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Edited Transcript of VYGR earnings conference call or presentation 6-Nov-19 1:00pm GMT

Q3 2019 Voyager Therapeutics Inc Earnings Call

CAMBRIDGE Nov 13, 2019 (Thomson StreetEvents) -- Edited Transcript of Voyager Therapeutics Inc earnings conference call or presentation Wednesday, November 6, 2019 at 1:00:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* G. Andre Turenne

Voyager Therapeutics, Inc. - CEO, President & Director

* Matthew P. Ottmer

Voyager Therapeutics, Inc. - COO

* Omar Khwaja

Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development

* Vasilis Kariolis;Assistant Controller

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Conference Call Participants

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* Aaron Welch

H.C. Wainwright & Co, LLC, Research Division - Analyst

* Charles Cliff Duncan

Cantor Fitzgerald & Co., Research Division - Senior Analyst

* Dane Vincent Leone

Raymond James & Associates, Inc., Research Division - Research Analyst

* James William Birchenough

Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst

* Jeff Hung

Morgan Stanley, Research Division - Equity Analyst

* Laura Kathryn Chico

Wedbush Securities Inc., Research Division - SVP of Equity Research

* Philip M. Nadeau

Cowen and Company, LLC, Research Division - MD & Senior Research Analyst

* Sumant Satchidanand Kulkarni

Canaccord Genuity Corp., Research Division - Analyst

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Presentation

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Operator [1]

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Good morning and welcome to the Voyager Therapeutics Third Quarter 2019 Financial Results and Corporate Highlights Conference Call. (Operator Instructions) Please be advised that this call is being recorded. At this time, I'd like to turn the call over to Vasilis Kariolis, Voyager's Assistant Controller. Please proceed.

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Vasilis Kariolis;Assistant Controller, [2]

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Thank you. Good morning, and thank you for joining us. With me on the call today are Andre Turenne, our President and Chief Executive Officer; Omar Khwaja, Chief Medical Officer and Head of R&D; and Matt Ottmer, Chief Operating Officer.

Earlier today, we issued a press release, which outlines the financial results and corporate highlights for the third quarter of 2019. The release is available at voyagertherapeutics.com.

Before we begin, just a reminder that the forward-looking statements included in this call represent the company's view as of today, November 6, 2019. Voyager disclaims any obligation to update these statements to reflect future events or circumstances, except as required by law. Please refer to today's press release as well as Voyager's filings with the SEC for information concerning risk factors that could cause actual results to differ materially from those expressed or implied by such statements.

With that, I'll pass the call over to Andre.

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [3]

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Thank you, Vasilis, and good morning, everyone. Welcome to our Q3 earnings and corporate highlights call. Our CFO, Allison Dorval, is unable to participate in the call this morning due to a death in her immediate family, which sadly occurred on Sunday. Our heartfelt thoughts are with Allison and her family. I thank Vasilis, our Assistant Controller, for stepping in and covering our financial highlights.

I'll begin today by walking you through some of our recent corporate developments. Omar will then provide a pipeline update, and Vasilis will wrap up with the financial results. Once we've concluded our remarks, we'll have some time to take your questions.

We've had another productive quarter in Q3 at Voyager, building on a transformative first half of the year during which we entered into 2 important collaborations and a restructured one. It's an exciting time at Voyager as we gain momentum and expand on our foundation. Voyager sits squarely at the intersection of gene therapy and neuroscience. This dual focus on AAV gene therapy and neurological diseases provides us with several advantages. For one, as we've continued to hire key talent, we've been able to add colleagues with specialized expertise precisely in our chosen area. Their experience is already proving to add significant value to our efforts.

Another benefit of our focus as we keep advancing our pipeline is that we're finding invaluable learnings translating from program to program. We're seeing this, for example, as we've begun planning for the rapid transition from IND to first patient treated in our Huntington's disease program. Given the similar nature of the neurosurgical procedure involved for the onetime HD treatment and the onetime PD treatment, we expect to more rapidly enable sites to enroll study participants than what have otherwise been possible without our prior experience.

The benefits of our focused experience also apply to our earlier-stage programs. Our work on a vectorized antibody against pathological species of alpha-synuclein with our partner, AbbVie, is progressing faster than expected in light of the early learnings from our anti-tau vectorized antibody efforts. These learnings in turn are now being applied to our own additional efforts in vectorized antibodies. Moving forward, we'll continue to rigorously apply our learnings and those from others working in the space as we further advance our pipeline and platform.

Regarding our lead program, VY-AADC for Parkinson's disease, which is partnered with Neurocrine, we expect to present final 3-year data from all 3 cohorts of the 1101 Phase I trial at a medical conference in 2020.

2020 is also expected to be an important year for our Huntington's program as we anticipate filing an IND application and beginning screening and enrollment into the clinical trial. As we announced in a press release this morning, we presented some positive data on VY-HTT01 at ESGCT last month. Omar will share more details on this shortly.

Finally, we're pleased to announce today that Allen Nunnally has been promoted to the position of Chief Business Officer, from his previous role as VP of Corporate and Business Development. Allen has been a key collaborator in my first year at Voyager, and I look forward to his continued success in his new role.

I'll now turn the call over to Omar to provide more detail on our pipeline programs.

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Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [4]

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Thank you, Andre. First, I'll go through recent updates on our Parkinson's disease program. As Andre mentioned, the collaboration with Neurocrine, which we entered earlier this year, is off to a good start. We've agreed to the proposed statistical analysis plan for RESTORE-1 and are requesting feedback from the FDA before year-end. Steady progress continues to be made towards enrollment of the RESTORE-1 trial. We'll provide a more detailed update on RESTORE-1 after we receive feedback from the agency.

As a reminder, our approach to Parkinson's disease with the VY-AADC program is highly differentiated. It consists of the targeted delivery of a small volume of gene therapy to the region of the brain where it is needed for motor function. The result is a regulatable system, controllable by the standard-of-care oral medication. This ability to regulate the transient activity is highly desirable and a rather unique feature for AAV gene therapy. By creating a reservoir of AADC, the enzyme needed to convert levodopa to dopamine in the putamen, we're bypassing dying presynaptic neurons and introducing AADC into healthy postsynaptic neurons, where it can then be used to produce dopamine. AADC delivered into the putamen will do nothing on its own. But AADC in combination with levodopa will produce dopamine. Our approach gives the patient the exogenous control as to the amount of dose they needed to manage their motor function and the ability to avoid the negative impacts of too much dopamine in brain regions where it is not needed.

The Phase Ib trial was initiated in 2014. So we're now starting to see longer-term results that may speak to both the durability of effect and in the context of a progressive degenerative disease, contrast against the predicted course of disease progression. We expect to present 36 months data from all 3 cohorts in PD 1101 as well as 2-year data from PD 1102 at scientific meetings in 2020. The patients completing the 3-year protocol on PD 1101 and PD 1102 are now enrolling in our longer-term extension study. This will eventually provide us with over 5 years of data in addition to the placebo-controlled data at the time of the BLA filing and payer discussions.

Our Huntington's disease program is also progressing well. We've held advisory meetings with both neurologists and neurosurgeons and have received positive feedback on our delivery approach as well as our proposed clinical trial design and biomarker assessment. Our delivery approach leverages our learnings from the Parkinson's program, with local delivery of VY-HTT01 into the putamen. For Huntington's disease, we're also delivering directly into the thalamus. We chose this delivery approach based on our understanding of the disease pathology and the importance of delivering vector to the striatum as well as to the cortex. Pathological changes of Huntington's disease are evident earliest in the striatum, with changes in the cortex becoming noticeable as the disease progresses.

In fact, certain areas of the brain of a patient with Huntington's disease are deteriorating well before symptoms appear. The thalamus, in contrast, is a largely preserved structure in the early stages of Huntington's disease. Delivery of our gene therapy to the thalamus as well as to the putamen should allow us to deliver enough vector to impact the striatum as well as leverage the rich connections between the thalamus and the cortex to reach the outer brain.

Last month, at the European Society of Gene and Cell Therapy Meeting in Barcelona, we presented an update on our VY-HTT01 program during an oral platform presentation. We've previously presented data on dose-dependent vector biodistribution as well as HTT mRNA knockdown in the brains of nonhuman primates. In our recent presentation, we provided new evidence that VY-HTT01 also efficiently lowers huntingtin protein, and that huntingtin protein reduction is commensurate with the mRNA lowering and vector genome distribution in the NHP brain regions analyzed. These findings provide further evidence that our gene therapy, delivered to the thalamus and putamen, results in significant reductions in HTT, mRNA and in huntingtin protein to levels that are predicted to be clinically efficacious.

We now expect filing an IND for VY-HTT01 for Huntington's disease during the first half of 2020. As the kinetics of Huntington knockdown appear to be different in nonhuman primates than in rodents, we plan on submitting an IND application with final 1-year data from our preclinical studies instead of the previously planned interim 6 months data. Our goal is to minimize the amount of time between IND acceptance and first patient dose. We will be leveraging our related clinical experience in Parkinson's disease to achieve this.

Activities towards site selection engagement have already begun and will continue to take place in the fourth quarter and the beginning of 2020. We continue to expect screening and dosing of the first patient planned clinical study during 2020.

Our other pipeline programs, including the Friedreich's ataxia program with Neurocrine, and our 2 vectorized antibody programs with AbbVie, continue to progress. We are working on studies to support lead candidate selection for Friedreich's ataxia and continue to deliver on or ahead of schedule against our work plans on the AbbVie collaborations. Additionally, we've agreed on the 2 discovery sets with Neurocrine and are working on our own discovery efforts against new targets.

With our focus and expertise in neurological disease, we're pursuing several opportunities that are compelling targets for AAV gene therapy. We expect to provide more information on new programs during 2020.

I'll now pass the call on to Vasilis with the financial update.

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Vasilis Kariolis;Assistant Controller, [5]

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Thank you, Omar. Voyager reported net loss of $15 million or $0.41 per share for the third quarter ended September 30, 2019, compared to net loss of $20.3 million or $0.63 per share for the third quarter of 2018. Collaboration revenues of $20.4 million for the third quarter ended September 30, 2019, compared to collaboration revenues of $2.1 million for the third quarter of 2018. These 2019 revenues reflect the recognition of noncash amounts for research services that were performed for various programs under the Abbvie and Neurocrine collaboration agreements, in addition to amounts expected to be reimbursed by Neurocrine as per that collaboration agreement. Amounts can vary based on quarterly assessments of our efforts under each of these collaborations.

The increase in collaboration revenue during the third quarter of 2019 compared to the same period in 2018 primarily relates to the recognition of amounts from the Neurocrine and AbbVie alpha-synuclein collaborations, both of which were entered into in Q1 2019. Additionally, revenue related to the Abbvie tau collaboration increased year-over-year as our efforts continue to increase. These increases were offset by a reduction in collaboration revenue from our collaboration with Sanofi Genzyme, which was restructured in June 2019.

R&D expenses of $29.8 million for the third quarter ended September 30, 2019, compared to $16.6 million for the third quarter of 2018. These expenses include costs incurred under the Neurocrine collaboration, which are expected to be reimbursed. The increase in R&D expenses in the third quarter of 2019 related primarily to external research and development costs and increased employee-related and facility costs to support the advancement of our pipeline programs, including our RESTORE-1 Phase II clinical trial for VY-AADC.

General and administrative expenses of $8.5 million for the third quarter ended September 30, 2019, compared to $6.6 million for the third quarter of 2018. The increase in G&A expenses in the third quarter of 2019 is primarily due to an increase in employee-related and facility costs to support the advancement of our pipeline programs and growing operations.

As of September 30, 2019, we had $307.4 million in cash, cash equivalents and marketable debt securities compared to $155.8 million at December 31, 2018. Operating expenses are anticipated to be $150 million to $155 million, exceeding our previously forecasted range of $140 million to $150 million, largely as a result of higher-than-planned noncash expenses. Nevertheless, we continue to project year-end cash, cash equivalents and marketable debt securities to be in the previously forecasted range of $280 million to $290 million. Based on our current operating plans, we expect these amounts to be sufficient to meet our operating needs and capital expenditure requirements into mid-2022.

With that, we would like to now open the call up for questions. Operator?

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Questions and Answers

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Operator [1]

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(Operator Instructions) And our first question comes from Phil Nadeau with Cowen and Company.

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Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [2]

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My question's on the Huntington's program. You mentioned in your prepared remarks that, I think, 1-year data is necessary for the IND, given the difference in kinetics in the knockdown between rodents and nonhuman primates. Can you talk a little bit more about the difference? What exactly are you seeing? And why is 1-year data more informative than 6 months in?

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [3]

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Yes. Thanks, Phil, for the question. I'll ask Omar to address it.

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Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [4]

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Yes. So in -- back in 2017, Voyager had a pre-IND meeting with the FDA. And in the discussions around the definitive toxicology and biodistribution study that was planned, the feedback from the FDA was that the selected time points for assessment of toxicology should match the kinetics of transient expression and the specific request was that the time points would co-onset with the onset peak and plateaued expression of the transgene. At 26 weeks, the -- in terms of the bioanalytics we have, we don't yet -- aren't yet confident that we can say that the transgene expression has plateaued, and that their knockdown impact is also at its plateau as well. So that's why -- that's the reason that we've decided to not submit with interim 26-week data, but to continue the study to 53 weeks and submit with a full data set.

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Philip M. Nadeau, Cowen and Company, LLC, Research Division - MD & Senior Research Analyst [5]

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That's helpful. And I guess, when you say hasn't plateaued, is the level of knockdown continuing to increase? Or is it decreasing towards a plateau? And what are the implications for the human data? When -- at what time point do you think human proof-of-concept data, therefore would be available? Is it going to take 52 weeks to follow-up for that as well?

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Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [6]

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Yes. That's a great question. I mean, I think it's not so much that the knockdown in protein levels haven't plateaued, but we really need another data time point to ensure that, that is a true plateau rather than, that's just 2 time points that we're saying that we've got knocked down and it's stable. I think we need to have a third one to be certain for that.

I think we'll probably have to directly extrapolate that to the human situation until we actually conduct the human study. It's going to be difficult to know how that extrapolates, but it certainly implies, based on what we've observed so far, that on the profile that we see so far, it means that it's likely that it's going to be at least 3 months in the human that we would see the maximum expression of the transgene.

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [7]

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To -- just to add to the clarification, Phil, what we're seeing is a continued reduction in the -- or increase in the knockdown over time. So that's the direction. So if that could be a positive clinically, that you have the peak lowering that is higher than what we've observed at the 5 weeks in the earlier studies, what -- as Omar said, what we're looking to have is just the comfort that we have an understanding of how low it goes and at what point that is achieved.

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Operator [8]

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And our next question comes from Charles Duncan with Cantor Fitzgerald.

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [9]

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Condolences to Allison. Had a question on the PD program and then a follow-up on the HD program. Regarding the PD program, I'm wondering, you said that you have agreed to the staff plan with Neurocrine for RESTORE. And I'm just kind of wondering if you can provide additional color now that you're thinking about what to do there. In terms of the patient population, sizing and timing for RESTORE-1, can you provide any additional color on that?

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [10]

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Yes. Thanks, Chaz, for the question. So at this stage, we're not ready yet to give the further guidance as to the exact size of the study. We anticipate, as we've said previously, that it will be in the range that we've guided, 75 to 100 patients. And the work that we've done is just to determine with our new partner what the precise target is going to be within that range and then to get that same alignment with the agency. So when we have that in alignment with the agency, we're going to be able to provide that update, along with an update on -- given the number of patients and where we're at in the enrollment, some new targets for when we expect to be able to complete the enrollment to the full enrollment of the study.

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [11]

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Okay. It sounds consistent with your previous thinking. And then, if I can ask a follow-up on that. There are other AADC gene therapy programs for neuro indications, and Omar did a great job in terms of talking about your differentiation with regard to where the drug is really administered. But I guess, if you look across AADC programs, how do you see you being differentiated from others in terms of, say, vector use or basic construct?

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [12]

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Yes. No, thanks for that question, and Omar can add to it. But I think in his prepared remarks, he touched on a key differentiation, which is this activity to modulate the response with the control of the exogenous levodopa. So that, I think, is in contrast with the alternative approach that's in development, which provides a more direct production of dopamine.

Our approach is, one, again, as highlighted, that allows for the dialing of the amount of dopamine to be produced, like in our delivery in the putamen is in common. And that's a good target, to have a stable reservoir of that enzyme, as it's a structure that is not too impacted in Parkinson's disease. And we've been able to observe in our experience to date, in our preclinical experience that a very durable expression of the enzyme production in the -- after administration in the putamen. I don't know if Omar, you want to highlight any additional points?

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Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [13]

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Yes, I think the only thing to add to that in terms of differentiation with the approach is that our approach is purposely collecting AAV2, because we want to restrict the distribution of the vector into the putamen.

And I think one of the things that we've learned through those H1B programs is that it's not just the actual concentration effect that's being delivered, but also the coverage of the putamen. And I think an important part of our program is use of interoperative MRI and the administration of gene therapy, together with a contrast agent to ensure that we are really restricting the placement of the vector into the right structure, but also with the right degree and distribution of the transgene within that structure as well.

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Charles Cliff Duncan, Cantor Fitzgerald & Co., Research Division - Senior Analyst [14]

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Got it. That's helpful. Last question on Huntington's. With regard to patient population, what are you thinking about in terms of what would be the best type of patient to evaluate initial activity?

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Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [15]

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Yes. That's been an important consideration for us. I mean, there are 2 factors. One is ultimately, obviously, the potential for gene therapy in Huntington's is going to be, for all patients who are gene positive and as in any neurodegenerative condition, that the earlier it's given the better. In early clinical development, of course, we can't take patients who are completely asymptomatic. But what we really want to do is kick off our development program in a population that as closely matches or will support the eventual use and uptake of the gene therapy in the broader safety population that can benefit.

The second thing is actually just the selection of the patient that has the intactness of the structures that the gene therapy is going to be placed into. And so again, just based on our 87-subject MRI study that's (inaudible) general, we really understand that both the cortex and eventually the putamen become very significantly degenerated as you move past Stage 1. And so we are going to target patients in the earlier stages of the disease.

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Operator [16]

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Our next question comes from Dane Leone with Raymond James.

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Dane Vincent Leone, Raymond James & Associates, Inc., Research Division - Research Analyst [17]

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I was -- one specific question regarding the Huntington's program. Since this is intraperitoneal, are you going to be able to use NfL as a biomarker for these patients potentially, versus what we've seen with the intrathecal approaches for the RNAi stuff with like Ionis and Roche? And then the second question is, when will we have a little bit more clarity? What do you expect in terms of enrollment updates and time line for the pivotal Parkinson's program?

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [18]

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Yes. Thanks, Dane, for the question. So yes, we do plan on the capturing filament, neurofilament light chain as one of our fluid biomarkers in the Huntington's program. We will have other biomarkers, fluid biomarkers. We will have some colorimetric biomarkers as well. So that's a -- that's part of the plan, to capture a lot of these data points in the early clinical experience.

As for the PD program and providing guidance, so we have to do this now jointly with our partner, with Neurocrine. And as stated previously, we are waiting to have the input of how many patients we're going to target to recruit in the full study, to align them with our enrollment rate to be able to provide an update on the enrollment target for completing the study.

We also plan to be able to share an update on the activities towards the second pivotal, which we're planning. So again, we're looking to get the regulatory guidance before the end of this year on the program. So as soon as we have that, we should be able to, jointly with our partner, provide these updates to give further clarity as to timing for this one in the subsequent trial that we continue to plan to do in staggered, parallel fashion ahead of the completion of the RESTORE-1 study.

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Dane Vincent Leone, Raymond James & Associates, Inc., Research Division - Research Analyst [19]

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Okay. And then last one for me. I guess, since it's November, maybe it's fair to ask. Is there any update in terms of what your team hopes against the clinic next year, with either wholly-owned programs or partner programs?

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [20]

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Yes. So the -- for it to get into the clinic as a second program for us, into the clinic, we're looking at our Huntington's program, as guided. And we -- our plan is -- has expressed that we'll look to have the first patient both screened and treated during the year next year.

We continue to look to all the opportunities also externally that may accelerate our pipeline. And it's a benefit, again, of our focus on AAV for neurological diseases that we have the ability to have an opinion on every program that's out there. And if there is, in the future, enabling technology or an early stage program that we think can compel in a compelling way, and to our portfolio, accelerate our efforts, we will -- we'll be in a good position to make an assessment of that.

So at this time, it's really about the Huntington's program becoming another clinical program. And following behind that is our Friedreich's ataxia effort, also in a co-development way with Neurocrine. And then right behind are a lot of these earlier-stage program that we are advancing in parallel. And against that discovery platform that have not yet been disclosed, we are expecting next year to find an opportunity to provide an update as to the progress we're making against these new targets.

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Operator [21]

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Our next question comes from Jim Birchenough with Wells Fargo.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [22]

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So just a couple of questions. On the Parkinson's disease program, as we look ahead to 1101 and 1102, longer through a follow-up, could you maybe speak to the expected natural history of those patients over a 2- to 3-year period, given their stage of disease? And what we should look for over the longer-term with the gene therapy?

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [23]

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Yes. Thanks, Jim, for the question. I'll ask Omar to start with the answer.

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Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [24]

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Yes. Thanks, and the -- one of the measures that we've taken as one of the exploratory end points in 1101 and 1102 are measures of disease staging, particularly the modified Hoehn and Yahr. And that basically is an assessment of the patient's overall parkinsonian symptoms as the disease progresses over several years and patients move along stages, depending on the degree of involvement of whether things are just happening on one side of the body or both and then also the degree of instability, which relates to one of the big morbidities in Parkinson's, which is a fall.

And the data that we presented a month ago at the Movement Disorder Society, and we'll present an update on long-term data, suggests that patients started prior to treatment in fairly advanced stages of the Hoehn and Yahr, so stages 3 and 4. And that at the time points that we've already published and then we'll provide the full data, their 3-year data from 1101 plus 2-year 1102 data, that these patients are actually moving back in stages. So that would be unanticipated by natural history alone.

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [25]

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Yes. I will add that we will continue to look at and we'll provide updates on both patient-reported outcomes and physician-assessed status, and the last one that Omar mentioned is in that category. So that we get a real full picture of the amelioration that the patients may have and over a longer time period. So there is natural history that we will leverage that exists for advanced PD, but we're also working with our partner to substantiate what exists with some patient cohorts that more closely match the ones that are enrolled in our trial. So more to come on this as well. But clearly, as Omar shared in his prepared remarks earlier, this contrast of patient-reported and finished and assessed improvement against the natural history as we get longer and longer data points becomes increasingly significant and likely in sharper and sharper contrast with what normally occurs in a neurodegenerative disease.

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Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [26]

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I think in things to look out for, as Andre said, I think it's going to be the [conference] of these measures as well, that they are -- whether or not they move in the same direction and stay like that over the long term.

And then I think the second thing that will be important to look for is, in terms of the patient's use of other dopaminergic medications and whether this is happening on the background or reduced, stable or actually patients are still needing to increase the amount of exogenous levodopa that they're taking.

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [27]

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Yes. So these long-term results are exciting for us. I think they're going to be important also for the field to have these types of long-term gene therapy results.

And one last point on this is that, as Omar noted, we have an extension study. So projecting forward, we will add even longer data points beyond the 3-year period of the 1101 and 1102 studies.

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James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [28]

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And then just, Andre, following up on your prior comments on evaluating external assets that leverage your capabilities, could you maybe speak to what are the kind of things that you're looking for, if you were to source an external AAV gene therapy opportunity? And maybe contrast that with Parkinson's as an example?

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [29]

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Yes. Yes, thanks, Jim. So our focus will remain on leveraging our internal expertise to be able, as we do -- are doing right now, to discover and advance programs. We have a lot of in-house expertise. And we've invested in our discovery engine to be able to have a consistent flow of IND opportunities behind our lead programs at the moment. So that's the primary approach.

But again, because we have the benefit of that focus, we are in, actively scanning the space and discussions actively with leaders in academia and certain companies that have that program, but less of a focus, less of that focus on the AAV area than we do, where we think our efforts and our capabilities could help accelerate efforts.

So in terms of the profile of what we look, it can be enabling technologies, that they complement what we have and what we're going to be looking for, for any program, whether they're de novo, in-house programs or external, are ones where we have a clear genetic or biological validation of the target, where we can have some clear and fairly rapid proof-of-concept attainment. And probably the most overarching criteria is where we think we can have the biggest impact for patients. So where we think the clinical utility would be the highest.

So these are guiding principles. But again, that's an inclination that we have to not only rely on our internal source of innovation, but make sure that we're very, very richly connected with the external environment. And that's what we've invested in doing in the past year.

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Operator [30]

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(Operator Instructions) Our next question comes from Jeff Hung with Morgan Stanley.

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Jeff Hung, Morgan Stanley, Research Division - Equity Analyst [31]

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To clarify, with over 20 active sites for RESTORE-1, have you begun to enroll patients?

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [32]

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Yes, we have. We have, as you note, pretty much all of our sites active and enrolling. So the study continues to move well. And we have earlier this year, or in fact, late last year, initiated the study, and it continues to progress well.

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Jeff Hung, Morgan Stanley, Research Division - Equity Analyst [33]

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Okay. And then for SOD102, I guess, can you provide an update on where you are preparing for an IND and what remains outstanding? And can you remind us if you'll continue preclinical studies while looking to partner the program? Or we wait for a partner to complete the studies needed for an IND?

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [34]

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Yes. Thanks, Jeff. So far, the SOD1 program, we are completing the work that was initiated as we continue to entertain discussions with others. So we can't comment, obviously, on potential transactions, but it remains our intention to partner on SOD1. So we continue to advance our efforts there on SOD1, but more broadly, in ALS.

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Operator [35]

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Our next question comes from Laura Chico with Wedbush Securities.

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Laura Kathryn Chico, Wedbush Securities Inc., Research Division - SVP of Equity Research [36]

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I guess, one on the Parkinson's program. You mentioned the Phase III program. If you could just step back and remind us on the dosing, what gives you confidence in the dose selected as the optimized one?

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [37]

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Yes. Thanks, Laura. Omar?

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Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [38]

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Yes. It's a great question. So we conducted 2 Phase Ib studies. So 1101 was single-ascending doses of the vector. And essentially, that has contributed in terms of understanding the pharmacological response to those increasing doses. And then PD 1102 was a collection of a dose between the doses and cohorts 2 and 3 in 1101, but this time using the posterior trajectory rather than a frontal trajectory for injection to the putamen. And this is because the pharmacological response seems to rely not just on the actual amount of vector that's placed into the putamen but also the distribution of the actual coverage of the putamen with the convection enhanced infusion.

So the dose that we selected for the principal program is the dose that we think ultimately combines coverage as well as the absolute number of exgenomes being placed in the putamen, and that has really given the most optimal responses in the 2 Phase Ib studies.

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Laura Kathryn Chico, Wedbush Securities Inc., Research Division - SVP of Equity Research [39]

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And just one quick follow-up, if I could. Could you talk a little bit more about your expected capacity to supply the market? Obviously, you're starting Phase III. But as you're getting to potential launch stage, what would be your capacity to supply the market on a patient number basis?

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [40]

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Yes, I'll ask Matt Ottmer, our Chief Operating Officer, to address your question, Laura.

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Matthew P. Ottmer, Voyager Therapeutics, Inc. - COO [41]

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We made the decision early in Voyager's history to invest in the baculovirus platform. And so our Parkinson's program was the first program to be transitioned from what had previously been a triple transfection platform for prior studies. We did the comparisons and an IND amendment with the FDA based on comparability, so that the material that we're using in this now planned for registrational study as well as the second -- that's in the process of being planned using that material.

With the productivity of that process, we have effectively an unlimited ability to supply the future of this product. It would be in single-digit batches per year anticipated, which we could readily handle through existing contract manufacturers or in the future, given our process expertise in developing the platform as well as analytical capability, we could transfer it to an internal site if we decided to at some point.

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [42]

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On the delivery side, Laura, to add to what Matt is describing on the manufacturing, the plan is to have a centers of excellence model. And there are dozens of sites in the U.S. that have the proper ability to do these stereotactic procedures on their MRI guidance. So that's the plan, to be able to meet the market demand once we get there is to be able to leverage sites like this that can function at a sufficiently high volume to meet the demand.

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Operator [43]

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Our next question comes from Sumant Kulkarni with Canaccord.

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Sumant Satchidanand Kulkarni, Canaccord Genuity Corp., Research Division - Analyst [44]

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This is a bit of a bigger picture one. As an organization, I know you've been focused on manufacturing relatively early in the company's evolution. So what are your latest thoughts on what cost of goods might look like given the transition from your old system to the new one? Any updates or latest thoughts there would be appreciated.

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [45]

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Yes. Well, thanks, Sumant, for the question. So for us, our 2 lead programs are intraparenchymal delivery of very small volumes of the gene therapy. So to Matt's point, we're able to run a single bioreactor that produces hundreds of doses. So we expect that the cost of goods is going to be quite low. And we don't have yet a guidance on this, but again, given the volumes involved for the lead programs, expect to be the case. The choice of the baculovirus system for a number of our programs moving forward, once we move into programs that we intend to deliver systemically and leverage a capsid's ability to cross the blood-brain barrier that we -- because of that choice to have a baculovirus system that is very proactive, we also expect to be able to keep the cost of goods relatively low.

So that's the current plan at the moment. Just to -- in the big picture of our strategy for manufacturing, we continue to execute on our stated strategy that we think it's important to have in-house the expertise on the process development and analytical development fronts. But we work with selected CDMOs to produce the clinical batches for a clinical program and future programs. Once we have the demand for continuous means to produce at a higher volume, then we'll consider eventually at the right time, internalizing, fully manufacturing. But for now, we continue to execute on this hybrid model, where we internalize some of the expertise and turn to partners for some production.

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Operator [46]

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Our next question comes from Debjit Chattopadhyay with H.C. Wainwright.

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Aaron Welch, H.C. Wainwright & Co, LLC, Research Division - Analyst [47]

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This is Aaron on for Debjit, and I just had a question about the main disease program, upcoming clinical studies. If you could tell us anything about the design of the trial? If it's going to be randomized included in the patient surgery control arm? And if you think that would impact enrollment? And also, if you have any minimum requirements on the number of CAG repeats for patients.

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Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [48]

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Yes, thanks for the question. So we don't anticipate the Phase I study to be blinded. We say we're not -- we do not anticipate to have a placebo arm in the initial thoughts of the development plan.

In terms of the CAG repeat number, we will be stratifying patients. But at this stage, we're not ready to disclose the details of how we're going to select patients for Phase I, other than that there will be patients in the early stages of the disease.

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Aaron Welch, H.C. Wainwright & Co, LLC, Research Division - Analyst [49]

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Okay. Great. And could you comment also on thoughts on -- of a relevant metric for the RNAi activity? If you're going to evaluate based on the CSF, considering that the decrease in the huntingtin protein not be reflective of the -- in the CSF versus the deep brain structures? Can you talk on that?

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Omar Khwaja, Voyager Therapeutics, Inc. - Chief Medical Officer and Head of Research & Development [50]

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Yes. It's a good question. I mean, the tough thing is to really to, to measure microRNA and mRNA in CSF, just in terms of the absolute amounts that are detectable, and then actually really have to extrapolate those to the pharmacokinetics of the drug.

It may ultimately that these -- that protein is the best pharmacodynamic measure that we can really take that we can really assess in the human. And -- but we are developing a model in terms of the pharmacokinetics of both the vector genome, but also the microRNA and mRNA in tissue and CSF of the nonhuman primate and use that to create a model to understand the PK/PD relationship in the human studies.

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Operator [51]

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I am not showing any further questions at this time. I would now like to turn the call back over to Andre Turenne for any closing remarks.

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G. Andre Turenne, Voyager Therapeutics, Inc. - CEO, President & Director [52]

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Yes, thank you, operator, and thank you, everyone, for joining us on the call. We look forward to updating all of you soon on our progress. Thank you.

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Operator [53]

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