Good afternoon, and welcome to the Voyager Therapeutics Fourth Quarter and Full Year 2019 Financial Results Conference Call. At this time, all participant lines are in a listen-only mode. This call is being webcast live on the Investor and Media section of Voyager's website at voyagertherapeutics.com. This call is the property of Voyager Therapeutics and recordings, reproduction or transmission of this call without the expressed written consent of Voyager Therapeutics is strictly prohibited. Please be advised that this call is being recorded. I would now like to introduce Paul Cox, Head of Investor Relations at Voyager.

Good afternoon 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 Allison Dorval, Chief Financial Officer. This afternoon after market close, we issued a press release, which outlines the financial results and corporate highlights for the fourth quarter and full year 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 views as of today March 3, 2020. 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 will turn the call over to Andre.

Thank you, Paul, and good afternoon, everyone. Welcome to our Q4 earnings and corporate update call. I'll begin by walking you through our recent updates. Omar will discuss our pipeline programs and plans and Allison will close with our financial results and guidance. Once we've concluded our remarks, we'll take analyst questions in the Q&A session. We continue to make progress to establish Voyager as the leading gene therapy company focused on severe neurological diseases. We believe that our combined expertise in gene therapy and neuroscience gives us the focus and ability to drive innovation in this area. In 2019, we continued to build on our experience and to enrich our toolbox for CNS gene therapy. A key feature of the Voyager pipeline is that our lead programs for Parkinson's disease and Huntington's disease were leveraging a targeted surgical delivery of our gene therapies to very precise regions of the brain. We believe that this intraparenchymal approach has the important advantage of potentially bypassing certain historical and present challenges of systemically delivered AAV gene therapies, such as, limited brain transduction, dose-limiting distribution to untargeted tissues and organs, systemic immunogenicity and production at large scale. At the same time, as we've advanced these two lead programs, we've continued to invest in the discovery of novel capsids, specifically engineered to enhance blood-brain barrier penetrants. These efforts may significantly broaden our ability to develop gene therapies that deliver a wide variety of payloads to specific regions, sales and genetic targets in the CNS. Another key feature of the Voyager pipeline is that, as we've shown with our Parkinson's program, we've developed a manufacturing process that we believe enables the production of high-quality AAV gene therapies at commercial scale. We'll continue to invest in these leading capabilities and expertise in AAV production and manufacturing…

Thank you, Andre. I'd now like to walk through some of these program updates in more detail. First I'll discuss the updates of the Parkinson's disease program which is partnered with Neurocrine. As a reminder our approach is to deliver the gene for the AADC enzyme locally to the putamen using an AAV viral vector. The goal is to use a onetime infusion of a small volume of gene therapy to create a stable reservoir of AADC enzyme in the putamen capable of converting levodopa to dopamine. The result is a regulatable system controllable by exogenous levodopa, the standard of care oral medication. We think there is an important advantage to this approach. Our physicians and patients are able to titrate oral levodopa medication to the patient's individual need, while avoiding side effects due to excess opening systemically or in other brain regions. The Phase I clinical program for VY-AADC was designed to establish safety and optimize dosing and delivery. The PD-1101 trial is evaluating escalating doses across three cohorts of five patients each using the transfrontal surgical delivery route, while the PD-1102 trial is studying eight patients and focused on using a posterior trajectory delivery. In our Phase I study results to-date we have observed that by replacing the AADC activity through our onetime gene therapy, we see increased AADC enzyme activity as measured by F-Dopa PET scans and improvements in motor function and quality of life in study participants across multiple endpoints together with a significantly reduced need for oral levodopa medication. As Andre mentioned, we expect to present final 3-year data from the PD-1101 trial and 2-year data from the PD-1102 trial at medical congresses this year. These longer-term results from patients with advanced Parkinson's disease at the time of VY-AADC treatment may speak to both the…

Thanks, Omar. I'll now review the highlights of our financial results and guidance. We ended 2019 in a strong financial position with $281.5 million in cash, cash equivalents and marketable debt securities compared to $155.8 million at the end of 2018. We booked collaboration revenues of $32.7 million in Q4 2019 and $104.4 million for the year compared to $2.0 million and $7.6 million respectively for the same periods of 2018. This increase reflects the recognition of amounts related to the Sanofi Genzyme collaboration in June and amounts related to our Neurocrine and AbbVie alpha-synuclein collaboration, both of which became effective in Q1 of 2019. Net loss was $12.6 million for Q4 2019 and $43.6 million for the full year, compared to $22.5 million and $88.3 million respectively for the same period of 2018. R&D expenses were $36.6 million for Q4 2019 and $119.7 million for the year, compared to $16.9 million and $64.9 million respectively for the same period of 2018. The increase in R&D expenses was primarily related to external costs and employee-related costs to support our pipeline programs, including advancing the RESTORE-1 trial for VY-AADC. G&A expenses were $9.9 million for Q4 2019 and $36.3 million for the year, compared to $8.3 million and $33.8 million respectively for the same periods of 2018. The increase in G&A expenses was primarily related to employee and facility costs to support the advancement of our pipeline programs and operations. Turning now to our financial guidance. We expect to end 2020 with cash, cash equivalents and marketable debt securities between $150 million and $170 million. Based on our current operating plan, we expect this cash balance along with the amounts that we expect to receive for reimbursement of development costs from our Neurocrine collaboration will be sufficient to meet our needs for projected operating expenses and capital expenditures into mid-2022. We believe we have established a strong capital position through our disciplined financial approach and strategic partnering strategy and we look forward to continuing our progress through multiple milestone events across our programs in 2020. With that, we would now like to open the call for questions. Operator?

Thank you. [Operator Instructions] Our first question comes from the line of Laura Chico with Wedbush. Your line is now open.

Hey, thanks very much for taking the question. I just have two for you. I think Omar, you were mentioning in terms of the amendments that were filed with regards to RESTORE. Could you elaborate a little bit more on some of those specific changes? I think specifically the exploratory measurements that you are going to be looking at? And then, maybe secondarily, what gave FDA confidence to permit that change in the randomization schedule?

Thanks, Laura. So, the main elements of the amendment were really structured around two things. One was going back to the FDA with our proposal for the statistical analysis plan and both incorporating the powering for efficacy, but also the number of exposures to safety. We came to an agreement on increasing the number of study participants in RESTORE-1 to 85. And then because the study has been active for about a year or so was also we had a number of operational learnings from -- and the conduct of the study at approximately 20 sites that we have active. And given that this now will serve as one of two potentially adequate and well-controlled trials to support the filing, we decided to reduce the number of exploratory assessments that were being conducted. These included things for example a number of visits where patients have been in the OFF state, which are actually uncomfortable for patients. And so, we reduced the number of those. We removed a number of more detailed, exploratory neuropsychological assessments that were fairly time-consuming. The FDA I think essentially is the proposal based on the powering and safety database, which got them comfortable with the change in the randomization scheme. And the fact that the amendment does not substantially change the eligibility criteria for enrollment in the study, so that there isn't a significant change in the patient population that will be enrolled under the amendment.

That's very helpful. And I guess maybe one follow-up question then. Just looking ahead to the longer-term data that you mentioned out of the Phase I study. I think one thing that we've struggled a little bit was to put maybe some natural history context around the results. These are going to be 2- and 3-year endpoints. Just wondering if you could point to certain population metrics or criteria that we should be using to help put a little context around these results that are anticipated to come out in the coming months here?

Yes absolutely. So, there are essentially two sources of data which I think are helpful for natural history. So, one are looking at the control arms as well as the treatment arms of other therapeutic approaches. For example deep brain stimulation or other types of dopaminergic formulations that are studies that have collected long-term data three to four years out from the initial onset of treatments. And I think, those are going to be helpful for context setting for the 1101 three-year data. The second our assessments of disease progression in Parkinson's and more natural history cohorts and particularly not just looking at the primary outcome measures such as diary or UPDRS, but other metrics that impact patient quality of life and functioning. So, for example, global disease stage the modified Hoehn and Yahr for example activities of daily living captured by the UPDRS-II and other disease comorbidities for example falls. So I think looking at natural history data sets, which are out in the metro, I think will be helpful to give that context to the 1101 data.

Thanks very much guys.

Thanks a lot.

Thank you. Our next question comes from the line of Charles Duncan with Cantor Fitzgerald. Your line is now open.

Thank you. Hi, Andre and team congrats on a great year of progress, especially partnering last year. I wanted to ask a couple of more questions regarding the RESTORE-1 change. If we look at the drivers were there -- was there any new information? I think, you mentioned operational information that you took to the agency. Are you able to enroll patients as you had anticipated? Or do you think that two to one is better than a one to one? Or is that not the driver to the change in RESTORE-1?

Yeah. Thanks for the question. So as we have guided last year, we were looking at a 75 to 100 patients to get to the right level of powering and increase of the safety exposure data on the program. And now with our partner with Neurocrine, we were able to map out statistically what we get from a one to one versus a two to one. And in discussion with the sites, I think we will get some -- likely some benefit from the proposition of adding one and three chance versus one and two chance of the sham surgery for the patients enrolling into trial. So that can only be a positive from the perspective of continued enrollment, but it was a full review of the statistical plan and the safety exposure that led us to compare that there was not much of a cost between the one to one and two to one to justify sticking with the one to one as a -- for a study like this.

That makes sense. And it seems to be a real positive in terms of moving forward. Could you see perhaps quicker time lines to data? And how do you think about that?

Yeah. So we're going to provide an update once we get a little bit further in the implementation of the new profile at the site level. That's going to give us and our partner more information to be able to map out what the impact would be on completing the study and getting to data. But yes we anticipate that as we discussed with investigators of the change in randomization scheme here. And as Omar referred to reducing some of the assessments that are more burdensome on the patient may also even further facilitate the decision to enter the study.

And my last question Andre is regarding RESTORE-2 timing. It seems like you've done a rigorous analysis on RESTORE-1 recently and discussions with the agency. I guess, I'm wondering what are the rate-limiting steps to kicking off RESTORE-2? And can you provide any additional at least guideposts to think about the sizing of RESTORE-2?

Yeah. Thanks for the question. So we expect we'll be in a position with our partner with Neurocrine to start this at the end of the year. Generally speaking, we expect that the study will have very similar characteristics to RESTORE-1 in terms of size, design and endpoints. So we -- until we finalize that protocol, we won't be getting more specific but we expect it's going to be quite similar. The one aspect that we will look to do with RESTORE-2 that goes beyond RESTORE-1 is to include a number of international sites. So the study is intended to be a global study, whereas, RESTORE-1 only has U.S. sites.

Probably good right now that RESTORE-1 is only U.S. sites. So appreciate the added color and update on the progress.

Thank you.

Thank you. Our next question comes from the line of Debjit Chattopadhyay with H.C. Wainwright. Your line is now open.

Hi, guys. This is Aaron on for Debjit. Thanks for taking the questions. So real quickly, can you tell us what exactly the powering assumptions are for RESTORE-1 ON time and the baseline change as expected from placebo?

Yes. Thanks for the question, Aaron. So the study is powered to be -- or is sized to be well powered for showing statistical significance at an hour or more against placebo. So that's how we ended up running our statistical analyses. So we're looking for something obviously as a pivotal study a registrational study that's going to be statistically significant and clinically meaningful. And that's what we achieved with the 85 patients with that 2:1 randomization based on the analyses done and based on the prior results that we've shown in the open-label setting.

Okay. And then a second quick question. So looking at the HTT data -- preclinical data, it looks like putamen and Caudate knockdown of Huntington may not as much of a problem at Cortical Neuron lowering. So is there a critical number below which you're trying to lower the Huntington's protein in those regions? Or are there concerns about lowering the wild-type Huntington too much in the striatum as unintended...

Yes, thanks for your question. So Omar, if you can address this question.

Yes, it's a great question. I mean, I think that overall the field is reaching a little bit to try and understand what degree of cortical knockdown is necessary to predict clinical benefit. I mean the challenge has been is that the majority of preclinical efficacy data is being done in mouse transgenic models where primarily the striatum is the tissue of interest. And that's where efficacy sort of dose-efficacy has been anchored. The -- I think it's a bit of a moving target. I mean I think it's unlikely with any therapeutic modality, but with the gene therapy that we would get a 100% reduction of wild-type and mutant huntingtin in any particular brain region. I think for the cortex where we're currently aiming to get doses that would give reduction in mutant huntingtin protein in broad cortical regions in the ballpark of about 20%. But it's not as definitively anchored as the reductions in the striatum, which are at levels of around 60% reduction based on multiple efficacy studies in transgenic animals.

Okay, great. That was very helpful. Thank you guys.

Thank you.

Our next question comes from the line of Jeff Hung with Morgan Stanley. Your line is now open.

Hi. This is Hannah on for Jeff. You're running what remains outstanding ahead of the Huntington's IND? And then would you need the observational study to be included in it? And then what do you expect -- when do you expect to begin the Phase I study? Thanks.

Yes, thank you. Omar?

Yes, thanks for the question. The -- for the IND filing, we have a lot of bioanalytics which are still coming in from our GLP studies which are IND-enabling. And as we guided on our last call, we are running the study out to 53 weeks. So that's an increased number of samples. And then we're looking at a number of bioanalytics from including the vector genomes, but also the microRNA itself mRNA and protein in multiple tissues and also brain regions. So at the moment, we're really going through that data and reviewing it and analyzing it. So that's the sort of piece that lies between this time point and the IND. The observational study is not gated on the timing of the IND. And so that is in active study set up now and we anticipate that being active by midyear with first patients coming into that.

We expect -- just to add to that last point, we expect that observational study we would have patients of the disease severity, so that would be quite similar to the ones to be targeted for our clinical trial of – or therapeutics, so patients maybe eligible to participate also in the study. They're not – as Omar said, it's not rate limiting. It's not dependent, but we do expect that maybe a run in for patients to be able to participate in the study about the therapeutics.

Great. Thank you.

Thank you.

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

Hi. Thanks for taking the questions. This is Yanan dialing in for Jim. So first just to follow-up on the earlier question about powering. What was the assumption for placebo arms ON time used in the modeling?

Yep. Thanks Yanan for the question. So the – there's a range of scenarios that were mapped against what has been seen in prior trials, including prior placebo effect in the gene therapy trials at a similar time point at one year. So the modeling was based on some review of these and scenarios around them to get to the right powering. As we've shared previously, the range of placebo effect against the good ON time, which is our primary endpoint has a range from a fraction of an hour to an hour in a range of studies. So in our modeling, we also incorporate scenarios that go to an hour plus of placebo effect to get to the appropriate bar. Omar, if you want to add to this?

No. I think that's right. So we made assumptions on a range for the potential true effect in the placebo arm and then run simulations to help us decide on the final sample size that would be necessary to capture that potential range of outcomes in the placebo effect.

Got it. Very helpful. And on RESTORE-2 in terms of – I know you mentioned already the trial design is yet to be finalized and you will communicate that later. But could we get a sense of whether the primary endpoint will be identical? I thought previously you kind of had some optionality of having RESTORE-1 read out and RESTORE-2 – before RESTORE-2 is unblended, so you have some optionality on RESTORE-2 and primary endpoint, but not sure. Could you update on your thoughts on that?

Yeah. I mean, that situation still starts so that RESTORE-1 will be complete with top line data before they need to finalize the staff and database lock on RESTORE-2. So that optionality remains. I think as Andre said earlier RESTORE-2 will be substantially similar to RESTORE-1 in design and sample size with the main difference being that it will incorporate a number of ex-U.S. sites as well.

Got it. Any potential for competition of enrollment in the U.S. between the two trials when they were they're both running?

Yeah. It's a great question. I think based on how we're seeing recruitment to-date and also the number of sites that we're able to activate we're not anticipating that there would be a risk of one study cannibalizing the other. And that we'll handle this operationally. In other words making sure that, RESTORE-1 has priority for recruitment before sites are able to recruit patients into RESTORE-2.

Got it. Thank you very much for taking the questions.

Thank you.

Thank you. Our next question comes from the line of Jay Olson with Oppenheimer. Your line is now open.

Hi. This is Silvan Tuerkcan on for Jay Olson. Thanks for taking my questions and congrats on the quarter. Could you just talk about some changes in regional disease management that you're looking at when designing RESTORE-1 – RESTORE-2 versus RESTORE-1?

Yeah. So, I mean, one of the things that will account for in the design for RESTORE-2 will be variations in standard of care that go across geographies. One of the big drivers of that is the availability of deep brain stimulation. And so what we're looking for at least for the majority of RESTORE-2 ex-U.S. sites are countries where deep brain stimulation remains part of availability of care, so that there isn't a complete separation in the management of patients. So, that's going to be an important part of that. So, as we look at Europe and Japan and other countries where we're really anticipating going to countries where deep brain stimulation remains an option for patients.

All right. Great. And in terms of preclinical data sets that you're still generating for your Huntington's disease IND filing, could you maybe tell us what is left? And specifically maybe what you may publish or present this year that could be useful for us to look at?

Yes absolutely. So, we're really at the moment in the phase of completing analyzing bio-analytics from the large number of samples that have been taken during the GLP studies up to 53 weeks. So, it's a significant number of animals and a significant number of tissues that we're analyzing as well as brain regions. So, that's really where the team's activity is predominantly on the sort of -- for the IND filing. The second are the preparations for the Phase 1 as well as the observational study which are now very advanced stems and so there's a lot of team activity on that. We would anticipate presenting our non-human primate long-term data from our GLP studies at an appropriate time, but the predominant focus right now is on the IND preparation and readiness for dosing a patient in Phase 1.

Great. Thank you so much.

Thank you.

Thank you. Our next question comes from the line of Brian Skorney with Baird. Your line is now open.

Hi, this is Jack dialing in for Brian. Thank you so much for taking our questions. We just have one really brief one on the SOD1 program. I think previously you had indicated that you'd look to partner that program? I was wondering if you could just talk about your plans moving forward there. I know it's still preclinical but are you looking to partner that or are you going to develop that internally now moving forward? Thank you.

Yes, thanks for the question Jack. So, we are in discussions with the parties about SOD1, but also broader efforts in ALS and that's been our criteria to -- in the mix of other discussions about the -- in corporate development efforts both on the inbound and potentially on partnering certain of our assets. We've been prioritizing our effort. But on SOD1, we continue to have some low level activity as we've shifted the focus of our resources on advancing towards the HD IND and continue to have discussion with potential partners. Like I said, it would potentially include some effort broader than SOD1 leveraging what we are learning from SOD1 to be able to apply to other forms of ALS.

Awesome. Thank you so much.

Thank you.

Thank you. This concludes today's question-and-answer session. I would now like to turn the call back to Andre Turenne for closing remarks.

Perfect. So, thank you everyone for joining our call today and I look forward to the next opportunity we have to update you on our progress. Thank you.

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