SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Pursuant to Section 13 or 15(d)
of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): March 3, 2021
PASSAGE BIO, INC.
(Exact name of registrant as specified in its charter)
(State or other jurisdiction
Two Commerce Square
2001 Market Street, 28th Floor
(Address of principal executive offices)
(Registrant’s telephone number, including area code)
(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))
Title of each class
Name of each exchange on which registered
Common Stock, $0.0001 Par Value Per Share
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 ☒
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. ◻
On March 3, 2021, Passage Bio, Inc. issued a press release announcing its financial results for the year ended December 31, 2021. A copy of the press release is attached as Exhibit 99.1 to this report.
The information in this Item 2.02, including Exhibit 99.1 to this report, shall not be deemed to be “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 or Sections 11 and 12(a)(2) of the Securities Act of 1933, as amended (the “Securities Act”). The information contained in this Item 2.02 and in the accompanying Exhibit 99.1 shall not be incorporated by reference into any other filing under the Exchange Act or under the Securities Act, except as shall be expressly set forth by specific reference in such filing.
Item 7.01 Regulation FD Disclosure.
On March 3, 2021, the Company also updated its corporate presentation. A copy of the corporate presentation is attached as Exhibit 99.2 to this report.
The information in this Item 7.01, including Exhibit 99.2 to this report, shall not be deemed to be “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section or Sections 11 and 12(a)(2) of the Securities Act. The information contained in this Item 7.01 and in the accompanying Exhibit 99.2 shall not be incorporated by reference into any other filing under the Exchange Act or under the Securities Act, except as shall be expressly set forth by specific reference in such filing.
Financial Statements and Exhibits.
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: March 3, 2021
/s/ Richard Morris
Chief Financial Officer
|-||On track to initiate three Phase 1/2 clinical programs in the first half of 2021: PBGM01 for GM1 gangliosidosis (GM1), PBFT02 for frontotemporal dementia with granulin mutations, and PBKR03 for Krabbe disease|
|-||Opened first U.S. site for PBGM01’s Imagine-1 global clinical program and actively recruiting patients; other site activations in progress|
|-||Opening new CMC research and development site to support analytics, assay development, and product testing in 2Q 2021|
|-||Strengthened financial position with recent public offering that raised $166M in net proceeds|
|-||Management to host conference call today at 8:30 a.m. ET|
Philadelphia, PA – March 3, 2021 – Passage Bio, Inc. (Nasdaq: PASG), a genetic medicines company focused on developing transformative therapies for rare, monogenic central nervous system disorders, today reported financial results for the fourth quarter and full year ended December 31, 2020 and provided recent business highlights.
“At Passage Bio, we are on a mission to provide life-transforming therapies to patients with devastating CNS diseases, and we are pleased with the foundational work we accomplished in 2020 as we transition to a clinical-stage company in 2021,” said Bruce Goldsmith, Ph.D., president and chief executive officer of Passage Bio. “In the year ahead, our priorities are progressing three clinical development programs, all set to begin in the first half of 2021, and continuing to expand our pipeline and internal operations. We are confident that with the expertise of our talented internal team, our partnership with University of Pennsylvania’s Gene Therapy Program, and our relationships with patient and physician groups that we are well positioned for strong execution across all our upcoming milestones.”
Recent Corporate Highlights
|●||On track to dose first patient in Imagine-1 trial evaluating PBGM01 for the treatment of infantile GM1 gangliosidosis: In January 2021, the company announced that U.S. Food and Drug Administration (FDA) cleared its Investigational New Drug (IND) application for PBGM01 for the treatment of infantile GM1 gangliosidosis (GM1), a rare and often life-threatening CNS disorder with no approved disease-modifying therapies. The company has activated its first site in the United States and is currently recruiting patients. PGBM01 has also received regulatory clearance to begin studies in the United Kingdom and Canada. Site activation efforts are in progress in these countries as well as for additional sites in the United States. The company continues to expect to dose the first patient in the trial in first quarter of 2021 and to report initial 30-day safety and biomarker data mid-year 2021. The investigational therapy has also received orphan drug and rare pediatric disease designations from FDA, as well as an orphan drug designation from the European Medicines Agency for the treatment of GM1.|
|●||IND cleared and preparations on track to initiate Phase 1/2 trial for PBKR03 for treatment of patients with Krabbe disease, a rare pediatric disease: The company announced FDA clearance of the IND application for PBKR03 for Krabbe disease, a rare lysosomal storage|
|disease, in February 2021. PBKR03 was also previously granted both orphan drug and rare pediatric disease designations for the treatment of Krabbe disease by FDA. The European Medicines Agency has also recently adopted a positive opinion for an orphan drug designation for PBKR03. Final endorsement of the designation by the European Commission is expected later in the first quarter. Passage Bio anticipates the start of the PBKR03 clinical program in the first half of 2021 with an initial 30-day safety and biomarker data readout planned for late 2021 or early 2022.|
|●||IND cleared and preparations on track to initiate Phase 1/2 trial for PBFT02 for treatment of patients with frontotemporal dementia with granulin mutations (FTD-GRN), an adult indication: In January, the company announced that FDA cleared its IND application for PBFT02 for FTD-GRN, a devastating form of early onset dementia. FDA has recently granted fast track designation for PBFT02. Fast track is a process designed to facilitate the development and expedite the review of drugs to treat conditions and fill unmet medical need. PBFT02 was also granted orphan drug designation by FDA earlier this year for the treatment of FTD-GRN. Passage Bio anticipates the start of PBFT02 clinical program in the first half of 2021 with initial data readouts planned late 2021 or early 2022.|
|●||Raised $166M in net proceeds via a public offering of common stock: In January 2021, the company announced a public offering of 7,000,000 shares of its common stock at a price of $22 per share. The underwriters also exercised their option to purchase an additional 1,050,000 shares of common stock for a total offering net proceeds of $166 million.|
|●||Continue to license and advance assets through partnership with the University of Pennsylvania (Penn)’s Gene Therapy Program (GTP): The company recently advanced PBML04 for the treatment of metachromatic leukodystrophy (MLD) into IND-enabling studies in partnership with Penn GTP. Through its partnership with GTP, the company also licensed a seventh unnamed program for the treatment of an adult neurodegenerative rare monogenic CNS disorder. Passage Bio has licensing options for a total of 17 gene therapy research programs focused on rare monogenic CNS disorders and continues to evaluate additional programs for further development.|
|●||Establishing internal and external manufacturing capabilities to meet the needs of growing pipeline: In December 2020, Passage Bio announced that it had completed construction and initiated vector manufacturing at its dedicated Current Good Manufacturing Practices (CGMP) manufacturing suite at Catalent Cell & Gene Therapy’s facility in Maryland. The company also announced its plans to open a Chemistry, Manufacturing and Controls (CMC) research and development site at the Princeton West Innovation Campus in Hopewell, New Jersey, for CMC laboratory operations to support analytics, assay development, and product testing for the company’s gene therapy programs in the second quarter of 2021. The company has completed clinical supply and established global clinical distribution to support clinical development of PBGM01 as well manufactured clinical supplies to initiate clinical trials for PBFT02 for FTD-GRN and PBKR03 for Krabbe disease.|
|●||Strengthened patient identification and engagement efforts, including:|
|o||Sponsorship of ScreenPlus pilot program, in which GM1 has been added to the New York newborn screening pilot program led by Melissa Wasserstein, M.D.|
|o||Collaboration with Invitae, a leading genetic testing company, to support its Detect Lysosomal Storage Disorders program to encourage early diagnosis of GM1 and to provide educational information to patients and clinicians regarding clinical trials.|
|o||Engagement with Informed DNA to design and support a genetic screening and counselling program that will be free of charge to patients with FTD.|
|o||Working with investigators participating in the ALL FTD study and the Genetic Frontotemporal Dementia Initiative and supporting the Bluefield Project to Cure FTD.|
Anticipated Upcoming Milestones
|●||Dose the first patient in the global Phase 1/2 trial for PBGM01, Imagine-1, for the treatment of infantile GM1 in the first quarter of 2021. Report initial 30-day safety and biomarker data mid-year 2021.|
|●||Open CMC research and development site in Hopewell, NJ, in the second quarter of 2021.|
|●||Initiate Phase 1/2 trial for PBKR03 for the treatment of early infantile Krabbe disease in the first half of 2021. Report initial 30-day safety and biomarker data in late 2021 or early 2022.|
|●||Initiate Phase 1/2 trial for PBFT02 for the treatment of FTD-GRN in the first half of 2021. Report initial 30-day safety and biomarker data in late 2021 or early 2022.|
|●||Continue to advance preclinical programs for PBML04 (Metachromatic leukodystrophy), PBAL05 (Amyotrophic lateral sclerosis) and PBCM06 (Charcot-Marie-Tooth Disease Type 2A), and an undisclosed adult CNS program.|
Fourth Quarter and Full Year 2020 Financial Results
|●||Cash Position: Cash, cash equivalents and marketable securities were $304.8 million as of December 31, 2020 as compared to $158.9 million as of December 31, 2019. In January of 2021, the company raised an additional $166 million in net proceeds from a public offering.|
|●||Research and Development (R&D) Expenses: R&D expenses were $27.9 million for the quarter and $81.8 million for the full year ended December 31, 2020, compared to $10.0 million and $29.7 million for the same quarter and year in 2019.|
|●||General and Administrative (G&A) Expenses: G&A expenses were $10.1 million for the quarter and $30.1 million for the full year ended December 31, 2020, compared to $3.6 million and $7.0 million for the same quarter and year in 2019.|
|●||Net Loss: Net loss was $38.9 million, or a net loss of $0.85 per basic and diluted share, for the quarter and $112.2 million, or a net loss of $2.91 per basic and diluted share, for the year ended December 31, 2020, compared to $13.2 million, or a net loss of $3.07 per basic and diluted share, for the quarter and $45.6 million, or a net loss of $10.77 per basic and diluted share, for the year ended December 31, 2019.|
Conference Call Details
Passage Bio will host a conference call and webcast today at 8:30 a.m. ET. To access the live conference call, please dial 833-528-0605 (domestic) or 830-221-9711 (international) and reference conference ID number 6758094. A live audio webcast of the event will be available on the Investors & Media section of Passage Bio’s website at investors.passagebio.com. The archived webcast will be available on Passage Bio's website approximately two hours after the completion of the event and for 30 days following the call.
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 unparalleled 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.
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 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 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, Inc.
(in thousands, except share data)
Cash and cash equivalents
Prepaid research and development
Total current assets
Liabilities, convertible preferred stock and stockholders’ equity (deficit)
Accrued expenses and other current liabilities
Total current liabilities
Convertible preferred stock, $0.0001 par value:
Series A‑1 convertible preferred stock: 63,023,258 shares authorized, issued and outstanding at December 31, 2019
Series A‑2 convertible preferred stock: 22,209,301 shares authorized; issued and outstanding at December 31, 2019
Series B convertible preferred stock: 33,592,907 shares authorized, issued and outstanding at December 31, 2019
Total convertible preferred stock
Commitments and Contingencies (note 7)
Stockholders’ equity (deficit):
Common stock, $0.0001 par value: 300,000,000 shares authorized; 45,917,084 shares issued and 45,614,807 shares outstanding at December 31, 2020 and 5,194,518 shares issued and 4,293,039 shares outstanding at December 31, 2019
Additional paid‑in capital
Accumulated other comprehensive loss
Total stockholders’ equity (deficit)
Total liabilities, convertible preferred stock and stockholders’ equity (deficit)
Statements of Operations and Comprehensive Loss
Three Months Ended December 31,
Year Ended December 31,
(in thousands, except share and per share data)
Research and development
Acquired in‑process research and development
General and administrative
Loss from operations
Change in fair value of future tranche right liability
Interest income, net
Per share information:
Net loss per share of common stock, basic and diluted
Weighted average common shares outstanding, basic and diluted
Unrealized loss on available-for-sale securities
Corporate Presentation March 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 of, the Private Securities Litigation Reform Act of 1995, including, but not limited to: our expectation about timing and execution of anticipated milestones, including our planned initiation of clinical trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; estimates regarding our cash forecasts; the expected impact of the COVID-19 pandemic on our operations; and the ability of our lead product candidates to treat 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, obtain regulatory approval for and commercialize PBGM01, PBFT02, PBKR03 and future product candidates; the timing and results of preclinical studies and clinical trials; 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; 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; failure to protect and enforce our intellectual property, and other proprietary rights; failure to successfully execute or realize the anticipated benefits of our strategic and growth initiatives; risks relating to technology failures or breaches; our dependence on collaborators and other third parties for the development 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; risks associated with current and potential future healthcare reforms; risks relating to attracting and retaining key personnel; failure to comply with legal and regulatory requirements; risks relating to access to capital and credit markets; and the other risks and uncertainties that are described in the Risk Factors section of our most recent filings with the U.S. Securities and Exchange Commission. These statements are based on our current beliefs and expectations and speak only as of the date of this presentation. We do not undertake any obligation to publicly update any forward-looking statements except as required by law. By attending or receiving this presentation you acknowledge that you are cautioned not to place undue reliance on these 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 potential 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 CNS1 790+ are rare monogenic CNS diseases with few treatment options2 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. Market research conducted by Health Advances 80% of rare diseases have a genetic component1 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 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 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 5
Passage Bio’s Differentiated Path for Clinical Success 17 program license options from GTP focused on rare monogenic CNS disorders 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 6
PROGRAM1 GENE DISCOVERY CANDIDATE SELECTION IND-ENABLING PHASE 1/2 PIVOTAL PEDIATRIC PBGM012 GM1 Gangliosidosis GLB1 PBKR03 Krabbe GALC PBML04 Metachromatic Leukodystrophy ARSA PBCM06 Charcot-Marie-Tooth Type 2A MFN2 ADULT PBFT02 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 1 10 additional new pipeline license options 2 Program includes ongoing natural history study of infantile and juvenile GM1 gangliosidosis patients 7
PBGM01 GM1 Gangliosidosis
GM1 Gangliosidosis: A Devastating Pediatric Disease 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. 9
PBGM01 Potential Transformative Therapy For 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, MHRA and Health Canada 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 Source: NIH, CHOP, American Journal of Neuroradiology 10
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 11
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 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 12
Pathway to Patient Identification and Trial Recruitment 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 13
Goal of 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 14 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 • Hypotonia • Neurodegeneration • Developmental regression • Seizures • Skeletal dysplasia • Survival: <2 years without supportive care Type IIa (Late-Infantile) • Onset 6-24 months • Developmental plateau, followed by regression • Impaired ambulation • Impaired 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 Adapted from Regier DS, et al. 2016 GLB-1 Disorders, In Adam MP, et al. GeneReviews.
Imagine-1 Global Phase 1/2 Trial with PBGM01 First patient enrollment expected in 1Q21 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 planned for mid-2021 Duration ◼ Two years, with rollover into a separate long-term follow-up study Primary Endpoints ◼ Safety and tolerability ◼ Efficacy COHORT 4 Early Infantile n = 2 DOSE 2 DOSE 1 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 IDMC review 15
PBKR03 Krabbe Disease
Krabbe Lysosomal Storage Disease PBKR03 — A potential transformative therapy for a rare, underserved disorder 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 ▪ PBKR03-treated Krabbe dogs had 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 and positive opinion by EMA adopted for Orphan Drug Disease designation ▪ Received FDA IND clearance for phase 1/2 clinical trial ▪ Clinical trial initiation in 1H21 Infantile Krabbe PBKR03 17
PBKR03 Disease Model Data – Twitcher Mouse and Dog Models Meaningful brain and peripheral transduction with improved pathophysiology and function 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) 20,000 15,000 10,000 0 5,000 +/+ twi/twi twi/twi PBS GTP-206 Brain PBKR03 GALC Activity (FU/50 µg) 2,000 1,500 0 500 +/+ twi/twi twi/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 Supported by Data From Canine Disease Model Survival Extended by AAV Treatment Euthanized due to disease progression Euthanized as planned per protocol Euthanized for seizure (K937) and weight loss (K993) Myelination Improvement in CNS and PNS Brain Peripheral Nerves Animal ID Average Severity Score (Grade 1 - 4) Vehicle AAV WT Vehicle AAV All AAV-treated dogs had improvement in CNS and peripheral nerve myelination compared to sham-treated controls, with nerve conduction velocities comparable to wild type dogs (data not shown), supporting advancing PBKR03 into clinical trial development. 19
COHORT 2 4m to < 9m n = 3 COHORT 3 >1 to < 4m of age n = 3 COHORT 1 >4m to < 9m n = 3 PBKR03 Global Phase 1/2 Trial in Early Infantile Krabbe Disease First patient enrollment expected in 1H21 Trial Design ◼ Phase 1/2, multi-center, open-label, single-arm, dose-escalation and confirmatory study of PBKR03 in patients with early infantile Krabbe disease who are >1 to 9 months of age at enrollment ◼ Separate dos- escalation cohorts based on age at enrollment ◼ Dosing initially in subjects >4 to < 9 months of age, with initiation of dosing in subjects >1 to 4 months of age gated by safety in cohort 1 Intervention ◼ Single ICM dose of AAVhu68.CB7.CI.hGALCco.rBG (PBKR03) First Read Out ◼ 30-day safety and biomarker data of cohort 1 to planned for late 2021 or early 2022 Duration ◼ 2 years; with additional 3 years of follow-up for safety and durability of effect Primary Endpoints ◼ Safety and tolerability ◼ Efficacy IDMC review Confirmatory Cohort >1 to < 4m n = 6 20 Confirmatory Cohort 4m to < 9m n = 6 COHORT 4 >1 to < 4m n = 3 DOSE 2 DOSE 1
PBFT02 Frontotemporal Dementia - GRN
FTD-GRN Frontotemporal Dementia Caused by Progranulin Deficiency PBFT02 – A potential transformative therapy for a rare, underserved disorder 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 FTD-GRN 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 ▪ Increases in CSF PGRN concentrations in NHP studies to >50-fold normal human CSF PGRN concentrations ▪ Received FDA Orphan Drug and Fast Track designations ▪ Received FDA IND approval for phase 1/2 clinical trial ▪ Clinical trial initiation in 1H21 FTD-GRN PBFT02 22
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 23
PBFT02 Supportive NHP Preclinical Studies Utilizing ICM PBFT02 Showed Dose-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 20 30 40 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 R A3155 RA3160 A A V hu 68 A A V hu 68 (v 2) AAV1 AAV5 RA2981 RA2982 RA3027 RA3153 RA3151 RA3170 R A3155 RA3160 A A V hu 68 A A V hu 68 (v 2) 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 A single administration of PBFT02 to NHPs via the optimized AAV1-GRN vector demonstrated transduction broadly across the brain, including a very high transduction of ependymal cells that line the ventricles of the brain and are involved with CSF production, resulting in CSF progranulin levels of more than 50-fold normal. 24
PBFT02 Global Phase 1/2 Trial in Early Symptomatic FTD-GRN First patient enrollment expected in 1H21 Trial Design ◼ Phase 1/2, multicenter, open-label, single-arm, dose escalation study of PBFT02 in early symptomatic adult subjects with frontotemporal dementia and mutations in the progranulin gene Intervention ◼ Single ICM dose of AAVh1.hPGRN (PBFT02) First Read Out ◼ 30-day safety and biomarker data of cohort 1 to be reported late 2021 or early 2022 Duration ◼ 2 years; with additional 3 years of follow-up for safety and durability of effect Primary Endpoints ◼ Safety and tolerability ◼ Efficacy COHORT 2 n = 3 (60 days between subject enrollment) COHORT 1 n = 3 (60 days between subject enrollment) OPTIONAL COHORT 3 n = 3 (60 days between subject enrollment) OPTIONAL DOSE 3 IDMC review DOSE 2 DOSE 1 25
Manufacturing That is Dedicated, Flexible, and Scalable In-House CMC Capabilities Investment in CMC laboratory with state-of-the-art technologies for analytical and process development, clinical product testing, and clinical and biomarker assay development 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 27
Corporate Foundation 28 SOURCE: www.brandywinerealty.com
Financial Summary Cash balance of $305M at 12/31/20 Raised additional $166M in net proceeds in 1/21 Cash on hand to fund operations for at least 24 months Runway to potentially deliver meaningful catalysts over multiple programs 29
Anticipated Upcoming Milestones 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, and undisclosed adult indication ADVANCE Evaluate and expand pipeline by pursuing new licenses in partnership with Penn’s GTP BUILD INITIATE PBGM01 safety and biomarker data mid-2021 REPORT PBFT02 safety and biomarker data end of 2021 or early 2022 REPORT PBKR03 safety and biomarker data end of 2021 or early 2022 REPORT GM1 FTD-GRN KRABBE PIPELINE ADVANCEMENT Phase 1/2 trial for PBKR03 in patients with early infantile Krabbe disease in 1H21 30
The Passage Bio Advantage Corporate model designed for success 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 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 31
www.passagebio.com NASDAQ GS: PASG THANK YOU
Demonstrated Leadership Deep experience in rare disease, CNS disorders and gene therapy LEADERSHIP TEAM BOARD OF DIRECTORS Tachi Yamada, M.D. (Chair) Frazier Athena Countouriotis, M.D. Turning Point Bruce Goldsmith, Ph.D. Passage Bio Maxine Gowen, Ph.D. Tamuro Bio Patrick Heron Frazier Saqib Islam, J.D. SpringWorks Sandip Kapadia Intercept Liam Ratcliffe, M.D., Ph.D. Access Industries 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 33
Cutting-Edge Gene Therapy R&D Collaboration 17 program license options for Passage Bio focused on rare monogenic CNS disorders 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 34