Good day, ladies and gentlemen, welcome to Voyager Therapeutics' Fourth Quarter 2016 and Year End Investor Update Call. At this time, all participant lines are in a listen-only mode to reduce background noise, but later we'll be holding a question-and-answer session, and instructions will follow at that time. [Operator Instructions] As a reminder, today's conference call is being recorded. I would now like to introduce your first speaker for today, Matt Osborne, Head of Investor Relations and Corporate Communications. You have the floor, sir.

Thank you, Operator. Good morning and welcome to the Voyager Therapeutics' fourth quarter and full-year 2016 financial and operating results conference call. This morning we issued a press release which outlines these results. The release is available at voyagertherapeutics.com. Today, on our call, Dr. Steve Paul, Voyager's President and CEO will discuss the corporate highlights and goals; Dr. Bernard Ravina, Voyager's Chief Medical Officer will review the clinical program highlights; Jane Henderson, Voyager's CFO will review the fourth quarter and full-year financials and provide 2017 financial guidance. And then we will open up the call for your questions. Before we begin, just a reminder that the estimates and other forward-looking statements included in this call represent the company's view as of today, March 15, 2017. Voyager disclaims any obligation to update these statements to reflect future events or circumstances. Please refer to today's earnings 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 Steve.

Thank you, Matt, and good morning everyone. 2016 was a very strong operational year for the company as we progressed our lead program for advanced Parkinson's disease further into the clinic, and our additional preclinical program towards lead candidate selection. These efforts culminated last year when we reported positive interim results from our Phase 1B trial of VY-AADC01 in advanced Parkinson's disease, and more recently when we announced lead candidate selection for our ALS program targeting the SOD1 mutation. During 2016, through careful capital allocation we continue to invest in our baculovirus/Sf9 cell production and manufacturing process and capabilities to ensure both high quality and yield, and that our product engine runs at full potential. These investments in our pipeline programs, vector engineering and manufacturing form the foundation for what should be exciting years ahead. Indeed our systematic approach to progressing our Parkinson's disease program in our ongoing Phase 1B trial has been rewarding for us and inspiring to investigators. Looking back nearly one year ago we had presented efficacy data from really only a single patient treated at one center with only one dose, and at only three months of follow-up. Fast forward to today, and we have successfully treated 15 patients, provided positive interim results from 10 patients at six months of follow-up, and from eight patients at 12 months of follow-up, treated at two clinical trial sites and at three dose levels varying both the volume and concentration of vector delivery. And the interim data we provided served as proof of concept that a one-time targeted delivery of a gene therapy was well tolerated and could enhance patients' responses to levodopa, while at the same time producing durable dose-related and clinically meaningful improvements in motor function in these very advanced patients. We are encouraged by the safety…

Thank you, Steve, and good morning everyone. As Steve mentioned, the interim results we provided in December for VY-AADC01 represented an important milestone for the program providing what we believe is early proof of concept that well tolerated in accurate onetime delivery can increase AADC enzyme activity in the putamen, enhance the patient's response to levodopa while delivering durable and clinically meaningful improvements in measures of motor function. Although we underscore that our study was not placebo controlled, the dose dependent improvements in biomarkers indicating an enhanced response to levodopa that markedly reduced levodopa doses post versus pre-treatment would be VY-AADC01, especially in cohort 2 and the improvement in motor symptoms observed at these doses are very encouraging. This was especially evident in cohort 2 patient diaries were on time increased by 43% or 4.1 hours at 12 months with a 48% or 2.2 hour reduction in diary off-time from a baseline of only 4.2 hours. Importantly, decrease in off-time in cohort 2 corresponded with meaningful reductions in troublesome dyskinesia. So, patients were spending there on-time in a better state, if you will. Importantly, these durable improvements in motor function occurred with a substantial 34% or over 500 mg reduction in cohort 2 in average daily doses of oral levodopa and related medications from a baseline of over 1600 mg per day. This speaks right to the goal of our program to turn back the clock to when patients were more responsive to levodopa, requiring lower doses and achieving improvement in motor function. This is equally compelling in our opinion because oral levodopa doses were not reliably reduced in past gene therapy trials although direct comparisons must be made with caution. And we are thrilled to be able to present these data at the upcoming American Academy of Neurology meeting…

Thank you, Bernard, and good morning. I will spend the next few moments reviewing the financials and guidance before we move to Q&A. Voyager reported a GAAP net loss of 14.7 million or $0.57 per share for the fourth quarter ended December 31, 2016, compared to a GAAP net loss of $8.8 million or $0.67 [ph] per share for the same period in 2015. The company reported a net loss of $40.2 million or $1.59 per share for the full year ended December 31, 2016 compared to a net loss of $38.3 million or $0.914 per share for the same period in 2015. Collaboration revenues of $2.4 million for the fourth quarter of 2016 compared to collaboration revenues of $4.9 million for the fourth quarter of 2015. Collaboration revenues reflect Sanofi Genzyme's recognized payments for research and development services, and decreased year-over-year mainly due to the de-prioritization of the development of VY-SMN101 for SMA, as well as the reduction of certain services provided by Sanofi Genzyme. R&D expenses of $12.7 million for the fourth quarter ended December 31, 2016 compared to $9.2 million for the same period in 2015. The increase in R&D expenses year-over-year for the quarter and full year was largely due to expenditures associated with the development of Voyager's clinical and preclinical pipeline, product engine, and personnel costs. G&A expenses of $3.5 million for the fourth quarter ended December 31, 2016 compared to $3.2 million for the same period in 2015. G&A expenses of $13.3 million for the year ended December 31, 2016 compared to $9.9 million for the same period in 2015. The increase in G&A expenses was primarily due to personnel costs to support Voyager's growth and facility costs. Total cash, cash equivalents, and marketable securities as of December 31, 2016 was $174.4 million, and the company has no long-term debt. Now turning towards guidance, as we enter 2017 with the exciting progress of the lead and pipeline programs as Steve and Bernard have discussed and with the ongoing investments in manufacturing, and to the Vector product engine we expect to end 2017 with total cash, cash equivalents and marketable securities of approximately $90 million to $100 million. We continue to project that our existing cash, cash equivalents and marketable securities will be sufficient to fund operating expenses and capital expenditure requirements into 2019. With that, we would like now to open the call up for questions. Operator?

Ladies and gentlemen, the question-and-answer queue is now open. [Operator Instructions] We'll be taking our first question from the line of Christopher Marai from Nomura. Your line is open.

Hi, good morning. Thanks for taking the questions and congrats on the AAN abstract [ph]. So really I wanted to maybe circle back on two things regarding the potential pivotal trial. Number one, maybe could you give us a little bit of guidance about the size of the trial you're thinking, obviously some Phase 3 could be in that 200 patient range, and then how many sites. As well as do you anticipate doing PET imaging as part of this trial specifically to get an idea of duration of expression or should we be looking at a continued sort of follow-up from the Phase 1 trial? Thanks.

Yes, thank you. Thanks for the question. So what's important is we have all the pieces in place to learn what we need to know to plan that trial. So we'll get the Cohort 3 data towards the middle of the year. We're also initiating the post-year [ph] delivery study. And so together that'll help us figure out dose as well as what the optimal surgical approach is. In terms of additional discussions around that we're obviously talking with our partner Sanofi Genzyme as well as regulators to fully understand what will be required for the registrational studies. We've previously talked about approximately 120 patients and our thinking on that hasn't changed. But we'll be able to provide more guidance and information around that in the second half of the year as we get that Cohort 3 data in the post-year delivery and have those conversations. Regarding the PET scans, we absolutely plan to continue doing the fluorodopa PET scans going forward. It's an important biomarker that will show evidence of enzyme activity. We also expect to continue to repeat those scans in some of the patients that we've already dosed to demonstrate the durability.

Great. And then just on that point about Cohort 3, when we think about how the surgical procedure is improving with physicians, how do you look to control that procedure in the Phase 3 or pivotal trial? Is that going to add any time to the timelines to maybe get sites prepped and then the surgeons ready in terms of their ability? Thanks.

Yes, that's for the question. That's really an important part of the studies that we're doing right now, which is to get the surgeons experienced with doing these with understanding how much coverage they're getting. So this current posterior trajectory study as well as the prior study with Cohorts 1 through 3 has really given us the surgical experience. And we'll continue to do surgical training, and make sure that before they start the registrational trial that they have adequate surgical experience.

And Chris, this is Steve. There'll be a limited number of sites. We haven't announced how many, but as you know we're going to have a number more in place very soon. These are the same surgeons that do DBSs or stereotactic surgeons. There will need to be some cross training, and we're already doing that from site to site already. So we think we're going to be in pretty good shape to get this up and running. And as evident from our data, even now the surgeons are getting better at actually doing the procedure. And so we're optimistic that we can pull this off with a modest number of sites.

Our next question comes from the line of Jeff Chen from Cowen and Company. Your line is open.

Hi, good morning. Thank you for taking my questions, and congrats as well on the AAN abstract, maybe for -- AAN abstract or presentation, are we expecting to see any additional data disclosure versus what we saw already in December?

So, we'll be presenting an overview of the data that we released at the end of the year. If you recall the data at the end of the year had all five patients at 12 months from Cohort 1, and three of the five had made it to that time point for Cohort 2. Those additional two patients will not have completed the 12-month follow-up by the time of AAN, so we'll be presenting that later, perhaps with the Cohort 3 data in the middle of the year. We will however be providing some additional data on some of the other endpoints, on visibility, on quality of life, and some non-motor measures. So we'll be flushing out the dataset and showing how it relates to the top line data we presented in December.

Great, that's very helpful. And in terms of the posterior trial that will be soon initiated, will you be disclosing data from that trial at mid-year, and can you tell us sort of how do you intend to evaluate coverage, I guess, versus the current administration method, and how do you decide which method to take forward from there?

Yes, so we'll be looking to update you on that posterior delivery study by around mid-year what we hope to have is a sufficient number of subjects dosed so that we can tell you how those surgeries have gone, and what kind of coverage we've gotten. And what we know from the data we've presented already is that the coverage that we have, like in Cohort 2, as well as the coverage we've presented in Cohort 3 looks like its quite robust in terms of the clinical effect. So the real question for this posterior delivery study is, yes, we may be able to get more coverage, but we're particularly looking for a more efficient surgery. So can we reduce the surgical time, can we get the same kind of coverage with only a single pass, whereas in the sort of top-down approach we've done two, and in some cases three different infusions.

Thanks. And if I may, just one last one, so Cohort 3 data with the 42% coverage looks better then the Cohort 2 with 34%. So at this point is there any reason to think that the Cohort 2 administration and dosing should be moving forward rather than Cohort 3?

So, overall surgical coverage in Cohort 3 was a little bit better, 42% versus 34% Cohort 2. What we know from Cohort 2 already is that 34% coverage at that concentration yielded what looked like very robust clinical effects. And as mentioned, we'll get the reminder of that cohort in towards the middle of the year. Cohort 3, if you remember, had a three-fold increase in concentration. So don't yet know how that will play out clinically, and the reason we're doing it is to make sure that we fully understand what the dose range is. We may see similar results but we've got to understand what the full range of the dose response is with that increase in concentration.

Yes, for most drug treatments you can imagine there may be too low a dose, and there may be too high a dose, we're not sure. We don't anticipate any issues. We've not seen any major safety issues with Cohort 3 obviously or we would've reported those. We just want to find the optimal dose. And so with Cohort 3 not only are we measuring coverage, and that is comparable -- a little higher, as Bernard said, than Cohort 2, but we're also increasing the vector concentration. So the total dose is at roughly 3X what it is in Cohort 2. Question is, what's the effect size look like, and is it better. What we'd like to emphasize though is what we're seeing already in Cohort 2 is clinically quite meaningful, and we're pretty happy with that dose and volume.

Thank you very much.

Our next question comes from the line of Jim Birchenough from Wells Fargo. Your line is open.

Yes, hi guys. Let me add my congratulations on all the progress in the upcoming AAN presentation. Just following up on the surgical training question, how long does it take to train surgeons currently to dose the drug? And do you expect that all the surgeons that would enroll through this pivotal study would be trained in advance of the study or should we expect some lag [indiscernible]?

Yes, no bottom line it really takes a couple of cases. And the way we do it is we have the whole team go observe a case at an existing site. And then we have our people present for their initial cases. So we do expect, as Steve said, that we will really have our surgical sites by and large trained prior to starting the registrational studies. And that's one of the goals of these un-blinded studies that we have going now is to make sure they're trained, experienced. But we really understand now if we need to add a surgical site how to do that and how to do this training. It's pretty straightforward as we've said. It's observation, and then we make sure that we're present for their initial cases, and we monitor ongoing quality.

And then just in terms of the posterior delivery study, I guess beyond improved efficiency of the surgery, would there be any point to that if you don't see a dose effect between Cohort 2 and Cohort 3? And I guess, as we think about coverage going from 34% to 42%, and a three-fold increase in concentration, if that doesn't really make a difference in Cohort 3 would there be a point, is there anything to read into your progress into that posterior delivery study?

So, the posterior delivery study is really about efficiency of the surgery. And I think what we're going to learn from the Cohort 2 and Cohort 3 is really the dose ranging with respect to concentration. And as Steve articulated, we're going to make sure that we understand the effects of that concentration, and then decide if they're really not different we'll cross that bridge when we get to it whether or not to go with the lower concentration or the higher concentration.

Yes, so Jim, three questions to be answered with the posterior study. One is that posterior trajectory speed up the time of the surgery, simplify it a bit. By the way, it's been used before even with the device that we're using. So we're not just sort of picking that at random. And we hope that that will be the case, and that could augur well for using that posterior trajectory in our pivotal trial. Second, of course, is volume coverage which likely to go up in that with the posterior trajectory, we have seen another study with increased coverage using that same trajectory in a different type of drug being delivered. And then, third of course is the increase in coverage times, concentration, and total dose, and this increase the effectiveness or efficacy of the treatment. So the three questions being addressed, any one of those we're positive would allow us then to incorporate that trajectory into the pivotal trial.

And maybe just one final one, if I could, Steve, just on the SOD1 opportunity [ph], I think that mutation affects maybe 2% of ALS patients, so could you talk about just the commercial opportunity, or just the addressable market for SOD1 silencing approach?

Yes, for the patients that have SOD1 ALS, that mutation, is a relatively modest number, its 2% to 3% of all ALS patients about 20% of the heritable form, the 10% of ALS patients that are monogenic in inheritance. So, it's a relatively modest form. It is a very bad disease, so it's uniformly fatal, medium survival is about two years. So, our goal now, Jim, is really it can be silence and really prolonged life in a big way to prevent people from, for example, having to go on ventilators, and have all the kinds of upper motor neuron respiratory issues that occur with this disease. Now, one other factoid is that there are folks that believe and some data that suggest that misfolded SOD1 maybe downstream and the more sporadic forms of the disease as well. We are not necessarily going after those initially, we're going after once where we know that the mutation exist that this is dominantly inherited disease from parent-offspring et cetera, but it is a modest -- relatively modest number of subjects.

Great, thanks for taking the questions.

Thank you. Our next question comes from the line of Katherine Breedis from Stifel. Your line is open.

Oh great, thank you for taking my questions, and congratulations as well on your continued on-track progress, and Bernard and Dinah's promotions. Just wanted to hear your thoughts, if you could, about the evolving competitive landscape in Parkinson's disease both in terms of what we're seeing in deep brain stem, perhaps any feedback on St. Jude's new Affinity DBS platform, new therapeutics and development such as SAGE-217, and also if you have any insights on where Unicare may be standing currently and their gene therapy program?

Yes. In so terms of the evolving landscape, I think DBS is sort of making incremental improvements. I think overall, we're very pleased with the approach we're taking relative to DBS, in terms of this being one-time durable with no indwelling hardware. So, DBS has been moving along, well-established therapy with those incremental improvements. I will let Steve comment in terms of the SAGE pipeline.

Well, let me captain before I get to 217, you know, what we see happening out there is some incredibly good news for patients with Parkinson's disease, we are seeing affects of smoothing out the PK of levodopa/carbidopa combinations, it's being quite interesting; still early days in terms of placebo-controlled trials, but what we see is a treatment -- our treatment being quite complementary to all of those ways of delivering levodopa, because obviously smoothing out pharmacokinetics is very, very important, but in our case, increasing the brain's ability to respond to the medicine, particularly just the motor symptoms of the brain. So we look at these in combination potentially as getting very, very good control over the motor symptoms of the disease. And the other treatments, including SAGE-217, yet to be determined whether they have any efficacy at this point at all, but again, we feel there is going to be a very important niche for our treatment to enhance the activity of a very well-established compound namely levodopa.

And really no major advances in terms of the addressable population in advanced Parkinson's disease, it would appear?

Not, I think we are all -- yes -- no, I would agree with that comment, I think we're all going after that 100 - 150,000, 15% of revenue of prevalent patients that have very difficult to treat, very advance disease, and that's a big marketplace as you can imagine. So, I think there is going to be a room for a number of products. We also like the alternative formulations in delivery routes [ph] for levodopa because again we think that's complementary and synergistic with what we are attempting to do in the brain. And we know of no one else as competitive to what we are doing.

That's great. Thank you. And then, with respect to manufacturing, do you have any updates for us in terms of how things are progressing as you move toward potentially starting a pivotal study later in 2017?

Making good progress week by week, month by month, but we are on track. We haven't gotten off track with respect to producing the VY-AADC01 GMP lot material for the pivotal trial. We have obviously already made progress on the ALS SOD1 vector as well because again we'll need that data for filing the IND late this year. So, so far so good.

Right. Thank you for taking my questions.

Thank you. Our next question comes from the line of David Nierengarten from Wedbush. Your line is open.

Hey, thanks for taking the question. I have maybe a little bit of a question timeline and regulatory pathway for the pivotal study. Let's say you decide on the back of the head, the posterior infusion for your pivotal study. I mean what are the chances that that changes your timeline a bit on initiating the phase 3? Maybe you could walk us through if there's potential changes in timeline because of the FDA meetings or any changing or thinking about new IRBs, just maybe if you can help us think about that timeline? Thanks.

Yes, so the posterior trajectory -- so, I think this is one of the other questions was getting at as well, right, it's simply a different trajectory to accomplish what we already showed with cohort 2 and 3 which is to get good coverage of the putamen. As Steve mentioned, this posterior trajectory is used for other purposes. So, it's really a change in the surgical angle. But it doesn't fundamentally change the risk, benefits nor do we expect that it will change the timeline. So, IRB's regulatory issues really aren't any different based on the trajectory that we are taking.

Got it, just wanted to double-check on that. Thank you.

Yes.

Good.

Okay, I believe that…

Ladies and gentlemen -- sorry, go ahead, sir. Sorry.

I was going to say I don't think there are any other questions. This concludes our call. Let me thank everyone for attending morning and for you very thoughtful questions. We look forward to update you more on our progress. It will be a busy year for Voyager. Thank you.

Ladies and gentlemen, thank you again for your participation in today's conference. This now concludes the program, and you may now disconnect at this time. Everyone, have a great day.