PBFT02 / Passage Bio - LARVOL DELTA

Non-clinical and early clinical vector shedding studies following intra-CSF delivery of PBFT02, an AAV1 investigational product, in FTD patients with GRN mutations (FTD-GRN) (ASGCT 2026) - P1/2 | "The observed profiles of rapid distribution and short duration of excretion are similar to other AAV products delivered using tissue-targeted approaches (including intra-ocular and intra-parenchymal CNS delivery) in the reported literature to date. While additional studies are needed to gauge the reproducibility of these data, these observations may provide the initial foundation to guide future designs for non- clinical and clinical vector DNA distribution and shedding studies and biosafety management following AAV ICM delivery."

Clinical • First-in-human • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • GRN • MAPT

upliFT-D: A Study of PBFT02 in Participants With FTD and Mutations in the Granulin Precursor (GRN) or C9ORF72 Genes (clinicaltrials.gov) - P1/2 | N=30 | Active, not recruiting | Sponsor: Passage Bio, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Plasma NfL

Updated interim upliFT-D data from FTD-GRN patients treated with PBFT02 (GlobeNewswire) - "PBFT02-treated patients with a global CDR score of 1 at baseline experienced a 64% reduction in whole brain atrophy at 12 months, on average, as compared to vMRI analysis of untreated global CDR 1 patients from the ALLFTD natural history data. o PBFT02-treated global CDR 1 patients (n=2): 3.1% atrophy at 12 months o ALLFTD natural history global CDR 1 sample (n=7): 8.7% atrophy at 12 months...Plasma NfL levels among PBFT02 treated patients showed an average reduction of 1.0 pg/mL (n=6) at 12 months compared to baseline...Dose 1 PBFT02 (4.5e13 total genome copies) resulted in a robust and durable increase in CSF PGRN expression through 18 months post-treatment....PBFT02 continued to be generally well-tolerated, with no new treatment-related serious adverse events (SAEs) reported."

P1/2 data • Frontotemporal Lobar Degeneration

Regulatory & Program Update (GlobeNewswire) - "The Company has completed a Type C meeting with the FDA to seek guidance on key elements of a future registrational trial of PBFT02 for FTD-GRN patients. Based on the feedback received, the FDA has indicated that a randomized controlled registrational study design is required for PBFT02 in this indication. A randomized controlled registrational trial poses substantial ethical concerns for patients and their families as well as logistical and financial challenges. As such, the Company is evaluating potential next steps in the clinical development of PBFT02 in FTD-GRN and FTD-C9orf72 in the upliFT-D trial."

FDA event • New trial • Trial status • Frontotemporal Lobar Degeneration

Treated first FTD-C9orf72 patient with Dose 2 PBFT02 in Cohort 4 of upliFT-D study (GlobeNewswire) - "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."

Trial status • Frontotemporal Lobar Degeneration

Enrolled first three FTD-GRN patients in Cohort 3 of ongoing upliFT-D study (GlobeNewswire) - "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."

Biomarker • P1/2 data • Trial status • Dementia • Frontotemporal Lobar Degeneration

INTERIM SAFETY AND BIOMARKER DATA FROM UPLIFT-D TRIAL OF PBFT02 IN FTD-GRN (ADPD 2026) - P1/2 | "Interim safety and biomarker data from the upliFT-D trial provides early evidence that PBFT02 has potential as a one-time therapy for FTD-GRN, thus supporting further clinical development."

Biomarker • Clinical • First-in-human • Alzheimer's Disease • Cardiovascular • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Hematological Disorders • Thrombosis • MAPT • Plasma NfL

Drug Development. (PubMed, Alzheimers Dement) - P1/2 | "Interim safety and biomarker data from the upliFT-D trial provides early evidence that PBFT02 has potential as a one-time therapy for FTD-GRN, thus supporting further clinical development."

Biomarker • Journal • Alzheimer's Disease • Cardiovascular • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Hematological Disorders • Thrombosis • GRN • MAPT • Plasma NfL

Non-clinical and early clinical development of PBFT02, an AAV gene therapy for FTD with GRN mutations (FTD-GRN) (ESGCT 2024) - P1/2 | "PBFT02 was generally well-tolerated with a steroid immunosuppression regimen of 1 g IV methylprednisolone on study days 1 to 3, followed by 60 mg oral prednisone on days 4 to 60. In summary, the favorable non-clinical profile of PBFT02 led to the initiation of a Phase 1/2 clinical study in FTD-GRN individuals. Interim safety and biomarker data from the upliFT-D trial provides initial evidence that PBFT02 has potential as a one-time therapy for FTD-GRN and supports its further clinical development."

Clinical • Gene therapy • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Gene Therapies • Inflammation • GRN • MAPT

Interim safety and biomarker data from upliFT-D trial of PBFT02, an AAV gene therapy for FTD with GRN mutations (ESGCT 2025) - No abstract available

Biomarker • Clinical • Gene therapy • Gene Therapies • GRN

Scalable Production of an AAV Manufacturing Platform: Transitioning from Adherent to Suspension-Based Triple Transfection (ASGCT 2025) - "Clinical supply of Passage Bio's PBFT02, an AAV1-based gene therapy candidate for treating FTD-GRN and FTD-C9orf72, has been produced to date using a triple transfection adherent process in HEK293 cells...Additionally, this high productivity and adaptable suspension process represents a significant step towards the establishment of a scalable platform for the manufacturing of future AAV products. Disease Focus of Abstract:None"

Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Gene Therapies

Passage Bio Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Recent Business Highlights (GlobeNewswire) - "Anticipated Upcoming Milestones: FTD-GRN - Report 12-month data from Dose 1 and interim safety and biomarker data from Dose 2 in 2H 2025; Seek regulatory feedback on registrational trial design in 1H 2026. FTD-C9orf72 - Initiate dosing of FTD-C9orf72 patients in 1H 2025."

P1/2 data • Trial status • Dementia

upliFT-D: A Study of PBFT02 in Participants With FTD and Mutations in the Granulin Precursor (GRN) or C9ORF72 Genes (clinicaltrials.gov) - P1/2 | N=25 | Recruiting | Sponsor: Passage Bio, Inc. | N=15 ➔ 25 | Trial completion date: Aug 2027 ➔ Aug 2031 | Trial primary completion date: Aug 2024 ➔ Aug 2028

Enrollment change • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • GRN

Passage Bio Announces Interim Data from upliFT-D Study in FTD-GRN and Provides Business Updates (GlobeNewswire) - "P1/2 | N=15 | upliFT-D (NCT04747431) | Sponsor: Passage Bio, Inc. | "PBFT02 consistently increased CSF PGRN expression in all patients from below 3 ng/mL at baseline to 13 – 27 ng/mL at six months (n=4) and 22 – 34 ng/mL at 12 months (n=2). CSF PGRN levels generally plateaued by month 6 and have remained durable through the longest available follow-up of 18 months (n=1). Plasma NfL levels were 13% lower than baseline on average at 12 months (n=2) post-treatment...In 5 of 7 patients, all treatment emergent adverse events (AEs) were mild to moderate in severity. 2 of 7 patients experienced a total of 3 serious adverse events...No evidence of clinically significant immune responses in any patient who received the revised immunosuppression regimen...Report 12-month data from Dose 1 and interim safety and biomarker data from Dose 2 in 2H 2025; Seek regulatory feedback on registrational trial design in 1H 2026...Initiate dosing of FTD-C9orf72 patients in 1H 2025."

P1/2 data • Regulatory • Trial status • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Passage Bio Reports Third Quarter 2024 Financial Results and Provides Recent Business Highlights (GlobeNewswire) - "Anticipated Upcoming Milestones: FTD-GRN: i) Report 12-month Cohort 1 and interim Cohort 2 data in 1H 2025; ii) 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."

FDA event • P1/2 data • Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Passage Bio Presents Preclinical and Interim Clinical Data for PBFT02 in FTD-GRN at the European Society of Gene & Cell Therapy (ESGCT) 31st Annual Conference (GlobeNewswire) - "Preclinical data demonstrated that an AAV1 vector achieved superior human progranulin levels in the CSF as compared to AAV5 and AAVhu68 (an AAV9 variant); Nonclinical data showed PBFT02 improved lysosomal histopathology and reduced neuroinflammation in Grn knockout mice, and achieved widespread vector distribution throughout the nervous system in non-human primates...Interim safety and biomarker data from the upliFT-D clinical study demonstrated that Dose 1 of PBFT02 was generally well-tolerated after ICM administration and led to consistent, durable increases in levels of CSF progranulin in all treated Cohort 1 patients, with elevated CSF progranulin levels sustained up to 12 months post-administration."

P1/2 data • Preclinical • CNS Disorders • Dementia

Interim Safety and Biomarker Data From upliFT-D, a Phase 1b Trial of PBFT02 in Frontotemporal Dementia and Mutations in the Granulin Gene (FTD-GRN) (CTAD 2024) - No abstract available

Biomarker • Clinical • P1 data • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • GRN

Passage Bio to Present Positive Interim Data from Cohort 1 Patients with FTD-GRN in upliFT-D Study at 14th International Conference on Frontotemporal Dementias (ISFTD2024) (GlobeNewswire) - P1b/2 | N=15 | upliFT-D (NCT04747431) | Sponsor: Passage Bio, Inc. | "Dose 1 of PBFT02 was well-tolerated in all patients (patients 2, 3, 4, and 5) who received an enhanced immunosuppression regimen following protocol amendment. No serious adverse events (SAEs). All treatment emergent adverse events (AEs) were mild to moderate in severity. No evidence of clinically significant immune response, hepatotoxicity or safety related imaging abnormalities. Relative to baseline, PBFT02 increased CSF PGRN expression in all patients; up to 6-fold at one month (range of 10.7 to 17.3 ng/mL; n=5) and up to 10-fold at six months (range of 21.7 to 27.3 ng/mL; n=2). The effect of PBFT02 was consistent across all patients, with CSF PGRN levels exceeding the range found in healthy adult controls of 3.3 to 8.2 ng/mL (n=61)."

P1/2 data • CNS Disorders • Dementia

Passage Bio Reports Second Quarter 2024 Financial Results and Provides Recent Business Highlights (GlobeNewswire) - "We are also pleased the FDA is aligned with our proposed expansion of our upliFT-D trial to include FTD-C9orf72 patients and expect to initiate dosing of these patients in the first half of 2025...Anticipated Upcoming Milestones: FTD-GRN: Report updated safety and biomarker data from Cohort 1 patients at ISFTD2024 in September 2024; Report 12-month Cohort 1 and interim Cohort 2 data in 1H 2025...FTD-C9orf72 and ALS; Obtain regulatory feedback on the pathway to treating amyotrophic lateral sclerosis (ALS) patients with PBFT02 in 2H 2024; Initiate dosing of FTD-C9orf72 patients in 1H 2025."

FDA event • New trial • P1/2 data • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Passage Bio Announces Positive Feedback from FDA on Expansion of upliFT-D Trial of PBFT02 to Include FTD-C9orf72 Patients (GlobeNewswire) - "Passage Bio, Inc...today announced that the company received positive feedback in its Type C meeting process with the U.S. Food and Drug Administration (FDA) on its proposal to evaluate PBFT02 for treating frontotemporal dementia (FTD) patients with mutations in the C9orf72 gene. Compelling preclinical evidence, coupled with available safety and robust progranulin (PGRN) expression data from the first cohort of FTD-GRN patients treated with PBFT02, supported FDA alignment on the proposed trial expansion. The company intends to amend the protocol for the ongoing upliFT-D Phase 1/2 global study for FTD-GRN to introduce a new population of FTD-C9orf72 patients...The company plans to submit the revised trial protocol to health authorities and ethics committees promptly and expects to initiate dosing of FTD-C9orf72 patients in 1H 2025."

Clinical protocol • FDA event • CNS Disorders • Dementia

A Study of PBFT02 in Patients With Frontotemporal Dementia and Progranulin Mutations (FTD-GRN) (clinicaltrials.gov) - P1/2 | N=15 | Recruiting | Sponsor: Passage Bio, Inc. | Phase classification: P1b ➔ P1/2

Phase classification • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • GRN

Passage Bio Announces Promising Initial Data From Phase 1/2 Clinical Trial of PBFT02 in FTD-GRN and Updated Strategic Priorities (GlobeNewswire) - P1b/2 | N=15 | upliFT-D (NCT04747431) | Sponsor: Passage Bio, Inc. | "Passage Bio, Inc...announced initial safety and biomarker data from three Cohort 1 patients in the ongoing global Phase 1/2 upliFT-D clinical trial evaluating PBFT02, an adeno-associated virus (AAV)-delivery gene therapy for the treatment of patients with frontotemporal dementia (FTD) with granulin (GRN) mutations....Dose 1 of PBFT02 was generally well-tolerated in patients 2 and 3, who received an enhanced steroid regimen following protocol amendment....Dose 1 of PBFT02 treatment resulted in a 3.6 to 6.6-fold increase in CSF PGRN at day 30 (n=3) relative to baseline. CSF PGRN increased to supraphysiologic levels of 10.7 to 17.3 ng/mL at day 30, exceeding the range found in healthy adult controls of 3.3 to 8.2 ng/mL (n=61)."

Biomarker • P1/2 data • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Passage Bio Announces Promising Initial Data From Phase 1/2 Clinical Trial of PBFT02 in FTD-GRN and Updated Strategic Priorities (GlobeNewswire) - "Anticipated Upcoming Milestones: FTD-GRN: Initiate dosing for Cohort 2 FTD-GRN patients in 1H 2024; Report full 6-month safety and biomarker data from Cohort 1 patients in 2H 2024; Report 12-month follow-up data from Cohort 1 patients in 1H 2025; Report initial safety and biomarker data from Cohort 2 patients in 1H 2025. FTD-C9orf72 and ALS: Obtain regulatory feedback on the pathway to treating FTD-C9orf72 and ALS patients with PBFT02 in 2H 2024."

Biomarker • P1/2 data • Regulatory • Trial status • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Passage Bio Reports Second Quarter 2023 Financial Results and Provides Recent Business Highlights (GlobeNewswire) - "Present initial safety and biomarker data for Cohort 1 in upliFT-D clinical trial for FTD in Q4 2023."

P1/2 data • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Passage Bio Reports First Quarter 2023 Financial Results and Provides Recent Business Highlights (GlobeNewswire) - "Anticipated Upcoming Milestones: Present initial safety and biomarker data from Cohort 4 (early infantile, high dose) in the Imagine-1 clinical trial for GM1 in mid-2023. Dose first patient at higher dose (Dose 3) in Imagine-1 clinical trial for GM1 in the second half of 2023. Present initial safety and biomarker data for Cohort 1 in upliFT-D clinical trial for FTD in the second half of 2023."

P1/2 data • Trial status • CNS Disorders • Frontotemporal Lobar Degeneration • Genetic Disorders