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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): November 13, 2024

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.)

One Commerce Square
2005 Market Street, 39th 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

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 2.02 Results of Operations and Financial Condition.

On November 13, 2024, Passage Bio, Inc. (the “Company”) issued a press release announcing its financial results for the quarter ended September 30, 2024. 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 November 13, 2024, the Company updated its corporate presentation. A copy of the corporate presentation is attached as Exhibit 99.2 to this Current Report on Form 8-K.

The information in this Item 7.01, including Exhibit 99.2 to this Current Report on Form 8-K, 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.

Item 9.01 Financial Statements and Exhibits.

(d)Exhibits

Exhibit No.

Description

99.1

Press release issued by Passage Bio, Inc. regarding its financial results for the quarter ended September 30, 2024, dated November 13, 2024.

99.2

Corporate Presentation.

104

Cover Page Interactive Data File (formatted as Inline XBRL).

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: November 13, 2024

By:

/s/ Kathleen Borthwick

Kathleen Borthwick

Chief Financial Officer

3

Graphic Ex 99.1

PASSAGE BIO REPORTS THIRD QUARTER 2024 FINANCIAL RESULTS AND PROVIDES RECENT BUSINESS HIGHLIGHTS

Enrolled 4 patients in Cohort 2 of the upliFT-D trial for FTD-GRN, with patient dosing advancing as planned; 12-month Cohort 1 and interim Cohort 2 data expected in 1H25

Updated interim data from Cohort 1 FTD-GRN showed PBFT02 was generally well-tolerated and elevated CSF progranulin levels for up to 12 months following treatment

Highlighted robust preclinical data supporting PBFT02 as a potential best-in-class progranulin-raising therapy in an oral presentation at ESGCT

Execution backed by strong balance sheet, with cash runway to the end of Q2 2026

PHILADELPHIA – November 13, 2024 – Passage Bio, Inc. (Nasdaq: PASG), a clinical stage genetic medicines company focused on improving the lives of patients with neurodegenerative diseases, today reported financial results for the third quarter ended September 30, 2024 and provided recent business highlights.

“This quarter, we’ve made important strides in advancing our PBFT02 gene therapy program,” said Will Chou, M.D., president and chief executive officer of Passage Bio. “Execution of our ongoing upliFT-D trial for FTD-GRN remains our core priority, and we are pleased to share that 4 patients in Cohort 2 have been enrolled, with patient dosing progressing as planned. We remain on track to share 12-month Cohort 1 and interim Cohort 2 data in the first half of 2025, which will strengthen our understanding of the therapeutic potential of PBFT02. Furthermore, our presentations of preclinical and positive interim safety and biomarker data at key scientific conferences underscore the potential of PBFT02 to be a market leading progranulin-raising therapy. Our commitment to disciplined execution and a strong balance sheet strategically position us to achieve several key milestones over the coming quarters.”


Graphic Ex 99.1

Recent Highlights

Sustained enrollment progress in global Phase 1/2 upliFT-D trial of PBFT02 for the treatment of patients with FTD-GRN: The company has enrolled 4 patients in Cohort 2, which will continue to evaluate Dose 1 of PBFT02, and patient dosing is underway and advancing as planned. With this momentum, the company remains on track to report 12-month data from Cohort 1 and interim data from Cohort 2 in 1H25.

Presented encouraging interim data from Cohort 1 patients in upliFT-D trial of PBFT02 for FTD-GRN at the ISFTD2024 and CTAD conferences: The company presented updated safety and biomarker data from Cohort 1 patients in the upliFT-D trial during an oral presentation at the International Conference on Frontotemporal Dementias (ISFTD2024) conference in September and a poster session at the Clinical Trials on Alzheimer’s Disease conference (CTAD) in October. The data showed that PBFT02 produced consistent and durable increases in CSF PRGN expression in all treated Cohort 1 patients, with elevated levels maintained for up to one-year post-treatment. Furthermore, PBFT02 continued to exhibit a favorable safety profile in all patients who received the enhanced immunosuppression regimen, with no serious adverse events or clinically significant immune responses observed.

Presented preclinical and interim clinical data for PBFT02 in FTD-GRN at the ESGCT conference: In October, the company delivered an oral presentation highlighting preclinical data for PBFT02 at the European Society of Gene & Cell Therapy (ESGCT) conference. The presentation reviewed the robust preclinical findings informing vector and dose selection and demonstrated the positive effects of elevating progranulin levels in vivo. Preclinical non-human primate (NHP) data found the AAV1 vector achieved superior human progranulin levels in the CSF compared to AAV5 and AAVhu68 (an AAV9 variant). Additionally, a dose escalation study in Grn knockout mice showed that PBFT02 improved lysosomal histopathology and reduced neuroinflammation in brain regions impacted by FTD pathology with evidence suggesting that the greatest pathological benefit was associated with the highest PGRN levels in the CSF. An NHP biodistribution study also showed that intra-cisterna magna (ICM) administration of PBFT02 resulted in widespread vector distribution in the brain and spinal cord.

Appointed Tom Kassberg to the company’s board of directors: In September, the company announced the appointment of Tom Kassberg, Chief Business Officer and Executive Vice President at Ultragenyx, to its board of directors and his appointment to the Audit Committee. Mr. Kassberg brings extensive experience in corporate development and strategic planning to the company, having successfully led multiple business development and alliance management initiatives that advanced late-stage gene therapies for rare diseases.


Graphic Ex 99.1

Anticipated Upcoming Milestones:

FTD-GRN

Report 12-month Cohort 1 and interim Cohort 2 data in 1H 2025
Seek regulatory feedback on pivotal trial design in 2H 2025

FTD-C9orf72 

Initiate dosing of FTD-C9orf72 patients in 1H 2025

ALS

Obtain regulatory feedback on the pathway to treating amyotrophic lateral sclerosis (ALS) patients with PBFT02 in 2H 2024

Third Quarter 2024 Financial Results

Cash Position: Cash, cash equivalents and marketable securities were $84.8 million as of September 30, 2024, as compared to $132.8 million as of September 30, 2023. The company expects current cash, cash equivalents and marketable securities, together with the remaining initial payments from our out-licensing agreements with GEMMA Biotherapeutics, to fund operations to the end of Q2 2026.
Research and Development (R&D) Expenses: R&D expenses were $8.7 million for the quarter ended September 30, 2024, as compared to $15.1 million for the quarter ended September 30, 2023.
General and Administrative (G&A) Expenses: G&A expenses were $7.3 million for the quarter ended September 30, 2024, as compared to $8.2 million for the quarter ended September 30, 2023.
Net Loss: Net loss was $19.3 million, or $0.31 per basic and diluted share, for the quarter ended September 30, 2024, as compared to a net loss of $27.1 million, or $0.49 per basic and diluted share, for the quarter ended September 30, 2023.


Graphic Ex 99.1

About Passage Bio

Passage Bio (Nasdaq: PASG) is a clinical stage genetic medicines company on a mission to improve the lives of patients with neurodegenerative diseases. Our primary focus is the development and advancement of cutting-edge, one-time therapies designed to target the underlying pathology of these conditions. Passage Bio’s lead product candidate, PBFT02, seeks to treat neurodegenerative conditions, including frontotemporal dementia, by elevating progranulin levels to restore lysosomal function and slow disease progression. 

To learn more about Passage Bio and our steadfast commitment to protecting patients and families against loss in neurodegenerative conditions, please visit: 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 the initiation of dosing of FTD-C9orf72 patients, feedback from regulatory authorities, the progress of clinical studies and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; our ability to receive milestone and other payments from our partners; our expectations about cash runway; and the ability of our product candidates to treat their respective target 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; 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.


Graphic Ex 99.1

Passage Bio, Inc.

Balance Sheets

(Unaudited)

(in thousands, except share and per share data)

    

September 30, 2024

    

December 31, 2023

Assets

 

  

 

  

Current assets:

 

  

 

  

Cash and cash equivalents

$

32,292

$

21,709

Marketable securities

52,534

92,585

Prepaid expenses and other current assets

 

1,210

 

923

Prepaid research and development

 

1,180

 

2,742

Total current assets

 

87,216

 

117,959

Property and equipment, net

 

10,036

 

15,295

Right of use assets - operating leases

14,037

 

16,858

Other assets

 

463

 

433

Total assets

$

111,752

$

150,545

Liabilities and stockholders’ equity

 

 

  

Current liabilities:

 

 

  

Accounts payable

$

1,489

$

1,298

Accrued expenses and other current liabilities

 

6,729

 

11,670

Non-refundable sublicense payments received

5,000

Operating lease liabilities

3,733

 

3,373

Total current liabilities

 

16,951

 

16,341

Operating lease liabilities - noncurrent

 

22,085

 

22,921

Total liabilities

 

39,036

 

39,262

Stockholders’ equity:

 

 

  

Preferred stock, $0.0001 par value: 10,000,000 shares authorized; no shares issued and outstanding at both September 30, 2024 and December 31, 2023

Common stock, $0.0001 par value: 300,000,000 shares authorized; 61,767,286 shares issued and outstanding at September 30, 2024 and 54,944,130 shares issued and outstanding at December 31, 2023

 

6

 

5

Additional paid-in capital

 

719,188

 

705,789

Accumulated other comprehensive income (loss)

32

(43)

Accumulated deficit

 

(646,510)

 

(594,468)

Total stockholders’ equity

 

72,716

 

111,283

Total liabilities and stockholders’ equity

$

111,752

$

150,545


Graphic Ex 99.1

Passage Bio, Inc.

Statements of Operations and Comprehensive Loss

(Unaudited)

Three Months Ended September 30, 

Nine Months Ended September 30, 

(in thousands, except share and per share data)

    

2024

    

2023

2024

    

2023

Operating expenses:

 

  

 

  

  

 

  

Research and development

$

8,656

$

15,098

$

30,621

$

49,258

General and administrative

 

7,251

 

8,184

 

20,276

 

35,295

Impairment of long-lived assets

4,795

5,390

5,233

5,390

Loss from operations

 

(20,702)

 

(28,672)

 

(56,130)

 

(89,943)

Other income (expense), net

 

1,362

 

1,562

 

4,088

 

4,639

Net loss

$

(19,340)

$

(27,110)

$

(52,042)

$

(85,304)

Per share information:

 

  

 

 

  

 

  

Net loss per share of common stock, basic and diluted

$

(0.31)

$

(0.49)

$

(0.87)

$

(1.56)

Weighted average common shares outstanding, basic and diluted

 

61,763,346

 

54,789,410

 

59,920,537

 

54,697,967

Comprehensive loss:

Net loss

$

(19,340)

$

(27,110)

$

(52,042)

$

(85,304)

Unrealized gain (loss) on marketable securities

99

148

75

774

Comprehensive loss

$

(19,241)

$

(26,962)

$

(51,967)

$

(84,530)

For further information, please contact:

Investors:

Stuart Henderson

Passage Bio

267.866.0114

shenderson@passagebio.com

Media:

Mike Beyer
Sam Brown Inc. Healthcare Communications
312.961.2502
MikeBeyer@sambrown.com 


Exhibit 99.2

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Nasdaq: PASG © 2024 Passage Bio. All rights reserved. Corporate Presentation November 2024

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2 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 expectations about timing and execution of anticipated milestones, including the initiation of dosing of FTD-C9orf72 patients, feedback from regulatory of authorities, the progress of clinical studies and the availability of clinical data from such trials; our expectations about our collaborators’ and partners’ ability to execute key initiatives; our ability to receive milestone payments from our partners; our expectations about cash runway; and the ability of our product candidates to treat their respective target 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; 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.

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3 REDEFINING THE COURSE OF NEURODEGENERATIVE CONDITIONS Advancing potential best-in-class, one-time progranulin raising FTD-GRN gene therapy In-house manufacturing process development to support program execution Strong cash position with runway expected to the end of 2Q 2026* Exploring benefits of elevated progranulin in multiple adult neurodegenerative diseases * Based on cash, cash equivalents and marketable securities as of September 30, 2024 and initial proceeds from out-licensing of pediatric programs.

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4 Validating the Therapeutic Potential of PBFT02 Promising data from initial clinical study of PBFT02 in FTD-GRN Genetic form of FTD caused by GRN mutations, which lead to progranulin (PGRN) deficiency No approved disease-modifying therapies One-time therapy Proprietary AAV1 construct Nonsurgical injection directly to cerebrospinal fluid (CSF) Durable, elevated CSF PGRN levels* Urgent Patient Need in FTD-GRN Differentiated, Potential Best-in-Class Profile Fast Track and Orphan Drug Designation * Based on interim data.

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5 Significant Market Opportunity for PBFT02 Across Multiple Neurodegenerative Diseases ~18,000 ~21,000 ~72,600 ~3.9M FTD-GRN1–3 FTD-C9orf722–4 AMYOTROPHIC LATERAL SCLEROSIS (ALS) 5–6 ALZHEIMER’S DISEASE (GRN SNP)*7–8 * rs5848 single nucleotide polymorphism (SNP) 1. Greaves CV, et al. J Neurol 2019; 266:2075-2086. 2. Galvin JE, et al. Neurology 2017; 89:2049-2056. 3. Onyike CU, et al. Int Rev Psychiatry 2013; 25:130-137. 4. Moore KM, et al. Lancet Neurol 2020; 19: 145–156. 5. Brown et al. Neuroepi 2021; 55:342-353. 6. CDC ALS Registry Dashboard. 7. Sheng J, et al. Gene 2014; 141-145. 8. Alz Assoc. 2023 Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2023;19. Estimated Prevalence (US and EU)

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6 Anticipated Upcoming Milestones and Data Readouts 2H 2024 1H 2025 2H 2025 Obtain regulatory feedback on the pathway to treating ALS patients Report 12-month Cohort 1 and interim Cohort 2 data FTD-C9orf72 and ALS Milestones Initiate dosing of FTD-C9orf72 patients Seek regulatory feedback on pivotal trial design FTD-GRN Milestones

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PBFT02 Frontotemporal Dementia-GRN

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8 FTD: A Devastating Adult Disease OVERVIEW • Fatal adult-onset neurodegenerative disease affecting the frontal and temporal lobes of the brain, characterized by a decline in behavior, language and executive function • One of the most common causes of early-onset dementia worldwide, disproportionately affecting individuals aged 40-65 years CLINICAL SYMPTOMS Disease progression is rapid and degenerative, including loss of speech, loss of expression, behavioral changes and immobility On average, people with FTD live 8 years after the onset of symptoms

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9 Progranulin Deficiency is the Defining Characteristic of FTD-GRN and Leads to Neurodegeneration Progranulin is critical to maintaining CNS cell homeostasis Rhinn H et al. Trends Pharm Sci. 2022, 43:641-652.

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10 Elevated PGRN Increases Potential for Improved Cellular Function • Progranulin is a secreted protein that binds to cell membrane receptors to affect multiple intracellular pathways –Major role is regulating intracellular lysosomal activity –Extracellular PGRN is endocytosed via multiple receptors • Driving elevated PGRN levels in the extracellular space increases the amount of PGRN available to enter target CNS cells • Able to leverage cross-correction mechanism: secreted PGRN can be taken up by non-transduced cells Paushter et al., Acta Neuropathol. 2018;136(1):1-17., Rhinn et al., Trends in Pharmacological Sciences 2022; 43.8:641-652.

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11 Preclinical NHP: AAV1 Achieved the Highest Levels of CSF PGRN • AAV1 resulted in superior CSF hPGRN levels, 5x higher than AAV5 and AAVhu68 (an AAV9 variant) vectors, after ICM administration Rhesus macaques (n=2/gp) ICM-delivered AAV.hPGRN (3.3 x 1011 GC/g brain), day 0 Size and duration of elevation muted by immune response to human PGRN. * Decrease in PGRN levels due to NHP antibody response to human PGRN Shading: Reference range for healthy adult controls’ CSF PGRN, n = 61 (Passage Bio data) Reference: Hinderer et al., Annals Clin Trans Neurology. 2020 Human PGRN in NHP CSF Vector Comparison BL 0 7 14 21 28 35 0 10 20 30 40 50 60 70 80 Human PGRN in NHP CSF Vector Comparison Days hPGRN (ng/mL) AAV1.CB7.hPGRN AAV5.CB7.hPGRN AAVhu68.CB7.hPGRN AAVhu68.UbC.hPGRN Healthy adult range *

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12 LLoQ Brain Spinal Cord DRG, TRG Preclinical NHP: ICM Administration of PBFT02 Led to Broad Distribution of Vector Throughout Brain/Spinal Cord Vector Biodistribution in NHPs 90 days post-ICM PBFT02 • Robust, dose-dependent vector delivery to cortical and sub-cortical brain regions affected in FTD • NHP Dose 1, equivalent to clinical Dose 1 of PBFT02 in upliFT-D study, resulted in ~10⁴ GC/μg DNA in all sampled areas throughout the brain n=3/gp. Data are mean +/- SEM. Abbreviations: CBL, cerebellum; Cerv, cervical; DRG, dorsal root ganglion; FCX, frontal cortex; GC, genome copies; Hipp, hippocampus; LLoQ, lower limit of quantitation; Lumb, lumbar; OCX, occipital cortex; PCX, parietal cortex; TCX, temporal cortex; Thor, thoracic; VEH, vehicle

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13 Preclinical Grn–/– Mice: hPGRN Delivery Improved Lysosomal Dysfunction and Neuroinflammation in the Brain Greatest pathological benefit was associated with the highest PGRN levels in the CSF Lipofuscin deposition and microglial activation are hallmark pathologies seen in FTD; Improvements in both measures were seen in cerebral cortex, thalamus, and hippocampus Grn–/– and WT mice (n=14-15/gp) ICV-administered PBFT02 or vehicle (V). Baseline controls are untreated mice on Day 1. Bars: mean +/- SEM. # ## p < 0.01, ### p < 0.005 vs WT control; *p < 0.05, ***p < 0.005 vs GRN-/-+ V , one-way ANOVA followed by Tukey’s multiple comparisons test. Abbreviations; GRN, granulin gene; ICV, Intra-cerebroventricular; PGRN, progranulin; WT, wildtype PBFT02 reduced lipofuscin deposition at all doses, suggesting improved lysosomal dysfunction Dose-dependent elevations in CSF PGRN after PBFT02 led to progressive reductions in microglial activation Thalamus Lipofuscin Thalamus CD68 Immunohistochemistry - - Veh Veh 1 2 3 4 0 200 400 600 800 1000 Lipofusc ni Count WT Dose 1 Dose 2 Dose 3 Dose 4 GRN-/- WTV PBFT02 Baseline GRN-/- Day 90 V PBFT02 ### ### *** *** *** * Thalamus Lipofuscin - - Veh Veh 1 2 3 4 0 1000 2000 3000 4000 5000 CD68 Area (μm2 ) WT Dose 1 Dose 2 Dose 3 Dose 4 GRN-/- WTV PBFT02 Baseline GRN-/- Day 90 V PBFT02 ## ### *** Thalamus CD68 Immunohistochemistry *** *

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14 upliFT-D: Global Phase 1/2 Trial with PBFT02 DURATION 2 years; with additional 3 years of follow-up for safety and durability of effect PRIMARY ENDPOINTS Safety and tolerability SECONDARY ENDPOINTS Biomarkers • Progranulin (CSF, plasma) • GFAP (CSF, plasma) • vMRI • Retinal nerve fiber layer and retinal lipofuscin deposits via OCT • NfL (CSF, plasma) Clinical • CDR + NACC FTLD sum of boxes EXPLORATORY BIOMARKERS • Cathepsin D (CSF) • LAMP 1 (CSF) • Lys-GL1 (CSF) COHORT 1 Dose 1 (3.3e10 GC/g)* COHORT 2 Dose 2 (1.1e11 GC/g)* OPTIONAL COHORT 3 Optional dose 3 Recruiting IDMC review Phase 1/2 Multicenter Open-label Dose escalation study Up to 15 patients across 3 cohorts 1/2 TRIAL DESIGN COHORT 1 (n=5) Dose 1 COHORT 2 (n=5) Dose 1 COHORT 3 (n=3-5) IDMC review Phase Multicenter Open-label Dose escalation study Up to 15 patients across 3 cohorts 1/2 Complete Dose 1: 3.3e10 GC/g estimated brain weight.

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15 Intra-Cisterna Magna (ICM) Administration • Directly deliver vector into the CSF via a single injection to reach both CNS and peripheral tissues1 –Allows for broad CNS biodistribution –Lower doses compared to IV systemic delivery –Reduced impact of neutralizing antibodies • Brief (<60 min), non-surgical, CT-guided procedure to allow for precise delivery to the cisterna magna –Procedure avoids penetration of brain tissue Cisterna magna 1. Hinderer et. al, Human Gene Therapy. 2018 Jan; 29(1):15-24​.

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16 upliFT-D: Interim Data from Cohort 1 Patients • PBFT02 was well-tolerated among the four patients (P2-5) who received revised immunosuppression regimen** –Among these patients, there were no SAEs; only mild-to-moderate treatment emergent AEs were reported • No evidence of DRG toxicity, as measured by nerve conduction studies • No complications during ICM administration observed Safety* Efficacy / Target Engagement • Interim data demonstrates PBFT02 potential for best-in-class efficacy at Dose 1 • Relative to baseline, PBFT02 increased CSF PGRN expression in all patients consistently; up to 6-fold at Day 30 (n=5) and up to 10-fold at Day 180 (n=2) • CSF PGRN levels remained elevated at Day 360 (n=1) SAE: serious adverse event; AE: adverse event; DRG: dorsal root ganglion; ICM: intra-cisterna magna *Patient safety follow-up ranged from 2 to 12 months post-dosing as of data cutoff of August 20, 2024 **Patient 1 received oral prednisone 60 mg daily through day 60 and had two SAEs (hepatotoxicity and venous sinus thrombosis); subsequent patients received a revised immunosuppressive regimen of 1g methylprednisolone IV daily to day 3, followed by oral prednisone 60 mg to day 60, then taper

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17 • Potential best-in-class PGRN profile at Dose 1 • Continued elevation of CSF PGRN at 6-months (n=2) and 12-months (n=1) –Patient 2 rate of increase slowed between Day 180 and 360 (D30-180: 58% vs. D180-360: 26%) • Consistent response across all treated patients Initial Patients Treated with PBFT02 Have Seen a Substantial Increase in CSF PGRN Dosing D30 D60 D180 D360 Patient 1 1.9 12.7 N/A N/A N/A Patient 2 2.8 17.3 N/A 27.3 34.2 Patient 3 2.9 10.7 13.7 21.7 Patient 4 2.2 12.3 N/A Patient 5 2.3 13.6 N/A CSF Progranulin (ng/mL) Shading: Reference range for healthy adult controls’ PGRN levels in CSF (range: 3.28 – 8.15 ng/mL, mean: 4.76 ng/mL, n = 61) (Passage Bio data) CSF=Cerebrospinal fluid 0 3 6 9 12 15 18 21 24 27 30 33 36 0 30 60 180 360 CSF PGRN, ng/mL Time (days) Dose 1 Progranulin, CSF Patient 1 Patient 2 Patient 3 Patient 4 Patient 5

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18 • Plasma PGRN levels remained below normal levels at up to 12 months post-dose • PGRN increased only in the CSF, where it has potential to correct neurodegeneration Plasma PGRN Levels Remained Below Normal Levels Post-Dose Shading: Lower limit of normal reference range for healthy adult controls’ PGRN levels in plasma (91.6 – 372.4 ng/mL, n = 56) (Passage Bio data) 0 10 20 30 40 50 60 70 80 90 100 0 7 14 30 60 90 180 360 Plasma PGRN, ng/mL Time (days) Dose 1 Progranulin, Plasma Patient 1 Patient 2 Patient 3 Patient 4 Patient 5

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19 Summary SAFETY1 PBFT02 Dose 1 generally well-tolerated to date among the four Cohort 1 patients who received revised steroid regimen following protocol amendment • No serious AEs • All AEs mild to moderate in intensity • No evidence of clinically significant immune response, hepatotoxicity or venous sinus thrombosis • No evidence of DRG toxicity • No complications during ICM administration observed BIOMARKERS • Potential best-in-class PGRN profile at Dose 1 • Continued elevation of CSF PGRN at 6-months (n=2) and 12-months (n=1) • Consistent response across Cohort 1 patients (n=5) •No increase in plasma PGRN levels up to 12-months ANTICIPATED NEXT STEPS • Report 12-month Cohort 1 and interim Cohort 2 data in 1H 2025 • Seek regulatory feedback on pivotal trial design in 2H 2025 AEs=adverse events; ICM=intra-cisterna magna; DRG=dorsal root ganglia 1. Patient safety follow-up ranged from 2 to 12 months post-dosing as of data cutoff of August 20, 2024

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Looking Ahead

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21 PBFT02 has Potential to Correct Underlying Pathology in FTD-GRN, FTD-C9orf72 and ALS TDP-43 pathology is a hallmark of multiple neurodegenerative diseases1 • TDP-43 mislocalizes from nucleus to cytoplasm • Forms inclusion bodies associated with neurodegeneration 1. Rhinn H et al. Trends Pharm Sci. 2022, 43:641-652

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22 TDP-43 pathology due to lysosomal dysfunction (GRN/ TMEM106 double knockout, DKO) reduced by AAV.hPGRN1 Elevated PGRN Ameliorates TDP-43 Pathology in Preclinical Models AAV delivered hPGRN to DKO mouse brain TDP-43 pathology in DKO mice reduced by AAV.hPGRN Elevated PGRN reduced insoluble TDP-43 in mouse spinal cord Elevated PGRN extended survival of TDP-43 mutant mice Elevated PGRN ameliorated TDP-43 pathology and disease course in a preclinical model2 • Elevated PGRN also prevented degeneration of large axon fibers in TDP-43 mice • PGRN neuroprotection from pleiotropic effect, not single pathway 1. Reich et al. (2023) bioRxiv preprint 07.14.549089; 2. Beel et al (2018) Mol Neurodegen; Laird et al. (2010) Plos One. DKO=double gene knockout; GRN=granulin gene; PGRN=progranulin; TDP-43=transactive response DNA binding protein 43 kDa. † PGRN increased to >2x endogenous levels

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23 GRN rs5848 SNP associated with accelerated disease in FTD-C9orf72 patients Decreased PGRN Associated with Greater Disease Severity in Multiple CNS Conditions GRN rs5848 SNP associated with accelerated disease in FTD-C9orf72 patients 1. van Blitterswijk et al (2014) Mol Neurodegen. AD=Alzheimer’s disease; ALS=amyotrophic lateral sclerosis; GRN=granulin gene; PGRN=progranulin; SNP=single nucleotide polymorphism. PGRN SNPs are genetic risk factors for CNS diseases • GRN rs5848 SNP results in ~15% reduction in PGRN levels • PGRN SNPs increase risk for, and worsen severity of, FTD/ALS-C9orf72 and AD1

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24 • GRN SNP rs5848 carriers have reduced PGRN levels and increased risk for AD • AD patients with GRN SNP rs5848 show reduced PGRN levels and increased CSF tau • GRN SNP rs5848 is estimated to occur in 30% of the general population, with a similar prevalence rate among AD patients2 • PGRN ablation exacerbates AD pathology in mice • PGRN overexpression reduces pathology burden in AD models Genetic Risk1 Prevalence Supporting Preclinical Evidence3 PBFT02 has Potential to Modulate Alzheimer’s Disease SNP=single nucleotide polymorphism. Third-party preclinical data. Sources: 1. Chen Y et al. J Neurol. 2015, 262:814-22; Takahashi H et al. Acta Neuropathol. 2017, 133:785-807. 2. Fenoglio C et al. J Alzheimers Dis. 2009, 18:603-612 (allele frequency used to estimate prevalence among AD patients). 3. Hosokawa M et al. J Neuropath Exp Neurol. 2015, 74:158-65; Minami SS et al. Nat Med. 2014, 20:1157-64; Van Kampen JM & Kay DG. PLoS ONE 2017, 12:e0182896.

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25 Leading In-House CMC Capabilities to Support PBFT02 Development Proven analytical development capabilities In-House CMC Analytical Capabilities to Support Program Advancement and Future Commercialization of PBFT02 Integrated process development GMP QC capabilities Strong regulatory CMC scientific expertise Scale-up capability

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26 Upcoming Milestones and Corporate Updates PIPELINE • Advancing Huntington’s disease preclinical program BALANCE SHEET • Cash balance of $85 million as of 9/30/24* • Cash runway to the end of 2Q 2026* * Based on cash, cash equivalents and marketable securities and initial proceeds from out-licensing of pediatric programs. TIMING MILESTONE FTD-GRN 1H 2025 Report 12-month Cohort 1 and interim Cohort 2 data 2H 2025 Seek regulatory feedback on pivotal trial design PBFT02 Additional Indications 2H 2024 Obtain regulatory feedback on clinical pathway for treating ALS patients 1H 2025 Initiate dosing of FTD-C9orf72 patients

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27 REDEFINING THE COURSE OF NEURODEGENERATIVE CONDITIONS Advancing potential best-in-class, one-time progranulin raising FTD-GRN gene therapy In-house manufacturing process development to support program execution Strong cash position with runway expected to the end of 2Q 2026* Exploring benefits of elevated progranulin in multiple adult neurodegenerative diseases * Based on cash, cash equivalents and marketable securities as of September 30, 2024 and initial proceeds from out-licensing of pediatric programs.

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Thank You passagebio.com | NASDAQ: PASG

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29 Program Indication US/EU prevalence Discovery Preclinical Phase 1/2 Pivotal PBFT02 Frontotemporal dementia - GRN 18,0001-3 Frontotemporal dementia - C9orf72 21,0002-4 Amyotrophic lateral sclerosis 72,6005-6 Alzheimer’s disease with rs5848 SNP 3.9M7-8 Unnamed Huntington’s disease 60,0009 Focused Pipeline Addressing Rare and Prevalent Neurodegenerative Indications 1. Greaves CV, et al. J Neurol 2019; 266:2075-2086. 2. Galvin JE, et al. Neurology 2017; 89:2049-2056. 3. Onyike CU, et al. Int Rev Psychiatry 2013; 25:130-137. 4. Moore KM, et al. Lancet Neurol 2020; 19: 145–156. 5. Brown et al. Neuroepi 2021; 55:342-353. 6. CDC ALS Registry Dashboard. 7. Sheng J, et al. Gene 2014; 141-145. 8. Alz Assoc. 2023 Alzheimer’s Disease Facts and Figures. Alzheimers Dement 2023;19. 9. Crowell et al. Neuroepi. 2021; 55:361-368

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30 Demonstrated Leadership LEADERSHIP TEAM Deep experience in rare disease, CNS disorders and genetic medicines Eden Fucci SVP Technical Operations BOARD OF DIRECTORS Maxine Gowen, Ph.D. Chairwoman Athena Countouriotis, M.D. Avenzo Therapeutics Derrell Porter, M.D. cTRL Therapeutics Dolan Sondhi, Ph.D. Weill Cornell Medicine Sandip Kapadia Harmony Biosciences Saqib Islam, J.D. SpringWorks Thomas Kassberg Ultragenyx William Chou, M.D. President & Chief Executive Officer Stuart Henderson Chief Business Officer William Chou, M.D. President & Chief Executive Officer Chip Cale General Counsel & Corporate Secretary Kathleen Borthwick Chief Financial Officer Karl Whitney SVP Global Regulatory Affairs Sue Browne, Ph.D. Chief Scientific Officer

v3.24.3
Document and Entity Information
Nov. 13, 2024
Document and Entity Information [Abstract]  
Document Type 8-K
Document Period End Date Nov. 13, 2024
Entity File Number 001-39231
Entity Registrant Name PASSAGE BIO, INC.
Entity Incorporation, State or Country Code DE
Entity Tax Identification Number 82-2729751
Entity Address, Address Line One One Commerce Square
Entity Address, Adress Line Two 2005 Market Street, 39th Floor
Entity Address, City or Town Philadelphia
Entity Address, State or Province PA
Entity Address, Postal Zip Code 19103
City Area Code 267
Local Phone Number 866-0311
Written Communications false
Soliciting Material false
Pre-commencement Tender Offer false
Pre-commencement Issuer Tender Offer false
Title of 12(b) Security Common Stock, $0.0001 Par Value Per Share
Trading Symbol PASG
Security Exchange Name NASDAQ
Entity Emerging Growth Company true
Entity Ex Transition Period false
Entity Central Index Key 0001787297
Amendment Flag false

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