the label of an approved product candidate;

 

·                  the effect of competing technological and market developments; and

 

·                  the cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights, and the cost of defending any other litigation claims.

 

Any failure to complete the development of our product candidates in a timely manner could have a material adverse effect on our operations, financial position and liquidity. A discussion of the risks and uncertainties associated with completing our development and commercialization efforts on schedule, or at all, and some consequences of failing to do so, are set forth under Part I, Item 1A “Risk Factors” of this Annual Report on Form 10-K.

 

General and Administrative Expenses

 

Our general and administrative expenses consist primarily of salaries and other related costs for personnel serving executive, finance, legal, human resources, information technology, and investor relations functions.  General and administrative expenses also include facility costs, insurance costs, and professional fees for legal, accounting, and public relation services.  We expect our general and administrative expenses for fiscal year 2014 to decrease from fiscal year 2013 due to the reduction in force that was implemented in October 2013.

 

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Critical Accounting Policies and Significant Judgments and Estimates

 

Our management’s discussion and analysis of our financial condition and results of operations is based on our financial statements, which have been prepared in accordance with accounting principles generally accepted in the United States of America.  The preparation of these financial statements requires us to make estimates and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and liabilities at the date of the financial statements as well as the reported revenues and expenses during the reporting periods.  On an ongoing basis, we evaluate our estimates and judgments related to revenue recognition, income taxes, intangible assets, long-term service contracts, share-based compensation, and other contingencies.  We base our estimates on historical experience and on various other factors that we believe are reasonable under the circumstances, the results of which form the basis for making judgments about the carrying value of assets and liabilities that are not readily apparent from other sources.  Actual results may differ from these estimates under different assumptions or conditions.

 

While our significant accounting policies are more fully described in Note 2 to our financial statements appearing at the end of this Annual Report on Form 10-K, we believe that the following accounting policies are most critical to aid you in fully understanding and evaluating our reported financial results.

 

Research and Development Expenses

 

Research and development expenses include, but are not limited to, our expenses for personnel, supplies, and facilities associated with research activities, screening and identification of product candidates, formulation and synthesis activities, manufacturing, preclinical studies, toxicology studies, clinical trials, regulatory and medical affairs activities, quality assurance activities and license fees.  We expense these costs in the period in which they are incurred.  We estimate our liabilities for research and development expenses in order to match the recognition of expenses to the period in which the actual services are received. As such, accrued liabilities related to third party research and development activities are recognized based upon our estimate of services received and degree of completion of the services in accordance with the specific third party contract.

 

Share-Based Compensation

 

We have stock option and equity incentive plans that provide for the purchase of our common stock by certain of our employees and non-employee directors.  We measure compensation expense for our share-based payments based on the fair value of the awards on the grant date and recognize the expense over the period during which an employee or non-employee director is required to provide service in exchange for the award.

 

The determination of the fair value of stock options on the date of grant include the expected life of the award, the expected stock price volatility over the expected life of the awards, and risk-free interest rate.  We estimate the expected life of options by calculating the average of the vesting term and contractual term of the options.  We estimate the expected stock price volatility based on the historical volatility of our common stock.  The risk-free interest rate is determined using U.S. Treasury rates where the term is consistent with the expected life of the stock options.  Expected dividend yield is not considered as we have not made any dividend payments and have no plans of doing so in the foreseeable future.  The amount of share-based compensation expense recognized is reduced ratably over the vesting period by an estimate of the percentage of options granted that are expected to be forfeited or canceled before becoming fully vested.  This estimate is adjusted periodically based on the extent to which actual forfeitures differ, or are expected to differ, from the previous estimate.

 

Share-based compensation also includes, beginning October 2013, restricted stock units, or RSUs, granted to employees under our 2013 equity incentive plan.  We estimate the fair value of RSUs using the closing price of our stock on the grant date.  The fair value of RSUs is amortized on a straight-line basis over the requisite service period of the awards.

 

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The following table summarizes share-based compensation expense included within the statements of operations for the years ended December 31, 2013, 2012 and 2011:

 

 

 

Years ended December 31,

 

 

 

2013

 

2012

 

2011

 

 

 

(in thousands)

 

Research and development expenses

 

$

1,875

 

$

1,046

 

$

1,972

 

General and administrative expenses

 

1,993

 

1,771

 

2,432

 

Total share-based compensation

 

$

3,868

 

$

2,817

 

$

4,404

 

 

Share-based compensation expense recorded in the statement of operations as general and administrative expense for the years ended December 31, 2013, 2012 and 2011 included share-based compensation expense related to deferred compensation arrangements for our non-employee directors of $135,000, $169,000 and $178,000, respectively.  At December 31, 2013, the total compensation cost related to non-vested stock options not yet recognized was approximately $4.4 million with a weighted average expense recognition period of 1.97 years.  At December 31, 2013, the total compensation cost related to non-vested RSUs not yet recognized was approximately $1.4 million with a weighted average expense recognition period of five months.

 

Income Taxes

 

We account for deferred taxes by recognition of deferred tax assets and liabilities for the expected future tax consequences of events that have been included in the financial statements or tax returns. Under this method, deferred tax assets and liabilities are determined based on the difference between the financial statement and tax basis of assets and liabilities using enacted tax rates in effect for the year in which the differences are expected to reverse.  A valuation allowance is provided when it is more likely than not that some portion or all of the deferred tax assets will not be realized.  Accordingly, at December 31, 2013 and 2012, net of the valuation allowance, the net deferred tax assets were reduced to zero.

 

We have recognized the tax effect of discontinued operations in the statements of operations in accordance with the intra-period accounting rules for the year ended December 31, 2012 and 2011.  An offsetting tax benefit is recorded in continuing operations in each year in which tax expense was recognized for discontinued operations.

 

Impairment of Long-Lived Assets

 

We review long-lived assets for impairment whenever events or changes in facts and circumstances are present, both internally and externally, that may indicate impairment of long-lived assets.  An impairment loss is recognized when estimated future cash flows are less than the carrying amount.  The cash flow estimates are based on management’s best estimates, using appropriate and customary assumptions and projections at the time.

 

In 2011, after discontinuing our toremifene 80 mg development program, we recorded an impairment charge of $1.6 million.  The impaired intangible asset consisted of capitalized license fees paid to Orion Corporation related to our toremifene 80 mg program.  The impairment charge was included in research and development expenses in the statement of operations for the year ended December 31, 2011.

 

Discontinued Operations

 

Effective September 30, 2012, we completed the sale of FARESTON® for a total cash purchase price of $21.7 million, including payment for purchased inventory.  We have accounted for FARESTON® as a discontinued operation.  As a result, revenue, cost of goods sold, and operating expenses relating to FARESTON® have been excluded from their respective captions in the statements of operations and have been included in discontinued operations for the years ended December 31, 2012 and 2011.

 

Revenue Recognition

 

Our revenues for the years ended December 31, 2012 and 2011 consisted of product sales of FARESTON®, which is included in income from discontinued operations before income taxes, and in 2011, also consisted of revenues derived from our former collaboration and license agreements.

 

Revenue from product sales of FARESTON® was recognized less deductions for estimated sales discounts and sales returns.  Revenue from product sales was recognized when persuasive evidence of an arrangement existed, title passed, the price was fixed or determinable, and collectability was reasonably assured.  We accounted for rebates to

 

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certain governmental agencies as a reduction of product sales.  We allow customers to return product within a specified time period prior to and subsequent to the product’s labeled expiration date.  Although we sold our rights and certain assets related to FARESTON® effective September 30, 2012, we retain the liability for future product returns relating to sales of FARESTON® by us prior to September 30, 2012.  Therefore, we estimate an accrual for product returns based on factors which include historical product returns and estimated product in the distribution channel which is expected to exceed its expiration date.  At December 31, 2013 and December 31, 2012, our accrual for product returns, was $918,000 and $1.2 million, respectively.

 

Collaboration revenue for the year ended December 31, 2011 consisted of non-refundable upfront payments and license fees associated with our former collaboration and license agreement with Ipsen Biopharm Limited, or Ipsen, and was based on the performance requirements of the agreement.  We analyzed the agreement, which included multiple element arrangements, to determine whether the deliverables under the agreement, including license and performance obligations such as joint steering committee participation and research and development activities, could have been separated or whether all of the deliverables must have been accounted for as a single unit of accounting.

 

Results of Operations

 

Collaboration Revenue

 

There was no collaboration revenue recognized for the years ended December 31, 2013 and 2012.  Collaboration revenue was $8.1 million for the year ended December 31, 2011, which resulted from recognition of all remaining unamortized deferred revenue due to the termination of our former license and collaboration agreement with Ipsen in March 2011.

 

Research and Development Expenses

 

The following table identifies the research and development expenses for each of our clinical product candidates, as well as research and development expenses pertaining to our other research and development efforts, for each of the periods presented.  Research and development spending for past periods is not indicative of spending in future periods.

 

 

 

 

 

Years Ended December 31,

 

Proposed Candidate / Proposed Indication

 

Program

 

2013

 

2012

 

2011

 

 

 

 

 

(in thousands)

 

Enobosarm

 

 

 

 

 

 

 

 

 

3 mg

 

 

 

 

 

 

 

 

 

Prevention and treatment of muscle wasting in patients with advanced non-small cell lung cancer

 

SARM

 

$

18,541

 

$

24,320

 

$

10,474

 

 

 

 

 

 

 

 

 

 

 

Enobosarm

 

 

 

 

 

 

 

 

 

9 mg

 

 

 

 

 

 

 

 

 

Treatment of women with AR positive and ER positive metastatic breast cancer

 

SARM

 

 

1,980

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

GTx-758

 

 

 

 

 

 

 

 

 

Secondary hormonal therapy in men with metastatic and nonmetastatic CRPC

 

Selective ER alpha agonist

 

5,492

 

7,458

 

12,052

 

 

 

 

 

 

 

 

 

 

 

Other research and development

 

 

 

6,305

 

7,109

 

9,412

 

 

 

 

 

 

 

 

 

 

 

Total research and development expenses

 

 

 

$

32,318

 

$

38,887

 

$

31,938

 

 

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Research and development expenses decreased 17% to $32.3 million for the year ended December 31, 2013 from $38.9 million for the year ended December 31, 2012.  The $5.8 million decrease in enobosarm 3 mg research and development expenses was due primarily to a decrease in expenses as the last patients completed the POWER 1 and POWER 2 Phase 3 clinical trials for enobosarm 3 mg in May 2013.   Research and development expenses for enobosarm 9 mg increased as we initiated in the second quarter of 2013 a Phase 2 clinical trial evaluating enobosarm 9 mg for the treatment of AR positive and ER positive metastatic breast cancer in women who have previously responded to hormonal therapy for the treatment of their metastatic breast cancer.  Additionally, research and development expenses related to GTx-758 decreased $2.0 million from the year ended December 31, 2012. During year ended December 31, 2013, we were conducting our ongoing Phase 2 clinical trial evaluating GTx-758 as secondary hormonal therapy in men with metastatic and nonmetastatic CRPC, which was initiated in the third quarter of 2012. In the first quarter of 2012, we discontinued our three Phase 2 clinical trials of GTx-758 to treat men with advanced prostate cancer.

 

Research and development expenses increased 22% to $38.9 million for the year ended December 31, 2012 from $31.9 million for the year ended December 31, 2011.  The $13.8 million increase in research and development expenses related to enobosarm 3 mg was due primarily to an increase in the costs related to the enrollment of and operations related to the two POWER Phase 3 clinical trials for enobosarm.  The decrease in research and development expenses related to GTx-758 was due to the discontinuance in the first quarter of 2012 of the three Phase 2 clinical trials of GTx-758 to treat men with advanced prostate cancer that were placed on full clinical hold by the FDA, partially offset by the initiation in the third quarter of 2012 of the Phase 2 clinical trial to evaluate lower doses of GTx-758 as secondary hormonal therapy in men with metastatic CRPC.

 

 “Other research and development” expenses include the cost of personnel, supplies and facilities associated with preclinical and discovery research and development activities for the years ended December 31, 2013, 2012 and 2011.  For the year ended December 31, 2011, Other research and development” also included research and development expenses of $2.0 million, which included an impairment charge of $1.6 million, for toremifene 80 mg development and $486,000 for toremifene 20 mg development.

 

General and Administrative Expenses

 

General and administrative expenses increased 4% to $11.3 million for the year ended December 31, 2013 from $10.8 million for the year ended December 31, 2012.  This increase was primarily due to increased legal expenses related to intellectual property activities and the preparation of new equity incentive plans.

 

General and administrative expenses decreased 10% to $10.8 million for the year ended December 31, 2012 from $12.0 million for the year ended December 31, 2011.  This decrease was primarily due to reduced salary and benefit expenses related to employee attrition of $739,000 and decreased legal expenses of $373,000.

 

Other (Expense) Income, Net

 

Other income, net for the year ended December 31, 2013 was $1.5 million compared to other expense, net of $19,000 for the year ended December 31, 2012.  For the year ended December 31, 2013, we recorded a gain of $1.4 million from the sale of research and development property and equipment sold subsequent to the workforce reduction that occurred in October 2013.  Other expense, net for the year ended December 31, 2012 was $19,000 compared to other income, net of $398,000 for the year ended December 31, 2011.

 

Discontinued Operations

 

Income from discontinued operations before income taxes was $22.7 million for the year ended December 31, 2012 and consisted of FARESTON® operating income of $3.8 million and the recognition of a gain of $18.8 million on the sale of rights and certain assets related to FARESTON®.  Income from discontinued operations before income taxes for the year ended December 31, 2011 consisted of FARESTON® operating income.

 

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The components of FARESTON® operating income for the years ended December 31, 2012 and 2011 were as follows:

 

 

 

Years Ended December 31,

 

 

 

2012

 

2011

 

 

 

(in thousands)

 

Product sales, net

 

$

5,284

 

$

6,673

 

Cost of product sales

 

(784

)

(1,055

)

Operating expenses

 

(655

)

(3,411

)

FARESTON® operating income

 

$

3,845

 

$

2,207

 

 

FARESTON® product sales, net decreased for the year ended December 31, 2012 compared to the prior year due primarily to the sale of the rights and certain assets related to FARESTON®, effective September 30, 2012.  FARESTON® operating expenses decreased for the year ended December 31, 2012 as compared to the prior year due to the sale of FARESTON® and due to a reduction in FARESTON® marketing and medical education expenses.

 

Liquidity and Capital Resources

 

We have financed our operations to date primarily through public offerings and private placements of our common stock, as well as payments from our former collaborators.  We have incurred significant losses since our inception in 1997 as we have devoted substantially all of our resources to research and development, including our clinical trials.  As of December 31, 2013, we had an accumulated deficit of $455.4 million, which resulted primarily from:

 

·             our research and development activities associated with:

 

·                     the preclinical and clinical development of our SARM compounds, including enobosarm for the prevention and treatment of muscle wasting in patients with cancer;

 

·                     the preclinical and clinical development of GTx-758 for the treatment of advanced prostate cancer;

 

·                     the development of our discontinued toremifene 80 mg product candidate to reduce fractures and treat other estrogen deficiency side effects of androgen deprivation therapy in men with prostate cancer, including two Phase 2 clinical trials, a Phase 3 clinical trial, and the preparation and submission of a NDA to the FDA;

 

·                     the development of our discontinued toremifene 20 mg product candidate for the prevention of prostate cancer in high risk men with high grade prostatic intraepithelial neoplasia, including a Phase 2b clinical trial and a Phase 3 clinical trial;

 

·                     the preclinical development of other product candidates; and

 

·                  general and administrative expenses.

 

We expect to incur significant operating losses for the foreseeable future as we continue our clinical development activities and potentially seek regulatory approval of our product candidates.  We do not expect to obtain FDA or EMA approval, or any other regulatory approvals, to market any of our product candidates, including enobosarm, for the foreseeable future, and it is possible that none of our product candidates will ever receive regulatory approvals.

 

At December 31, 2013, we had cash, cash equivalents and short-term investments of $14.7 million, compared to $56.1 million at December 31, 2012 and $74.4 million at December 31, 2011.  On March 6, 2014, we completed a private placement of units consisting of 11,976,048 shares of common stock and warrants to purchase 10,179,642 shares of our common stock for gross proceeds of approximately $21.3 million.  The warrants, which have a one year term, have a per share exercise price of $1.67 that is payable only in cash.  If exercised in full, the warrants could result in additional gross proceeds of approximately $17.0 million.

 

In October 2012, we increased our cash and short-term investments when we received net cash proceeds of $18.9 million related to the sale of our rights and certain assets related to FARESTON®.

 

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In June 2011, we completed an underwritten public offering of 11,023,000 shares of our common stock at a price to the public of $4.75 per share.  Net cash proceeds from the public offering were approximately $49.0 million, after deducting the underwriting discount and offering expenses.

 

In November 2010, we completed an underwritten public offering of 15,285,715 shares of our common stock at a price to the public of $2.80 per share.  Net cash proceeds from the public offering were approximately $40.3 million after deducting underwriting discounts and commissions and other offering expenses.

 

In September 2006, we entered into a collaboration and license agreement with Ipsen, under which Ipsen paid us €21.5 million (approximately $27.1 million) as a license fee and expense reimbursement and paid us €1.5 million in equal installments over a three year period from the date of the agreement.  In September of 2009, 2008, and 2007, we received €500,000 (approximately $726,000, $711,000, and $688,000, respectively) from Ipsen for the three annual installment payments.  In February 2008, we earned a milestone of €1.0 million (approximately $1.5 million) with the achievement of the primary endpoint in the toremifene 80 mg Phase 3 clinical trial.  As a result of the termination of our collaboration with Ipsen in March of 2011, we will not receive any future milestone payments, royalties or reimbursement of clinical development expenses from Ipsen that were provided for under our former collaboration with Ipsen.

 

In December 2007, we entered into an exclusive license and collaboration agreement with Merck, or the Merck Collaboration Agreement, which was terminated in March 2010.  In connection with entering into this agreement, we received an upfront licensing fee of $40.0 million in January 2008, and Merck purchased approximately $30.0 million of our common stock in December 2007.  Merck also paid us $15.0 million in guaranteed cost reimbursements for research and development activities in equal annual installments over a three year period beginning on the first anniversary of the effective date of the agreement.  We received the three annual payments of $5 million from Merck in December 2010, 2009, and 2008, respectively.  As a result of the termination of our collaboration with Merck, we will not receive any milestone payments or royalties from Merck that were provided for under our former collaboration with Merck.  We have no ongoing collaborations for the development and commercialization of our product candidates, and we do not currently have any commitments for future external funding.

 

 

 

Years Ending December 31,

 

 

 

2013

 

2012

 

2011

 

 

 

(in thousands)

 

Net cash used in operating activities

 

$

(43,971

)

$

(37,109

)

$

(33,089

)

Net cash provided by (used in) investing activities

 

9,237

 

21,405

 

(10,299

)

Net cash provided by financing activities

 

1,219

 

3

 

48,952

 

Net (decrease) increase in cash and cash equivalents

 

$

(33,515

)

$

(15,701

)

$

5,564

 

 

Net cash used in operating activities in all periods resulted primarily from funding our operations.

 

Net cash provided by investing activities for the year ended December 31, 2013 resulted from the maturities of short-term investments of $9.3 million and proceeds from the sale of property and equipment of $1.4 million, offset partially by the purchase of short-term investments of $1.4 million and the purchase of information technology equipment and research and development equipment of approximately $32,000.  Net cash used in investing activities for the year ended December 31, 2012 resulted from the proceeds from the sale of FARESTON®, net of cash expenses, of $18.9 million and the maturities of short-term investments of $14.6 million, offset by the purchase of short-term investments of $12.0 million and the purchase of information technology equipment and research and development equipment of approximately $142,000.  Net cash used in investing activities for the year ended December 31, 2011 resulted from the purchase of short-term investments of $15.1 million and the purchase of information technology equipment and research and development equipment of approximately $54,000, offset by the maturities of short-term investments of $4.9 million.

 

Net cash provided by financing activities for the year ended December 31, 2013, 2012 and 2011 reflected proceeds from the exercise of employee stock options of $1.2 million, $85,000 and $55,000, respectively.  For the year ended December 31, 2011, net cash provided by financing activities also reflected net proceeds from our underwritten public offering of common stock of $49.0 million in June 2011.  Proceeds in all years presented were reduced by payments on our capital lease and financed equipment obligations.

 

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As of the date of this Annual Report on Form 10-K, we estimate that our current cash, cash equivalents and short-term investments, together with interest thereon, will be sufficient to meet our projected operating requirements for at least the next twelve months.  We have based this estimate on our current business plan and assumptions that may prove to be wrong.  We could utilize our available capital resources sooner than we currently expect, and we could need additional funding sooner than currently anticipated.  In any event, to complete the development of and seek regulatory approval for enobosarm and GTx-758, we will need to obtain substantial additional funding.  Based on our current business plan and assumptions, we will need to obtain substantial additional funding to conduct any additional clinical development of our product candidates beyond the Phase 2 clinical trials we are currently conducting and the Phase 1 clinical trials we plan to conduct to support a potential MAA submission to the EMA for enobosarm 3 mg.

 

Our estimate of the period of time or events through which our financial resources will be adequate to support our projected operating requirements is a forward-looking statement and involves risks and uncertainties, and actual results could vary as a result of a number of factors, including the factors discussed under Part I, Item 1A “Risk Factors” section of this Quarterly Report on Form 10-Q.  Because of the numerous risks and uncertainties associated with the development and potential commercialization of our product candidates and other research and development activities, including risks and uncertainties that could impact the rate of progress of our development activities, we are unable to estimate with certainty the amounts of increased capital outlays and operating expenditures associated with the future development of our product candidates, if any.  Our future funding requirements will depend on many factors, including:

 

·                  the scope, rate of progress and cost of our clinical development programs, including our ongoing and any future clinical trials of enobosarm and GTx-758;

 

·                  the terms and timing of any potential collaborative, licensing and other strategic arrangements that we may establish;

 

·                  the amount and timing of any licensing fees, milestone payments and royalty payments from potential collaborators, if any;

 

·                  future clinical trial results;

 

·                  the cost and timing of regulatory filings and/or approvals to commercialize our product candidates and any related restrictions, limitations, and/or warnings in the label of an approved product candidate;

 

·                  the effect of competing technological and market developments; and

 

·                  the cost of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights, and the cost of defending any other litigation claims.

 

We do not currently have any commitments for future external funding nor do we currently have any sources of revenue. Until we can generate a sufficient amount of product revenue, which we may never do, we expect to finance future cash needs through public or private equity offerings, debt financings or collaboration and licensing arrangements, or a combination of the above, as well as through interest income earned on the investment of our cash balances and short-term investments.  In October 2013, following our receipt of the negative results in our POWER 1 and POWER 2 clinical trials evaluating enobosarm 3 mg, we announced and implemented a workforce reduction of approximately 60%.  If we are unable to raise additional funds when needed, we may need to further reduce our expenditures, perhaps significantly, to preserve our cash. Cost-cutting measures that we may take in the future may not be sufficient to enable us to meet our cash requirements, and they may negatively affect our business and growth prospects.

 

To the extent that we raise additional funds through potential collaboration, partnering or other strategic arrangements, it may be necessary to relinquish rights to some of our technologies or product candidates, or grant licenses on terms that are not favorable to us, any of which could result in the stockholders of GTx having little or no continuing interest in our enobosarm and/or GTx-758 programs as stockholders or otherwise.  To the extent we raise additional funds by issuing equity securities, our stockholders may experience significant dilution, particularly given our currently depressed stock price, and debt financing, if available, may involve restrictive covenants. For example, we announced in March 2014 that we completed a private placement of common stock and warrants to purchase common stock for gross proceeds of approximately $21.3 million, which financing was substantially dilutive, and our stockholders may experience additional, perhaps substantial, dilution should we again raise additional funds by issuing equity securities. Any debt financing or additional equity that we raise may contain terms that are not favorable to us or our stockholders. Our ability to raise additional funds and the terms upon which we are able to raise such funds have been severely harmed by the failure of the two enobosarm 3 mg Phase 3 clinical

 

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trials to meet both of the co-primary endpoints, and may in the future be adversely impacted by the uncertainty regarding our ability to obtain approval of enobosarm 3 mg in the European Union in the absence of additional Phase 3 development of enobosarm 3 mg and the terms of any such approval.  As a result of these and other factors, we cannot be certain that additional funding will be available on acceptable terms, or at all.  If adequate funds are not available when we need them, we may be required to delay, reduce the scope of or eliminate one or more of our research or development programs, including our enobosarm and GTx-758 programs, or conduct additional workforce or other expense reductions, any of which could have a material adverse effect on our business and our prospects.

 

Contractual Obligations

 

At December 31, 2013, we had contractual obligations as follows:

 

 

 

Payment Due by Period
(in thousands)

 

Contractual Obligations(1)

 

Total

 

Less than
1 year

 

1-3 years

 

4-5 years

 

More than
5 years

 

 

 

 

 

 

 

 

 

 

 

 

 

Operating lease obligations(2)

 

$

738

 

$

553

 

$

185

 

$

 

$

 

 


(1)

This table does not include any royalty obligations under our license agreement with UTRF as the timing and likelihood of such payments are not known. In addition to the minimum payments due under our current license agreement, we may be required to pay royalties on any net sales of product if we receive regulatory approval for a SARM product candidate, including enobosarm, and successfully market the product. Additionally, if we sublicense rights under our SARM License Agreement, we also are obligated to pay a sublicense royalty on any licensing fee or milestone payments we may receive from a sublicensee.

 

 

(2)

Our long-term commitment under the operating lease consists of payments relating to a sublease for office space at 175 Toyota Plaza, Memphis, Tennessee. The sublease for the premises at 175 Toyota Plaza expires on April 30, 2015 and includes escalating rental payments.

 

Off-Balance Sheet Arrangements

 

We have not engaged in any off-balance sheet arrangements, including the use of standard finance, special purpose entities or variable interest entities.

 

ITEM 7A.                                       QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET RISK

 

Our exposure to market risk for changes in interest rates relates to our cash equivalents on deposit in highly liquid money market funds and investments in Federal Deposit Insurance Corporation insured certificates of deposit.  The primary objective of our cash investment activities is to preserve principal while at the same time maximizing the income we receive from our invested cash without significantly increasing risk of loss.  We do not use derivative financial instruments in our investment portfolio.  The effect of a hypothetical decrease of ten percent in the average yield earned on our cash equivalents and short-term investments would have resulted in an immaterial decrease in our interest income for the year ended December 31, 2013.

 

In addition, we have exposure to fluctuations in certain foreign currencies in countries in which we conduct clinical trials.  Most of our foreign expenses incurred are associated with conducting clinical trials for enobosarm at clinical trial sites in Europe.  Consequently, changes in exchange rates could result in material exchange losses and could unpredictably, materially and adversely affect our financial position, results of operations and cash flows.  A hypothetical 10% increase or decrease in foreign exchange rates would result in an immaterial change in our financial assets and liabilities denominated in euros.  This potential change is based on a sensitivity analysis performed on our financial position at December 31, 2013.  Actual results may differ materially.   We have elected not to hedge our exposure to foreign currency fluctuations.

 

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ITEM 8.                                                FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA

 

Our financial statements and the reports of our independent registered public accounting firm are included in this Annual Report on Form 10-K beginning on page F-1.  The index to these reports and our financial statements is included in Part IV, Item 15 below.

 

ITEM 9.                                                CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND FINANCIAL DISCLOSURE

 

Not applicable.

 

ITEM 9A.                                       CONTROLS AND PROCEDURES

 

Disclosure Controls and Procedures

 

We maintain disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) of the Securities Exchange Act of 1934, as amended (the “Exchange Act”)) that are designed to ensure that information required to be disclosed in the reports that we file or submit under the Exchange Act is recorded, processed, summarized, and reported within the time periods specified in the SEC’s rules and forms and that such information is accumulated and communicated to our management, including our principal executive officer and principal financial officer, as appropriate, to allow for timely decisions regarding required disclosures.

 

We have carried out an evaluation, under the supervision and with the participation of our management, including our principal executive officer and principal financial officer, of the effectiveness of the design and operation of our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act) as of the end of the period covered by this report.  Based on the evaluation of these disclosure controls and procedures, our principal executive officer and principal financial officer have concluded that our disclosure controls and procedures were effective.

 

Management’s Report on Internal Control Over Financial Reporting

 

We, as management of GTx, Inc., are responsible for establishing and maintaining adequate internal control over financial reporting, as such term is defined in Securities Exchange Act Rule 13a-15(f).  Internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial statements for external purposes in accordance with United States generally accepted accounting principles.  Any system of internal control, no matter how well designed, has inherent limitations, including the possibility that a control can be circumvented or overridden and misstatements due to error or fraud may occur and not be detected.  Also, because of changes in conditions, internal control effectiveness may vary over time.  Accordingly, even an effective system of internal control will provide only reasonable assurance that the objectives of the internal control system are met.

 

Under the supervision and with the participation of management, including our principal executive officer and principal financial officer, we conducted an evaluation of the effectiveness of our internal control over financial reporting as of December 31, 2013 using the criteria for effective internal control over financial reporting as described in “Internal Control — Integrated Framework,” issued by the Committee of Sponsoring Organizations of the Treadway Commission (1992 framework).  Based on this evaluation, we concluded that, as of December 31, 2013, our internal control over financial reporting was effective.  The effectiveness of our internal control over financial reporting has been audited by Ernst & Young LLP, independent registered public accounting firm.

 

Attestation Report of the Independent Registered Public Accounting Firm

 

Ernst & Young LLP, an independent registered public accounting firm, has issued an audit report on our internal control over financial reporting, which report is included elsewhere herein.

 

Changes in Internal Control Over Financial Reporting

 

There were no changes in our internal control over financial reporting during the fourth quarter of 2013 that have materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.

 

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ITEM 9B.                                       OTHER INFORMATION

 

None.

 

PART III

 

Certain information required by Part III is omitted from this Annual Report on Form 10-K because we will file our definitive proxy statement for our 2014 Annual Meeting of Stockholders with the U.S. Securities and Exchange Commission pursuant to Regulation 14A (the “2014 Proxy Statement”) not later than 120 days after the end of the fiscal year covered by this Annual Report on Form 10-K, and certain information included in the 2014 Proxy Statement is incorporated herein by reference.

 

ITEM 10.                                         DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE

 

(1)  The information required by this Item concerning our directors and nominees for director, including information with respect to our audit committee and audit committee financial experts, may be found under the section entitled “Proposal No. 1 — Election of Directors” and “Additional Information About the Board of Directors and Certain Corporate Governance Matters” appearing in the 2014 Proxy Statement.  Such information is incorporated herein by reference.

 

(2)  The information required by this Item concerning compliance with Section 16(a) of the Securities Exchange Act of 1934 may be found in the section entitled “Section 16(a) Beneficial Ownership Reporting Compliance” appearing in the 2014 Proxy Statement.  Such information is incorporated herein by reference.

 

(3)  The information required by this Item concerning our executive officers is set forth in the section entitled “Management — Executive Officers of Registrant” in Part I, Item 1 of this Form 10-K.

 

(4)   Our Board has adopted a Code of Business Conduct and Ethics applicable to all officers, directors and employees as well as Guidelines on Governance Issues.  These documents are available on our Web site (www.gtxinc.com) under “About GTx” at “Governance.”  We will provide a copy of these documents to any person, without charge, upon request, by writing to us at GTx, Inc., Director, Corporate Communications and Financial Analysis, 175 Toyota Plaza, Suite 700, Memphis, Tennessee 38103.  We intend to satisfy the disclosure requirement under Item 5.05 of Form 8-K regarding an amendment to, or waiver from, a provision of the Code of Business Conduct and Ethics by posting such information on our Web site at the address and the location specified above.

 

ITEM 11.                                         EXECUTIVE COMPENSATION

 

(1)  The information required by this Item concerning director and executive compensation is incorporated herein by reference to the information from the 2014 Proxy Statement under the sections entitled “Compensation Discussion and Analysis,” “Executive Compensation” and “Director Compensation.”

 

(2)  The information required by this Item concerning Compensation Committee interlocks and insider participation is incorporated herein by reference to the information from the 2014 Proxy Statement under the section entitled “Compensation Committee Interlocks and Insider Participation.”

 

(3)  The information required by this Item concerning our Compensation Committee’s review and discussion of our Compensation Discussion and Analysis is incorporated herein by reference to the information from the 2014 Proxy Statement under the section entitled “Compensation Committee Report.”

 

ITEM 12.                                         SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND RELATED STOCKHOLDER MATTERS

 

(1)  The information required by this Item with respect to security ownership of certain beneficial owners and management is incorporated herein by reference to the information from the 2014 Proxy Statement under the section entitled “Security Ownership of Certain Beneficial Owners and Management.”

 

(2)  The information required by this Item with respect to securities authorized for issuance under our equity

 

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compensation plans is incorporated herein by reference to the information from the 2014 Proxy Statement under the section entitled “Equity Compensation Plan Information.”

 

ITEM 13.                                         CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR INDEPENDENCE

 

(1)  The information required by this Item concerning related party transactions is incorporated herein by reference to the information from the 2014 Proxy Statement under the section entitled “Certain Relationships and Related Party Transactions.”

 

(2)  The information required by this Item concerning director independence is incorporated herein by reference to the information from the 2014 Proxy Statement under the section entitled “Additional Information About the Board of Directors and Certain Corporate Governance Matters — Director Independence.”

 

ITEM 14.                                         PRINCIPAL ACCOUNTING FEES AND SERVICES

 

The information required by this Item is incorporated herein by reference to the information from the 2014 Proxy Statement under the section entitled “Proposal No. 3 — Ratification of Appointment of Independent Registered Public Accounting Firm.”

 

PART IV

 

ITEM 15.                                         EXHIBITS AND FINANCIAL STATEMENT SCHEDULES

 

(a)(1)  Index to Financial Statements

 

Page

 

Description

F-2

 

Management’s Report on Internal Control Over Financial Reporting

F-3

 

Reports of Independent Registered Public Accounting Firm

F-5

 

Balance Sheets at December 31, 2013 and 2012

F-6

 

Statements of Operations for the Years Ended December 31, 2013, 2012 and 2011

F-7

 

Statements of Stockholders’ Equity for the Years Ended December 31, 2013, 2012 and 2011

F-8

 

Statements of Cash Flows for the Years Ended December 31, 2013, 2012 and 2011

F-9

 

Notes to Financial Statements

 

(a)(2)  Financial statement schedules are omitted as they are not applicable.

 

(a)(3)  See 15(b) below.

 

(b)  Exhibits — The following exhibits are included herein or incorporated herein by reference:

 

Exhibit

 

 

 

Incorporation By Reference

Number

 

Exhibit Description

 

Form

 

SEC File No.

 

Exhibit

 

Filing Date

 

 

 

 

 

 

 

 

 

 

 

2.1

 

Asset Purchase Agreement dated as of September 28, 2012 between the Registrant and Strakan International S.à r.l.

 

8-K

 

000-50549

 

2.1

 

10/03/2012

 

 

 

 

 

 

 

 

 

 

 

3.1

 

Restated Certificate of Incorporation of GTx, Inc.

 

S-3

 

333-127175

 

4.1

 

08/04/2005

 

 

 

 

 

 

 

 

 

 

 

3.2

 

Certificate of Amendment of Restated Certificate of Incorporation of GTx, Inc.

 

8-K

 

000-50549

 

3.2

 

05/06/2011

 

 

 

 

 

 

 

 

 

 

 

3.3

 

Amended and Restated Bylaws of GTx, Inc.

 

8-K

 

000-50549

 

3.2

 

07/26/2007

 

 

 

 

 

 

 

 

 

 

 

4.1

 

Reference is made to Exhibits 3.1, 3.2 and 3.3

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

4.2

 

Specimen of Common Stock Certificate

 

S-1

 

333-109700

 

4.2

 

12/22/2003

 

 

 

 

 

 

 

 

 

 

 

4.3

 

Amended and Restated Registration Rights Agreement between Registrant and J. R. Hyde, III dated August 7, 2003

 

S-1

 

333-109700

 

4.4

 

10/15/2003

 

56



Table of Contents

 

4.4

 

Consent, Waiver and Amendment among Registrant, J. R. Hyde, III and Pittco Associates, L.P. dated December 3, 2007

 

S-3

 

333-148321

 

4.6

 

12/26/2007

 

 

 

 

 

 

 

 

 

 

 

4.5+

 

Waiver and Amendment Agreement among Registrant, J.R. Hyde, III and Pittco Associates, L.P. dated March 6, 2014

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

4.6+

 

Registration Rights Agreement among Registrant, J.R. Hyde, III and The Pyramid Peak Foundation, dated March 6, 2014

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

4.7+

 

Form of Common Stock Warrant, issued by Registrant pursuant to the Securities Purchase Agreement, dated March 3, 2014, among the Registrant, J.R. Hyde, III and The Pyramid Peak Foundation

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

10.1†

 

Consolidated, Amended, and Restated License Agreement dated July 24, 2007, between Registrant and University of Tennessee Research Foundation

 

10-Q

 

000-50549

 

10.40

 

11/09/2007

 

 

 

 

 

 

 

 

 

 

 

10.2

 

First Amendment, dated December 29, 2008, to the Consolidated, Amended and Restated License Agreement dated July 24, 2007 between the Registrant and University of Tennessee Research Foundation

 

10-K

 

000-50549

 

10.47

 

03/03/2009

 

 

 

 

 

 

 

 

 

 

 

10.3*

 

Form of Indemnification Agreement

 

S-1

 

333-109700

 

10.12

 

12/22/2003

 

 

 

 

 

 

 

 

 

 

 

10.4*

 

Genotherapeutics, Inc. 1999 Stock Option Plan, as amended through December 10, 2009, and Form of Stock Option Agreement

 

10-K

 

000-50549

 

10.1

 

03/15/2010

 

 

 

 

 

 

 

 

 

 

 

10.5*

 

GTx, Inc. 2000 Stock Option Plan, as amended through December 10, 2009, and Form of Stock Option Agreement

 

10-K

 

000-50549

 

10.2

 

03/15/2010

 

 

 

 

 

 

 

 

 

 

 

10.6*

 

GTx, Inc. 2001 Stock Option Plan, as amended through November 3, 2009, and Form of Stock Option Agreement

 

10-K

 

000-50549

 

10.3

 

03/15/2010

 

 

 

 

 

 

 

 

 

 

 

10.7*

 

GTx, Inc. 2002 Stock Option Plan, as amended through November 3, 2009, and Form of Stock Option Agreement

 

10-K

 

000-50549

 

10.4

 

03/15/2010

 

 

 

 

 

 

 

 

 

 

 

10.8*

 

GTx, Inc. 2004 Equity Incentive Plan and Form of Stock Option Agreement

 

S-1

 

333-109700

 

10.5

 

01/15/2004

 

 

 

 

 

 

 

 

 

 

 

10.9*

 

GTx, Inc. 2004 Equity Incentive Plan, as amended effective April 30, 2008

 

8-K

 

000-50549

 

10.6

 

05/06/2008

 

 

 

 

 

 

 

 

 

 

 

10.10*

 

GTx, Inc. 2004 Equity Incentive Plan, as amended effective November 4, 2008 and Form of Stock Option Agreement 

 

10-K

 

000-50549

 

10.52

 

03/03/2009

 

 

 

 

 

 

 

 

 

 

 

10.11*

 

GTx, Inc. 2004 Non-Employee Directors’ Stock Option Plan and Form of Stock Option Agreement

 

S-1

 

333-109700

 

10.6

 

01/15/2004

 

 

 

 

 

 

 

 

 

 

 

10.12*

 

Amended and Restated GTx, Inc. 2004 Non-Employee Directors’ Stock Option Plan, effective April 26, 2006

 

8-K

 

000-50549

 

10.1

 

04/27/2006

 

 

 

 

 

 

 

 

 

 

 

10.13*

 

Form of Stock Option Agreement under the Amended and Restated GTx, Inc. 2004 Non-Employee Directors’ Stock Option Plan

 

10-Q

 

000-50549

 

10.35

 

08/09/2006

 

 

 

 

 

 

 

 

 

 

 

10.14*

 

Amended and Restated GTx, Inc. 2004 Non-Employee Directors’ Stock Option Plan, as amended effective November 4, 2008 

 

10-K

 

000-50549

 

10.51

 

03/03/2009

 

 

 

 

 

 

 

 

 

 

 

10.15*

 

GTx, Inc. 2013 Equity Incentive Plan

 

S-8

 

333-188377

 

99.1

 

05/06/2013

 

 

 

 

 

 

 

 

 

 

 

10.16*

 

Form of Stock Option Grant Notice and Option Agreement under the GTx, Inc. 2013 Equity Incentive Plan (Standard Form)

 

10-Q

 

000-50549

 

10.2

 

07/22/2013

 

 

 

 

 

 

 

 

 

 

 

10.17*

 

Form of Retention Stock Option Grant Notice and Option Agreement under the GTx, Inc. 2013 Equity Incentive Plan

 

10-Q

 

000-50549

 

10.3

 

11/12/2013

 

 

 

 

 

 

 

 

 

 

 

10.18*

 

Form of Retention Restricted Stock Unit Grant Notice and Restricted Stock Unit Award Agreement under the GTx, Inc. 2013 Equity Incentive Plan

 

10-Q

 

000-50549

 

10.4

 

11/12/2013

 

 

 

 

 

 

 

 

 

 

 

10.19*

 

GTx, Inc. 2013 Non-Employee Director Equity Incentive Plan

 

S-8

 

333-188377

 

99.2

 

05/06/2013

 

 

 

 

 

 

 

 

 

 

 

10.20*

 

Form of Stock Option Grant Notice and Option Agreement under the GTx, Inc. 2013 Non-Employee Director Equity Incentive Plan

 

10-Q

 

000-50549

 

10.4

 

07/22/2013

 

 

 

 

 

 

 

 

 

 

 

10.21*

 

Amended and Restated Employment Agreement dated February 14, 2013, between Registrant and Mitchell S. Steiner, M.D.

 

10-K

 

000-50549

 

10.19

 

03/05/2013

 

 

 

 

 

 

 

 

 

 

 

10.22*

 

Amended and Restated Employment Agreement dated February 14, 2013, between Registrant and Marc S. Hanover

 

10-K

 

000-50549

 

10.20

 

03/05/2013

 

 

 

 

 

 

 

 

 

 

 

10.23*

 

Amended and Restated Employment Agreement dated February 14, 2013, between Registrant and Mark E. Mosteller

 

10-K

 

000-50549

 

10.21

 

03/05/2013

 

57



Table of Contents

 

10.24*

 

Amended and Restated Employment Agreement dated February 14, 2013, between Registrant and Henry P. Doggrell

 

10-K

 

000-50549

 

10.22

 

03/05/2013

 

 

 

 

 

 

 

 

 

 

 

10.25*

 

Amended and Restated Employment Agreement dated February 14, 2013 between Registrant and James T. Dalton

 

10-K

 

000-50549

 

10.23

 

03/05/2013

 

 

 

 

 

 

 

 

 

 

 

10.26*

 

Form of Retention Benefits Letter Agreement for Mitchell S. Steiner and Marc S. Hanover

 

10-Q

 

000-50549

 

10.1

 

11/12/2013

 

 

 

 

 

 

 

 

 

 

 

10.27*

 

Form of Retention Benefits Letter Agreement for James T. Dalton and Henry P. Doggrell

 

10-Q

 

000-50549

 

10.2

 

11/12/2013

 

 

 

 

 

 

 

 

 

 

 

10.28*+

 

Confidential Separation Agreement and General Release, dated December 20, 2014, between Registrant and Mark E. Mosteller

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

10.29*

 

Amended and Restated GTx, Inc. Executive Bonus Compensation Plan, effective November 4, 2008

 

10-K

 

000-50549

 

10.53

 

03/03/2009

 

 

 

 

 

 

 

 

 

 

 

10.30*

 

2013 Compensation Information for Registrant’s Executive Officers

 

10-K

 

000-50549

 

10.26

 

03/05/2013

 

 

 

 

 

 

 

 

 

 

 

10.31*+

 

2014 Compensation Information for Registrant’s Executive Officers

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

10.32*

 

Directors’ Deferred Compensation Plan, as amended effective November 4, 2008

 

10-K

 

000-50549

 

10.49

 

03/03/2009

 

 

 

 

 

 

 

 

 

 

 

10.33*

 

Directors’ Deferred Compensation Plan, as amended and restated effective February 14, 2013

 

10-K

 

000-50549

 

10.28

 

03/05/2013

 

 

 

 

 

 

 

 

 

 

 

10.34*

 

Non-Employee Director Compensation Policy of GTx, Inc., effective February 18, 2011

 

10-Q

 

000-50549

 

10.50

 

05/09/2011

 

 

 

 

 

 

 

 

 

 

 

10.35*

 

Non-Employee Director Compensation Policy of GTx, Inc., effective February 14, 2013

 

10-K

 

000-50549

 

10.30

 

03/05/2013

 

 

 

 

 

 

 

 

 

 

 

10.36

 

Lease Agreement, dated March 7, 2001, between The University of Tennessee and TriStar Enterprises, Inc.

 

S-1

 

333-109700

 

10.13

 

10/15/2003

 

 

 

 

 

 

 

 

 

 

 

10.37

 

Sublease Agreement dated October 1, 2000, as amended, between Registrant and TriStar Enterprises, Inc.

 

S-1

 

333-109700

 

10.14