Passage Bio Inc (PASG) 2021 Q1 法說會逐字稿

Thank you for holding. Good morning, and welcome to the Passage Bio First Quarter 2021 Financial and Operating Results Conference Call. (Operator Instructions) 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 Passage Bio website at investors.passagebio.com under the News & Events section. On today's call, Bruce Goldsmith, President and Chief Executive Officer, and Rich Morris, Chief Financial Officer, will review our first quarter 2021 financial results and discuss recent business highlights. Eliseo Salinas, our Chief Research and Development Officer; Gary 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 expectation 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 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 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. I will begin my remarks by highlighting our company's overall progress. In just 2 years since the launch of Passage Bio, I am proud to report that we have successfully transitioned to a clinical stage company with differentiated therapies in our pipeline. This is a credit to our talented and committed team who have successfully obtained multiple global regulatory authorizations for our 3 most advanced programs in the past few months.

We are driven by our mission to develop life-transforming gene therapies for infants and adults who suffer from rare and devastating neurological diseases, who desperately need our treatments. Their journey inspires us to move with urgency in executing our ambitious strategy, which is underpinned by 4 strategic pillars. One, our partnership with the University of Pennsylvania's Gene Therapy Program, or GTP; two, the broad and robust pipeline that we have established; three, the integrated manufacturing supply chain that we are continuing to build out; and, four, our solid corporate foundation, which includes a highly experienced team and a strong cash position.

We started 2021 with strong execution. For example, in a period of less than 2 months, we obtained 3 IND approvals. On April first, we also announced a major milestone for the company, and for patients, with the dosing of our first patient in our global Imagine-1 trial of PBGM01 for infantile GM1 gangliosidosis. These recent accomplishments reflect the tremendous efforts of our team, and our partnership with GTP. We are continuing to focus on activating additional clinical sites for our GM1 program, and initial sites for our other 2 programs in frontal temporal dementia and Krabbe disease.

While we are diligently working to activate sites across our programs, we are experiencing some impact due to COVID-19 on site openings. This includes meeting delays with various investigation review bodies or Ethics Committees, that have prioritized COVID-19-related clinical trials over ours, and also staffing levels at site hospitals. Given the situation, we have updated our expected timelines for the upcoming clinical milestones for the 3 clinical stage programs. For GM1, we are now expecting to report initial safety and 30-day biomarker data in the fourth quarter of this year. We now expect to enroll the first patient in our Phase I/II FTD-GRN trial in the second or third quarter of this year. And expect to enroll our first patient in our Phase I/II Krabbe trial in the third quarter. Additionally, we expect to report initial data for these programs in the first half of 2022.

Patient identification and recruitment remain key areas of focus, and we have established a variety of initiatives to support this, including planned clinical trial sites on 3 continents at centers of excellence, establishing free genetic screening, and forming partnerships with advocacy groups to raise awareness of our clinical trial programs.

Today, I will review the status of each of our lead programs, highlighting certain key aspects that will be important to keep in mind in the year ahead. Before delving into each program, I would like to review their commonalities, which are also important to keep in mind. First, all 3 lead programs address rare monogenic CNS conditions with devastating impact. For all 3 conditions, disease progression is rapid following symptom onset and survival is severely shortened. This is why, again, we have made early patient identification a priority. Since the severe symptoms of these disorders are driven by CNS disease manifestation, and because of our strong supporting preclinical data, we are using direct CSF delivery via intra-cisterna magna, or ICM, administration for our 3 most advanced therapies. This direct route into the CSF achieves broad CNS distribution. It requires relatively low doses compared to IV systemic delivery and reduces the impact of neutralizing anti-capsid antibodies. ICM is administered to patients under anesthesia while using modern neuro-imaging to support a painless and precise delivery into the cisterna magna while avoiding blood vessels and neuro structures. For these reasons, ICM administration is being increasingly used to deliver gene therapy to the CNS and is currently in use for at least 7 other clinical studies in both pediatric and adult patients. Finally, I will point out that while all 3 of our lead programs are in disease areas where there are competing programs, we believe our programs are highly differentiated. From our vantage point, competition is raising awareness of these rare diseases, both for the need to identify patients early and bringing forward the possibility of treatments for patients.

Turning our attention specifically to GM1, I want to stress again how pleased we are to have dosed the first patient in our global Imagine-1 trial, and I want to extend our gratitude to the family, patient and health care providers for their support in helping us begin to realize the potential of PBGM01 treat patients with GM1 gangliosidosis. As a reminder, our Imagine-1 trial is focused on the infantile form of the disease, which is the most severe form, with a very rapid disease course and no current treatment options beyond supportive care. The Phase I/II trial is a global, open-label study of PBGM01 administered by a single injection into the cisterna magna in subjects with early and late-onset infantile GM1. Our study will enroll a total of 4 cohorts of 2 patients each, with separate cohorts for late-onset infantile and early-onset infantile GM1. Our ultimate aim with this study is to develop a transformative gene therapy that will preserve neurologic function and improve developmental potential, survival and quality of life for patients with GM1. The primary goal of the initial data from the trial is to assess safety and tolerability to allow for dose escalation and progress into our early infantile cohorts. We also plan to measure beta-galactosidase enzyme activity in the CSF and serum. This is important, because we know that earlier onset and greater severity of disease generally correlate with lower levels of beta-gal activity.

As I mentioned earlier, we expect to report initial safety and tolerability data, and 30-day enzymatic activity of beta-gal for the first cohort of late infantile patients in the fourth quarter of 2021. As we reported in our press release last month, our first patient has been dosed in the United States. We also have received regulatory clearance in the UK, Canada, and very recently, Brazil. We plan to open 10 sites globally and are also focused on countries like Brazil and Turkey, in which there is a higher incidence of GM1 due to a founder's effect, which we believe will help with patient enrollment.

Additionally, we are ramping up patient identification efforts through partnerships such as the ones we have with Invitae and New York's ScreenPlus pilot program. We have also built a strong network with patient advocacy groups and site coordinators and investigators at centers of excellence specializing in lysosomal storage disorders. This comprehensive approach has been immensely useful in helping us to identify patients for our initial cohort, and we are confident that these efforts will be able to support enrollment in our ongoing program.

Now, turning our attention to the PBKR03 program and Krabbe disease. We have received regulatory clearance to initiate our clinical trial for this program from FDA, the MHRA in the United Kingdom, and Health Canada. Krabbe disease progresses rapidly, damaging both the brain and peripheral nervous system and resulting in a life expectancy of only 2 years. Our global Phase I/II trial, GALax-C, will be an open-label dose escalation study of PBKR03 that will use an AAV-capsid to deliver the GALC enzyme via ICM in patients with early infantile Krabbe disease. As discussed, we expect that we will dose our first patient for the GALax-C study in third quarter of 2021, and we will report initial safety and 30-day biomarker data in the first half of 2022. Our first goal of the study is to demonstrate that PBKR03 is safe for patients with early infantile Krabbe disease. Our second goal is to demonstrate an increase in GALC. We hope to demonstrate an increase in this biomarker in both the CSF and serum. The dose escalation portion of the trial will look very similar to the design for our GM1 program, separated by dosage and age group. We will begin enrolling a total of 4 cohorts of 3 subjects each, with separate dose escalation cohorts based on age at enrollment.

We are optimistic about the transformative potential of our therapy as a single agent, based on animal models. To remind you, in the naturally occurring Krabbe canine model, a single ICM injection of an AAV vector carrying a functional canine GALC gene resulted in normalization of GALC activity, reduced CSF cytokine levels, normalized peripheral nerve conduction velocity, improved brain myelination, reduced brain inflammation and increased survival. These beneficial effects on peripheral nerve function are especially encouraging because if it translates to humans, it will potentially treat the peripheral neuropathy that causes severe disabling motor deficits in Krabbe disease.

Newborn screening is especially important for rare pediatric diseases like Krabbe, where it is ideal to identify pre- or early symptomatic babies for treatment, to hopefully produce the best outcomes. For Krabbe newborn screening, we are working state by state with advocacy groups and key stakeholders to support the development of additional testing and Krabbe newborn screening to support early and accurate identification of babies with Krabbe disease. We believe that by refining newborn screening, we can reduce the rate of false positives and aid in differentiating between newborns at high risk of developing early-onset Krabbe disease versus late-onset Krabbe disease. We have also expanded our collaboration with Invitae to include Krabbe disease in its lysosomal storage disease genetic testing program, which provides access to free genetic testing and counseling as well as referrals to appropriate clinical trial programs.

Next, let's discuss our third global clinical trial program for PBFT02 for the treatment of frontotemporal dementia with granulin mutations. This global Phase I/II clinical trial called upliFT-D now has regulatory authorizations to initiate clinical trial sites in the United States and Canada. As many of you know, FTD is one of the more common causes of early onset dementia. We are specifically focused on FTD-GRN where the disease occurs because of mutations in the GRN gene causing a deficiency of progranulin. To help identify patients for the upliFT-D trial, we have entered into a collaboration with InformedDNA in which we are offering free genetic testing and counseling to patients who have been diagnosed with FTD. The program will facilitate identification of FTD patients with an inherited genetic mutation, providing an important step for designing individualized treatment approaches as well as potential support for clinical trial enrollment. It is estimated that about 5% to 10% of FTD is caused by GRN gene mutations, leading to a deficiency of progranulin. This translates to about 3,000 to 6,000 patients in the United States. upliFT-D will be an open-label dose escalation study of PBFT02, which utilizes an AAV1 vector to deliver to the brain a functional granulin gene encoding the progranulin protein administered by a single injection into the cisterna magna in subjects with early symptomatic FTD-GRN. We now anticipate dosing our first patient later in the second or in the third quarter of this year and reporting initial safety and 30-day biomarker in the first half of 2022. Our first goal for this study is to demonstrate that PBFT02 is safe for patients with FTD-GRN. Our second goal is to demonstrate increased progranulin levels in the CSF. On May 17th, we have scheduled an R&D webinar during which we will go into deeper role of progranulin as it relates to FTD. We will also review the preclinical data supporting our clinical development plans and we'll discuss our clinical trial design and what we hope to see from the trial.

As I mentioned at the outset, we are sharply focused this year on the successful clinical development of our 3 most advanced programs. We are also focused on advancing and expanding our preclinical pipeline in collaboration with GTP. To lead these efforts, we are truly excited to have recently appointed Eliseo Salinas as our Chief Research and Development Officer. Eliseo brings deep and broad R&D experience, having worked in the pharmaceutical and biotech industry for more than 3 decades. He also has extensive experience in neuroscience and rare diseases, which is well aligned with our company's focus on rare CNS disorders.

As we advance our robust pipeline, flexible and scalable manufacturing capabilities and control of our supply chain are other important components for our company's success. To complement our dedicated manufacturing suite at Catalent and our established clinical supply distribution relationships, we look forward to opening our gene therapy manufacturing R&D site in New Jersey this quarter.

We are also pleased to have added Maxine Gowan to our company's Board of Directors as we continue to evolve as a clinical stage company. Maxine brings significant public company leadership and clinical development expertise having co-founded and led a startup biotech company and served in a variety of leadership roles at GlaxoSmithKline over a period of 15 years.

And with that, I will turn the call over to Rich to give a financial update.

Thank you, Bruce. Before reviewing our expenses for the quarter, I want to reiterate our strong cash position as a result of our follow-on financing in January. As we reported in our press release this morning, we ended the quarter with cash, cash equivalents and marketable securities of approximately $438 million as compared to $305 million as of December 31, 2020. We expect these cash, cash equivalents and marketable securities to fund our operations for at least the next 24 months.

R&D expenses increased by $12 million to $25 million for the quarter ended March 31st compared to $13 million for the first quarter of 2020. The increase was primarily due to an increase of $5 million in clinical manufacturing costs, a $400,000 increase in clinical development and professional services expense, and a $600,000 increase in facility and other costs. We also had a $9 million increase in personnel related costs, including a onetime share-based compensation charge of $5 million. These increases were offset by a $3 million decrease in preclinical research and development costs incurred associated with our IND filings for our lead indications. We also incurred $1.5 million of in-process R&D expenses during the 3 months ended March 31, 2021 in connection with the development milestone. There were no such expenses in the first quarter of 2020.

G&A expenses increased by $7.7 million to $12.5 million for the quarter ended March 31, 2021 compared to $4.8 million for the first quarter of 2020. The increase was primarily due to a $4 million increase in personnel related and share-based compensation expense due to increases in employee head count. Our professional fees and facility costs also increased by $3 million as we expanded our operations to support our research and development efforts. Net loss was $39 million for the quarter ended March 31, 2021 compared to $18 million for the first quarter of 2020.

Now I'll turn the call back to Bruce for closing remarks.

Thanks, Rich. As we look ahead to the remainder of 2021, we are focused above all on execution across our 3 clinical trials. In addition to our ongoing programs, investing in R&D initiatives and our preclinical pipeline advancement remain key imperatives for us in 2021 and beyond. We look forward to attending ASGCT next week where our partner GTP will be presenting several posters, including on metachromatic leukodystrophy and delivering a presentation related to discovery research in gene therapy that we helped support.

Looking ahead, our key anticipated milestones for our company in the upcoming year are: reporting initial safety and 30-day biomarker data in the fourth quarter of this year for the Imagine-1 Phase I/II trial of PBGM01 for infantile GM1; initiating Phase I/II trials for the treatment of FTD-GRN in the second or third quarter of this year, and for the treatment of early infantile Krabbe disease in the third quarter of this year; opening our CMC research and development site in the quarter; and continuing to advance preclinical programs for MLD, ALS and CMT2A and our undisclosed program, and bring additional candidates forward.

Before taking your questions. I'd like to take this opportunity to recognize and thank the team here at Passage Bio for their commitment to our programs and our patients as we work to change the lives of patients suffering from rare CNS disorders.

At this time, we would like to open the call up for your questions. Operator?

(Operator Instructions) Our first question comes from Anupam Rama with JPMorgan.

It seems that you have for GM1 regulatory clearance in multiple countries here; I count 4. Can you remind us of the time period that the second patient can enroll after the first patient has enrolled? And have you identified this second patient and has the site been selected as well? And do you have line of sight on activating this site to get the second patient enrolled? I'm really trying to understand if there's further risks to timeline delays here for GM1.

Anupam, thanks very much for the question. I'll start and then I'll turn it over to Gary Romano for a few more comments. But essentially the interval between patients as we've described is mandated by the discussions with the FDA. It's a 60-day window in order to ensure that there's enough and proper safety follow-up. Obviously this is a new agent and we and the FDA are just focused on making sure that there is proper safety review, and then the next patient can enroll. It does take several weeks for a patient to go through all of the formal testing and then potentially be enrolled.

As we've described before, it is sometimes the same site or sometimes other sites that may enroll each patient. I would just note that the investigators have been working together to potentially identify patients. And we have employed a group called Concierge to facilitate any travel that might be necessary for a patient to move from one location to another, for both the evaluation, administration and then initial follow-up, of course.

So Gary, I don't know if you want to talk a little bit more about the identification efforts, without getting into maybe so much detail about what we expect for the next study -- next patient enrollment, but maybe you could just comment on how we've been identifying patients today.

Yes. Thanks, Bruce. To answer your question directly, we haven't yet identified the next patient for enrollment but we have identified a number of patients who are interested in enrolling and with whom we are going through eligibility. So there is a queue. We're not ready to disclose, of course, anything more about that at this time.

Regarding the sites, the first site that we enrolled our first patient is a very busy site that may or may not have the capacity to enroll another patient in the next month or 2. We do have other sites that are coming on board very soon. And so multiple sites potentially coming on board in the next, let's say, several months beginning this month, next month or early third quarter.

Yes. So I think to summarize, you're absolutely right; we're focused on the same question you are, which is, are there going to be sites available? Are there going to be patients available to enroll the second patient? We hope that there's not a large interval in between the eligibility for -- after the 60 days. But as Gary said, while we do have patients identified in the queue, it's important to note that those patients do need to go onsite and get the final screening before they are actually dosed. So we're building all of that into our timelines and projections and the site initiations may or may not play a role into that, but we're watching all of that very carefully as we learn more about, as Gary said, when those sites will come on and the final identification of the patients.

Next question comes from Salveen Richter with Goldman Sachs.

So just following up on Anupam's question here, just maybe comment on your confidence that this 4Q '21 timeline for data for GM1 is intact and what the outstanding risks could be here. And then whether the other programs are on track just given what's played out with GM1. And then secondly would love just an update on the FTD program with results -- with regard to kind of learning from the competitive landscape as you look to start that trial.

Sure. Thanks very much for the question. The reason we were comfortable changing the guidance by approximately a quarter for the programs and also the overall timelines is really because we're getting increasing insights by further interactions with each site that we're trying to initiate. And because of the -- we definitely needed the regulatory clearance first in order to dig into each of the site initiation timelines and also just the operational details. Further, to your point, as we've initiated the GM1 study, we've obviously had increasing learnings about the overall COVID-19 impact for these sites and how this is being played out. That's why, if we put all of that together, we are comfortable with the 4Q 2021 timelines for data. We absolutely understand that changing the timelines could raise questions about whether -- how confident we are in those timelines. But we've looked, as Gary alluded to, when site activations are now projected based on the interactions with the Ethics Review Committee and the sites themselves as well as, as Gary said, the identification of patients. And GM1 mirrors, I think, Krabbe to a certain extent in terms of patient identification. And it's just giving us more clarity on the overall process. Krabbe does have one difference in that 10 sites now are doing newborn screening and so that could change the dynamic in terms of potentially identifying patients more rapidly, but it still is the site initiations that we're getting much more clarity on, especially in the COVID-19 era. So I think those are the rationale of why we changed the guidance. And on the new programs, similarly, once we had regulatory clearance, we were able to really start to work with the ethics review and the institutional review boards, not only in United States but elsewhere, and that feedback has given us much more clarity on those timelines. So I think that's the first part to your question.

The second part on FTD, we really haven't seen very much more data at this time from other programs. What we've seen -- what we do anticipate is some updates over time, but we haven't really seen a significant change from the first or second quarter of this year. Obviously we're really focusing on the 2 studies that are in clinical trials. One is the humanized monoclonal antibody against sortilin and the other is obviously the gene therapy using AAV9 vector. And those studies are enrolling. But we've also seen similarly, I think, one learning is, maybe not in the elector study, but in the other gene therapy studies, we have seen, similarly, a very slow opening of clinical trial sites. And that's one thing that we can take away is that we're not alone in this site initiation journey.

Our next question comes from Yaron Werber with Cowen.

I have a couple. The first one for GM1, maybe just give us a little bit of a sense, based on the preclinical models, how fast do you see that the stabilization from baseline to maximal reduction in the biomarker? I'm talking about GM1 first and then maybe Krabbe second. And then secondly, the new CMC research and development site, are you going to have -- is it also a CMC center for optimization or can you actually make clinical material there? And can that actually bridge you to commercialization, or do you need to go to a different site?

Yes. Thanks, Yaron. Thanks for the questions. So first I'll ask Gary to add some commentary on this. In both GM1 and Krabbe, we're looking at multiple different biomarkers for pharmacodynamic outcomes, and certainly we're looking at the enzyme activity and then downstream markers. Gary, maybe you can use GM1 and then I'll turn it over to Jill perhaps to just talk a little bit about the site -- the R&D manufacturing site. Gary, do you want to talk about the various biomarkers we're looking at in GM1 and Krabbe, and some of the kinetics we might see?

Yes, sure, sure. So in the near term, we're going to be reporting out on safety tolerability and our 30-day beta-gal activity. That will be in mid 2021. This is in -- or I should say fourth quarter. This is in line with our first goal of demonstrating that PBGM01 is safe and well tolerated in the patient population. Our second goal is, again, to measure effects on beta-gal enzyme in CSF and serum. We expect to be able to measure that within the first 30 days as we have in animals. And later on, we'll be measuring treatment effects on biomarkers of neurodegeneration such as NFL, and also biomarkers of brain structure and function, including MRI and EEG. We expect the NFL data to take at least 90 days before we would see a treatment effect there given the half-life of 2 to 3 months of that protein. And we expect it will take between 1 and 2 years to observe treatment effects on rates of progression in brain lesions on MRI or an EEG deterioration. With longer follow-up, we'll be assessing treatment effects on the clinical outcomes. The duration of our study is 24 months to reflect that. Using variety of validated scales to measure treatment effects on patient milestones -- developmental milestones to demonstrate that they have an improved developmental potential and positive effects on quality of life.

Did you also want me to comment on Krabbe, Bruce? I didn't hear you.

Yes, please.

Yes. So in Krabbe Disease, again, we're measuring a number of biomarkers there as well. We'll start off with, again, safety and tolerability and looking at the enzyme GALC and also one of the enzyme substrates psychosine, which is responsible for the negative effects on myelin-producing cells. We'll be measuring GALC at 30 days. We'll be measuring psychosine after that. Probably also we wouldn't expect to see necessarily effects as rapidly as you see effects on the enzyme activity, but later probably 90 days at a minimum. We have other -- a number of other biomarkers which we know track the disease progression, including nerve conduction studies where we look at nerve conduction velocities, and remind you that in the canine model we saw preservation and improvement in peripheral nerve myelination and central myelination. Also for brain structure, again, MRI studies and EEG and a number of other evoked responses that measure conduction in the central nervous system.

Thanks, Gary. And I think -- in summary, it just means that we're going to have readouts that are near term, which are really the enzymatic activity and then following these other markers over time. And I think that's the theme for all of our programs. So thanks for that summary, Gary. Jill, do you mind taking us through a little bit of the second question on the CMC R&D site?

Yes, of course. Importantly, as we think strategically about our manufacturing capabilities, our overall goal is to have those capabilities meet the needs of our growing clinical development programs running simultaneously. So what we're doing really is to establish a flexible end-to-end supply chain with dedicated manufacturing capability and global distribution through partnerships from clinical development through initial commercialization.

Specifically with regards to the CMC lab, that's going to be equipped initially with state-of-the-art analytical capabilities and will allow us to conduct assay development and validation as well as biomarker assay development and validation and clinical product testing, all of which are of course critical as you think about the development of gene therapies. We will not be producing clinical supply in that facility when it opens in the second quarter. That said, as we think strategically down the road, the location in Hopewell, New Jersey will allow us to expand to either add additional labs for QC testing and other activities and/or to add TT&P facilities as we start to understand the needs in the supply chain with regards to redundancy and we look towards commercialization.

Our next question comes from Neena Bitritto-Garg with Citi.

Just one quick kind of clarification on what we'll see in the fourth quarter of this year. I just want to confirm that the intention would be to essentially wait until you have the go-ahead okay for enrolling the second and third cohorts, kind of at the time that you provide us with data. So that's just my first clarification question.

And then a question on FTD really quickly. Just given that there are multiple other studies enrolling patients right now, and I know -- I think you are using some of the same sites like UCSF and Penn that are enrolling in some of the antibody studies, for example. I guess just if you could talk a little bit about how we should expect patient enrollment in that study to go just given competition from some of the other studies?

Thanks, Neena. Thanks for the question. So in the fourth quarter -- and then I'll turn it over to Gary to talk a little bit about how we select the sites and our interactions with the investigators on FTD. So in fourth quarter, you're absolutely right, we're expecting to report not only the 30-day beta-gal data from the cohort, also safety data and hopefully we'll also have the 60-day follow-up. And as we've highlighted in the clinical trial charts, we do anticipate having an IDMC meeting and review at the end of the cohort 1. And that IDMC review would obviously look at all of the data that's coming out of the cohort 1 and also have a recommendation or discussion on advancing to cohort 2 and 3. So that's what our anticipation is at this time. And it's certainly, I think, very important not only to have the data but also have the pathway forward, to your point.

So in addition to that discussion, on FTD, we've obviously looked at the sites very carefully and thought about sites that potentially have patients identified and sites that could identify patients in the network. Gary, do you want to talk a little bit more about the sites and the competition?

For FTD, we are -- we ran on patients out there. Not all of them have yet been identified genetically. So we're taking a two-pronged approach to patient identification. First, we're partnering with leading academic sites across the globe who are following families with known granulin mutation carriers. These are -- some of the sites you pointed out. We also have others in Europe where there's less direct competition. And these are investigators who are very enthusiastic to enroll eligible granulin mutation carriers that they're currently following.

But a second approach we're taking has to do with, as I said, many FTD patients out there who don't know their genetic status, haven't had genetic testing, 5% to 10% of which are expected to have granulin mutations. So to help identify those eligible patients with granulin mutations, we've recently engaged with InformedDNA to design and support a genetic screening and counseling program. This is going to be free of charge to FTD-diagnosed patients. And we're also working with other third parties to provide clinical trial information regarding ongoing FTD granulin studies. So we're feeling confident of being able to enroll this study as soon as we get our sites open. And also I should point out that we're also opening our first site later this month in the U.S. We are also targeting sites, as I mentioned, globally, in the U.K., in Europe, Brazil, Canada, which are advancing through IRB or ethics submissions at this time.

Our next question comes from Gbola Amusa with Chardan.

I think some of this has been answered, but we'll offer it out to anyhow just for additional detail. It's on your timeline's adjustment for the global Phase I and II due to COVID-19 except that the 1 quarter delay roughly is par for the course given external global forces. But could you talk a little bit more about your risk mitigation strategies that you now have in place with regards to your external partners? So what are the areas where there is some risk? And what are you doing to sort of ensure the timelines that have been put forward today?

Gbola, thanks very much for the question. So I think there's 2 or 3 primary groups that we would think about from a partnership perspective. One is certainly manufacturing and the partnership that we have with Catalent. And I will give a lot of credit to Alex Fotopoulos, our Chief Technical Officer, and his team by thinking very carefully about both the upstream work that goes into securing supplies and supply chain to make sure that we can stay on track for our manufacturing. And very pleased with the progress that he's made and building that team and then executing against that strategy to ensure that we can make the supply in our suite -- the dedicated suite that we brought online in December of last year and got qualified even during the pandemic. And I think that just -- and we're already manufacturing in that suite. I think that demonstrates part of the commitment to owning our own destiny in terms of manufacturing.

I will add to that that Alex and team have been very focused on downstream aspects as well. And that's obviously one of the reasons we have established partnerships with thinking about product testing and release, but we also want to own more of that going forward and that's why we're opening the R&D site that Jill highlighted. That's one aspect.

I think the second part is clearly working and continuously thinking about our partnerships with our CROs and work externally on regulatory partners, et cetera. And that just requires very careful management from our internal team. And it's kind of part of the standard operating work that we're doing, anticipating how those CROs and regulatory interactions are going, and then ultimately on the ethics reviews and IRBs. We do have a lot of activity ongoing because there are 3 studies that we're launching simultaneously. I think that the regulatory approvals that we've obtained really demonstrate that this is working very, very well. I think where we're getting some delays is obviously on the interactions at the site level, but those are productive. They're just, as you said, kind of the new reality.

And then, thirdly, and most importantly possibly, is our relationship with the University of Pennsylvania. And I will say that while UPenn obviously and the Gene Therapy Program that Jim has built is on paper and the relationship is moving forward to IND and then we obviously take over for all the regulatory interactions moving forward, but there is a continual support from people like Julie Johnston, who runs the manufacturing vector core, from the Head of Regulatory, et cetera. And there's a continuous relationship with Jim and his team that really provide just so such great expertise that we draw on constantly.

So those are the 3 primary groups. And I should mention that they're also obviously responsible for advancing our earlier pipeline as well, such as the MLD work that's going to be highlighted a little bit at ASGCT, and also they'll participate in the meeting that's coming up on FTD and highlight the work that they've done there. So I think those are the 3 external groups that we've spent a lot of time thinking about and working on. And I really want to thank Alex, Gary and his team for managing all of the complicated regulatory interactions, and obviously Jim and his team who have been instrumental in moving all this forward.

Our next question comes from Laura Chico with Wedbush Securities.

I actually have 2 -- and sorry to go back to the phone, but on the GM1 program, I guess first, if you wouldn't mind elaborating just a little further on the site activation and the COVID bottlenecks. I guess I just want to make sure I understand where the hang-ups are coming here. Is this more just kind of a buildup of activity that has not been able to get through the queue just given the pandemic constraints, or is this something more to do with the protocols, training, getting through the committees? Just any clarity you can give there.

And secondarily, then, on FTD, you mentioned the InformedDNA collaboration. Just wondering what is your sense as to the proportion of FTD patients today that are currently receiving genotype assessments after diagnosis? And also curious what led you to select InformedDNA as your partner here?

Absolutely. Thanks very much, Laura. So I'll take the first question and then turn it over to Jill for more discussion on InformedDNA and why we chose them, and what we know about the percent of genotyping. So on the programs, Gary, I think, highlighted this absolutely appropriately. It's really the queue on getting into the ethics review committee queue, and IRBs. There's just one idiosyncrasy, I think, from COVID-19, which is that there are many protocols that are being -- essentially had been delayed because of the prioritization of COVID-19. There's also obviously in some of the hospitals just in terms of virtual meetings and queues, it's been quite long to get into those queues.

We definitely had to because of -- as you recall, when we started the GM1 study, we did start with a protocol that had the single cohort that mixed both early and late infantile, and then we did change that. Similarly, Krabbe also had to change that too. But that was part of the understanding of the initial timelines. So we definitely had to submit different protocols, but that's really standard operating approaches that other companies have as well. So we don't think that that's, in particular to your question, idiosyncratic to any program. It's more about the turnaround time then at the Ethics Committee and IRBs that has really impacted the timelines. So it's a long-winded answer to say. I think that what we've laid out is really the majority of the impact. And that's why I think as we get clarity -- I think looping back to earlier questions, that's why, as we've gotten clarity and had these interactions and understood the potential timelines for the various sites' openings, that we've adjusted these timelines with more confidence.

So Jill, do you want to talk about why we chose InformedDNA, and then a little bit about the estimation?

Yes, let's talk about the estimation first, because I think that drives why we engaged InformedDNA. Most FTD that has a genetic component, those folks have not been genetically tested. Primarily family history is not always clear and it's not traditionally been, except at most academic centers. It's estimated that less than 10% of FTD patients with GRN mutations have been identified so far. And so as we think about that, and we think about programs coming to light, clinical programs for these patients, that was in part why we decided to form a partnership with InformedDNA. There's a need for genetic testing and screening, and our partnership with InformedDNA, that is why we went along that path. It's very important for patients. And we engaged with InformedDNA because they have a history of running programs in other genetic diseases, in other areas for other industry partners. And they're a well-established firm that's well-known.

Importantly, with our InformedDNA program, we're not just screening for FTD with GRN mutations, we're also screening for C9orf and MAPT genes. And again, this is a service to patients as we think about programs coming to be available that they may be able to enroll in.

Next question comes from Debjit Chattopadhyay with Guggenheim Securities.

This is Aaron on for Debjit. So, the first GM1 patient was dosed back March. Do you have any early readouts on safety? And has the 60-day safety review been performed on this patient? And could you talk about, in patients that are being screened for GM1, has there been any screen failures?

So, well, first of all, thanks for the question, Aaron. So we're not going to comment on any interim information that we may receive from the studies. As we laid out, we're going to talk about cohort-level data, and that'll come later this year as we've described, but appreciate the question and interest. I think we're doing this just in order to make sure we have as much data as possible in-house and understood.

So the second question, in terms of screen failures. So the way that Gary described this is that there is a network of patients that are being looked at and assessed, but the screening actually occurs when the patient -- the formal screening in terms of the screen failure rate that you would -- that you're referring to, actually occurs when the patient would come to the site and have the final assessment, because then they are actually enrolled and the final screening occurs. What's occurring now in -- for patients with GM1 and other patients with rare disease in studies like this is that the network of investigators and also patient information forms that are filled out, for example, on requests for information, are an informal way of looking at patient age and whether they qualify, patient -- any genetic testing that may have occurred and whether the patient would have qualified, et cetera. So that's not considered a true screen failure rate at this time. So I think what we'll look at is, when we finalize the cohort, we'll provide more information if there were any patients that did indeed fail the screening, but we're focused right now instead on the patients that we're enrolling. It's a great question, and I don't think we have enough information to comment on that further at this time.

And I'm showing no further questions in the queue at this time. Ladies and gentlemen, thank you for participating in today's conference. This does conclude your program and you may now disconnect. Everyone, have a great day.