Passage Bio (NASDAQ: PASG) narrows 2025 loss and advances PBFT02 trial
Rhea-AI Filing Summary
Passage Bio reported fourth-quarter and full-year 2025 results and highlighted progress in its PBFT02 gene therapy program for frontotemporal dementia. The company enrolled the first three FTD-GRN patients in Cohort 3 and treated the first FTD-C9orf72 patient with Dose 2 PBFT02 in Cohort 4 of the upliFT-D study.
Net loss for 2025 was $45,522 thousand, narrowing from $64,767 thousand in 2024, as research and development expenses fell to $23,276 thousand from $40,179 thousand and general and administrative expenses declined to $19,875 thousand from $24,988 thousand. Cash and cash equivalents were $46,303 thousand at December 31, 2025, and the company projects a cash runway through the first quarter of 2027.
The upliFT-D Phase 1/2 trial continues to enroll FTD-GRN and FTD-C9orf72 patients, focusing primarily on safety and tolerability, with biomarker and clinical outcomes as secondary measures. Passage Bio plans updated interim safety and biomarker data and regulatory feedback on an FTD-GRN registrational trial design in the first half of 2026, and expects to select a clinical candidate for its Huntington’s program in the second half of 2026.
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Insights
Losses narrowed in 2025 as Passage Bio advanced key gene therapy programs and extended cash runway.
Passage Bio reduced its 2025 net loss to
Cash and cash equivalents of
Operationally, PBFT02 progress in the upliFT-D study and planned interim safety and biomarker data in
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
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FORM
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Item 2.02 Results of Operations and Financial Condition.
On March 3, 2026, Passage Bio, Inc. (the “Company”) issued a press release announcing its financial results for the year ended December 31, 2025. 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, 2026, 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 year ended December 31, 2025, dated March 3, 2026. | |
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: March 3, 2026 | By: | /s/ Kathleen Borthwick |
Kathleen Borthwick | ||
Chief Financial Officer | ||
3
Exhibit 99.1
PASSAGE BIO REPORTS FOURTH QUARTER AND FULL YEAR 2025 FINANCIAL RESULTS AND PROVIDES RECENT BUSINESS HIGHLIGHTS
Enrolled first three FTD-GRN patients in Cohort 3 of ongoing upliFT-D study
Treated first FTD-C9orf72 patient with Dose 2 PBFT02 in Cohort 4 of upliFT-D study
On track to report updated interim safety and biomarker data from upliFT-D and obtain regulatory feedback on FTD-GRN registrational trial design in 1H 2026
Advancing differentiated preclinical program for Huntington’s with clinical candidate selection expected in 2H 2026
Cash runway through 1Q 2027
PHILADELPHIA – March 3, 2026 – 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 fourth quarter and year ended December 31, 2025, and provided recent business highlights.
“We are proud of the progress made in 2025 as we meaningfully advanced our PBFT02 clinical program for the treatment of genetic forms of frontotemporal dementia,” said Will Chou, M.D., president and chief executive officer of Passage Bio. “As we enter 2026, we are excited by the strong enrollment momentum in our upliFT-D clinical study and look forward to sharing important data and regulatory updates in the first half of the year. FTD is a devastating disease, and the clinical unmet need remains substantial. We remain committed to advancing our program in the hope that we might one day offer patients and their families a therapy to redefine the course of their disease.”
Recent Highlights
| ● | Enrolled first three FTD-GRN patients in Cohort 3 of ongoing upliFT-D study: The first three patients in Cohort 3 of the upliFT-D trial have been enrolled and patient dosings are anticipated over the coming weeks. Cohort 3 will evaluate Dose 2 PBFT02 and is expected to consist of a total of 10 patients, with patient enrollment occurring in parallel across current active trial sites in Australia, Brazil, Canada, Portugal, and the United States. The cohort will be enrolled under the recently amended protocol, which focuses on patients earlier in their disease progression and includes a short course of low-dose prophylactic anticoagulation. The company plans to report updated interim safety and biomarker data from upliFT-D and obtain regulatory feedback on registrational trial design for FTD-GRN in the first half of 2026. |
| ● | Treated first FTD-C9orf72 patient with Dose 2 PBFT02 in Cohort 4 of upliFT-D study: Cohort 4 is expected to consist of up to a total of five patients, and multiple prospective study participants have been identified and are being evaluated for trial eligibility. Initial safety data from the first Cohort 4 patient will be reviewed by the Independent Data Monitoring Committee, IDMC, given this is the first administration of PBFT02 to this patient population. Upon completion of the IDMC review, we expect to enroll subsequent Cohort 4 patients in parallel. |
| ● | Advancing differentiated preclinical program for Huntington’s disease: Huntington’s disease, HD, is an autosomal dominant, progressive neurodegenerative disease caused by a mutation in the huntingtin gene, HTT, in which a CAG trinucleotide repeat tract in the DNA is expanded. Elongation of these CAG repeat tracts over time, termed somatic instability, above a certain threshold leads to neurodegeneration. MSH3, a DNA repair protein, has been shown to play a key role in driving somatic instability in HD by erroneously incorporating extra CAG repeats into the HTT gene. The company’s approach aims to slow neurodegeneration in HD by delivering an AAV containing a miRNA gene to suppress expression of MSH3 and decrease somatic instability in the HTT gene. The company expects to declare a clinical candidate for this program in the second half of 2026. Huntington’s disease is estimated to affect approximately 70,000 individuals across the United States and Europe with no disease-modifying therapies currently approved. |
Anticipated Upcoming Milestones:
| ● | Report updated interim safety and biomarker data from Dose 2 in 1H 2026 |
| ● | Seek regulatory feedback on registrational trial design in FTD-GRN in 1H 2026 |
| ● | Declare clinical candidate for Huntington’s disease in 2H 2026 |
Fourth Quarter and Full-Year 2025 Results
| ● | Cash Position: Cash and cash equivalents were $46.3 million as of December 31, 2025, as compared to cash, cash equivalents, and marketable securities of $76.8 million as of December 31, 2024. The company expects current cash and cash equivalents to fund operations through 1Q 2027. |
| ● | Research and Development (R&D) Expenses: R&D expenses were $5.4 million for the quarter ended December 31, 2025, and $23.3 million for the year ended December 31, 2025, compared to $9.6 million and $40.2 million for the same quarter and year ended in 2024, respectively. |
| ● | General and Administrative (G&A) Expenses: G&A expenses were $4.9 million for the quarter ended December 31, 2025, and $19.9 million for the year ended December 31, 2025, compared to $4.7 million and $25.0 million for the same quarter and year ended in 2024, respectively. |
| ● | Net Loss: Net loss was $13.0 million, or $4.09 per basic and diluted share, for the quarter ended December 31, 2025 and $45.5 million, or $14.35 per basic and diluted share, for the year ended December 31, 2025, compared to a net loss of $12.7 million, or $4.00 per basic and diluted share, for the quarter ended December 31, 2024 and $64.8 million, or $21.04 per basic and diluted share, for the year ended December 31, 2024. |
About upliFT-D (NCT04747431)
upliFT-D is a Phase 1/2 global, multi-center, open-label clinical trial of PBFT02 administered by single injection into the cisterna magna in patients aged 35 to 75 years with FTD-GRN or FTD-C9orf72. The clinical trial will sequentially enroll three FTD-GRN cohorts and two FTD-C9orf72 cohorts. Enrollment is currently ongoing. The primary endpoint of the clinical trial is to evaluate the safety and tolerability of PBFT02. Secondary endpoints include disease biomarkers and clinical outcome measures. upliFT-D is a two-year clinical trial with a three-year safety extension.
Passage Bio is pursuing several initiatives to support clinical trial recruitment and enrollment, including a collaborative partnership with InformedDNA to provide no-cost genetic counseling and testing for adults who have been diagnosed by their physicians with FTD. More information about upliFT-D can be found here.
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 progress of clinical studies and the availability of clinical data from such trials; enrollment timing; timing of feedback from regulatory authorities; our expectations about our collaborators’ and partners’ ability to execute key initiatives; our expectations about cash runway; the ability of our product candidates to treat their respective target CNS disorders; and the potential development of other product candidates. These forward-looking statements may be accompanied by such words as “aim,” “anticipate,” “believe,” “continue,” “could,” “should,” “target,” “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.
Passage Bio, Inc.
Balance Sheets
| | December 31, | ||||
(in thousands, except share and per share data) | | 2025 | | 2024 | ||
Assets |
| | |
| | |
Current assets: |
| | |
| | |
Cash and cash equivalents | | $ | 46,303 | | $ | 37,573 |
Marketable securities | | | — | | | 39,183 |
Prepaid expenses and other current assets | |
| 629 | |
| 838 |
Prepaid research and development | |
| 830 | |
| 1,221 |
Total current assets | |
| 47,762 | |
| 78,815 |
Property and equipment, net | |
| 4,107 | |
| 9,331 |
Right of use assets - operating leases | | | 10,168 | |
| 13,803 |
Other assets | |
| 244 | |
| 463 |
Total assets | | $ | 62,281 | | $ | 102,412 |
Liabilities and stockholders’ equity | |
| | |
| |
Current liabilities: | |
| | |
| |
Accounts payable | | $ | 1,113 | | $ | 742 |
Accrued expenses and other current liabilities | |
| 4,653 | |
| 6,707 |
Non-refundable sublicense and transition services payments | | | 13,750 | | | 8,226 |
Operating lease liabilities | | | 3,567 | |
| 3,688 |
Total current liabilities | |
| 23,083 | |
| 19,363 |
Operating lease liabilities - noncurrent | |
| 20,443 | |
| 21,788 |
Total liabilities | |
| 43,526 | |
| 41,151 |
| | | | | | |
Stockholders’ equity: | |
| | |
| |
Preferred stock, $0.0001 par value: 10,000,000 shares authorized; no shares issued and outstanding at both December 31, 2025 and December 31, 2024 | | | — | | | — |
Common stock, $0.0001 par value: 300,000,000 shares authorized; 3,182,810 shares issued and outstanding at December 31, 2025 and 3,161,503 shares issued and outstanding at December 31, 2024 | |
| — | |
| — |
Additional paid‑in capital | |
| 723,512 | |
| 720,488 |
Accumulated other comprehensive income (loss) | | | — | | | 8 |
Accumulated deficit | |
| (704,757) | |
| (659,235) |
Total stockholders’ equity | |
| 18,755 | |
| 61,261 |
Total liabilities and stockholders’ equity | | $ | 62,281 | | $ | 102,412 |
Passage Bio, Inc.
Statements of Operations and Comprehensive Loss
| | Year Ended December 31, | ||||
(in thousands, except share and per share data) | | 2025 | | 2024 | ||
Operating expenses: | | | |
| | |
Research and development | | $ | 23,276 | | $ | 40,179 |
General and administrative | |
| 19,875 | |
| 24,988 |
Impairment of long-lived assets | | | 6,145 | | | 5,233 |
Loss from operations | |
| (49,296) | |
| (70,400) |
Other income (expense), net | |
| 3,774 | |
| 5,633 |
Net loss | | $ | (45,522) | | $ | (64,767) |
Per share information: | |
| | |
| |
Net loss per share of common stock, basic and diluted | | $ | (14.35) | | $ | (21.04) |
Weighted average common shares outstanding, basic and diluted | |
| 3,172,870 | |
| 3,078,665 |
Comprehensive loss: | | | | | | |
Net loss | | $ | (45,522) | | $ | (64,767) |
Unrealized gain (loss) on marketable securities | | | (8) | | | 51 |
Comprehensive loss | | $ | (45,530) | | $ | (64,716) |
For further information, please contact:
Investors:
Stuart Henderson
Passage Bio
shenderson@passagebio.com
Media:
Mike Beyer
Sam Brown Inc. Healthcare Communications
312.961.2502
MikeBeyer@sambrown.com
| © 2026 Passage Bio. All rights reserved. Corporate Presentation Redefining the Course of Neurodegenerative Conditions March 2026 |
| 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 progress of clinical studies and the availability of clinical data from such trials; enrollment timing; timing of feedback from regulatory authorities; the potential of our product candidates versus other treatment options and clinical candidates; our expectations about cash runway; the ability of PBFT02 to treat FTD-GRN or FTD-C9orf72, and the potential development of other product candidates. 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, the timing of and our ability to obtain and maintain regulatory approvals; our expectations about the willingness of healthcare professionals to use our product candidates, the timing, or amount, 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; the timing, or amount, of receipt of any potential future milestone and royalty payments; 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. 2 March 2026 |
| 3 March 2026 Redefining the Course of Neurodegenerative Conditions * Based on cash, cash equivalents, and marketable securities as of December 31, 2025. Advancing clinical stage, potential best-in-class, one-time progranulin raising gene therapy for FTD Pursuing preclinical development of differentiated gene therapy approach in Huntington’s disease Cash runway expected through 1Q 2027* |
| Validating the Therapeutic Potential of PBFT02 4 March 2026 * Based on interim data. Urgent Patient Need in FTD-GRN Differentiated, Potential Best-in-Class Profile Fast Track and Orphan Drug Designation 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, gene replacement therapy Proprietary AAV1 construct Nonsurgical injection directly to cerebrospinal fluid (CSF) Durable, elevated CSF PGRN levels* |
| Significant Market Opportunity Addressing Neurodegenerative Diseases Estimated Prevalence (US and EU) 5 March 2026 Huntington’s disease5 FTD-C9orf722–4 FTD-GRN1–3 ~18K ~21K ~70K 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. Crowell et al. Neuroepi. 2021; 55:361-368. CURRENT PRECLINICAL PROGRAM CURRENT CLINICAL PROGRAM CURRENT CLINICAL PROGRAM |
| PBFT02 Frontotemporal Dementia |
| 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 Frontotemporal Dementia (FTD): A Devastating Adult Disease On average, people with FTD live 8 years after the onset of symptoms 7 March 2026 Loss of inhibition Apathy Social withdrawal Hyperorality (mouthing of objects) Ritualistic compulsive behaviors |
| Progranulin Deficiency is the Defining Characteristic of FTD-GRN and Leads to Neurodegeneration 8 March 2026 Progranulin is critical to maintaining CNS cell homeostasis Rhinn H et al. Trends Pharmacol Sci. 2022, 43:641-652. Decrease in PGRN levels Neuronal dysfunction, pathological changes, and inflammation Vulnerability of neurons in affected regions Neurodegeneration |
| Elevated PGRN Increases Potential for Improved Cellular Function 9 March 2026 Paushter et al. Acta Neuropathol. 2018;136:1-17. Rhinn et al. Trends Pharmacol Sci. 2022; 43:641-652. 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 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 |
| Preclinical NHP: AAV1 Achieved the Highest Levels of CSF PGRN 10 March 2026 After ICM administration to NHPs: • AAV1 capsid resulted in CSF hPGRN levels 5x higher than AAVhu68 (an AAV9 variant) • Superior hPGRN response led to selection of AAV1 capsid for PBFT02 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. Shading: Healthy adult sample range for CSF PGRN, n = 61 (Passage Bio data) CSF, cerebrospinal fluid; GC, genome copies; ICM, intra-cisterna magna; NHP, non-human primate. Reference: Hinderer et al., Ann Clin Trans Neurol. 2020; 7:1843-1853. Human PGRN in NHP CSF Vector Comparison Healthy adult range Days BL 0 7 14 21 28 35 hPGRN *ng/mL) 80 70 60 50 40 30 20 10 0 AAV1.CB7.hGRN AAV5.CB7.hGRN AAVhu68.CB7.hGRN AAVhu68.UbC.hGRN |
| Preclinical NHP: ICM Administration of PBFT02 Led to Broad Distribution of Vector Throughout Brain/Spinal Cord • Robust, dose-dependent vector delivery to cortical and sub-cortical brain regions affected in FTD • NHP low dose, equivalent to clinical Dose 1 of PBFT02 in upliFT-D study, resulted in ~10⁴ GC/μg DNA in all sampled areas throughout the brain 11 March 2026 n=3/gp. Data are mean +/- SEM. CBL, cerebellum; Cerv, cervical; DRG, dorsal root ganglion; FCX, frontal cortex; GC, genome copies; Hipp, hippocampus; ICM, intra-cisterna magna; LLoQ, lower limit of quantitation; Lumb, lumbar; OCX, occipital cortex; PCX, parietal cortex; TCX, temporal cortex; Thor, thoracic; TRG, trigeminal root ganglion; Veh, vehicle Vector Biodistribution in NHPs 90 Days Post-ICM PBFT02 GC/µg DNA 107 106 105 104 103 102 101 FCX PCX TCX OCX Hipp Medulla CBL Cerv Lumb Thor Cerv Lumb Thor TRG LLoQ Veh Low Medium High dose Cortex DRG |
| Preclinical Grn–/– Mice: Expression of hPGRN Improved Lysosomal Dysfunction and Neuroinflammation in the Brain 12 March 2026 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 after PBFT02 administration Grn–/– and WT mice (n=14-15/gp) ICV-administered PBFT02 or vehicle (V). Baseline controls were 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. Grn, granulin gene; ICV, Intra-cerebroventricular; PGRN, progranulin; WT, wildtype Thalamus Lipofuscin Thalamus CD68 Immunohistochemistry 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 Lipofuscin Count 1000 800 600 400 200 0 Baseline Day 90 Baseline Day 90 CD68 Area (µm2) 5000 4000 3000 2000 1000 0 PBFT02 Dose 1 Dose 2 Dose 3 Dose 4 PBFT02 Dose 1 Dose 2 Dose 3 Dose 4 WT Grn-/- WT Grn-/- WT Grn-/- WT Grn-/- V V PBFT02 V V PBFT02 |
| TRIAL DESIGN upliFT-D: Global Phase 1/2 Trial with PBFT02 Currently enrolling patients in Cohort 3 and Cohort 4 13 March 2026 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) • vMRI • NfL (CSF, plasma) Clinical • CDR + NACC FTLD sum of boxes EXPLORATORY BIOMARKERS • Cathepsin D (CSF) • GFAP (CSF, plasma) • LAMP 1 (CSF) • Lys-GL1 (CSF) Multicenter Open-label Dose exploration study Phase 1/2 Complete IDMC review Dose 1: 4.5e13 GC Dose 2: 2.2e13 GC COHORT 1 (n=5) Dose 1 COHORT 2 (n=4) Dose 1 / Dose 2 COHORT 3 (n=5-10) FTD Dose 2 -GRN COHORT 4 (n=3-5) Dose 2 COHORT 5 (n=3-5) FTD-C9orf72 |
| Cisterna magna Intra-Cisterna Magna (ICM) Administration 14 March 2026 Directly deliver vector into the CSF via a single injection • Allows for broad CNS biodistribution1 • Lower doses compared to IV systemic delivery • Reduced impact of neutralizing antibodies Brief (<60 min), non-surgical, CT-guided procedure for precise delivery to the cisterna magna Procedure avoids penetration of brain tissue 1. Hinderer et. al, Hum Gene Ther. 2018; 29:15-24. |
| Key Baseline Demographics for FTD-GRN Participants* Dose 1 (n=7); Dose 2 (n=1) (n=8) Mean / % / n Range Age (yrs) 64.4 51–72 Sex M: 50% F: 50% FTD-GRN phenotype (n) bvFTD: 5 PPA: 3 Disease duration at baseline (yrs) 2.9 1 –5 PGRN, CSF (ng/mL) 2.1 1.5 –2.9 PGRN, plasma (ng/mL) 36.6 22.4 –89.0 NfL, plasma (pg/mL) 51.9 12.4 –111 Clinical Dementia Rating Scale1, Global (%) 1: 50% 2: 50% Clinical Dementia Rating Scale1, Sum of Boxes 10.3 5–17 *Data as of June 15, 2025 1. CDR® +NACC FTLD. bvFTD, behavioral variant; PPA, primary progressive aphasia. 15 March 2026 |
| Healthy adult range 0 10 20 30 40 0 3 6 9 12 15 18 CSF PGRN, ng/mL Time (months) Dose 1 Dose 2 Progranulin, CSF PBFT02 Generated Robust, Durable Increases in CSF PGRN in FTD-GRN Patients Data as of June 15, 2025. Mean +/- SEM Shading: Healthy adult sample range for CSF PGRN (range: 3.28 – 8.15 ng/mL, mean: 4.76 ng/mL, n = 61) (Passage Bio data) Dose 1: 4.5e13 GC; Dose 2: 2.2e13 GC CSF, cerebrospinal fluid; M, month. Dose 1 N: 7 6 6 4 2 16 March 2026 First Dose 2 patient (Patient 8) increased from 1.5 ng/mL at baseline to 7.6 ng/mL at M1, approaching the upper healthy adult range |
| Plasma NfL Showed Early Evidence of Improvement in a Disease Progression Biomarker vs. Natural History • Plasma NfL is the only FTD-GRN disease progression biomarker with longitudinal natural history data available1,3 • PBFT02-treated patients with 12 months follow-up (n=4) had a reduced annual rate of change in plasma NfL compared to published natural history data 17 March 2026 29.0% 28.0% 3.7% -10% 0% 10% 20% 30% 40% % Change Published NHx (n=15) ALLFTD (n=11) PBFT02 (n=4) Natural History 1 2 Note: Annual rate of increase in plasma NfL in a healthy adult sample reported to be ~4%1. Plasma NfL Annual Rate of Change Data as of June 15, 2025. Mean +/- SEM PBFT02 patients (n=4, Dose 1): Baseline plasma NfL (neurofilament light chain) range: 39.6 to 45.6 pg/mL. Average time since diagnosis 2.3 years. 1. Published natural history. Chart (left): 15 symptomatic, untreated FTD-GRN patients; mean years since diagnosis: 2.9; Note (right): 65 healthy adults. (Saracino et al, J Neurol Neurosurg Psych 2021; 92:1278-1288). 2. Passage Bio analysis of ALLFTD natural history sample comprised of individuals with a pathogenic GRN mutation and a CDR+NACC FTLD global score between 0.5 and 2, inclusive. 3. van der Ende et al, Lancet Neurol 2019; 18:1103-11. |
| PBFT02 Interim Safety Profile PBFT02 was generally well tolerated • SAEs related to PBFT02 all asymptomatic; all occurred at Dose 1 • Venous sinus thrombosis (2) • LFT increase (1) • No SAEs related to PBFT02 at Dose 2 • No evidence of thrombotic microangiopathy • No evidence of dorsal root ganglion (DRG) toxicity in any patient • No complications from ICM procedure Data as of June 15, 2025 18 March 2026 N Events TEAE considered related to PBFT02 7 26 Serious TEAE unrelated to PBFT02 1 1 Serious TEAE related to PBFT02 2 3 SAE, serious adverse event; LFT, liver function test; ICM, intracisterna magna; TEAE, treatment emergent adverse event. |
| PBFT02 Offers Best-in-Class Therapeutic Potential PBFT02 Product Candidate AAV1 gene therapy delivering GRN AAV9 gene therapy delivering GRN PGRN replacement therapy via protein transport vehicle Stage of Development Phase 1/2 Phase 1/2 Phase 1/2 Route of Administration ICM (non-surgical, 1 hour procedure) Intrathalamic (neurosurgery, lengthy procedure) IV Frequency of Administration One-time One-time Chronic dosing (~every 4 weeks)1 CSF PGRN Level at 12m 26 ng/mL (mean; n=4) – – Durability of CSF PGRN Elevation1 Durable at 18 m (n=2) – – PBFT02 uniquely positioned to offer a one-time therapy capable of achieving highest progranulin levels 19 March 2026 Data for PBFT02 as of June 15, 2025 cutoff. Information for competitor programs based on publicly available information. 1 https://memory.ucsf.edu/research-trials/dnl593#:~:text=What%20to%20Expect,garages%20for%20all%20study%20visits (accessed on Feb 12, 2026). |
| PBFT02 has Potential to Correct Underlying Pathology in FTD-GRN, FTD-C9orf72 and ALS 20 March 2026 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 Pharmacol Sci. 2022; 43:641-652 |
| Elevated PGRN Ameliorates TDP-43 Pathology in Preclinical Models 21 March 2026 TDP-43 pathology due to lysosomal dysfunction (GRN/ TMEM106 double knockout, DKO) reduced by AAV.hPGRN1 AAV delivered hPGRN to 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. Sci Transl Med. 2024; 16(750); 2. Beel et al. Mol Neurodegen. 2018: 13:55.; Laird et al. PLoS One 2010; 5:e13368. DKO, double gene knockout; GRN, granulin gene; PGRN, progranulin; TDP-43, transactive response DNA binding protein 43 kDa † PGRN increased to >2x endogenous levels |
| • AAV delivery of functional GRN gene to express new PGRN, increasing levels both intra- and extra-cellularly • Preserves all natural pathways to properly traffic PGRN intracellularly where it is needed • ICM route of administration enables low doses of AAV and broad CNS biodistribution • Non-surgical, brief procedure (< 60 minutes) • Promise of a one-time therapy for patients • Durable elevation of CSF PGRN1 PBFT02: Summary of Approach 22 March 2026 1. Interim data from upliFT-D as of June 15, 2025. A novel and potentially transformative therapy for FTD-GRN patients |
| Huntington’s Disease Preclinical Program |
| OVERVIEW • Fatal, monogenic, autosomal dominant neurodegenerative disease • Caused by trinucleotide (CAG) expansion in the huntingtin (HTT) gene resulting in mutant huntingtin (mHTT) protein expression • More than 200,000 people estimated to be at risk in the US1 CLINICAL SYMPTOMS • Symptom onset typically occurs between 30–50 years old • Characterized by progressive motor, cognitive, and behavioral deterioration, due to neuronal dysfunction then degeneration Huntington’s Disease: A Fatal Neurodegenerative Disease with No Disease-Modifying Therapy Average life expectancy after symptom onset is 15–20 years 24 March 2026 Motor deterioration Cognitive deterioration Behavioral deterioration 1. HDSA; Fisher and Hayden Mov Disord. 29:105-14, 2014. |
| Unaffected HD Is Caused By A Mutation In Huntingtin (HTT) Gene: A Stretch Of CAG Nucleotides Is Expanded CAG repeat expansion leads to production of mutant huntingtin protein (mHTT) 25 March 2026 Normal huntingtin gene, HTT, CAG </= 35 Mutant huntingtin gene, mHTT, CAG > 35 GLUTAMINES Exon 1 Exons 2–67 SHORT CAG HTT DNA LONG GLUTAMINE STRETCH HTT PROTEIN Exon 1 Exons 2–67 LONG CAG mHTT DNA mHTT PROTEIN Huntington’s Disease |
| DNA Repair (DR) Proteins Play a Key Role in CAG Repeat Expansion • CAG expansion above a certain threshold leads to neurodegeneration • Longer CAG repeats associated with worse disease pathology • CAG expansion occurs at different rates in different neurons, and is fastest in the caudate and putamen brain regions which degenerate first 26 March 2026 1. Genetic Modifiers of Huntington’s Disease (GeM-HD) Consortium, Nat Genet. 2025; 57:1426-36. 2. Dragileva E et. al, Neurobio Dis. 2009; 33:37-47. 3. Mouro Pinto et. al, Nat Genet. 2025; 57:314-322. In Huntington’s disease (HD), the CAG repeat in the HTT gene can elongate over time, termed somatic instability • In the presence of certain CAG motifs, MSH3 can erroneously incorporate CAGs into DNA, leading to CAG expansion • In HD: certain genetic variants altering MSH3 function are associated with delayed onset and slowed progression1 • In HD mice: MSH3 is essential for CAG expansion, and MSH3 knock-down reduced somatic instability and HTT pathology2,3 MSH3, a DR protein, is a key driver of somatic instability |
| Program Status Our Approach: Decrease MSH3 to Reduce Somatic Instability in the HTT Gene Expect to declare a clinical candidate in 2H 2026 27 March 2026 Developing a differentiated approach to decrease MSH3 expression via AAV delivery of a miRNA Proof-of-concept studies completed, with additional preclinical studies ongoing Plan to utilize an optimized intraparenchymal delivery approach • One-time delivery • Direct delivery to critical brain regions • Reduced total procedure time • Limited peripheral exposure to reduce safety risks |
| Looking Ahead |
| Completed development of high-productivity, suspension-based manufacturing process Single production lot estimated to yield >1,000 doses1 with >70% full capsids Robust Manufacturing Process Aligned with the FDA on an analytical approach to establish comparability of suspension-based process Process Comparability Plan Developed assay and reached alignment with FDA on suitability of assay for PBFT02 release Functional Potency Assay Critical Manufacturing Milestones Achieved to Enable Late-Stage Development of PBFT02 29 March 2026 1. Estimated yield based on Dose 2. |
| Upcoming Milestones and Corporate Updates BALANCE SHEET • Cash balance of ~$46 million as of 12/31/25* • Cash runway through 1Q 2027 * Based on cash, cash equivalents and marketable securities. TIMING MILESTONE 1H 2026 Report updated interim safety and biomarker data from Dose 2 in FTD patients 1H 2026 Seek regulatory feedback on registrational trial design in FTD-GRN 2H 2026 Declare clinical candidate for Huntington’s disease 30 March 2026 |
| 31 March 2026 * Based on cash, cash equivalents and marketable securities as of December 31, 2025. Redefining the Course of Neurodegenerative Conditions Advancing clinical stage, potential best-in-class, one-time progranulin raising gene therapy for FTD Pursuing preclinical development of differentiated gene therapy approach in Huntington’s disease Cash runway expected through 1Q 2027* |
| © 2026 Passage Bio. All rights reserved. passagebio.com Thank you! |
| Program Indication US/EU prevalence Discovery Preclinical Phase 1/2 Pivotal PBFT02 Frontotemporal dementia — GRN 18,0001-3 Frontotemporal dementia — C9orf72 21,0002-4 Unnamed Huntington’s disease 70,0005 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. Crowell et al. Neuroepi. 2021; 55:361-368. 33 March 2026 ALS and Alzheimer’s disease represent additional pipeline expansion opportunities for PBFT02 |
| LEADERSHIP TEAM Demonstrated Leadership 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 Thomas Kassberg Former CBO Ultragenyx William Chou, M.D. President and Chief Executive Officer Deep experience in rare disease, CNS disorders and genetic medicines Eden Fucci SVP Technical Operations Stuart Henderson Chief Business Officer William Chou, M.D. President and Chief Executive Officer Kathleen Borthwick Chief Financial Officer Karl Whitney, Ph.D. SVP Global Regulatory Affairs Sue Browne, Ph.D. Chief Scientific Officer 34 March 2026 |
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