Operator: Good morning and welcome to Prevail Therapeutics Second Quarter 2020 Conference Call. Please note this call is being recorded. At this time, I would like to turn the call over to Brett Kaplan, Chief Financial Officer at Prevail. Please proceed.

Brett Kaplan: Thank you, operator. Good morning and welcome to Prevail's Second Quarter, 2020 Conference Call. Joining me today are Prevail's Chief Executive Officer and Founder Asa Abeliovich and Chief Medical Officer, Jeff Sevigny. First, Asa will provide a brief overview of Prevail and our business highlights during the second quarter. After that, Jeff will deliver a clinical update and I will discuss our second quarter financial results and cast position before we open the call to questions. Before we begin, I would like to remind everyone that this conference call will include forward-looking statements within the meaning of the private securities litigation reform act of 1995 as amended. Examples of these forward-looking statements include statements related to Prevail's clinical trials, the potential impact of COVID-19 on Prevail's ongoing and planned clinical trials, business and operations, the potential of Prevail's gene therapies to modify the course of neurodegenerative diseases and expectations regarding Prevail's business strategy and cash runway. Our actual results may defer materially from those expressed or implied in such forward-looking statements. Forward-looking statements involve risks and uncertainties which are described more fully in Prevail's filings with the Securities and Exchange Commission including the risk factors section in the company's most recent quarterly report on Form 10-Q and subsequent reports that it files with the SEC. All forward-looking statements made on this call speak only as the date thereof. Except to the extent required by law, Prevail undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date of this call. This morning, we issued a press release that outlines our second quarter financial results and business updates. You can access the press release along with the slides that we will be walking through by going to the investor section of our website at prevailtherapeutics.com. A replay of this call will also be available there for a limited time. I will now pass over the call to Asa.

Asa Abeliovich: Thank you, Brett. Good morning and welcome. As this is our first ever quarterly call, and as some of you may be new to the company, I will start with a brief overview of Prevail before we provide our Q2 updates. Turning to Slide 5, Prevail's mission is to develop disease modifying gene therapies for the major neurodegenerative disorders of aging, including Parkinson's disease with GBA1 mutations or PD-GBA and frontotemporal dementia with progranulin mutation or (FTD-GRN) as well as others. We are developing a broad pipeline of gene therapies all unified around a common strategy of precision genetic medicine approach through which we select our targets based on a deep understanding of the human genetics. By pursuing our gene therapies in genetically defined patient populations, we believe we increase the probability of creating disease modifying therapies that could improve these patients lives. We used the same underlying technology platform AAV9 which has a proven track record of efficacy and safety in patients for all of our initial programs. Today we will focus on our two programs in the clinical development stage. First is our lead program PR001 which uses AAV9 to deliver the GBA1 gene which encodes glucocerebrosidase also known as GCase to treat patients with Parkinson's disease with GBA1 mutation as well patients with Neuronopathic Gaucher Disease or NGD. About 7% to 10% of the total Parkinson's disease populations worldwide have an underlying GBA1 mutation, including at least 9000 patients in the United States alone. There are currently no disease modifying therapies that slow or stop the progression of this disease for these patients. We are also pursuing PR001 for the treatment of patients with NGD, including the most severe form Type 2 NGD, which is a devastating disease of infancy. There are currently no therapies approved by the FDA for the treatment of NGD, Type 2 NGD present in the first months of life and infants diagnosed with this disease progress rapidly and typically do not survive past the age of two. Our second clinical program PR006 is an AAV9 gene therapy that delivers the human progranulin gene for patients with frontotemporal dementia with progranulin mutations or FTD-GRN. FTD-GRN is a rapidly progressive and devastating form of dementia with prominent behavior and language components. It is estimated that approximately 5000 Americans suffer from FTD-GRN and many more patients worldwide and there is an urgent need for disease modifying therapies for these patients. Turning next to Slide 6. Since our inception in 2017, we have made tremendous progress in a relatively short period of time, moving from discovery into a clinical stage company in less than two years, achieving significant clinical and regulatory milestones across our portfolio and bringing the company public. Our ability to advance multiple candidates to the clinic over the last few years reflects the talent and dedication of our team, the potential reach of our platform, and the urgency with which we are developing potential disease modifying therapies. Moving on to Slide 7, the development status of our initial AAV9 gene therapy programs is summarized in the table below. We hold worldwide commercial rights to all of our programs. In addition to developing PR001 and PR006 we are also pursuing the development of PR004 for the treatment of patients with synucleinopathies. Turning to Slide 8, I encourage you to review our earnings press release in full, but let me touch upon some key business highlights during the second quarter. Although the clinical data we are presenting today is early stage, we are nonetheless tremendously excited about what we are seeing. At this point we have dosed two Type 2 nGD patients with PR001, both via compassionate use requests. As we have previously disclosed in January 2020 we dosed the first patient and today we can present key biomarker data from that patient specifically GCase activity in the cerebrospinal fluid or CSF. We dosed a second Type 2 nGD patient very recently just in the past week and therefore we do not yet have data to discuss for that second patient. As I mentioned, we are also very focused on developing PR001 to treat PD-GBA patients. Two patients have been enrolled in the PROPEL clinical trial and in keeping with the protocol one received PR001 whereas the other received a sham procedure as a control. Jeff will discuss the details, but at a high level the take away is that there are very exciting early key biomarker data to report from the patients treated with PR001, one nGD patient and one PD-GBA patient. That baseline both patients had undetectable CSF GCase activity levels as expected and remarkably though CSF GCase activity levels were fully normalized at a three-month time point following PR001 administration. To put this into context, based on our preclinical data, as well at the human genetics, our view has been that if we could achieve CSF GCase levels that are increased by at least 20% to 30% of normal levels, the treatment would be predicted to be efficacious. That same levels that have fully normalized is really what we have always considered an upside, and therefore we are very encouraged by this promising data in our first few patients. All of these patients tolerated the administration procedure of PR001 well. Among the nGD patients there were no PR001 related adverse events or AEs. A PD-GBA patient dose with PR001 experience serious adverse events or SAEs at about three months after dosing. These were consistent with an adaptive immune response to the viral AAV9 capsid proteins as has been described in other AAV gene therapy programs. And consistent with those other gene therapy programs the SAEs markedly resolved with administration of additional immunosuppression. Based on these early clinical observations, we have amended the protocol for the PROPEL clinical trial. We are also excited that startup activities are ongoing and on track for PROVIDE, the clinical trial for PR001 for Type 2 neuronopathic Gaucher disease patients and PROCLAIM, the clinical trial for PR006 for FTD-GRN patients. We expect both the PROVIDE and PROCLAIM trials to initiate in the second half of 2020. Finally, we continued to add talent and recently welcomed Kira Schwartz as Prevail's General Counsel. Kira joins us Allergan and has hit the ground running. We are thrilled to have her on board and to further strengthen our leadership team. With that, I will turn the call over to Jeff for our clinical update. Jeff?

Jeffrey Sevigny: Thanks Asa, and good morning everyone. It is my pleasure to provide further detail on the clinical advancement of our lead program, PR001 as well as the status of our pipeline. Turning first to Slide 10, two children with Type 2 Gaucher disease have received PR001 via a suboccipital injection into the cisterna magna. In both children, the treatment was administered under a compassionate use pathway with respective international regulatory body approval. Regarding our PROPEL Phase 1/2 trial for PD-GBA, two patients have been enrolled. Enrollment was temporarily paused due to COVID and is now paused as we implement a protocol amendment which I will speak to momentarily. We expect enrollment in the PROPEL trial to continue in the second half of 2020. Next, I would like to mentioned our PROVIDE trial. This is a Phase 1/2 trial for children with Type 2 Gaucher disease. This trial is expected to begin enrollment in the second half of 2020. Lastly, we have decided to postpone the initiation of our PROGRESS trial, a Phase 1/2 trial for children with Type 3 Gaucher disease until additional data from the PROPEL and PROVIDE trials are available to inform the clinical development strategy in this indication. Let's next turn to Slide 11. We are pleased to report some early clinical results from the child with Type 2 Gaucher disease. The child was approximately 22-months-old when dosed with 1.3x 10(14) vector genome of PR001 in January 2020. Following the administration, the child's CSF GCase enzyme activity increased from undetectable at baseline to a normal level at months four. The procedure was well tolerated and there have been no PR001 related adverse events. The child is clinically stable and there have been no apparent worsening of the child's neurological symptoms since PR001 administration. Turning next to Slide 12. We are also pleased to report early clinical results on the Parkinson's disease patient dosed with 1.4x 10 (14) vector gnomes of PR001 in our PROPEL trial. The route of administration of PR001 in this study is also via a suboccipital injection into the cisterna magna. The patient has moderately severe Parkinson's disease and Gaucher disease, meaning the patient has a biolevel [ph] of GBA1 mutation carrier. This patient's GCase enzyme activity increased from undetectable at baseline to a normal level at month three. As a reminder, CSF GCase enzyme activity is the key biomarker in these trials and the increases observed from undetectable to normal levels in both patients with Parkinson's disease and the childhood Type 2 Gaucher disease, provide clear evidence that PR001 transfuses cells in the CNS with a GBA1 transgene, that these cells are expressing the GCase protein, and most importantly, this GCase protein is in fact active. Furthermore, these early GCase activity results nicely demonstrate the translation of our work performed in most models to patients with GBA1 mutation. In this case, the models have thus been far successfully predicted the initial dose selected for use in patients with Parkinson's disease and Type 2 Gaucher diseases are potentially efficacious. With regard to safety, Parkinson's disease patient enrolled in the PROPEL trial experienced approximately three months following PR001 administration, three SAEs that included worsening of underlying hallucinations, worsening of underlying orthostasis, and encephalitis. The encephalitis SAE was based on worsening of mental status in the context of inflammation in the CSF. I would point out that the patient did have symptoms of hallucinations, orthostasis, and cognitive impairment at baseline. An extensive workup was performed including MRIs with contract of the brain and spinal cord which includes the dorsal root ganglia and nerve roots. There was no evidence of inflammation or any other changes from baseline found on these MRIs. The patient received additional immunosuppressive treatment and the SAEs have markedly resolved. As to the underlying cause of the SAEs, we believe it is most likely attributable to an immune mediated response to the AAV9 vector. This conclusion is based on our understanding of AAV9 and the types of immune reactions it can elicit to time course of the onset of the SAEs and the patient's response to additional immunosuppressive therapies. Accordingly, we have amended the PROPEL trial protocol to mitigate future risk of AAV9 immune mediated AAVs [ph]. This amendment is described on slide 13. Specifically the prophylactic immunosuppression regimen has been optimized by including a second agent, sirolimus, and by reducing the corticosteroid regimen, both dose and duration. This optimized regimen is designed to provide a more robust and targeted suppression of adaptive immune system and with the use of sirolimus is to some extent steroid sparing. Therefore this optimized regimen is predicted to be better tolerated from the high-dose corticosteroid regimen used previously. We have also modified the trial design to be open label with each of dose cohorts enrolling six patients or 12 patients in total, and moving the first followup lumbar puncture for CSF assessment from month three to month two. The assessment of the month two CSF will help guide investigators to the tapering of the immunosuppressive regimen in addition to providing a key biomarker readout. Lastly, the protocol has been amended to reflect dose levels established using an updated analytical method with an improved precision. Accordingly, the dose levels are 1.4x 10 (14) vector genomes in the low dose cohort and 2.8x 10 (14) vector genomes in the high dose cohort. These protocol changes have been endorsed on the independent data monitoring committee and discussed with and submitted to the FDA. As I noted earlier, taking into account the prior impacts of COVID-19 on trial enrollments as well as the protocol amendment, we anticipate enrollment in the PROPEL trial to continue in the second half of 2020. Furthermore, we anticipate providing the next biomarker and safety analysis on a subset of patients enrolled in the PROPEL trial by mid 2021. Turning next to Slide 14. Here you will find an overview of the modified design of the PROPEL trial incorporating the changes I previously mentioned. Moving next to Slide 15, to put the earlier GCase enzyme activity results in context, GCase activity is a stable biomarker in PD-GBA and correlated with behavioral improvement in a mouse model and these first few patients we met our upside goal of fully normalizing GCase levels at the initial time. Turning next to Slide 16, in addition to the great progress we have made with our PROPEL trial, we are also working diligently to advance the clinical development of PR001 for children with Type 2 Gaucher disease. Study startup activities are continuing for the PROVIDE trial and open label Phase 1/2 trial of PR001 for children up to two years old with Type 2 Gaucher disease. We expect that enrollment in this trial will begin in the second half of 2020. The optimized immunosuppression regimen being used in the amended PROPEL trial will also be implemented in the PROVIDE trial. Finally, turning to Slide 17, PR006 is our investigational gene therapy for the treatment of patients with FTD-GRN and in March 2020 we announced that our IND for PR006 for the treatment of FTD-GRN was active. PR006 will be evaluated in the PROCLAIM trial, which is an open label Phase 1/2 trial investigating the safety and tolerability of PR006 as well its effects on key biomarkers and clinical outcome measures in patients who have GRN mutation. This will potentially be the first gene therapy for FTD-GRN to enter the clinical trials. Study startup activities for the PROCLAIM trial are ongoing and we expect to start enrolling patients in the second half of 2020. The optimized immunosuppression regimen being used in the amended PROPEL trial will also be implemented in the PROCLAIM trial. We are pleased with the important clinical, operational, and regulatory progress made across our portfolio of novel AAV9 based investigational gene therapy and even with the limited data we have already learned a great deal about PR001. More specifically, we are encouraged by the normalization of GCase activity observed at the initial dose levels and we firmly believe that the changes made in the immunosuppression regimen across all our clinical programs increases their likelihood of success. We look forward to providing additional updates at an upcoming medical meeting. Now I will turn the call over to Brett for a brief financial update.

Brett Kaplan: Thank Jeff. In today's press release, we provided a financial update for the second quarter ended June 30, 2020. We ended the quarter with cash, cash equivalents and investments of $131.2 million. This compares to $149.6 million at the end of the last quarter of March 30, 2020. This was primarily due to an increase in OpEx commensurate with the progress of our portfolio. We continue to anticipate that our cash runway will extend into the first half of 2022. Research and development expenses increased to $12.9 million for the second quarter 2020 compared to $12 million for the second quarter of 2019. The increase was primarily due to an increase of $2.6 million in the direct clinical trial costs related to our PROPEL, PROVIDE and PROCLAIM clinical trials and other startup costs, and a $1.8 million increase in employee related costs. These increases were partially offset by decreases of $2.6 million in CMC costs, due to the timing of production of supply and $1.7 million decrease in license fees related to the option exercise under one of our license agreements with a Gen-X buyer during the three months ended June 30, 2019 General and administrative expenses for the second quarter were approximately $9.2 million compared to $3.7 million for the second quarter of 2019. This increase was mainly attributable to a $4.4 million increase in legal fees, primarily related to the costs associated with the ongoing arbitration matter, intellectual property pattern costs and costs to operate as a public company. In addition, we entered into $75 million ATM program. Finally, I would like to remind you that our management team will be participating at upcoming virtual investor conferences, kicking off with the 2020 Wedbush PacGrow Healthcare Conference today. We look forward to engaging further with the investment community at that time. And now we will open the line for your questions. Operator?

Operator: Thank you, sir. [Operator Instructions] Our first question comes from the line of Jeff Heun from Morgan Stanley. Please go ahead.

Jeffrey Heun: Yes, thanks for taking the questions and congratulations on the results. For the PD-GBA patients you had stated that the SAEs essays have markedly resolved. So if the patient is still on immunosuppressive treatment or how long were they on immunosuppressive treatment? And then what residual symptoms do they experience from the SAE compared to the baseline levels? I have a followup thanks.

Jeffrey Sevigny: Yes, hi Jeff, this is Jeff Sevigny. Yes, so at this point we're not going to provide any further details on the clinical status of the patients apart from saying the SAEs have markedly resolved. With respect to the immunosuppression at the time of the AE, he was not on any immunosuppression and subsequent to developing the AE an immunosuppression regimen was implemented, and he did markedly respond to that immunosuppression.

Jeffrey Heun: Okay, thanks. And then can you talk about the implications from a regulatory perspective, if any of removing the sham procedure from PROPEL, and then the patient that was treated with a sham procedure, are they excluded now from the study since you will only have treated patients? Maybe if you can talk about the implications of the protocol revision with regards to that patient? Thank you.

Jeffrey Sevigny: Yes, so with respect to our interactions with the FDA and SAE and the protocol changes we first of all had reviewed the SAE and our protocol changes with top leaders in the field. Number two with our independent Data Monitoring Committee, which have endorsed our changes, and our assessments. And number three, we have had discussions with the FDA including our assessments of this case and the protocol changes, and they have accepted our assessments, and the changes. So at this point we are in the process of, we've completed the amendment and we are in the process of pushing the amendment through the sites for IND approval. So that is an ongoing process now. With respect to sham patients, yes, the protocol current as amended doesn't contemplate the Sham patient. And this patient will have one of two options. If the patient will be invited to enroll in the new protocol and receive PR001 in the open label study or number two the patient could choose to drop out altogether.

Jeffrey Heun: Thank you.

Operator: Thank you. Our next question comes from the line of Paul Matteis from Stifel. Please go ahead.

Paul Matteis: Hey, thank you so much for taking my questions. I have a few, just one on efficacy. Can you can you confirm that the sham dose patient had no changes in GBA activity? And then second, I was wondering if you saw any changes in different downstream substrates of GBA that corroborated the increase in GBA is functional? And then third on the safety side, I was wondering if you could just maybe now going forward talk about the duration of the immunosuppression regime in your updated protocol? And I guess why shouldn’t we be worried that that might make this harder to recruit in the midst of a pandemic when you're targeting an elderly population? Thanks so much.

Jeffrey Sevigny: Hi, Paul, this is Jeff. I want - you got I think three separate questions, you can take the first and the third and maybe Asa can talk about substrates. With respect to the sham patient we, of course this study has multiple biomarkers and also with this patient many of the analyses are ongoing, are being planned and right now we simply don't have those results, so we cannot share that with you. With respect to the duration of the immunosuppression, we're not providing at this point the doses or the duration, but we are saying what the immunosuppression regimen is. It is a regimen that is more targeted to what we think probably underlying AEs, that is an adaptive immune response to AAV9 in the midst of more targeted in that sense and we also believe that it is going to be a better tolerated immunosuppression regimen. In the previous protocol we used high dose steroids and that was not tolerated by this Parkinson's patient who did have the SAEs, and in fact that patient had to truncate his or her use of steroids because of the usual AEs associated with steroids. The new immunosuppression regimen is to some extent steroid sparing. So with the use of steroid alignment the dose of steroids will be reduced and so will the duration of it will be reduced. As to the exact dosage and duration we are not disclosing that yet, but I think it has been well informed by spot leaders and gene therapy and immunology, and is generally consistent with what others are using other gene therapy programs that target CNS indications are using. With respect to substrates, maybe I'll pass that one to Asa.

Asa Abeliovich: Great and thanks, Paul. So, yes, so what we're providing at this point are really the data that we have completed, but other analyses of course are also exciting and basically they're simply ongoing and incomplete, but I would just really emphasize that what we're providing here is the key pharmacological endpoint. Right? So the key pharmacological endpoint is that we are delivering glucocerebrosidase activity here right? So that clearly means that we are able to transduce brain cells, we are able to produce and express GCase and, importantly, the GCase is in fact active. And it means that our pre-clinical dose finding studies were actually highly predictive, and that was not a given. So we're just really excited about that aspect. I mean, I think it's really worth recognizing that aspect. I would just say with immunosuppression, I would just emphasize that looking across all AV CNS programs that there's - all of them used some degree of transient immunosuppression. So we saw absolutely nothing pre-clinically in terms of adverse findings, but we used steroids which is sort of the lower end and other used other regimens and the regimen that we're describing [indiscernible] limit is probably the most typical if one looks across programs. So we would just, you know this again is a typical picture we would emphasize. And then you know recruitment has gone well. There's been a very, very strong interest in these programs. It's a reasonable question, but we would just emphasize, I just said steroids are used in some programs. But of course, have typical issues that patients have with steroids, and with a steroid sparing regimen and specifically, there's literature for this for older individuals. You know, it's certainly thought to be at least as safe and well tolerated, if not more so, and that's just as true we feel in the current context here with the pandemic is otherwise. And then the fact that we that we can do away with a sham arm, we do think you know is potentially very helpful and relevant for recruitment. So we feel that's very much on track.

Paul Matteis: Yes.

Asa Abeliovich: Anything else I’d ask if I know ask you had a few; did we miss anything Paul?

Paul Matteis: No, no, that was really helpful, awesome. Thank you. I guess, I just want to, I just want to make sure you'd be surprised if you saw GBA increases on sham right? Like when you, like I guess, when you track the history of this, there is not a ton of noise, right? If someone has no levels, they should consistently have no levels, is that fair to say?

Asa Abeliovich: Absolutely.

Paul Matteis: Okay. Thank you so much.

Asa Abeliovich: Thanks.

Operator: Thank you. Our next question comes from Jay Olson from Oppenheimer. Please go ahead.

Jay Olson: Oh hi. Congrats on the progress and thank you for taking my questions. I was wondering if you could comment anecdotally on whether the PD-GBA patient who received PR001 or the caregiver observed any improvements in clinical symptoms?

Asa Abeliovich: Yes, hi Jay thanks for that question. There's nothing more I can add apart from what I've already added.

Jay Olson: Okay. And then I think you said it took three months before the PD-GBA patient developed an immune response to PR001. Do you know why it took three months or they had prior exposure to viral type AAV?

Asa Abeliovich: Yes, Jeff maybe, yes, I can start maybe and Jeff can keep going. But I would again say that this is actually a typical picture. If you look across program and reviewed in the literature, what typically happens is the patient like this one do get brief transients or some transient course of immunosuppression. And it's really is that's weaned off that one can see adaptive immune changes in these patients and in this timeframe, and that's is responsive to immunosuppression, and that again this is an adaptive sort of immune response as expected. Whenever you to give and when you've given AAV to a patient, whether or not they have pre-existing exposure, they will certainly respond to the capsid and then of course different patients will have different degree to which that they have a vigorous response. But then again that's expected and typical, and that's why everyone uses some degree of immunosuppression. And then there's sort of a spectrum of immunosuppression that's used, but this is - the time course here is typical.

Jay Olson: Okay, great. Thanks again for taking the questions.

Asa Abeliovich: Sure. Thank you.

Jeffrey Sevigny: Thank you.

Operator: Thank you. Our next question comes from the line of Laura Chico from Wedbush Security. Please go ahead.

Unidentified Analyst: Hi, this is [indiscernible] for Laura. One question - well, a couple of questions for you and then I have a follow-up. Could you comment on any additional biomarker assessments that you have made beyond GCase levels such as α-Synuclein, or NfL just wondering about that consistency across measures at this stage? And then just one more, just one more question, what's your sense that these increases are still on the rise and have not plateaued yet?

Asa Abeliovich: Jeff, do you to answer that?

Jeffrey Sevigny: Sure. I apologize. I didn't catch the name of the person asking the question. But I'll start with the additional biomarkers. The PD-GBA PROPEL study and all our studies contain many biomarkers across multiple time points. And the only data that we've fully analyzed at this point is the GCase activity. So either the analyses are ongoing or will be performed at a later date for other biomarkers, and this includes NfL and á-Synuclein, but we have nothing we can comment on now on these other biomarkers. But we look forward to assessing them and disposing them in due time. The other question was about where I guess where we think we are on the curve of GCase activity. And, of course, we won't know till we do further assessment that further time points. But I think we can infer a lot from other studies that have used gene therapy, particularly those that have used AAV9 as a vector. And I think what we've learned is that starting around one month after delivery of the material, the vector almost transgene, you start to hit an Asymptote of uptrend reduction and protein expression and it probably continues over the course of multiple months, and maybe up to a year. But I think it's probably largely going to be incremental, over the ensuing months, at least from month three. So I'd say if we're not on an Asymptote, we're close to an Asymptote, but of course, this is speculation. And we, as a company really look forward to seeing the results of the CSF at months 12 and that's the next number comes to time points for the PD subjects.

Unidentified Analyst: Okay, and then just one more follow-up, just to put the magnitude of increases in GCase levels and in perspective for us. So one patients increase, one patient has increased, increases nearly like 5x and the other going from undetectable to say micromoles, so how does this compare to the preclinical NHP data in terms of the velocity of increases?

Asa Abeliovich: Yes, so I didn't totally get that. I mean, both of the patients we described went from undetectable to sort of snap in the middle of the normal range. The fact that they're undetectable is predicted in this, they both have, the one patient had Parkinson's with Gaucher and the other patient has Gaucher Type 2. So they both have mutations in both chromosomes. And that's why they have undetectable level at baseline. And they have a sort of dramatic increase over about, over this three to four month period. I didn't totally understand your question, can you maybe if you could just…?

Unidentified Analyst: Yes, if you can just compare this increase in Gaucher gene and preclinical NHP data in terms of velocity of GCase increases?

Asa Abeliovich: Yes, got it. Yes. So yeah, velocity as sort of Jeff said, you start around the, the typically across programs and our dose does go up from one month to six months. So, but it's, it starts to hit, it's a three month time course, therefore, we expect to start to reach to go toward maximal levels, but we do expect it to - it potentially keeps going up and based on the literature, but in very rapidly, what I would say is that we did expect, certainly minimally a 20% to 30% increase. And we have always stated that we predicted that to be efficacious from our efficacy studies, and that beyond that would be considered upside. So we're tremendously excited about going beyond that. Then NHP is a little bit different in that those are normal NHPs. They're very useful for bio distribution and safety. But we couldn't, of course, whether that would fully translate to the patient on what's something we needed to show and now we we've shown that in fact, we get quite an impressive level of expression. In fact, the preclinical studies did a great job of predicting the first dose and the first dose may be appears to be the correct dose. We may or may not choose to continue that later.

Unidentified Analyst: Okay, thank you so much.

Asa Abeliovich: Sure.

Operator: Thank you. Our next question comes from Tazeen Ahmad from Bank of America. Please go ahead.

Tazeen Ahmad: Good morning, guys. Thanks for taking my questions. Also, I was curious. Can you give us any more color on the steroid tapering that was done in the study? And do you think there's any possibility that the event you observed might have even been triggered by tapering?

Asa Abeliovich: Yes, Tazeen – Jeff, go ahead why don't you? That's great.

Jeffrey Sevigny: Yes, so of course, we can only speculate here. We were not going to give the exact details of how the patient, what the actual patient's course of steroids was, except to say that it was truncated because of tolerability issues. And, of course, we can only speculate as to the effectiveness of the shortened duration of the steroids. But we think it's reasonable to speculate that it certainly contributed to the underlying cause of the SAEs if not ultimately caused the SAEs. So that's something that we've considered and that consideration has been taken into account with our optimized immunosuppression regimen.

Asa Abeliovich: Yes - it's typical and expected that there would be some immuno reactivity of course, in that individual and when these are dosed and that's always considered transients. And that's why we give prophylactic steroids. So, of course shortening the immunosuppression it is reasonable to think that that would increase the likelihood of something like this. And this is where adding sirolimus, is generally, it's something we're excited about.

Tazeen Ahmad: Yes. So I think part of the reason why I was asking was I think, because you did observe such events about three months into the dose after the go. If you look at other companies that have recently reported events related to use of the AAV9 factor, many have actually reported is that, much earlier after dosing, and I'm just wondering what now your general thoughts are about the use of AAV9, and whether you would think about the safety profiles, that seems to be developing around it is something that you feel is manageable?

Asa Abeliovich: Yes. But that's a very helpful question and I think it's really important to separate these two kind, very, very different kinds of things that have been observed. So what you're bringing up is that at very high doses used intravenously, peripherally, there are very different kinds of issue, which is not an adaptive immune response. These are innate immune, sort of acute and sub acute inflammatory changes that have been described. Again, it's very, very high doses that are typically one, really two orders of magnitude 10 to 100 fold higher in intravenous doses, as you pointed out, and in those cases, there have been a very different kind of problem at a very different time point. So those are acute subacute inflammatory processes. And again, that's very different. What’s been seen on the other hand with CSF dosing and with AAV9 for CNS indications and perfect [ph] dosing, of course, one expects to get an adaptive immune response. And as you pointed out, that's a different timeframe and then one sees immuno activities. And again, this has been seen across programs and immunosuppression recommend very in detail, but I would just be very, very clear that it took a very different picture that's been seen inside of the programs. But overall, there's in human patients AAV9 for CNS has been remarkably I mean, and clearly safer for difficulties we're talking about. And there are multiple programs out there that have been - have appeared safe and that include, again marketed therapy.

Tazeen Ahmad: Yes. And especially given your GCase question like I think that would override any kind of concerns around safety. Maybe just one last question if I might, you've indicated that the next potential update, next expected update from this program as far as patients would be next year, I think you said is it the middle of next year? Just based on where you are, in terms of how you think the study will recruit, do you have any sense of how many additional patients you might be able to show data for at that point?

Jeffrey Sevigny: Yes, hi, this is Jeff. So well, first of all, I guess I think Paul asked this question earlier, just to underscore there has been a lot of enthusiasm for this study so far, and we believe that enthusiasm will continue. We believe the study is, that its new design is safer for patients, and will actually be more appealing for patients given the open label nature of the study. So we anticipate enrollment to begin soon, certainly this half of 2020. And at this point, we're not going to close up the data set of how many patients will be included in the data set in the middle of next year, apart from saying it will be a subset of patients that are intended to enroll in the overall study.

Tazeen Ahmad: Okay, and if there are any observed safety effects, would you then provide an update on that before the middle of next year if you do observe any?

Jeffrey Sevigny: Yes, I'm not sure we can commit to anything at this point. Of course if something as material, we have an obligation to report it, but I don't think we're going to commit to anything beyond what we've committed to already.

Tazeen Ahmad: Okay, thank you.

Operator: Thank you. Our next question comes from the line of Nicole Gabreski from Piper Sandler. Please go ahead.

Nicole Gabreski: Good morning. This is Nicole on for Chris Raymond. Thanks for taking our question. So maybe one on PROGRESS initiation, can you guys talk about what data from the PROPEL and PROVIDE studies would give you confidence to initiate dosing and progress? And would it be safety from a certain number of patients? Just any color there would be helpful.

Jeffrey Sevigny: Yes, this is Jeff. So I'll try to answer that question. Yes, so we’ve decided to postpone PROGRESS initiation for strategic reasons. Keep in mind that we have multiple clinical studies ongoing or are getting ready to start for PR001 and we have a portfolio of candidates that we are either in early development or pre clinical development. So, part of the consideration and how to develop a portfolio must take into account that the entire portfolio. So with PROGRESS, the feeling was essentially that given that this would be the third study in PR001, it would be best to ensure that it is well informed prior to starting the study. So, that includes many things including dose selection, immunosuppression, optimization, and things like that. Just to be clear, the postponement of PROGRESS and initiation was not due to any safety concerns. If I want to be crystal clear as a matter of fact, that was mainly a strategic decision taken around the portfolio.

Nicole Gabreski: Okay, that's helpful. And then maybe just a second question for the initial Gaucher patient treated under compassionate use, I guess, is there any additional background information that you could provide? I know you guys disclosed that they did not or decision did not have apparent worsening of neurological symptoms. But I guess, where was this patient in their disease course at baseline, is there any additional information that you could give us?

Jeffrey Sevigny: Yes, so we've disclosed a little bit about this child - it was a 22-month-old child, so quite advanced, as you know, children with Type 2 Gaucher disease typically die by the age of 24 months. So this child was quite advanced. But apart from that, and the fact that they had Type 2 Gaucher Disease and the dose and that clinically the child was stable and there have been no apparent neurological worsening since the administration of PR001, we really can't comment any further. I would also point out just to set up the appropriate context, this was a treatment protocol that means it was done under compassionate use. And it's really a protocol developed by a treating physician, not an investigator in the true sense of a clinical trial. And it's not our clinical protocol. So there shouldn't be an expectation that there will be the same level of details as there would be from a clinical trial itself, because this is a treatment protocol.

Asa Abeliovich: Yes, I would just add that, Nicole that yes, that's typically, yes, this is a rapidly progressive disease, and patients don't typically survive at just at age two. So the fact that this patient was stable we think is potentially very meaningful, and has been stable and continues to be stable.

Nicole Gabreski: Okay, that's helpful. Thanks for taking our questions again.

Operator: Thank you. I show next question comes from the line of Neena Bitritto-Garg from Citi. Please go ahead.

Neena Bitritto-Garg: Hey, guys, thanks for taking my question. Congrats on the update. So I just wanted to ask a question about how we should kind of interpret the data that you presented today in terms of thinking about future of PD-GBA patients that are enrolled that have only a single, a little mutation since the patient that was enrolled here could have the biological mutations. So that would be my first question? And then just my second question would be around dosing, I believe originally you were thinking to use a higher dose in the PROVIDE study versus PROPEL. But it looks like this initial patient under compassionate use had a slightly lower dose administered. So I guess, just any updated thoughts on the doses for PROVIDE would be great? Thanks.

Asa Abeliovich: So maybe I can answer the first question and Jeff, you can do the second one. But it is a great question. Yes, so the PROPEL study does treat both patients that have [indiscernible] have mutations in both chromosomes and very, very low levels, very low levels of GCase activity relatively as well as patients with mutations in one chromosome, so heterozygous - and, our preclinical data and the human genetics strongly support that we could - that PR001 would be beneficial for both of these populations. As, you know, there is a gene dosage effect. So [indiscernible] patients typically do worse than mutate - patients with mutations in one chromosome. But nonetheless, in both context, the preclinical and the human genetics point toward PR001 being beneficial in both contexts. So the answer is that we very – this study we find very, very much during support, treating both of them and look, it's exciting that even in an individual who has a very low level, we could fully rescue that certainly have implications that in heterozygous, who has a higher level or individuals with a variety of mutations in one chromosome are externally very supportive that we would certainly expect to be able to actually dose people who have to begin with a higher, higher levels. But again, the study does include both and then it happens to be that this first patient we're describing here had mutations in both chromosomes. Jeff, may be you can?

Jeffrey Sevigny: Right, so with respect to dosing, look so far we're really encouraged by the results we've seen. And PD in a child with PD2 and in the Parkinson’s side really GBA1 patients are also highly encouraged that are mouse models that predicted an initial dose that would appear to be efficacious at least by measure of GCase activity. So at this point, we just need to generate more data at the dose levels. And the decision will be made in conjunction with our Independent Data Monitoring Committee about whether to continue dose escalate or not. But it's a good problem to have and we'll take that problem in due time, or we'll drop that problem in due time. But it is possible we don't continue to dose escalate but we'll see. With respect to PROVIDE specifically, I don't think we've disclosed that dose with the PROVIDE study, but it is a dose that is certainly in the ballpark of the ones we've already mentioned today and based on the mouse models.

Neena Bitritto-Garg: Okay, thank you.

Operator: Thank you. [Operator Instructions] I show our next question comes from Yaron Werber from Cowen. Please go ahead.

Yaron Werber: Yes. Hi, thanks for taking the question. If you don't mind, I just have a few, can you give us a little bit of a sense? You're seeing good activity in the CSF in terms of GCase activity, but do you have a chance to look at plasma GCase levels? I recall preclinically they looked interesting, and they looked like you're seeing a benefit. What do you see here? And then I have a follow-up.

Asa Abeliovich: Yes, so the protocol certainly does contemplate the measurement and plasma GCase activity levels. At this point, those analyses are ongoing, and we will be presenting those at our next update.

Yaron Werber: Okay, but those are measured at baseline, I assume, and then periodically as patients…?

Asa Abeliovich: They are measured at, that's right measured baseline and on several time points thereafter, they are more measurements of blood GCase activity levels because we need to obtain blood more frequently than they are CSF, CSF again is at, well now we'll be at month two and month 12 and blood there, there's more and more time points.

Yaron Werber: Okay, so CSF is zero and then 2 and then 12?

Asa Abeliovich: That’s correct.

Yaron Werber: Okay. Got it and a question about, can you give us any sense at all on the immunosuppression regimen? When do you start it? Do you start it right away at baseline concomitantly with steroids or do you start it as you taper down steroids? Do you taper steroids and is that, is the thought that it's a chronic regimen or is it thought that it's time fixed regimen?

Asa Abeliovich: Yes, so as we've mentioned, we don't want to get into too much detail as of yet on that so let's say this, it is designed to be a prophylactic measure to mitigate and prevent adaptive immune response. So as such it is treated, it is started approximate the same time as when the patient goes – undergoes the procedure, the injection of PR001 or the other gene therapy products we're developing and it's for a period of time, it's not indefinite, again, to prevent, mitigate, adaptive immune response, that typically happens in a short period of time after injection. So it's not a chronic regimen. It's not right now designed to be a chronic regimen.

Jeffrey Sevigny: Yes, I can just, one other point I suggest to be clear. When you look at immunotherapy regimens used across gene therapy programs that targets CNS, I think you'll find that once this is disclosed, it's generally consistent with what other programs are using. But number two, some programs have to use more chronic immunosuppression because they're delivering a transgene that produces a protein, mutations or does not have. These are called negative patients. That's not the case in our program. So GCase that's been, the enzyme that’s being produced GCase is not a foreign protein to these patients, always patients produce GCase. So as such there's no need for an investment in a immunosuppression regimen. Our regimen is specifically tailored to mitigate or prevent an immune reaction to AAV9 itself.

Asa Abeliovich: Yes, I did, Yaron yes thanks for this. Yes just to reiterate that if you look across programs, yes, there's a spectrum. But for the CMS program, we would say that most, more than half or about half use [indiscernible] limits, rapamycin is part of the regimen. And they typically use it for a month, for a few months, and it varies a little across programs, whether 3, 6, 9, 12 months, and, and we don't want to detail that at this minute. But it’s there, what we're doing is very typical is what I would say across the program.

Yaron Werber: Okay, and then maybe just give us a little bit of a sense, the new dose in PROPEL, can you could, that it's, is it a lower dose than you used in the past and maybe just give us a sense at what point do you, are you planning on disclosing the doses for us across your studies?

Asa Abeliovich: Okay, I'm not sure I understood the first question, is it regarding the retitering of the dose and maybe yes this question isn’t…?

Yaron Werber: Yes, the new dose or the dose that you're not disclosing for PROPEL, the 1.4 and 2.8, the low dose and the high dose? Is that a different dose than you've used in the past or is it the same dose? And for the rest of the studies, when do you plan on letting us know what the doses are?

Asa Abeliovich: Yes, right. So for PROPEL the dose that has been used and will continue to be used are 1.4x 10 (14) vector genome. And then the high dose, which has not been used yet, but the high dose is 2.8x 10 (14). So as I mentioned this is - the doses have not changed. It's just that using more precise and accurate analytical method, we have pre-established what that dose level actually is. So I hope that's helpful there. So may be the doses are not actually changed, just reestablishing what the dose actually is. Number two, for doses for the other programs I don't think we've committed yet, so when we will disclose what those dose levels are so.

Yaron Werber: Okay, great. And then maybe just a final question, maybe it sounds like, it's just from what you said before, you're thinking this is AAV9 that this wasn't sort of this order specific, right? So is it conceptually, this is what you're going to do for all your programs, including, PR006 from this point onwards?

Asa Abeliovich: Yes. So again, what we see looks typical more or less for what's been seen across program. And most programs, yes more than half of the programs have used – use power, yes we have to make sure the limit in addition to steroids just at some, there are some more complicated situations where people use other, but and yes, we will use this regimen. And again, like we said, it's important that it's a steroid sparing regimen and meaning that it allowed us to use left steroids and steroids as we all know, have significant issues and people have to have issues of tolerance with tolerating them. So, it is always, so that's sort of generally seen as a benefit of this kind of a steroid bearing regimen where we use a lot less steroids and down and the steroid limits and so, yes, we will use this across the program.

Yaron Werber: Great, thank you so much.

Operator: Thank you. I show no further questions in the queue. At this time, I'd like to turn the call over to Mr. Brett Kaplan, CFO for closing comments.

Brett Kaplan: Thank you, operator and thank you everyone for participating in our first investor call. We look forward to continued engagement and have a good day.

Operator: Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.