Good afternoon, and welcome to the Voyager Therapeutics Third Quarter 2018 Financial Results and Corporate Highlights Conference Call. At this time all participants are in a listen-only mode. Following the formal remarks, we will open up the call for your questions. Please be advised that this call is being recorded at the company’s request. At this time, I'd like to turn it over to Matt Osborne, Voyager's Vice President of Corporate Affairs, Communications and Investor Relations. Please proceed.

Thank you. Good afternoon, and welcome to the conference call. This afternoon, we issued a press release, which outlines the recent corporate highlights and financial results for the third quarter of 2018 and provides financial guidance for 2018. We also issued a separate press release providing an update on the longer-term clinical results with VY-AADC for Parkinson's disease. These releases are available at voyagertherapeutics.com. Today on our call, Andre Turenne, Voyager's President and CEO, will review our recent corporate and clinical program highlights; Dinah Sah, Voyager's Chief Scientific Officer will review updates with our pre-clinical pipeline program; and Allison Dorval, Voyager's Chief Financial Officer will review the financials; and then we will open up the call for your questions. Before we begin, just a reminder that various remarks we make during the call about the company's future expectations, plans and prospects constitute forward-looking statements for purposes of the safe harbor provisions under the Private Securities Litigation Reform Act of 1995. These forward-looking statements represent the company's view as of today, August 7, 2018. Voyager disclaims any obligation to update these statements to reflect future events or circumstances. 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.

Thank you, Matt, and good afternoon everyone. Thank you for joining us on the call. As we highlighted in today's press releases, the third quarter was a productive one for the company with positive new data on both our lead program, VY-AADC for Parkinson's disease, and on our pipeline programs. We described today in a separate press release the positive longer term results from the ongoing open-label dose escalating Phase 1b clinical trial of VY-AADC. At the latest timepoint measured for each of the five patient cohorts, patients and the two highest dose cohorts experienced mean, durable improvements in good ON time, which is ON time without troublesome dyskinesia of 1.7 hours per day at 18 months for Cohorts 3 and 2.7 hours per day at years for Cohorts 2. Importantly these improvements in good ON time were achieved with large and sustained reduction in daily oral levodopa and related medications in these two highest dose cohorts. This included a 43% reduction from baseline for Cohort 3 at 18 months and 21% reduction from baseline for Cohorts 2 at two years. Since we've selected a dose of up to 2.5 e12 vector genomes for the Phase 2, which is between the doses used in Cohorts 2 and 3 of the Phase 1b combining the data from the 10 patients in these two cohorts provide the most relevant dataset. For this combined group of 10 patients VY-AADC improved patient's good ON time by 2.4 hours per day at 12 months, which is the timepoint for the primary endpoint of the Phase 2 trial and 2.6 hours per day at 18 months, which is the latest timepoint measured for both Cohorts. We've learned from the Phase 1b that patients with severe dyskinesia baseline could be more challenging to treat as they may…

Thanks Andre and good afternoon everyone. I'll spend the next few minutes describing some of the recent exciting preclinical data with our Huntington's disease program and our ALS program, targeting the SOD1 mutation. Before doing so, it's important to take a step back and understand our systematic approach to fully optimizing not only the payload or in these cases probably the microRNA cassettes, but for both programs, delivery of the vector as well. First on payload selection for AAV-RNAi program, we begin with the most potent RNAi sequences based on in vitro transfection experiments and then place these selected RNAi sequences within engineered primary microRNA cassettes for expression in AAV. Multiple studies have demonstrated that primary microRNA cassettes provide better precision and efficiency of processing than short hairpin RNAs. So we have chosen to use the primary microRNA cassettes in our RNAi platform. We screen a number of primary microRNA cassettes, RNAi sequences to select the most potent candidates in vitro. These are then tested head-to-head in the mouse for in vivo knockdown of the target. The top three or four sequences are finally tested in a lead selection study in the large mammals such as nonhuman primate for the selection of the clinical candidate. In the in vivo studies we not only access knockdown of the target, but also conduct deep sequencing to evaluate precision of processing and guide to passenger ratio. I recall that the guide strands to active drug whereas the passenger strand is just along for the ride, no intended pharmacological activity. The final selection is based on the most robust and potent pharmacology, in this case, knock down of the target, as well as most selective pharmacology. Our first RNAi program at Voyager with ALS, SOD1 program where we optimized this RNA platform mostly by…

Thanks, Diana. Good afternoon, everyone. Voyager reported a GAAP net loss of $20.3 million or $0.63 per share for the third quarter ended September 30, 2018, compared to a GAAP net loss of $23.3 million or $0.89 per share for the same period in 2017. Collaboration revenues of $2.1 million for the third quarter of 2018 compared to $1.1 million for the third quarter of 2017. This increase reflects the recognition of revenue related to research services performed under the AbbVie collaboration agreement announced in February and was offset by reductions in amounts recognized under the Sanofi Genzyme collaboration. These reductions related to lower research and development services revenue as well as the impact of adopting certain accounting rules related to our recognition methodology. Research and development expenses decreased to $16.6 million this quarter from $19.6 million in Q3 last year. This was primarily a result of higher manufacturing costs last year to support the VY-AADC clinical program. This reduction was offset by increases in personnel and facility costs to support the advancement of our clinical and preclinical program. General and administrative expenses of $6.6 million for the third quarter of 2018 increased from $4.9 million last year, primarily due to personnel and facility costs to support the advancement of our lead and pipeline program, our platform, and our manufacturing capabilities. We ended the quarter with cash, cash equivalents and marketable debt securities of $179.6 million. Based on our current operating plan, we expect to end 2018 with total cash, cash equivalents and marketable debt securities above the previously guided range of $125 million to $135 million. We continue to project the cash, cash equivalents and marketable securities to be sufficient to fund operating expenses and capital expenditure requirements into early 2020. With that, I’ll turn the call back to Andre.

Thanks, Allison. And with that, operator we can now take questions.

Thank you. [Operator Instructions] And our first question comes from Brian Skorney of Baird. Your line is now open.

Hey, good afternoon guys. Thanks for taking the question. I just wanted to kind of dig in a little bit on the changing sort of the FDA body language here with the addendum. Was there any new data submitted between getting the minutes back from the Type C meeting and this addendum that would trigger this? And is there any way you could just 8-K, the meeting minutes on the addendum for us. So we have an idea of what the FDA is new change of a possession us.

Yes, thanks for the question, Brian. So there are no new data between the Type C meeting and this addendum. And what we’re endeavoring to do next is to sign out more getting in touch with the agency and we have a Type B meeting scheduled between now and the end of the year. And we’re going to look to have access also through the channels, we have the RMAT designation. So as soon as we have greater clarity, we’re going to provide the update on this, but that’s the bat for us for next step is really to engage, continue to engage with the agency to clarify their latest comment.

Thank you. And our next question comes from Laura Christianson of Cowen. Your line is now open.

Hi, guys. Thanks for taking my question. My first one is just looking at the data you provided on the L-Dopa dose reduction. And particularly in cohort two at 24 months, I’m saying that there’s been a 21.2% reduction overall. I know previously, you had mentioned 34% at six months. So I’m just wondering if this changes your view of the long-term efficacy or whether the L-Dopa reductions were brought in initially and you anticipate the more gradual reductions will yield the same results?

Yes, thanks, Laura for the question. So when we look at the all the cohorts and the data we have to date overtime. We see clearly that we have a both a sustained reduction in levodopa, but one also that’s a different cohort by cohort. So where we’re seeing the lease reduction is with Cohort 1 and then there is a good dose response here where a Court 2 the dose response in the levodopa equivalent dose remains a low versus baseline. And then that’s even more the case for the third cohort where we have the highest and most sustained reduction in the levodopa equivalent doses. So for us, again, having now made a dose selection of choice that we’re having a dose that in between Cohort 2 and Cohort 3, when we look at the relevant group, the cohort of 10 patients or to seven as we highlight in the comments in the press release that would likely be eligible for that Phase 2. We see a nice consistent reduction in levodopa equivalent doses. As you go through 12 months and 18 months, it stays in the 30% to 40% reduction versus baseline. So that’s quite significant because that goes to the core of the mechanism of this AADC replacement. So to be able to improve motor function, while at the same time the patients have this large and sustained reduction in the levodopa equivalent dose is towards the clear sign that the pharmacology is very active and what we’re seeing something sustainable.

Got It. That’s helpful. And then just a quick one on the Phase 2, Phase 3, how consistent do you expect the dose concentration to be across patients in that trial with – the surgeon aiming for a concentration between Cohort 2 and Cohort 3, but potentially having some variability?

Yes. So the concentration is fixed. The variability is going to come from the exact volume that’s delivered. That’s going to vary depending on the patient, every anatomy of the putamen is a little bit different patient by patient. So we expect the volume differences to be relatively small and therefore the total vector genomes delivered to the difference range to be relatively tight with this route of administration. This is a single infusion that’s required with a posterior route. And again, having the lot of the motor function in the posterior region of the putamen, the way to surgery will work is a works with that trajectory is that the most important area is impacted first and covered more totally with the infuse it. But to answer your question, we don’t expect a large variation in that volume and therefore in the vector genomes delivered.

Perfect. That’s helpful. Thank you.

You’re welcome.

Thank you. [Operator Instructions] And our next question comes from Jeff Hung of Morgan Stanley. Your line is now open.

Thanks for taking the questions. Can you provide some color on what the agency said, if anything during the Type C meeting regarding their thoughts on the Phase 2 being more exploratory?

Yes. Thanks, Jeff. So as we reported after the Type C meeting – from our Type C meeting minutes responses to our question. The agency had responded to us that the Phase 2 alone likely maybe sufficient none of it would approved to be effective. To me it’s primary endpoint and to be safe for the submission of the BLA for submission. So that’s the feedback that we received at that time. And that’s why here we – we’re going to seek clarity on this addendum that we just received to be able to align with that agency on the next step. What’s clear that the Phase two, if the trial – that’s the right trial and this moving forward, what we’ll do once we have the benefit of getting greater clarity from the agency is that we’ll consider adjustments to the overall plans if necessary. So we can continue to be aligned with the guidance that they provide, once they clarified. But that’s where we stand right now. And again, we have the means of engaging with that agency having a Type B meeting in front of us and having access also again through the senior an accelerated type of engagement, we can get via the RMAT designation.

And I think you just answered it, but maybe if I can push a little bit on that last part. So does the addendum change your base case assumption that the Phase 3 will be required regardless of the outcome of the Phase 2? When with the Phase 3 be sufficient for filing, or do you think additional studies will be required beyond your Phase 2 and Phase 3?

Yes. So at this moment we won’t speculate on any changes to the plan. So we still believe that we have a robust plan with a Phase 2 and Phase 3 staggered design. And we’ll look to get the further dialogue with the agency to clarify. Again, any adjustments that – if any, that we make to the current plan. But the plan for the Phase 2, again, in terms of primary endpoint, in terms of the route of administration, the dose that we select in the patient population, the first placebo-controlled study for this therapy is absolutely what we believe is the right thing to do. So we’ll review with the agency, the plans in that totality via this therapy meeting and the other interactions we may have and we’ll provide updates as to the overall baggage in due time.

Okay. And then maybe one last one. You’re excluding patients who are severely dyskinetic in the Phase 2. Can you remind us what proportion of moderate and advanced Parkinson’s patients are severely dyskinetic?

Yes. So that’s a hard number to get the precise. But in our experience and working with our investigators, we think it’s a small portion, it’s a minority of patients with severe dyskinesia to the level that we – that would be excluded from this trial. So it’s small percent.

So just, I want to make sure that – so then do you think that the three out of 10 excluded from the Phase 1b is representative of what you might see in the real world?

No. So there were two reasons why the 10 patients that were in cohorts 2 and 3, likely may not be patients that would be enrolled in the Phase 2. One of the criteria was too severe of dyskinesia. But the other criteria, that’s not more stringent is the amount of OFF time at baseline, which is the disease severity of baseline. So we had a patient population here that we had – it will be more stringent than Phase 2 as stood at the minimum amount of minimum OFF time at baseline. So it's – these two factors that they are enriched if you well into Phase 2 versus Phase 1b experience.

All right, great. Thanks for taking the question.

Thank you. And your next question comes from Jim Birchenough of Wells Fargo. Your line is now open. Again, Jim Birchenough your line is now open. Please check your mute button. And our next question comes from Sumant Kulkarni of Canaccord. Your line is now open.

Hi. Thanks for taking my questions. The first one is on the ADC product. At the time, you are eventually in a position to receive Phase 3 data. You'd have a wealth of time build up on the patients that are in the Phase 1, which might inform whether this product is truly a one-time dose or not. So assuming that for some reason ADC does not turn out to be a one-time dose, how many years of an effect do you think it needs to have to compete credibly with deep brain stimulation?

Yes. So thanks for the question. So as you say, durability is an important feature of the program an appealing feature. So the evidence that we have – if you go back to the development of the program there, we have up to 15 years of preclinical model in monkeys that show that the durable sustain expression of ADC following treatment with VY-AADC. So that is one signed up. If you administer variety seemed to putamen, which does not degenerate in Parkinson, you have this potential for a very long duration. From the first clinical experience, with the VY-AADC, there is no data to five years prior to the Phase 1b that we've conducted that shows again, durable expression of ADC, and as you suggest, we have a Phase 1b that was a three-year consent and that will also look to have patients in an extension study to be able to continue to collect the data to be able to assess certain the durability of effect in this latest active group of patients. So all of this that definitely will be a part of the full picture by the time we get to BLA filing for the durability of effect. So anything from that experience that suggests multiple years of a durable improvement will be certainly a big, big improvement for these patients. Or otherwise, they really have plateaued and has peak and continue to increase their levodopa dose, while they continue to lose a motor function. So here it's not – what we're seeing today is not just the stabilization of disease, what the data suggests is an improvement in motor function with less background therapy. And if that can be sustained, this is a very important to clinical benefit that we believe.

And then given the wrinkle thrown in by the FDA addendum now, I know you said that you're going to announce when you will dose the first patient. How does the timeline on that change though, if, if at all?

The plan for such trail does not change. So again, this is the first placebo-controlled study that we're doing with VY-AADC, we think it's in the right patient population and the plan has been reviewed and discussed that with the agency. So I think the question here is the likelihood of the suitability of a single trial as currently size to be sufficient for a BLA filing and that's going to be the core of the question to continue to discuss with the agency. So we can again consider making any adjustments to our plans if and as necessary once we get the greater clarity. With the plan for the current study is as previously planned.

Thank you.

Thank you. And our next question comes from Jim Vrachnas, Wells Fargo. Your line is now open.

Hi. This is Yanan dialing for Jim. Thank you for the questions. So just want to ask about the FDA’s language under the bit more because of the Phase 2 is indeed a randomized design, I think – I think the design was pretty similar to the Phase3. And also given that you already have Phase 1b data, so it's a little curious about the language of a Phase 2 being exploratory. So I guess – what is your thought on that? And then secondarily a given that the Phase 2, Phase 3 are similarly designed. The current designs a staggered starts, but do you have the ability given that your comfort level now it's all the data, do you have the ability to move the famous restart time ahead so that you can still have the similar kind of a timeline for data. Yes. I guess, I'll stop there and have a follow up next.

Yes, thank you, Yan for your question. So we'll have to discuss with the agency again to clarify their statements and their position and we'll do as we've done today that we'll look to incorporate that feedback into to inform any adjustments to our plan. So this is a new information to us and we have an ability again to have the next set of discussion with the agency to try to their position and there for us then in turn to make any adjustments as we think helpful and necessary. And again, soon in front of us here before the end of the year, we have a scheduled a Type B meeting and again we have the benefit once again have this RMAT designation that’s the express purpose of this designation is to be able to have the right to access an accelerated type of feedback with the new agency and we’re going to absolutely look to both via the Type B meeting and via the cannel to get the clarity very quickly and then consider any change, if any to deal over all that plan to a BLA.

Got it. Thank you. And also on the posterior study, are we going to have some detailed data on the six months – at the six month follow-up time point or is it just the 12 months, in next year that’s the first time we will hear detail data. And also, have you shared the posterior study data with FDA yet? Thank you.

Yes. Thanks for your question there. So, we currently expect to share once we have the full cohort of eight patients, those with the posterior route get to 12 months, which is in Q2, 2019. We’ll expect to provide that full update at that time. And to your other question, the data is going to be submitted to the agency once we have a request for an additional meeting. We’re going to provide the relevant data set to put it in front of them, whether it’s from a updated longer-term results of the 1101 study or results from this 1102 with the posterior route, we will provide the freshest cuts of data relevant for discussions with the agencies moving forward.

Got it, got it. Last question on the preclinical program in Huntington’s. Just wondering, is there a role for coverage, in this disease as it is for Parkinson’s, and in the coverage by the gene therapy of the putamen and now you also mentioned thalamus is also going to be a targeted site, and if there is such a rolling for coverage than what a kind of a percentage of coverage should we expect to be therapeutically relevant? Thank you.

Yes. Thanks for the questions. I’ll ask Dinah to answer your question here.

Yes, it’s a good question. There is a role for coverage of both the putamen and the thalamus in Huntington’s disease, in the case of the putamen and of course, it’s involved in motor function, the medium spiny neurons throughout the putamen are degenerating, those the ones we want to protect by lowering Huntington. So the broader, the coverage, the more medium spiny neurons we protected, the more benefit to therapeutic benefit to function. With the thalamus, we’re leveraging the widespread and relative and preserved connections to the cortex, and different regions, different nuclei of the thalamus project to different regions of the cortex. So in order to maximize the distribution of our veterans of the cortex, and maximize knockdown of Huntington throughout the cortex, likewise the goal would be to maximize the distribution and coverage of the thalamus. So in both cases, for both structures of the goal would be to cover a large portion of both structures.

Got it. Thank you very much.

Thank you. And that concludes our question-and-answer session for today. I’d like to turn the conference back over to Andre Turenne for closing remarks.

Thank you, operator. So that concludes the call. Thank you all for attending. I appreciate all the thoughtful questions and we’ll look forward to being you on the progress in the near future. Thank you.

Ladies and gentlemen, thank you for participating in today’s conference. This does conclude the program. You may all disconnect. Everyone. Have a great day.