Good morning and welcome to the Voyager Therapeutics Fourth Quarter and Year-End 2017 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 the call up for your questions. Please be advised that this call is being recorded at the company's request. At this time, I would like to turn it over to Matt Osborne, Voyager's Vice President of Investor Relations and Corporate Communications. Please proceed.

Thank you, Shannon. Good morning and welcome to the conference call. This morning we issued a press release, which outlines the results and corporate highlights for the fourth quarter and year end of 2017 and provides our corporate goals and the financial guidance for 2018. The release is available at voyagertherapeutics.com. Today on our call, Steve Paul, Voyager's President and CEO, will briefly discuss our recent corporate and program highlights; Bernard Ravina, Voyager's Chief Medical Officer, will review the Parkinson's disease program; and Jane Henderson, Voyager's Chief Financial Officer and Senior VP of Corporate Development, will review the year-end financials and then we will open up the call for your questions. Before we begin, just to remind you that the forward-looking statements included in this call represent the Company's view as of today, March 14, 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 will pass the call over to Steve.

Thank you, Matt, and good morning, everyone. Voyager's strong performance in 2017 was evident across many functions of the business including clinical and preclinical development, manufacturing, operations, human resources and business development. This allows us to enter 2018 with an exciting program in Parkinson's disease that is about to enter a pivotal trial, a group of pipeline programs targeting other severe neurological diseases that continue to advance towards the clinic and an exciting new collaboration with AbbVie to deliver monoclonal bodies using AAV that allows us to pursue other important CNS disorders including Alzheimer's disease. For VY-AADC were recently reported longer-term followup data from the Phase 1b trial that we believe continues to demonstrate that VY-AADC can restore the brain's ability to make dopamine and offer patients better control of their motor function in response to levodopa therapy the way they initially did during the earlier stages of their disease. As Bernard will discuss, the goal of this trial and any well-designed Phase 1b clinical trial is to as fully as possible explore a range of doses for both safety and efficacy before proceeding into a pivotal placebo-controlled trial and we have accomplished this with our most recent data set. The results that Bernard will briefly highlight are clinically robust, durable and we believe no due to a placebo effect and we are confident that the design of the Phase 2/3 pivotal program allows flexibility with respect to maximizing our chances of success. Achieving success in this placebo-controlled program we've set a very high bar in the field of Parkinson's disease to address the hundreds of thousands of patients with a one-time treatment and the unique mechanism of action that could provide durable improvements in motor function and quality of life. Our pipeline programs continue to advance with two IND…

Thanks Steve and good morning everyone. We've recently provided the Phase 1b interim update with VY-AADC. I'll briefly recap those results and address some questions that have come up since the readout. At a high level, our first Phase 1 trial has led us to understand the dose response and identify what we think is the maximum tolerated dose or concentration that does not lead to too much dopamine. The second Phase 1 trial using posterior delivery has shown this approach to be a more efficient infusion strategy to take into the pivotal program than the transfrontal approach used in the first trial. This is exactly what we hope to achieve with both of our Phase 1 studies. The data from the first trial shows that one-time administration of VY-AADC increases enzyme activity and decreases the need for levodopa in related medications in a dose dependent manner thus confirming the mechanism of action. The recent data continues to show robust durable improvements in patients motor function along with sustained reductions in daily oral levodopa and related medications in the two higher dose cohorts. At 18 months, Cohort 2 generated a 3.5 hour improvement in quality on-time, or on time without troublesome some dyskinesia which is the primary endpoint of the pivotal program. At 18 months, Cohort 2 patients also had a mean increase of 5.1 hours a day of on-time without any dyskinesia and experienced 65% less off-time. These are very clinically meaningful results especially at this time point. These results are above what one would expect for placebo and they are in the same range as deep brain stimulation in a similar patient population. But diary data represent only to three days of function at a time. For an assessment of how patients are doing over a longer period,…

Thanks Bernard and good morning. I'll spend the next few minutes reviewing the financials and guidance before we move to Q&A. Voyager reported a GAAP net loss of $11.8 million or $0.40 per share for the fourth quarter ended December 31, 2017 compared to $14.7 million or $0.57 per share for the same period in 2016. For the full year ended December 31, 2017 we've reported a GAAP net loss of $70.7 million or $2.64 per share compared to a net loss of $40.2 million, or $1.59 per share, for the same period in 2016. Collaboration revenues were $6.3 million for the fourth quarter of 2017 compared to $2.4 million for the same period in 2016 and $10.1 million for the full year ended December 31, 2017 compared to $14.2 million for the full year ended 2016. Collaboration revenues reflect recognition of payment for research and development services provided by Voyager for various programs under the Sanofi Genzyme collaboration agreement. These revenues can vary based on the quarterly assessments of anticipated efforts under the collaboration. The increase in collaboration revenues for the fourth quarter of 2017 compared to 2016 reflect revenue recognition as a result of Sanofi Genzyme’s decision to not exercise its license option to the ex-U.S. rights to the Parkinson’s program and then Voyager’s recognition of the portion of the agreement allocated to the Parkinson's option. for the full year 2017 the decrease in collaboration revenues compared to the same period in 2016 reflects the changes in the estimated periods for reaching development milestones for certain preclinical programs under the ongoing Sanofi collaboration agreement. As of January 01, 2018 the company has adopted FASB's new guidance on revenue recognition known as ASC 606. So going forward we will make changes as to how we recognize revenue related to…

Thank you. [Operator Instructions] Our first question comes from Charles Duncan with Piper Jaffray. You may begin.

Hi good morning. This is Sarah on for Charles. So can you just remind me further posterior trajectory the dosing that you are using and how long the procedure is taking at this point in development? And then beyond procedure time what kind of patient reported or other outcomes for example, are pain medicine use will help characterize this procedure as a success?

Thanks, Sarah, thanks for the question. So just a reminder, the whole goal of that trial was really to develop an infusion approach that would be more scalable and efficient for the pivotal program and for commercial. So what we've been able to accomplish in that trial is say 2 to 3 hours off the overall procedure time we're down to 6 to 7 hours range which is given that it's one-time and not staged like DBS puts it probably well under the overall procedure time compared to DBS. So we're very pleased with that and we've gotten very good infusions that we think will be more repeatable and consistent going into the Phase 2 and 3 and then the transfrontal approach we used before. In terms of outcomes, we have basically all the same measures that we had in the initial trial and have been reporting on and will be updating all of you on six-month data that are available for subjects who have made it to that point near the end of the second quarter.

Great, thank you.

Thank you. Our next question comes from Jim Birchenough with Wells Fargo Securities. You may begin.

Hi, thanks for taking the questions. This is Yanan [ph] dialing in for Jim. So first off, could you talk about the baseline characteristics of the patients seen in posterior trajectory trial, in particular I'm interested in the severity of dyskinesia at the baseline and whether it's more similar to Cohort 1 and 2 or it's more similar to Cohort 3? Thanks.

Yes, thanks for the question Yuan. So we will have more for you as we report those results, but overall if you look at the first trial, the range of patients in there is quite representative of what you typically get and the second trial we should have that range as well with patients with more or less severe dyskinesias. We are using the Cohort 3 concentration in that study and so we'll see if it unfolds like Cohort 3 and we'll link that again as we have to our understanding of those baseline characteristics.

Got it, thanks. And in terms of the AADC enzyme activity, I've forgotten whether you are also measuring beyond six months from treatment. If you do could you share whether in Cohort 1 at three years do you see the same amount of enzyme or is there any change in enzyme levels? Thanks.

So we will be repeating the fluorodopa PET scans which are our measure of enzyme activity. Nobody has had their follow-up yet. That's going to occur in the long term extension study which is just starting up at UCSF that has the longest term follow up patients. So it will be a few months yet. A reminder, Cohort 1 had very modest changes in enzyme activity which is why we refer to them as minimally clinically active dose. And so, looking for durability of enzyme activity there may not be that informative versus Cohort 2 which has good measurable changes and will be able to tell about their stability.

But let me underscore that. In the academic study that preceded our study, this was done by Professor Bankiewicz, he literally PET scanned patients every year for four years and saw no diminution in two dose levels in AADC enzyme activity. and the monkey data, the non-human primate data, both by Bankiewicz, but also by a group in Japan have shown really stable expression out in the case of the Japanese group to 15 years in monkey. So we think given where we're placing the vector in these very stable neurons, these meetings finding neurons in the putainment [ph] that the expression is going to be very durable.

Great and lastly, try to understand a little more about the dose titrate adjustment in the pivotal trial design. I think is the dose adjustment may be up to the discretion of the patient according to their feeling of their multi function. So my question is, is that true that is entirely up to the patient and also once the patient dose reviews is there a way to prevent them from overshoot and also could they step back the dose and in case they did overshoot? Thanks.

Thanks for question. So this will definitive management of the substrate levodopa in related medications can be an important part of the pivotal program. And just take a step back, each dose reductions this is not something that people are accustomed to doing and it's a testament to the fact that we're getting real pharmacology here, especially seeing people go down 900 mg or even more that doesn't happen as part of the natural course. So we've learned a tremendous amount in the Phase 1 exactly what you want to do in terms of how to do it and how quickly to do it. The reductions are something that we will provide guidance on for the neurologists who will then work with the subjects in the study. I think what we've learned is not to reduce too quickly. We did see that in the third cohorts and over reductions. Now it's an important lesson that I think we're able to take forward and yes, you're absolutely able to titrate the dose back up and it importantly titration of medication is something that neurologists, Parkinson's experts, in patients with advanced PD are accustomed to doing, but it's almost always on the way up. They're increasing the titrate to optimal motor function and this is just now doing it on the way down. So we're confident in our ability to do that, especially with all that we've learned from these two Phase 1s.

Yes, as Bernard said, there's a bit of a learning curve here. This is very unusual to go from 1.5 grams per day of LED of levodopa equivalents to down significantly and this is not seen normally clinically, which is one reason we really believe this is working, but there are some lessons to be learned on how best to do this in control motor function and that's what we're doing.

Thank you. Our next question comes from Matthew Harrison with Morgan Stanley. You may begin.

Thanks. This is Vikram on for Matthew. So our question is about the upcoming Type C meeting, just wanted to get a sense of what you are looking to get from that meeting, what kind of questions you have from the FDA, what types of issues you're looking to get clarity on, any context you could provide there would be helpful? Thanks.

Sure. So we filed the IND and were given clearance to go ahead with the Phase 2 trial. So in terms of safety, the overall design of the study, the comparability around baculo compared to the triple transfection material, the agency is comfortable with those and really had no comments around those. So the Type C is going to be about the rest of the program in the Phase 2/3. So really what we're going to focus on is how much evidence is needed, what kind of overall and safety dataset. The other things to focus on of course are the endpoints, the analysis plan. The endpoints here are very well established in advanced Parkinson's disease, but we'll be able to understand other things like the role of fluorodopa PET given that this is an enzyme replacement, different than any other Parkinson’s program that has progressed this far. So we'll get an understanding of how they view those evidence, that kind of evidence, and as I mentioned the analysis plan. So I think those will be the key areas of discussion pretty typical at this point in development.

All right, thank you.

Thank you. Our next question comes from Christopher Marai with Nomura Instinet. You may begin.

Hey, good morning. Thanks for taking the question. Maybe to shift gears here a little bit, I'm thinking about your pipeline. Obviously there's been some great proof-of-concept work establishing Huntington's construct as being potentially helpful in that disease. I was wondering how you're looking at triaging [ph] the opportunity with respect to your pipeline of assets. Obviously you've talk about SOD1 as the next program. You know, help us or walk us through your decision making process there and how we should think about progress going forward? And then just secondarily, remind us of the stereotype you're using there, I think it was an AAV9, as it may be 9 variant and maybe why not use AAV9 and use context given the great proof-of-concept today? Thank you.

Yes, Christopher great question or questions. So for us the key is adequate delivery and in the case of both the SOD1 program and the Huntington's Program, adequate knockdown in relevant cells in the relevant tissue. So for SOD1 we need to see knockdown of SOD1 up and down the spinal cord in motor neurons and in the brain stem ideally. And frankly, we don't see a lot of that having been done already out in the literature and out in the world today. So we're intent on making sure we can do that before we get into the clinic. Similarly for Huntington's there's a bit more of a challenge in that Huntington's not only affects the basal ganglia, putamen, the caudate nucleus, the globus pallidus, but the whole cerebral cortex. And if you look at a late-stage patient that's very, very evident on a simple MRI scan. So we need to see silencing of Huntington's or knocking down of Huntington's to a sufficient degree. Now the antisense oligonucleotide data that you’re aware of has shown in CSF knockdown of Huntington's in CSF. Now that's encouraging, I agree, but only in so far as it reflects what's happening in the brain and in the cortex in particular. So in our monkey work we now are using, for example, for Huntington's AV1 and we're using sites of administration that we believe will give us very good knockdown of Huntington's throughout the brain and in those relevant brain regions. We're not obviously talking too much about exactly where those sites are, but with that capsid we're reasonably confident we can achieve those goals. And we're going to do that, make sure we do that in a monkey before advancing into the clinic, because if we can't do it in a monkey brain which is larger than a mouse brain obviously, but still much less, much smaller than a human brain, the chances of achieving that in humans is low. But we're cautiously optimistic we can get there and I would advise anyone who is evaluating any of these programs to make sure you've ascertained whether that kind of silencing or knockdown can be achieved.

Okay, then when might we see some of the monkey brain data, if you will? Thank you.

We’re hoping later this year we'll have some more data for you that will convince you of the route of administration and the capsid that we're using.

Thanks.

Thank you. Our next question comes from Brian Skorney with Robert Baird. You may begin.

Hey, good morning guys. Thanks for taking the question. Yes, also looking at the pipeline, I was just hoping maybe you can kind of comment a little bit when we look at SOD1, Huntington Friedreich’s ataxia in terms of what you think you're going to have to dose this, where do you think you can get away with local interaction as Friedreich’s ataxia are you thinking that's going to require systemic AV dosing? And then Steve maybe just kind of high level off of that any thoughts on Jim Wilson's recent publications and the risks that you saw highlighting around systemic high dose AV and any concerns on that number one?

Yes, great question. Just to remind everybody for Parkinson's disease we're going directly into the brain intraparenchymal injections. That avoids very significant systemic exposure. We get great transduction neurons and as you know it looks to be relatively safe at least based on many subjects that have been dosed with AAV2 which is the capsid we're using there. It also obviates the concern about preexisting immunity antibodies that could neutralize the vector before it actually transduces cells. So that one we feel very good about. Huntington's will be the same approach, different capsid and different route exact sites of administration will be different, but again we feel the same way about that program. It's kind of de-risk from some of that systemic exposure data that that Jim Wilson has reported. Now for Friedrichs on the other hand, we are looking at systemic exposure because there we want to get DRG's which are technically neuron, sensory neurons outside the blood-brain-barrier and also we have a capsid that transduces the heart which we're very excited about. And to be blunt, there is still a lot of work that needs to be done there, but using our capsids which are AAV9 derivatives we do not see the same kind of robust toxicity that that Jim Wilson has reported in his monkey studies. Now we're using different monkeys, he is using rhesus monkeys, we're using Cynos. There are differences in the transgene. We’re expressing their slight differences in the capsid. So they're not direct head-to-head comparisons, but all I can say is going up to doses very similar to the ones he used, one time either the fourteenth vector genomes per kilogram we have not seen a fatality yet in any of our monkeys. So we will be reporting on that later this year in a peer reviewed article and also presenting work at the upcoming ASGCT meeting in May.

Great. Thanks guys.

Thank you. Our next question comes from Reni Benjamin with Raymond James. You may begin.

Hey, good morning guys. Thanks for taking the questions. I guess I'm interested in the comparability test. Could you provide a little bit more color on those tasks? Are you looking at both enzyme level then and function? And can you remind us if any patients have been dosed with the new process and kind of as we're waiting for the Type C meeting and the start of the pivotal study, do you plan on exploring more patients at the relevant cohorts?

Thanks for the question. So as you know baculovirus materials been used in clinic and other programs, so there is a precedent clinically and agency of course is well aware that. In our discussions with them and as part of the IND we submitted we had clear criteria in terms of comparing baculo to the triple transfection material that is currently used in clinics. Criteria very straightforward involve the identity right that's AV2 with the same transgene, the same flanking elements. The purity of course as you would have with any release specs and then I think the key of what you were asking about was the potency. Does this make AADC, does it express AADC at the same levels and have the same kind of infectivity? So the answers to those are yes, so that puts us in a good position to really move forward with that material and we're comfortable with our understanding of how those match up on those characteristics.

Yes, and in addiction for the IND submission, we did a complete toxicology study with the new prep and that was obviously compared with the old prep and the older data that was done many, many years ago, but to achieve and be successful in that tox study, we had to achieve exposures that were comparable and produced enough enzyme activity. These were primarily rat studies, but nonetheless showed very nice comparability.

And I’ll add one other point which is our clinically our measure of expression is of fluorodopa PET scans. We have actually three fluorodopa PET scans in that Phase 2 trial baseline around 45 days and then at the primary endpoint one year. So we'll have an early look to make sure that we're getting good expression in patients.

Got it and maybe just as a follow up, regarding the AbbVie collaboration, can you provide us an idea as to how we should be thinking about the timelines associated with this program as this is something could be seeing an IND in 2019 or is it something that’s quite early and we should really be thinking about 2020 and beyond?

Yes it's early. It's a discovery research collaboration initially stage one will be for two or three years and then after that hopefully we'll be able to select a clinical candidate. Let me though underscore how excited we are about the collaboration. AbbVie is a terrific company. They have a lot of expertise in monoclonal antibodies, a terrific neuro science group and we like this for several reasons. Obviously we're focused initially on antibodies to Tau which we believe will and could be disease modifying in number of neurodegenerative disorders, Tauopathies and Alzheimer's perhaps, but also this gets us into an area, a new area for us which we're excited about and that is the delivery of monocle antibodies with AV vectors broadly speaking for a whole host of CNS diseases and conceivably non-CNS diseases. So it really does allow us to segue into a brand new platform we believe for the company.

Got it. And I’m sorry, the previous question I had asked about kind of while you're in this waiting period, before dosing the pivotal study does it - would it makes sense to continue to enroll in the ongoing Phase 1 at a given cohort with either the new perhaps [ph] or any of the other changes you’re thinking about?

So no, we’ve really learned what we needed to learn from that posterior delivery study about dosing and you can't readily switch material within a protocol. They're under different INDs, so we’ll do what we said we're going to do, start the Phase 2. We’ll have that PET scan as assurance on enzyme expression and we'll move forward from there.

Yes, and we'll continue to follow the 22 patients that we’ve already dosed and it will be very interesting to see what happens in Cohort 3 over time as we make dosage adjustments and the like. So we're going to continue to update you periodically on the activity that - the benefits in these patients over time.

Thank you. Our next question comes from Dane Leone with BTIG. You may begin.

Hi, thank you for taking the questions. Two from me, one on the PK efforts and then one on the pipeline. Starting with the PK efforts, I wanted to ask in terms of your design of the Phase 2/3 study, how are you thinking about analyses and pre-specified endpoints that could give you some level of - additional level of differentiation clinically on outcomes versus the DBS methods? I appreciate the obviously the differences and the procedure and the calibration et cetera, but just in terms of clinical outcomes, how do you think you can design the study to make it more compelling from an outcomes point of view?

Gotacha, thanks. I think I understand the core of your question there. How do we really differentiate this based on outcomes of interest from deep brain stimulation and it is a good reminder. All of the patients in our trials were candidates for deep brain stimulation and chose to enter one of these two studies, most of them because they didn't want to have indwelling hardware. In terms of differentiating anything further, the motor function measures are going to be very similar across our studies and what was seen in DBS. And so it becomes a question of magnitude of fact and are there differences across those endpoints, but even more important aspect we think here is that there are clear side effects to deep brain stimulation that we think we may not have. The most important one being cognitive function. So it became clear, a very nice paper published at the end of last year showing that deep brain stimulation, both the implantation of the electrodes in the electrical stimulation caused very specific cognitive deficits. And it makes sense because it's related to where the electrodes are going. So we believe we will not have those cognitive deficits and those cognitive deficits of DBS are clinically significant in communication and kind of attention. So we will be measuring cognitive function and some other behavioral endpoints that might provide a very important point of differentiation.

Great, thank you and then one on the pipeline if I may. I want to ask since we've hit on some of the To Do list in terms of getting these IND applications, I want to ask as you decide between the different programs or for the two INDs, how much is it factoring in to your decision making process whether these programs that you decide upon may or may not be partnered and/or whether they would be partnered before an IND is filed or after you have some clinical data? And then on the potential of an IP position whether there might be some debate whether you owe someone a royalty or something like that depending on the plate [ph] used?

Well, just to refresh everybody's memories, so the Huntington's Program and the Friedreich's program kind of remain under the rubric of our Sanofi-Genzyme agreement where they have an opt-in provision once we get into the clinic, the ARS program we have worldwide rights on. At this point, I think we're optimizing for technical feasibility and probability of success and we get good silencing in monkeys with SOD1 and Huntington's we will move those programs forward. We’re as I said earlier cautiously optimistic that we're going to achieve that kind of silencing and knockdown in that case. And from the standpoint of Friedreich’s we're very excited about that program because it's a major unmet medical need, but a very large population of patients relatively speaking. There are some 7000, 8000, 9000 Friedreich’s patients in the U.S. alone today and again given the data we've generated in this mouse model of Friedreich’s ataxia which is where toxin [ph] has been silenced in certain tissues, we see really remarkable correction of that of that disease phenotype. So we're excited about our programs. We're going to move them forward and we're going to base our decision based on our data and what we think the probability of technical success will be moving them into the clinic.

Thank you.

Thank you. Our next question comes from Sumant Kulkarni with Canaccord. You may begin.

Good morning, thanks for taking my questions. First one is a clarification. Is the piece of recruitment in the posterior trajectory trial as planned, because it appears that there was just one more patient dose relative to the last update during your R&D day?

Yes, it was exactly as planned and we're wrapped up enrolment. So we do have one more patient who was screened before we cut off enrolment, who will be having procedure soon. But no, we've wrapped up enrolment, the key there as I mentioned before is we've learned what we needed to learn and the surgeons at the sites got the experience they needed to take it into the Phase 2.

And something Bernard mentioned earlier, we recruited seven patients so far in that trial really the last half of last year, very, very rapid recruitment. I think it reflects a great deal of enthusiasm on the part of patients who would otherwise have an opportunity to have DBS, were elected nonetheless to have our treatment. So we're pretty excited about that, we think that augers well potentially for enrolment in the pivotal trial.

Sure. And my follow-up is given the number of patients with advanced PD, could you remind us about what interactions you might have had with the FDA on pursuing potential orphan drug exclusivity and what those interactions might mean for perhaps broadening the use of your program in a wider set of PD patients?

Great question, yes. It’s a great question, thank you. So we did have several interactions with both U.S. and European regulators around orphan designation. And yes, they agree this is a large population and this mechanism of action could apply not just to Advanced Parkinson's disease, but to more moderate Parkinson's disease. So in this case we’re happy to say that we didn’t and we will not further pursue orphan designation.

Thanks.

Thank you. I’m showing no further questions at this time. I will turn the call back over to Steve Paul for closing remarks.

Okay. Well, thank you and that concludes our call. We want to thank all of you for attending this morning and for your thoughtful questions. We look forward to updating you on our progress in the near future. Thanks so much.

Ladies and gentlemen, this concludes today’s conference. Thanks for your participation. Have a wonderful day.