Passage Bio, Inc. Q3 FY2022 earnings call

• Refocused efforts and streamlined operations, including a 23% workforce reduction and cost-cutting measures. • Continued focus on clinical trials: GM1's Imagine-1 trial has dosed 7 patients with plans to complete dosing by year-end and report initial safety and biomarker data from cohorts 2 and 3 in December; FTD's upliFT-D trial dosed the first patient in August, with efforts to increase genetic testing and enrollment. • Prioritized preclinical programs in ALS and Huntington's Disease through partnership with Penn's Gene Therapy Program. • Leveraged in-house analytical capabilities at the CNC lab in Princeton West. • Stopped clinical development of PBKR03 for Krabbe disease but will explore strategic alternatives for PBML04. • Expect existing cash resources to fund operations into the first half of 2025.

No detailed breakdown of product segments by revenue contribution was provided. The company has clinical programs in GM1 gangliosidosis, frontotemporal dementia, Krabbe disease, and metachromatic leukodystrophy, but specific financial performance and revenue contribution percentages for each segment weren't detailed in the transcript.

• Expect existing cash resources to fund operations into the first half of 2025. • Plan to report initial safety and biomarker data from GM1 cohorts 2 and 3 in December and update cohort 1 data. • Aim to align the registrational pathway for GM1 in 2023 and continue enrolling patients in the FTD trial.

• Forward-looking statements are subject to risks such as clinical trial timing and execution, collaborator performance, efficacy of lead product candidates, manufacturing plans, cash runway, impact of COVID-19, and cost management. These risks could cause actual results to differ significantly from forward-looking statements.

Q: Were there any safety issues that led to discontinuation of the Krabbe program? And in terms of FTD, how are you thinking about competing with other progranulin replacement drugs in the FTD space for patient recruitment? And how many of these patients are you looking to treat before disclosing data?

A: The decision to stop the Krabbe program was purely resource-driven. On FTD, screening for the mutation is important, and more people talking about screening helps. There are three sites open for FTD, with multiple patients with GRN mutation in enrollment process, and will share more data from cohort 1 of upliFT-D trial in 2023.

Q: Can you maybe remind us about the actual mechanism of action for the gene therapy and ALS that you're using? How are you actually looking to functionally correct the C9orf72 pathology? And then, wondering when we might actually get to see some preclinical data from that program. And then, similarly for Huntington's, obviously one concern some of these other people using genetic therapies in the space have run into is kind of penetration into some of the deeper brain structures. So, assuming you're planning ICM administration for that as well, what maybe gives you confidence you'll be able to avoid some of those pitfalls?

A: Our approach for ALS is a knockdown and replace strategy. Will share more data on Huntington's brain penetration next year.

Q: On PBFT02, can you clarify, are those patients definitely likely to actually meet the enrollment criteria and the screening criteria and ultimately get dosed? I'm just trying to kind of understand the timing for potential data next year.

A: Patient identification efforts have led to a funnel of individuals with FTD and GRN mutations being evaluated for suitability; will disclose more as data matures.

Q: On PBFT02, what are your assumptions around screening failure rates for FTD patients? And in the second cohort, is there that same 60-day waiting period between enrollment of different subjects? And lastly, just one on GM1. What areas specifically of alignment are you looking to get from regulators? I guess, any clarity in terms of how you're thinking about that and whether a U.S. launch may come second to other geographies?

A: For FTD, most patients with GRN mutations are eligible unless meeting specific exclusion criteria; there is a 60-day waiting period in the trial. For GM1, aligning with regulators on registrational pathway, focus on initiating registrational study and meeting agency requirements.

Q: Can you walk us through how you decided which programs to prioritize and the considerations that you made? And then, pertaining to the FTD GM1 program. I'm just curious, what's the biggest, like, bottleneck here? The challenge with recruitment, is it opening sites, identifying the suitable patients or I guess, motivating them to enroll in the study given competition?

A: Prioritized most advanced programs (GM1 and FTD) due to resource allocation. Bottlenecks include patient identification, site opening, and keeping patients through the process; laser-focused on execution across all aspects of clinical programs.

Q: For the Krabbe program, does this manual no longer be providing an update later this year? And for the preclinical portfolio, can you talk about factors that you're weighing in to prioritize advancing these programs with the GTP and of the available options that you have left? Can you remind us of the timelines opting in a selection criteria given the new strategies to streamline in we focus?

A: No further updates on Krabbe program. Prioritized most advanced preclinical programs; have eight options remaining through 2026.

Q: With regards to the Krabbe program, were you able to make a conclusion whether the safety finding was related to study treatment or study procedures? And do you think the GM1 patient or potentially FTD patient will have this kind of risk as well given the same procedure? And when you report clinical update in December from the GM1 study, is it reasonable to expect that we will be able to see functional measures from early infantile patient? And do you think Vineland and also Bayley would be the most appropriate measures to look at the functional endpoints, please?

A: SAE of acute hydrocephalus in Krabbe trial was possibly related to treatment, but no evidence of such risk in GM1 or FTD trials. In December, will disclose safety, beta galactosidase activity, and clinical milestones including Bayley and Vineland scales.