UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): January 11, 2021
PASSAGE BIO, INC.
(Exact name of registrant as specified in its charter)
Delaware | 001-39231 | 82-2729751 | ||
(State or other jurisdiction of incorporation) |
(Commission File Number) |
(IRS Employer Identification No.) |
Two Commerce Square 2001 Market Street, 28th Floor Philadelphia, PA |
19103 |
(Address of principal executive offices) | (Zip Code) |
(267) 866-0311
(Registrant’s telephone number, including area code)
N/A
(Former name or former address, if changed since last report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
¨ | Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425) |
¨ | Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12) |
¨ | Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b)) |
¨ | Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c)) |
Securities registered pursuant to Section 12(b) of the Act:
Title of each class | Trading symbol(s) | Name of each exchange on which registered |
Common Stock, $0.0001 Par Value Per Share | PASG |
The Nasdaq Stock Market LLC (Nasdaq Global Select Market) |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company x
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ¨
Item 7.01 Regulation FD Disclosure.
Passage Bio, Inc. (the “Company”) will present at the J.P Morgan 39th Annual Healthcare Conference being held virtually on Monday, January 11, 2021 at 7:30am ET. Additionally, on January 11, 2021, the Company issued a press release regarding its corporate outlook detailing the expansion of the Company’s pipeline, new regulatory filings, projected program milestones, and research and development progress.
A copy of the press release and corporate presentation are attached as Exhibits 99.1 and 99.2, respectively, to this Current Report on Form 8-K.
The information furnished with this report, including Exhibits 99.1 and 99.2, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference into any other filing under the Exchange Act or the Securities Act of 1933, as amended, except as expressly set forth by specific reference in such a filing.
Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
Exhibit No. |
Description | |
99.1 | Press Release by Passage Bio, Inc. | |
99.2 | Corporate Presentation. |
2
SIGNATURE
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
PASSAGE BIO, INC. | ||
Date: January 11, 2021 | By: | /s/ Richard Morris |
Richard Morris | ||
Chief Financial Officer |
3
Exhibit 99.1
Passage Bio Announces Plan to Deliver on Multiple Meaningful Catalysts in 2021
- Investigational New Drug Applications (IND) submitted for PBFT02 for Frontotemporal Dementia with
Granulin Mutation (FTD-GRN) and PBKR03 for Krabbe Disease –
- Three clinical programs to begin in 1H21 –
- Metachromatic leukodystrophy program, PBML04, advanced to IND-enabling phase –
- Additional option exercised from Penn’s world-class Gene Therapy Program for undisclosed program focused on an adult CNS disorder –
- New manufacturing laboratory to support analytical capabilities, clinical product testing and assay validation slated to open in 2Q21 –
- PBFT02 for FTD-GRN becomes latest of company’s three most advanced programs to receive FDA orphan drug designation –
PHILADELPHIA, January 11, 2021 — Passage Bio, Inc. (Nasdaq: PASG), a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system (CNS) disorders, today provided a corporate outlook detailing the expansion of the company’s pipeline, new regulatory filings, projected program milestones, and research and development progress. Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio, will highlight the company’s recent progress and plans for the future in his presentation today at the 39th Annual J.P. Morgan Healthcare Conference.
In his remarks, Dr. Goldsmith will highlight several components of the Company’s progress and timelines, including:
- | Planned initiation of patient dosing in clinical studies for three novel adeno-associated virus (AAV) gene therapies: |
o | Received FDA and MHRA clearance for PBGM01 for infantile GM1 gangliosidosis (GM1) |
o | Submitted IND for PBKR03 for the treatment of Krabbe disease |
o | Submitted IND for PBFT02 for treatment of Frontotemporal Dementia (FTD) with granulin (GRN) mutation. |
- | Advancement of PBML04 for the treatment of metachromatic leukodystrophy (MLD) into IND-enabling studies |
- | License of a seventh program from the University of Pennsylvania (Penn) for the treatment of an adult rare monogenic CNS disorder |
- | Planned opening of a manufacturing laboratory to support analytical capabilities, clinical product testing and assay validation |
“It is widely reported that there are approximately 7,000 rare diseases. Less discussed is that out of these 7,000 rare diseases, there are more than 790 rare monogenic CNS diseases, the area where we are focused,” said Dr. Goldsmith. “The diseases we are targeting are particularly devastating and have no approved disease-modifying treatment options, which means there is tremendous opportunity to make a difference for patients. At Passage Bio, we believe we are well positioned with our collaboration with Penn’s Gene Therapy Program, our corporate model, robust pipeline, manufacturing capability, strong cash position, and experienced team to succeed in our mission to deliver on the promise of gene therapies for patients with rare monogenic CNS disorders.”
Passage Bio’s collaboration with Penn’s world-class Gene Therapy Program (GTP) provides the company with access to cutting-edge research, expertise and next-generation technologies. GTP is recognized worldwide for its innovative gene therapy capabilities, AAV vector technology manufacturing, and IND expertise. Through the Penn GTP collaboration, Passage Bio has licensing options for a total of 17 gene therapy research programs focused on rare monogenic disorders of the CNS through 2025. The company has exercised seven options to date, including four programs for pediatric and three programs for adult rare monogenic CNS disorders.
“Through our relationship with GTP coupled with our business model, we have a well-defined path for clinical success,” explained Dr. Goldsmith. “We believe our pipeline has a higher probability of technical and regulatory success, in part because we are able to optimize delivery approaches, select candidates based on empirical research findings and integrate next-generation innovations from GTP as appropriate. Additionally, all our current therapies are designed for direct delivery to the CNS, which we believe offers a number of benefits, including avoiding crossing the blood brain barrier, better CNS biodistribution and lower dosing compared to systemic delivery.”
Dr. Goldsmith added: “We spent 2020 establishing a solid foundation for our company to execute seamlessly against our ambitious future plans. Our progress has laid the groundwork for clinical trial preparedness and manufacturing readiness, which will be critical to successfully deliver on several meaningful catalysts this year.”
The company’s three most advanced programs are: PBGM01 for infantile GM1 and PBKR03 for Krabbe disease, which are pediatric programs; and PBFT02 for FTD-GRN, which is an adult program. Passage Bio is also continuing to progress preclinical pediatric programs PBCM06 for Charcot-Marie-Tooth neuropathy type 2A (CMT2A) and PBML04 for MLD, which was recently advanced into IND-enabling studies. The company’s additional adult preclinical programs are PBAL05 for amyotrophic lateral sclerosis (ALS) and a seventh program, for which the company recently exercised an option and has not yet disclosed the therapeutic target.
Significant Pipeline and Corporate Advancement
The company’s lead program PBGM01 is entering the clinic to study its safety and efficacy in addressing infantile GM1, a rare and often life-threatening CNS disorder with no approved disease-modifying therapies. The global Phase 1/2 study, Imagine-1, is expected to enroll the first patient in the first quarter of 2021 and is expected to report initial 30-day safety and biomarker data mid-year 2021. PBGM01 has received regulatory agency clearance from FDA and MHRA. The investigational therapy has also received orphan drug and rare pediatric disease designations from FDA, as well as orphan drug designation from the European Medicines Agency for the treatment of GM1.
The company has submitted investigational new drug (IND) applications to FDA for Phase 1/2 clinical studies of PBFT02 in FTD-GRN, a devastating form of early onset dementia; and PBKR03 in Krabbe disease, a pediatric disease with rapid progression, typically resulting in death by 2 years old. The company recently received orphan drug designation from FDA for PBFT02 for FTD-GRN. PBKRO3 has orphan drug and rare pediatric disease designations from FDA for treatment of Krabbe disease. Passage Bio anticipates the start of both clinical programs in the first half of 2021. Initial data from these trials are anticipated to potentially readout in late 2021 or early 2022, depending on the timing of first patient treated in each study.
In parallel with pipeline advancement, the company has focused on establishing manufacturing and global distribution from clinical development through initial commercialization. Clinical supply for PBGM01 for our phase 1 / 2 global trial, manufactured through our partnership with Catalent, is already in place. We have also manufactured clinical supplies to initiate clinical trials for our next two most advanced programs – PBKRO3 for Krabbe disease and PBFT02 for FTD-GRN. In December, Passage Bio announced that it had completed construction and started production at its dedicated Current Good Manufacturing Practices (CGMP) manufacturing suite at Catalent Cell & Gene Therapy’s facility in Maryland. The company also announced the planned opening in the second quarter of 2021 of a gene therapy manufacturing research and development site at the Princeton West Innovation Campus in Hopewell, New Jersey, for Chemistry, Manufacturing and Controls (CMC) laboratory operations to support analytics, assay development, and product testing for the company’s gene therapy programs.
About Passage Bio
At Passage Bio (Nasdaq: PASG), we are on a mission to provide life-transforming gene therapies for patients with rare, monogenic CNS diseases that replace their suffering with boundless possibility, all while building lasting relationships with the communities we serve. Based in Philadelphia, PA, our company has established a strategic collaboration and licensing agreement with the renowned University of Pennsylvania’s Gene Therapy Program to conduct our discovery and IND-enabling preclinical work. This provides our team with access to a broad portfolio of gene therapy candidates and future gene therapy innovations that we then pair with our deep clinical, regulatory, manufacturing and commercial expertise to rapidly advance our robust pipeline of optimized gene therapies into clinical testing. As we work with speed and tenacity, we are always mindful of patients who may be able to benefit from our therapies. More information is available at www.passagebio.com.
Forward-Looking Statements
This press release contains “forward-looking statements” within the meaning of, and made pursuant to the safe harbor provisions of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectations about timing and execution of anticipated milestones, including our planned IND submissions, initiation of clinical trials and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; our expectations about manufacturing plans and strategies; our expectations about cash runway; and the ability of our lead product candidates to treat the underlying causes of their respective target monogenic CNS disorders. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “may,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These statements involve risks and uncertainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop and obtain regulatory approval for our product candidates; the timing and results of preclinical studies and clinical trials; risks associated with clinical trials, including our ability to adequately manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities may require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of adverse safety events; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early stage clinical trials may not be predictive of results in later stage clinical trials; failure to protect and enforce our intellectual property, and other proprietary rights; our dependence on collaborators and other third parties for the development and manufacture of product candidates and other aspects of our business, which are outside of our full control; risks associated with current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; and the other risks and uncertainties that are described in the Risk Factors section in documents the company files from time to time with the Securities and Exchange Commission (SEC), and other reports as filed with the SEC. Passage Bio undertakes no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.
For further information, please contact:
Passage Bio Investors:
Sarah McCabe and Zofia Mita
Stern Investor Relations, Inc.
212-362-1200
sarah.mccabe@sternir.com
Zofia.mita@sternir.com
Passage Bio Media:
Gwen Fisher
Passage Bio
215-407-1548
gfisher@passagebio.com
Exhibit 99.2
39th Annual J.P. Morgan Healthcare Conference Bruce Goldsmith, PhD | CEO January 11, 2021 NASDAQ GS: PASG Fulfilling the Promise of Gene Therapies for Central Nervous System Disorders
Forward - Looking Statement This presentation includes “forward - looking statements” within the meaning of, and made pursuant to the safe harbor provisions o f, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectation about timing and execution of antici pat ed milestones, including our planned IND submissions and initiation of clinical trials; our expectations about our collaborators’ and partne rs’ ability to execute key initiatives; estimates regarding our cash forecasts; the expected impact of the COVID - 19 pandemic on our operations; and the abi lity of our lead product candidates to treat the underlying causes of their respective target monogenic CNS disorders. These forward - looking stat ements may be accompanied by such words as “aim,” “anticipate,” “believe,” “could,” “estimate,” “expect,” “forecast,” “goal,” “intend,” “ma y,” “might,” “plan,” “potential,” “possible,” “will,” “would,” and other words and terms of similar meaning. These statements involve risks and un cer tainties that could cause actual results to differ materially from those reflected in such statements, including: our ability to develop, obtain reg ulatory approval for and commercialize PBGM01, PBFT02, PBKR03 and future product candidates; the timing and results of preclinical studies and clinica l t rials; the risk that positive results in a preclinical study or clinical trial may not be replicated in subsequent trials or success in early st age clinical trials may not be predictive of results in later stage clinical trials; risks associated with clinical trials, including our ability to adeq uat ely manage clinical activities, unexpected concerns that may arise from additional data or analysis obtained during clinical trials, regulatory authorities m ay require additional information or further studies, or may fail to approve or may delay approval of our drug candidates; the occurrence of advers e s afety events; failure to protect and enforce our intellectual property, and other proprietary rights; failure to successfully execute or realize th e a nticipated benefits of our strategic and growth initiatives; risks relating to technology failures or breaches; our dependence on collaborators and othe r t hird parties for the development of product candidates and other aspects of our business, which are outside of our full control; risks associated wit h current and potential delays, work stoppages, or supply chain disruptions caused by the coronavirus pandemic; risks associated with curre nt and potential future healthcare reforms; risks relating to attracting and retaining key personnel; failure to comply with legal and regulat ory requirements; risks relating to access to capital and credit markets; and the other risks and uncertainties that are described in the Risk Factor s s ection of our most recent filings with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expect ati ons and speak only as of the date of this presentation. We do not undertake any obligation to publicly update any forward - looking statements e xcept as required by law. By attending or receiving this presentation you acknowledge that you are cautioned not to place undue reliance on the se forward - looking statements, which speak only as of the date such statements are made; you will be solely responsible for your own assessment of the market and our market position; and that you will conduct your own analysis and be solely responsible for forming your own view of the p ote ntial future performance of Passage Bio. 2
~7,000 Rare diseases OUR VISION: To fulfill the promise of gene therapy by developing groundbreaking therapies that transform the lives of patients with rare monogenic CNS diseases 70% of rare genetic diseases produce abnormalities of the CNS 1 790+ are rare monogenic CNS diseases with few treatment options 2 Passage Bio is currently targeting rare CNS disorders that affect: BABIES ADULTS 1. Lee, C., Singleton, K., Wallin, M., Faundez, V. (2020). Rare Genetic Diseases: Nature’s Experiments on Human Development . iScience 2020 May 22;23(5): 101123 2. M arket research conducted by Health Advances Approved disease - modifying treatment options for our targeted rare diseases 80% of rare diseases have a genetic component 1 who suffer from severe clinical manifestations and severely shortened survival 3
Patients with rare CNS disorders need therapeutic options.
The Passage Bio Advantage Corporate model designed for success 5 PENN GTP PARTNERSHIP Led by renowned innovator James M. Wilson, MD, PhD Access to cutting - edge research and development Access to next - generation technologies BROAD AND ROBUST PIPELINE 17 total program license options 3 clinical - stage therapies expected in 2021 4 research - stage pipeline candidates 10 additional new pipeline license options INTEGRATED MANUFACTURING SUPPLY CHAIN Flexible, scalable Dedicated CGMP suite Internal CMC analytics and assay infrastructure State - of - the - art technology WELL - POSITIONED CORPORATE FOUNDATION Robust financial position Leaders in pediatric and adult neurodegenerative disease therapy development Deep experience in gene therapy manufacturing
Passage Bio’s Differentiated Path for Clinical Success 17 program license options from GTP focused on rare monogenic CNS disorders 6 GTP expertise and insights into research and development Optimization of delivery approaches Disease - specific existing and novel capsid selection Integration of next - generation research advances . Patient need Optimal capsid, transgene and promoter Preclinical safety and efficacy data Availability of measurable, predictive biomarkers Avoids need to cross blood brain barrier Better CNS biodistribution Lower dose compared to systemic delivery Reduced immune response RIGOROUS PRODUCT CANDIDATE SELECTION DIRECT DELIVERY TO CNS PIPELINE WITH HIGHER PROBABILITY OF TECHNICAL AND REGULATORY SUCCESS
PROGRAM 1 / INDICATION GENE DISCOVERY CANDIDATE SELECTION IND - ENABLING PHASE 1/2 PIVOTAL PEDIATRIC PB GM01 2 Infantile GM1 Gangliosidosis GLB1 PB KR03 Krabbe GALC PBML04 Metachromatic Leukodystrophy ARSA PBCM06 Charcot - Marie - Tooth Type 2A MFN2 ADULT PB FT02 Frontotemporal Dementia - GRN GRN PBAL05 Amyotrophic Lateral Sclerosis C9orf72 Undisclosed CNS Undisclosed A Broad and Robust Pipeline with Global Rights Multiple potential value creating catalysts in 2021 7 1 10 additional new pipeline license options 2 Program includes ongoing natural history study of infantile and juvenile GM1 gangliosidosis patients
PBGM01 Infantile GM1 Gangliosidosis
GM1 Gangliosidosis A D evastating Pediatric Disease 9 FATAL, PEDIATRIC NEUROLOGICAL LYSOSOMAL STORAGE DISORDER caused by GLB1 gene mutations characterized by destruction of neurons in the brain and spinal cord. Characterized by rapidly progressive neurological decline resulting in reduced muscle tone, progressive CNS dysfunction, deafness, blindness, rigidity and skeletal dysplasia. RARE AND UNDERSERVED populations with incidence of up to ~1 per 100,000 live births worldwide. No disease - modifying therapies are presently available.
PBGM01 A Potential Transformative Therapy For a Rare, Underserved Disorder ▪ Next - generation, proprietary AAVhu68 capsid delivers functional GLB1 gene encoding β - gal to the brain and peripheral tissues ▪ Meaningful transduction of both central nervous system and critical peripheral organs in preclinical models ▪ Received regulatory clearances from FDA and MHRA, for global Phase 1/2 clinical trial program ▪ Received Orphan Drug and Rare Pediatric Disease designations by FDA and Orphan Drug designation by EC for treatment in GM1 ▪ First patient enrollment planned for 1Q21 in Phase 1/2 trial ▪ Initial 30 - day safety and biomarker data planned for mid - 2021 10 Source: NIH, CHOP, American Journal of Neuroradiology
11 PBGM01 Supportive Preclinical Findings Improvement in biomarker and pathophysiology in knock - out mouse model p<0.05, p<0.01, NS=not significant. GLB1 +/ - + PBS GLB1 - / - + PBS GLB1 - / - + AAV 10,000 10 1 10.1 CSF 100 1,000 ß - gal activity ( nmol /mL/h) GLB1 +/ - + PBS GLB1 - / - + PBS GLB1 - / - + AAV GLB1 +/ - + PBS GLB1 - / - + PBS GLB1 - / - + AAV 10,000 1,000 100 10 NS Liver GLB1 +/ - + PBS GLB1 - / - + PBS GLB1 - / - + AAV NS Increased Biomarker Activity Histological Confirmation GLB1 +/ - + vehicle GLB1 - / - + vehicle GLB1 - / - + PBGM01 ▪ Dose - dependent reduction of brain lysosomal storage lesions as measured by LAMP1 positive cells ▪ Stable, dose - dependent increases in β - gal enzyme activity in brain, cerebrospinal fluid, serum, and critical peripheral tissues
Dose - Related Effect on Survival GLB1 - / - (KO) GLB1 +/ - (HET) Dose 4 (highest) Dose 3 Dose 2 Dose 1 (lowest) Vehicle Vehicle Percent Survival 0 Day 100 200 300 0 50 100 Preservation of Neurological Function 0 5 10 15 20 Total score ( + SEM) Days 240 180 120 60 0 Neurological Examinations GLB1 – / – (KO) GLB1 +/ – (HET) Dose 4 (highest) Dose 3 Dose 2 Dose 1 (lowest) Vehicle Vehicle 12 PBGM01 Supportive Preclinical Findings Improvement in neurological function and survival in knock - out mouse model ▪ Treated mice demonstrated increased survival at all doses tested ▪ Top 2 doses achieved 100% survival to study endpoint ▪ Dose related improvements in neurological function demonstrated ▪ Top two doses similar to GLB +/ - vehicle
Pathway to Patient Identification and Trial Recruitment 13 Newborn Screening / Diagnosis Patient Recruitment and Advocacy Strategies Patient and Caregiver Activities Sponsoring ScreenPlus Pilot Program ▪ GM1 has been added to the New York newborn screening pilot program led by Dr. Melissa Wasserstein Implementing caregiver and physician outreach programs Supporting Invitae Detect LSD Program ▪ Offer free genetic testing and counseling to support earlier diagnosis of GM1 ▪ Provide clinical trial information to clinicians and patients Maintaining strong relationships with site, study coordinators and investigators Decreasing patient and site trial burden ▪ Implement remote visits and video capture for relevant endpoints ▪ Utilize Clincierge for travel and accommodation support Increasing GM1 clinical trial awareness ▪ Engage patient advocacy groups ▪ Partner with medical specialists and organizations
Adapted from Regier DS, et al. 2016 GLB - 1 Disorders, In Adam MP, et al. GeneReviews. Goal of the Imagine - 1 Trial in Early and Late Infantile GM1 Elevate β - gal activity to preserve neurological function and improve developmental potential and survival CLINICAL TRIAL OBJECTIVES 1. Assess the safety and tolerability of a single intra - cisterna magna dose of PBGM01 2. Demonstrate treatment - related increase in β – Gal enzyme activity in CSF and serum 3. Demonstrate resultant normalization of disease biomarkers and pathophysiology 4. Demonstrate improvement in clinical outcomes through developmental milestone assessment GM1 Gangliosidosis is a Continuum Disease Severity Residual Enzyme Activity Imagine - 1 Trial will include Type I (Early Infantile) and Type IIa (Late Infantile) patients Negligible to 5% ~ 1 - 5% ~ 3 – 10% Type I (Early Infantile) • Onset <6 months • Skeletal dysplasia • Developmental regression • Hypotonia • Seizures • Survival: <2 years Type IIa (Late - Infantile) • Onset 6 - 24 months • Developmental plateau, followed by regression • Impaired ambulation • Decreased cognition • Seizures • Survival: 5 to 10 years Type II (Juvenile) • Onset 2 - 5 years • Impaired ambulation • Dysarthria • Variable skeletal disease • Decreased cognition • Survival into 2nd decade 14
Imagine - 1 Global Phase 1/2 Trial with PBGM01 First patient enrollment expected in 1Q21 15 Trial Design Phase 1/2, multi - center, open - label, single - arm, 2+2 dose escalation and confirmatory study Separate cohorts of pediatric subjects with Late Onset Infantile GM1 in cohorts 1 and 2 and Early Onset Infantile GM1 in cohort 3 and 4 Intervention Single ICM dose of AAVhu68.hGLB1 First Read Out 30 - day safety and biomarker data of cohort 1 to be reported mid - 2021 Duration Two years, with rollover into a separate long - term follow - up study Primary Endpoints Cohorts 1 - 4: Safety and tolerability Expansion Cohorts: Efficacy, safety and tolerability COHORT 4 Early Infantile n = 2 H IGH D OSE L OW D O S E Expansion Cohort Early Infantile n = 6 Expansion Cohort Late Infantile n = 6 COHORT 2 Late Infantile n = 2 COHORT 3 Early Infantile n = 2 COHORT 1 Late Infantile n = 2 DSMB review
PBKR03 Krabbe Disease
Krabbe Lysosomal Storage Disease PBKR03 — A potential transformative therapy for a rare, underserved disorder 17 Source: NIH, CHOP, American Journal of Neuroradiology, Third Party Research Severe form of disease ▪ Infantile Krabbe disease is the most severe form, accounting for 60% to 70% of diagnoses ▪ Disease progression is highly predictable and includes loss of acquired milestones, staring episodes, peripheral neuropathy, seizures, blindness and deafness ▪ Rapid progression with mortality by ~2 years Rare and underserved ▪ Estimated worldwide incidence of Krabbe is 2.6:100,000 births ▪ Currently no approved disease - modifying therapies PBKR03 — Our solution ▪ Next - generation, proprietary AAVhu68 capsid delivers a functional GALC gene encoding galactosylceramidase (GALC) to the brain and peripheral tissues ▪ In preclinical models, observed meaningful transduction of both CNS and peripheral nerves ▪ PBKR03 - treated Krabbe dogs improved central and peripheral myelination, reduced neuroinflammation and increased survival rates with full phenotypic recovery ▪ Received Orphan Drug and Rare Pediatric Disease designations by FDA for treatment in Krabbe disease ▪ Filed Investigational New Drug application ▪ Clinical trial initiation in 1H21 Infantile Krabbe PBKR03
PBKR03 Disease Model Data – Twitcher Mouse and Dog Models Meaningful brain and peripheral transduction with improved pathophysiology and function 18 GALC Increase in Brain and Periphery Twitcher Mouse Model: • Increased GALC activity in brain, liver and serum • AAV treated twitcher mouse showed clinical scores comparable to wt mice GALC Activity (FU/50 µg) 2 0,000 15,000 10,000 0 5,000 +/+ t wi / twi t wi / twi PBS GTP - 206 Brain PBKR03 GALC Activity (FU/50 µg) 2, 000 1,500 0 500 +/+ t wi / twi t wi / twi PBS GTP - 206 1,000 Liver PBKR03 GALC and Psychosine Normalization 200 240 280 320 WT (untreated) AAV-treated (6M post- treatment) FU / 10 µl CSF CSF GALC Activity (6M post - treatment ) CSF Psychosine Levels (70 days post - treatment) ng/ml Canine Model: • Increased GALC activity in CSF • Decreased psychosine levels in CSF 0 0.5 1 1.5 2 Vehicle-treated AAV-treated
Naturally occurring Krabbe Dog model study showed substantial benefit with AAV treatment, including full phenotypic recovery and increased survival 0 20 40 60 80 K948 K930 K938 K939 K937 K933 Weeks PBKR03 Patient Enrollment Expected in 1H 2021 Supported by extensive preclinical studies 19 TRIAL DESIGN A Phase 1/2 Dose Escalation Study of a Single ICM Dose of PBKR03 in in pediatric subjects with infantile Krabbe disease ENDPOINTS Primary: Safety and tolerability Secondary: CSF and serum GALC levels; disease biomarkers; Clinical outcome measure Phase 1/2 Study Summary Survival Extended by AAV Treatment Euthanized due to disease progression Euthanized as planned per protocol Euthanized for seizure (AAV3) and weight loss (AAV4) Myelination Improvement in CNS and PNS Brain Peripheral Nerves Animal ID Average Severity Score (Grade 1 - 4) Vehicle AAV WT Vehicle AAV
PBFT02 Frontotemporal Dementia - GRN 20
FTD - GRN Frontotemporal Dementia Caused by a Progranulin Deficiency PBFT02 – A potential transformative therapy for a rare, underserved disorder 21 Devasting form of dementia ▪ FTD is one of the more common causes of early - onset dementia ▪ Approximately 5 - 10% of FTD is caused by a GRN gene mutation, causing progranulin (PGRN) deficiency ▪ Progresses to immobility and severe behavioral changes and loss of speech and expression ▪ Rapid progression, with average survival of 8 years, after onset of symptoms Rare and underserved ▪ Estimated prevalence of F TD - GR N in the United States is ~3,000 to 6,000 patients ▪ Currently no approved disease - modifying therapies PBFT02 — Our solution ▪ Proprietary AAV1 capsid - based product candidate ▪ Designed to deliver to the brain a functional GRN gene encoding PGRN ▪ Meaningful transduction in NHP studies showing high transduction of ependymal cells that line brain ventricles ▪ Increases in CSF PGRN concentrations in NHP studies to >50 - fold normal human CSF PGRN concentrations ▪ Received Orphan Drug designation by FDA ▪ Filed Investigational New Drug application ▪ Clinical trial initiation 1H21 FTD - GRN PBFT02
PBFT02 Biomarker Improvement Across Brain Regions Decreases markers of lysosomal function and microgliosis *** * PBFT02 high dose vs vehicle in GRN - / - mice; post baseline data is 90 days post - dose * = p< 0.05*** = p<0.001 0% 20% 40% 60% 80% 100% 120% Baseline Vehicle PBFT02 0 0.2 0.4 0.6 0.8 1 1.2 Baseline Vehicle PBFT02 Lipofuscin Accumulation Stopped in Thalamus Hexosaminidase Activity Normalization in Cortex Reduced CD68 in Hippocampus • Lipofuscin accumulation is implicated in various neurodegenerative conditions • Treatment stopped lipofuscin accumulation across brain regions • Hexosaminidase activity is upregulated in setting of lysosomal dysfunction • Treatment reduced enzyme activity at the highest dose • CD68 is a lysosomal protein expressed by macrophages and activated microglia with increases reflecting higher inflammation • Treatment reduced CD68 levels across brain regions 22
PBFT02 Patient Enrollment Expected in 1H 2021 Supported by extensive NHP preclinical studies utilizing ICM delivery 23 Phase 1/2 study summary PBFT02 Showed D ose - Related Increase in CSF PGRN at 14d PD 0 2 4 6 8 10 12 High Dose Medium Dose Low Dose Vehicle Human PGRN (ng/ml) Production of Human PGRN in CSF CSF PGRN (ng/mL) 0 10 2 0 30 4 0 CSF 0.1 1 10 100 LLOQ Normal Day RA2981 RA2982 RA3027 RA3153 RA3151 RA3170 RA3155 RA3160 AAVhu68 AAVhu68 (v2) AAV1 AAV5 RA2981 RA2982 RA3027 RA3153 RA3151 RA3170 RA3155 RA3160 AAVhu68 AAVhu68 (v2) AAV1 AAV5 RA2981 RA2982 RA3027 RA3153 RA3151 RA3170 RA3155 RA3160 AAVhu68 AAVhu68 (v2) AAV1 AAV5 AAVhu68 AAVhu68 (v2) AAV5 AAV1 Normal LLOQ AAVhu68 AAV1 Ependyma 1 – 2% transduction 48% transduction AAV1 Vector Expressing GFP 48% transduction of the ependymal cells in the animals treated with AAV1 Trial Design A Phase 1/2 Dose Escalation Study of a Single ICM Dose of PBFT02 in Subjects with Frontotemporal Dementia and Heterozygous Mu tat ions in the Granulin Precursor GRN Gene Primary Endpoints Primary: Safety and tolerability Secondary: CSF progranulin levels; disease biomarkers (e.g., NfL, MRI); Clinical outcome measure
State - of - the - Art Manufacturing
Manufacturing That is Dedicated, Flexible, and Scalable 25 CMC Infrastructure Capability Investment in CMC laboratory with state - of - the - art analytical capabilities, clinical assay development and validation, biomarker assay validation, and clinical product testing End - to - End Supply Chain Establishing manufacturing and global distribution from clinical development through initial commercialization Dedicated Manufacturing Suite Partnership with gene therapy manufacturing leader Catalent facilitates flexible and scalable capacity Qualified CGMP suite dedicated to Passage Bio is completed and manufacturing initiated
Corporate Foundation 26 SOURCE: www.brandywinerealty.com
Financial Summary 27 Strong cash balance of $335M at September 30, 2020 Cash on hand to fund operations into 2023 Runway to potentially deliver meaningful catalysts over multiple programs
Anticipated Upcoming Milestones 28 Phase 1/2 trial for PBGM01 in patients with infantile GM1 1Q21 INITIATE Phase 1/2 trial for PBFT02 in patients with FTD - GRN in 1H21 INITIATE Advance preclinical programs for MLD, ALS CMT2A ADVANCE Evaluate and expand pipeline by pursuing new licenses in partnership with Penn’s GTP BUILD Phase 1/2 trial for PBKR03 in patients with Krabbe disease in 1H21 INITIATE PBGM01 safety and biomarker data mid - 2021 REPORT
The Passage Bio Advantage Corporate model designed for success 29 PENN GTP PARTNERSHIP Led by renowned innovator James M. Wilson, MD, PhD Access to cutting - edge research and development Access to next - generation technologies BROAD AND ROBUST PIPELINE 17 total program license options 3 clinical - stage therapies expected in 2021 4 research - stage pipeline candidates 10 additional new pipeline license options INTEGRATED MANUFACTURING SUPPLY CHAIN Flexible, scalable Dedicated CGMP suite Internal CMC analytics and assay infrastructure State - of - the - art technology WELL - POSITIONED CORPORATE FOUNDATION Robust financial position Leaders in pediatric and adult neurodegenerative disease therapy development Deep experience in gene therapy manufacturing
www.passagebio.com NASDAQ GS: PASG THANK YOU 30
Appendix
Demonstrated Leadership Deep experience in rare disease, CNS disorders and gene therapy 32 LEADERSHIP TEAM BOARD OF DIRECTORS Tachi Yamada, M.D. (Chair) Frazier Athena Countouriotis, M.D. Turning Point Bruce Goldsmith, Ph.D. Passage Bio Patrick Heron Frazier Saqib Islam, J.D. SpringWorks Sandip Kapadia Intercept Liam Ratcliffe, M.D., Ph.D. Access Industries Stephen Squinto, Ph.D. OrbiMed Tom Woiwode, Ph.D. Versant Rich Morris Chief Financial Officer Chip Cale General Counsel Alex Fotopoulos Chief Technology Officer Bruce Goldsmith, Ph.D. Chief Executive Officer Jill M. Quigley Chief Operating Officer Gary Romano, M.D., Ph.D. Chief Medical Officer Stephen Squinto, Ph.D. Acting Head of R&D
Cutting - Edge Gene Therapy R&D Collaboration 17 program license options for Passage Bio focused on rare monogenic CNS disorders 33 Founded by renowned innovator and pioneer James M. Wilson, M.D., Ph.D. Chief Scientific Advisor, Passage Bio Director, Gene Therapy Program Rose H. Weiss Professor and Director, Orphan Disease Center Professor of Medicine and Pediatrics, Department of Medicine Cutting - edge research, expertise, next - generation technologies ~300 full - time employees Research contributed to successful clinical programs for approved gene therapies Glybera ® , Luxturna ® and Zolgensma ® Supporting natural history studies and early patient identification World - class Gene Therapy Program
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