Passage Bio, Inc.

Thank you for holding. Good morning and welcome to the Passage Bio first quarter 2022 financial and operating results conference call. All participants are in a listen-only mode. Following the formal remarks, we will open the call for your questions. Please be advised this call is being recorded at the company's request. At this time, I'd like to turn the call over to Stuart Henderson, Vice President of Corporate Development and Investor Relations. Stuart, please proceed.

Thank you, Operator. This morning, we issued a press release that outlines the topics we plan to discuss today. This release is available on the Passage Bio website under the Press Releases and Statements section of Investors & News. On today's call, Bruce Goldsmith, President and Chief Executive Officer, will review our first quarter 2022 and recent business highlights, and Simona King, our Chief Financial Officer, will review our first quarter 2022 financial results. Before we begin, please note that today's call may include a number of forward-looking statements, including but not limited to comments on our expectations about timing and execution of anticipated milestones, including the initiation of clinical trials and the availability of clinical data from such trials, our expectation about our collaborators' and partners' ability to execute key initiatives, the ability of our lead product candidates to treat their respective target CNS disorder, manufacturing plans and strategies, trends with respect to financial performance and cash flows, the company's ability to fund research and development programs, impact of the COVID-19 pandemic on the company's operations, and its ability to manage costs along with the uses of cash and other matters. These forward-looking statements are based on assumptions that are subject to risks and uncertainties that could cause the company's actual results to differ significantly from those suggested by these statements. Given these risks and uncertainties, you should not place undue reliance on these forward-looking statements. Please refer to the company's filings with the SEC for information concerning risk factors that could cause its actual results to differ materially from expectations, including any forward-looking statements made on this call. Except as required by law, the company disclaims any obligation to publicly update or revise any forward-looking statements to account for or reflect events or circumstances that occur after this call. It is now my pleasure to pass the call over to CEO, Bruce Goldsmith. Bruce?

Thanks, Stuart, and thank you all for joining us this morning. We continue to make considerable progress across our programs as we remain committed to our mission of developing transformative therapies for devastating CNS disorders with limited or no approved treatment options. Recent examples of this progress include positive interim safety, biomarker, and clinical efficacy data from cohort one of our IMAGINE-1 trial for GM1 gangliosidosis. Dosing of the first patient in cohort two and completion of dosing of cohort three in this IMAGINE-1 trial. Dosing of the first patient in cohort one of the GALAXY clinical trial for early infantile Crab A disease. Opening of additional clinical trial sites in the U.S. and Brazil for our UPLIFT-D trial for frontal temporal dementia, bringing our total current active sites to three. We have established a global network of trial sites across our three clinical programs with active sites in the United States, Brazil, Canada, UK, Israel, and the Netherlands. We are also thrilled to announce that we recently submitted an IND for a phase one trial of PBM-L04 in metachromatic leukodystrophy, a rare pediatric lysosomal storage disorder. This marks the achievement of another of our corporate goals and brings us closer to having a fourth program in clinical development. As we continue to advance our programs and mission, we have continued to evaluate our business needs and adapt accordingly. In March, we announced the strategic decision to focus our organizational priorities, reduce our operating expenses, and invest in programs that support our forward-looking plans by aligning our organization and foundational partnership with Penn's GTP, or gene therapy program, around a more focused R&D strategy. Key elements of this strategic prioritization include continued commitment to the advancement of our three ongoing clinical programs for GM1 gangliosidosis, Krabbe disease, and FTD. focusing of our preclinical pipeline with continued investment in our programs for MLD, ALS, and Huntington's disease, as well as our exploratory research programs for Alzheimer's disease and temporal lobe epilepsy. As a result, rights to our programs for Canavan disease, Charcot-Marie-Tooth type 2a, and Parkinson's disease have been returned to the University of Pennsylvania for future development by GTP or external parties. Through this prioritization, we have retained balance in our CNS portfolio with three rare pediatric programs, three rare adult programs, and two exploratory research programs in large adult indications. We also continue to retain eight additional license options for future CNS indications through our productive partnership with Penn's GTP. Operationally, we streamlined our organization via a 13% workforce reduction and have slowed investment in our pilot manufacturing suite. This strategic prioritization and associated reductions to our operating expenses extends our cash runway into the second quarter of 2024, and we believe we are well positioned to deliver on multiple value-creating clinical milestones over the next two years. I will now review the progress made across each of our three ongoing clinical programs. First, let me discuss our lead program, PBGMO1 for GM1 gangliosidosis. GM1 is a fatal neurological lysosomal storage disease caused by a GLB1 gene mutation that results in low activity of the beta-galactosidase enzyme. This leads to rapid neurological decline and in the most severe forms, unfortunately, to mortality within several years. Our IMAGINE 1 clinical trial focuses on the early and late infantile forms of GM1, which are the most severe forms of the disease. This global phase 1-2 trial is an open-label dose escalation study with PBGMO1 enrolling four distinct cohorts divided by age and dose level. As a reminder, our approach uses a next-generation proprietary AAVHU68 capsid administered via the cisterna magna to deliver a codon-optimized GLB1 transgene to increase beta-galactosidase enzyme activity in the brain and peripheral tissues. We were pleased to report positive interim safety biomarker and clinical efficacy data from cohort one at the World Symposium in February. These data showed that PVGMO1 was well-tolerated and had a positive safety profile with no serious adverse events and no complications related to ICM delivery. We demonstrated no evidence of DRG toxicity based on nerve conduction studies and substantially increased beta-galactositis enzyme activity in both CSF and serum after ICM delivery. As we have previously discussed, we believe improvement in milestones is a very important clinical outcome for children with lysosomal storage diseases. We are extremely pleased to see meaningful improvement in developmental milestones for these children, including the regaining of lost milestones. Our IMAGINE 1 trial has experienced strong momentum. We have now dosed the first patient in the high-dose late infantile cohort 2 and have completed dosing of both patients in the low-dose early infantile cohort 3. We remain on track to report initial safety and biomarker data from each of these cohorts in the second half of 2022. We also look forward to sharing additional clinical data from Cohort 1 during a late-breaker oral presentation on Wednesday this week during the American Society of Gene and Cell Therapy 25th Annual Meeting. Moving on to our global PDKRF3 program in Krabbe disease called Galaxy, Krabbe disease is a condition that progresses rapidly, damaging both the brain and the peripheral nervous system and resulting in a life expectancy of only two years in the severe cases. Krabbe disease is a fatal neurological lysosomal storage disease caused by a GALC gene mutation that results in a decreased enzyme activity of galactosylcirimidase. Preclinical data supporting this program were recently published by our GTP colleagues in the journal Human Gene Therapy. These robust preclinical results reported marked improvements in both disease progression and key biomarkers in large and small animal models of Krabbe disease following a single administration of PBKR3 with no observed dose-limiting toxicities. Like GM1, this is also a pediatric leukodystrophy and lysosomal storage disease with an underserved population with a very devastating disease progression. Our approach is also similar, utilizing the same proprietary capsid and ICM delivery to potentially address both CNS and peripheral disease manifestations. GALX-C is an open-label dose escalation study of PBKR3 in patients with early infantile Krav-A disease. We have now opened four sites for recruiting globally, including in the United States, Canada, the Netherlands, and Israel. In March, we announced the dosing of the first patient in cohort one of our Galaxy clinical trial. As with all our trials, we are committed to patient safety and transparency, and in this spirit, we want to share that the first patient experienced a grade four adverse event. Following review of the safety data by the Independent Data Monitoring Committee, or IDMC, we are proceeding with the study. To review in a little detail, 26 days after dosing, the patient experienced a grade 4 adverse event of acute hydrocephalus, which is a buildup of the CSF in the brain. The patient underwent a procedure to manage this condition and has been stable post-procedure. Following an investigation, this adverse event was assessed to be possibly related to either study treatment or study procedures due to the temporal proximity of the adverse event to the administration of treatment. At the time of the event, there was no evidence of an inflammatory reaction to the AAV vector or transgene in blood or cerebral spinal fluid. However, the role of disease progression may also be a factor. Hydrocephalus has been reported in the literature in association with Krabbe disease, and baseline imaging showed evidence of changes in the ventricles of the brain that did progress following dosing in this patient. We have also noted that preliminary biomarker data showed rapid normalization of GALC activity and reduction of psychosine in both serum and CSF within 30 days. As I mentioned, patient safety is of the highest importance to us. We have been working closely with IDMC and external experts to gather further information and to advance the development of PBK-R03. We also notified health authorities and study investigators of this event. The IDMC has reviewed all available information and has recommended continuation of the clinical trial with specific modifications. These modifications include changes to the inclusion and exclusion criteria to limit potential risk of hydrocephalus and additional safety monitoring following administration of PBKR3. We are implementing these modifications expeditiously. In addition, we are increasing the number of subjects in cohort one from three to four per study protocol following this adverse event. We are actively recruiting patients for cohort one and look forward to reporting initial safety and biomarker data by the end of 2022. Our third clinical program, PBFTO2, is for frontal temporal dementia with granular mutations. FTD is a devastating form of early onset dementia affecting patients between the ages of 40 to 65. The form of the disease we are seeking to treat with our therapy is caused by a granulin or GRN gene mutation, which results in a deficiency of progranulin. It is estimated that about 5 to 10% of FTD is caused by a GRN mutation. We are utilizing the AAV1 capsid to deliver the GRN gene via ICM to the CSF. The goal of this treatment and delivery approach is to potentially provide higher than normal levels of progranulin protein to the CNS to overcome the progranulin deficiency in GRN gene mutation carriers. We plan to enroll two cohorts of three patients each, receiving two different ascending doses of PBFTO2, with an optional third cohort treated with a higher dose, depending on safety and biomarker results observed in the first two cohorts. We now have three active clinical trial sites, including two in the United States and one in Brazil, and activation efforts at additional sites continue. Patient identification also remains a key area of focus and continues to be a challenge to enrolling the initial patient on our study. We have been and continue to be working closely with referral centers and are employing strategies to improve the rate of the genetic testing among FTD patients. including sending testing kits free of charge to clinical sites and offering education on genetic testing. We believe these efforts, in addition to opening additional clinical trial sites, will improve patient recruitment, and we expect to dose the first patient in our FTD trial by mid-2022. Turning lastly to our program for metachromatic leukodystrophy, or MLD. Infantile MLD is a fatal inherited disease caused by mutations in the ARSA, or the aryl sulfatase A gene, which reduces enzyme activity. MLD is characterized by muscle weakness, rigidity, gait disorder, and developmental delays, and unfortunately, children typically die by the age of five. Worldwide incidence is approximately 1 in 100,000 live births. We are excited to have recently submitted an IND to FDA for a Phase 1-2 clinical trial of PBM-L04 in MLD, which we set out to accomplish by mid-2022. Following FDA review, we plan to provide more information about our clinical program. The study will utilize ICM administration to deliver an AAV HE68 capsid to express ARSA and hopefully address both the central nervous system and peripheral manifestations of this devastating disease. Preclinical data supporting this program will be presented in a poster from our GTP colleagues at the ASGCT meeting this week. We also look forward to sharing more about our clinical plans for this program in the future. Our clinical focus and mission are highlighted by the similarities across our GM1, CRABA, and MLD programs. All three indications are lysosomal storage disorders affecting children, and our approach to developing novel therapies for each of these programs utilizes a proprietary HU68 capsid and ICM delivery. With that, I will now turn the call over to Simona to review our financials.