PBFT02 / Passage Bio - LARVOL DELTA

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

Non-clinical and early clinical development of PBFT02, an AAV gene therapy for FTD with GRN mutations (FTD-GRN) (ESGCT 2024) - No abstract available

Clinical • Gene therapy • Gene Therapies • GRN

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

Passage Bio Reports Fourth Quarter and Full-Year 2022 Financial Results and Provides Recent Business Highlights (GlobeNewswire) - “Expect to report initial safety and biomarker data from Cohort 1 patients in upliFT-D trial of PBFT02 for the treatment of patients with frontotemporal dementia (FTD) with granulin mutations (GRN) in the second half of 2023: upliFT-D is a global Phase 1/2, multi-center, open-label, dose-escalation study of PBFT02 administered by single injection into the cisterna magna in patients aged 35 to 75 years with early symptomatic FTD-GRN. Enrollment is ongoing at three sites globally.”

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

Passage Bio Doses First Patient in Global Clinical Trial of PBFT02 Gene Therapy for Frontotemporal Dementia with Granulin Mutations (GlobeNewswire) - “Passage Bio, Inc…announced that the first patient has been dosed in the global Phase 1/2 upliFT-D clinical trial evaluating PBFT02…for the treatment of patients with frontotemporal dementia (FTD) with granulin (GRN) mutations….upliFT-D continues to enroll patients with early symptomatic FTD-GRN.”

Trial status • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Passage Bio Reports First Quarter 2022 Financial Results and Provides Recent Business Highlights (GlobeNewswire) - “Anticipated Upcoming Milestones: Dose first patient in Phase 1/2 study with PBFT02 for FTD-GRN in mid-2022. Additional clinical data milestone timing to be provided following dosing of first patient.”

Trial status • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration

Passage Bio Announces 2022 Research and Clinical Development Goals to Advance Robust CNS Pipeline (GlobeNewswire) - “Key Anticipated Company Highlights in 2022: upliFT-D – Global Phase 1/2 Trial for PBFT02 for Frontotemporal Dementia with Granulin Mutations: Expect to dose first patient in early 2022; Advance pipeline programs for amyotrophic lateral sclerosis, Charcot-Marie-Tooth Type 2A, Parkinson’s disease, Canavan disease and Huntington’s disease; Progress target identification research programs for Alzheimer’s and temporal lobe epilepsy.”

New trial • Trial status • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • Huntington's Disease • Parkinson's Disease

Passage Bio Announces Pipeline Expansion and Clinical Program Update (GlobeNewswire) - "The company also expects to dose the first patients in the global Phase 1/2 trials for PBFT02 for frontotemporal dementia with granulin mutations...in early 2022."

Trial status • CNS Disorders • Frontotemporal Lobar Degeneration

Passage Bio Reports Third Quarter 2021 Financial Results and Provides Recent Business Highlights (Yahoo Finance) - “Activated multiple clinical sites across three global clinical programs, despite Covid-19 headwinds: This accomplishment, along with a variety of patient identification initiatives, paves the way for first participants to be dosed in global phase 1/2 clinical trials upliFT-D for PBFT02 in frontotemporal dementia with granulin mutations…by the end of the fourth quarter 2021. The company plans to report initial safety and 30-day biomarker data for both trials in the first half of 2022.”

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

A Study of PBFT02 in Patients With Frontotemporal Dementia and Progranulin Mutations (FTD-GRN) (clinicaltrials.gov) - P1b; N=6; Recruiting; Sponsor: Passage Bio, Inc.; Not yet recruiting ➔ Recruiting; Initiation date: Mar 2021 ➔ Sep 2021

Clinical • Enrollment open • Trial initiation date • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • GFAP • MRI

Passage Bio Reports First Quarter 2021 Financial Results and Recent Business Highlights (BioSpace) - "The global clinical trial upliFT-D for PBFT02 for FTD-GRN is expected to initiate in 2Q/3Q 2021 with initial safety and 30-day biomarker data to be reported in 1H22....Host R&D day focused on FTD-GRN, May 17..."

New P1/2 trial • P1/2 data • CNS Disorders • Frontotemporal Lobar Degeneration

Passage Bio Partners with InformedDNA to Offer Genetic Counseling and Testing for Patients with Frontotemporal Dementia (FTD), a Form of Early Onset Dementia (BioSpace) - "Passage Bio...and InformedDNA...today announced a collaboration to provide no-cost genetic counseling and testing for adults who have been diagnosed by their physicians with Frontotemporal Dementia (FTD)....Passage Bio is evaluating gene therapy candidate, PBFT02, for treatment of FTD with granulin mutations..."

Licensing / partnership • CNS Disorders • Frontotemporal Lobar Degeneration