Passage Bio, Inc.

Thank you for holding. Good morning, and welcome to the PassageBio fourth quarter and full year 2020 financial and operating results conference call. At this time, all participants are in listen-only mode. Following the formal remarks, we will open the call up for your questions. Please be advised that this call is being recorded at the company's request. At this time, I'd like to turn it over to Stuart Henderson, Vice President of Investor Relations and Strategic Finance. 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 PassageBio website at investors.passagebio.com under the News and Events section. On today's call, Bruce Goldsmith, President and Chief Executive Officer, and Rich Morris, Chief Financial Officer, will review our fourth quarter and full year 2020 financial results and discuss recent business highlights. Terry Romano, our Chief Medical Officer, and Jill Quigley, our Chief Operating Officer, will also be available for the Q&A portion of the call. 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 expectations about our collaborators' and partners' ability to execute key initiatives, the ability of our lead product candidates to treat their respective target monogenic 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, impacts 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. Let me begin by remarking on the incredible year of accomplishments we had at Passage Bio in 2020, despite the COVID-19 pandemic and other challenges we all faced last year. Our company's work is grounded in the mission to develop life transforming therapies for patients with devastating CNS disorders. We view 2020 as a foundational year in which we focused on preparing for a successful transition to a clinical stage company in 2021. We began 2020 with a successful IPO, which gave us a strong financial position from which to build. We further strengthened our financial position earlier this year with a public offering that raised $166 million in net proceeds. Our work over the past year focused on advancing three programs, all of which are set to begin clinical development in the first half of this year. PB-GMO1 for GM1 gangliosidosis, PB-KRO3 for Krabbe disease, and PBFT02 for frontal temporal dementia with granulone mutations. We recently received regulatory clearance in the U.S., U.K., and Canada for the global PBGMO1 Phase 1-2 clinical study, IMAGINE1, for the treatment of patients with infantile GM1. We have also activated our first site in the U.S. and are currently recruiting patients. Other site activations are in progress, and we continue to expect to dose our first patient in the first quarter of 2021. In early 2021, we also received FDA clearance for the IND applications for two additional programs in early infantile Krav-A disease and in frontotemporal dementia with granulin mutations. Other recent regulatory actions to take note of are orphan drug and rare pediatric disease designations from FDA for both the GM1 and Crab A programs. Adoption of a positive opinion by the European Medicines Agency for PBKRO3 and Crab A disease for a orphan drug designation. We expect the European Commission to endorse the positive opinion by the end of the quarter. Just recently, FDA granted our FTD program, Fast Track Designation, which is designed to facilitate the development and expedite the review of drugs to treat serious conditions and fill unmet medical need. Our FTD program also received orphan drug designation earlier this year from FDA. We have also made important strides expanding our patient identification and engagement efforts, which are crucial to advancing successful gene therapy programs. For our GM1 program, in addition to our ongoing natural history study with the Penn's Orphan Disease Center, We have collaborations with Invitae and New York Screen Plus to help identify patients as early as possible who may be able to benefit from our investigational therapies. We are also sponsoring genetic screening and counseling for patients with FTD, while also engaging FTD trial sites that are participating in the ongoing all-FTD and gen-phi natural history studies, which may be helpful to identify patients for enrollment in our clinical study. On the manufacturing side, we are establishing internal and external manufacturing capabilities to meet the needs of our growing pipeline. This includes initiation of vector manufacturing in our dedicated CGMP suite at Catalan late last year, as well as the planned opening of our own CM&C lab in the second quarter of this year to support analytical development, clinical product testing, and assay validation. These, together with our supply chain partnerships, will enable us to advance our growing pipeline and will provide us with increased control and flexibility across our global end-to-end clinical supply chain. As I said at the outset, we have been able to support all these initiatives, from advancing our pipeline programs to supporting various patient identification and engagement initiatives, to bolstering our manufacturing capabilities, in large part because of our strong financial position and our experienced team. In 2021, we continue to operate from a position of financial strength, and our priority will be progressing our three most advanced programs through clinical development, as well as continuing to expand our pipeline and internal operations. The advancement of PassageBio to deliver three programs to the clinical stage, as well as continued advancement in our earlier pipeline, demonstrates the extremely productive collaboration between PassageBio and Jim Wilson and the gene therapy program at Penn. We anticipate 2021 and beyond to continue that strong partnership with a shared goal of advancing programs to patients with rare CNS disorders. I will spend the next portion of my remarks updating you on each of our planned clinical development programs. Let's start with our Imagine One study for infantile GM1. As I mentioned, we are extremely excited to have received regulatory clearance and be moving our first asset into clinical development. As a reminder, GM1 is a devastating rare monogenic recessive lysosomal storage disease that impacts patients worldwide. It is caused by mutations in the GLB1 gene encoding the enzyme beta-galactosidase. We are targeting the infantile form of the disease, which is the most severe, with a very rapid disease course and no current treatment options beyond supportive care. PBGMO1 utilizes a next-generation AAVHU68 capsid administered through the intercisterna magna to deliver a functional GLB1 gene encoding beta-gal to the brain and also to peripheral tissues. Published preclinical data from GTP in the peer-reviewed journal Human Gene Therapy supports the potential of PBGMO1 as a treatment for GM1. Our Phase I-II trial, IMAGINE-1, is a global open labeled dose escalation study of PBGMO1 administered by a single injection into the cisterna magna in subjects with early and late onset infantile GM1. The study will enroll a total of four cohorts of two patients each with separate dose escalation cohorts for late onset infantile and early onset infantile GM1. As I mentioned earlier, we have activated our first site and expect to dose our first patient in this quarter. We also expect to report 30-day initial safety and biomarker data, specifically the impact on beta-gal enzyme activity from our initial cohort in mid-2021. We are actively screening eligible patients for the trial, and activations are underway for additional sites. We plan to open 10 sites globally and currently have clinical trial authorizations in the U.S., U.K., and Canada. We are also in discussion with regulatory agencies and key physicians in Brazil and Turkey both countries in which there's a higher incidence of GM1 due to a founder's effect. As we continue to bring on clinical sites, we are ramping up patient identification and education efforts. This includes our partnership with Invitae, a leading medical genetic testing company, as well as our sponsorship of the New York Screen Plus pilot program, which offers newborn screening for rare diseases. Additionally, we have strong relationships with the site coordinators and investigators that are driving the study forward. Turning to CRAB-A disease and FTD-GRN, we were very happy to receive IND clearance from FDA for both programs, and preparations for the Phase I-II trials are continuing. We anticipate the start of both trials to occur in the first half of this year, with initial 30-day safety and biomarker data readouts in late 2021 or early 2022. As we seek to expand our reach to patients around the globe for these two indications, we are also filing for clinical trial authorizations in countries outside the U.S., and will provide further updates on those regulatory filings as appropriate. Next, I will give you a brief overview of the programs for Krabbe disease and FTGGRN, starting with Krabbe disease. PBKRO3 is being developed for the treatment of early infantile Krabbe disease, or globoid cell leukodystrophy, a rare lysosomal storage disease caused by mutations in the gene encoding the enzyme galactosylcerimidase, or GALC. This results in rapid progressive damage to both the brain and peripheral nervous system and, if untreated, leads to mortality by two years of age. PVK-RR3 utilizes a next-generation AAV HE68 capsid to deliver DNA-encoding galactosyl cervidase enzyme to patient cells. Our Phase I-II trial will be an open-label dose escalation study of PVK-RR3 administered by a single injection into the cisterna magna in pediatric subjects with early infantile Krabbe disease. Our first goal of the study is to demonstrate that PDKRO3 is safe for patients with early infantile Krabbe disease. Our second goal is to demonstrate an increase in GALC. We hope to demonstrate this increase in the biomarker in both cerebral spinal fluid and serum of patients. The dose escalation portion of the trial will look very similar to the design for our GM1 program, separated by dosage and by age group. We will be enrolling a total of four cohorts of three subjects each with separate dose escalation cohorts based on age at enrollment. We will initiate dosing with the low dose of PVKR3 in the first cohort of subjects who are between four and nine months of age. If deemed safe and tolerable, we will move into a high dose cohort in subjects who are also between four and nine months of age and a low dose cohort in subjects who are between one and four months of age. Our final dose escalation cohort plan to evaluate a high dose in subjects between one and four months of age. These dose escalation cohorts will be followed by a confirmatory expansion cohort for both age groups. The initial data readout from the first cohort will include 30-day biomarker and safety data. As I've discussed for other programs, and as is the case with all rare diseases, patient identification is a main focus point, especially when considering the early and devastating impacts of a disease such as Crab A. To support this, we are working with leading physicians and patient groups on initiatives to expand newborn screening. Turning our attention to BBFTO2 for FTD granulin, which is an adult condition generally affecting patients in their 50s, but can impact adults as young as the 30s. FTD is one of the most common causes of early onset or midlife dementia. causing impairment in behavior, language, and executive function, and it occurs at a similar frequency to Alzheimer's disease in patients younger than 65 years old. In approximately 5 to 10% of individuals with FTD, 3 to 6,000 patients in the United States, this disease occurs because of mutations in the GRN gene, causing a deficiency of progranulin. The mechanism by which progranulin deficiency results in FTD is uncertain, but increasing evidence points to progranulins' role in lysosomal function. The rapid progression of FTD results in an average survival of only eight years after onset of symptoms. As a reminder, PBFTO2 is a gene therapy that utilizes an AAV1 vector to deliver to the brain a functional granulin gene encoding the progranulin protein. In a preclinical study by GTP published in the peer-reviewed scientific journal of Annals of clinical and translational neurology, a single administration of PBFTO2 via the optimized AAV1-GRN vector demonstrated CSF progranulin reaching levels of more than 50-fold, supporting our advancement of PBFTO2 into clinical study. The Phase I-II program will be an open-label dose escalation study of PBFTO2 administered by a single injection into the cisterna magna in subjects with early symptomatic FTD and pathogenic mutations in the progranulin gene, or FTD-GRN. We have two key goals for the Phase 1-2 study. Our first goal is to demonstrate that PB-FTO2 is safe for patients with FTD-GRN. Our second goal is to demonstrate increased progranulin levels in the CSF. We will enroll two cohorts of three patients each with an optional third cohort, and we'll initiate dosing with a low dose of PB-FTO2 in the first cohort, As is typical for a dose escalation study, if the low dose is well tolerated, we will study a higher dose in the second cohort. The initial data readout from the first cohort will include safety data and 30-day biomarker data, including change from baseline and CSF progranular levels. As we have discussed, FTD is a devastating disease that impacts patients worldwide, and we are dedicated to serving patients in the U.S. and across geographies. We have continued to build relationships with patient groups to help increase the potential reach of our programs and are working to support genetic screening and counseling to patients with FTD free of charge. As we embark on all three clinical development programs, the safety of our patients is our top priority. To address the current challenges associated with COVID-19, we have implemented approaches such as remote assessments where possible and concierge services through third-party vendors to facilitate travel due to increased burdens and restrictions. We believe these measures will provide patient support while also maintaining the rigor of our clinical trials and our ability to provide these potentially life-altering therapies to patients. Again, we are very excited to have received regulatory clearance for all three of our lead programs and look forward to providing further updates as we begin dosing patients in the coming months. Turning to manufacturing, as I mentioned earlier, we have made important progress this year towards establishing both our internal and external manufacturing capabilities. Manufacturing capacity has been a key tenet of our strategy since launching the company, and securing control of our supply chain is an important part of our differentiated approach as we continue to advance and grow our pipeline. Some recent accomplishments include initiated vector manufacturing in our dedicated CGMP suite at the Catalan Cell and Gene Therapy Facility in Maryland, signed a lease for our manufacturing laboratories at the Princeton West Innovation Campus in Hopewell, New Jersey, which we plan to open in the second quarter of 2021, and which will support analytical development as well as clinical product testing and assay validation. established a flexible global end-to-end clinical supply chain by entering into a number of partnerships and supply agreements. These agreements span from plasmid production for our vectors to clinical packaging and on-demand global distribution to our clinical sites based on patient need. We are pleased to share that our clinical supply for PBGMO1 for our Phase I-II IMAGINE I trial, manufactured through our partnership with Catalan, is already in place. We have also manufactured clinical supplies to support initiation of our clinical study for our next two of us advanced programs for Crab A disease and for FTD-GRN. Finally, we want to note that in 2020, we invested to substantially expand our R&D and manufacturing internal expertise. In 2021, we are continuing to hire key talent to ensure superb execution of our clinical trial programs, and our end-to-end manufacturing processes with the goal to be a leader in delivering transformational gene therapies to patients. And with that, I will turn the call over to Rich to give a financial update.