Good morning, and welcome to the Voyager Therapeutics Second Quarter 2019 Financial Results and Corporate Highlights Conference Call. [Operator Instructions]. At this time, I'd like to turn the call over to Allison Dorval, Voyager's Chief Financial Officer. Please, proceed.

Thank you. Good morning, and welcome to the call. Earlier today, we issued a press release, which outlines the financial results and corporate highlights for the second quarter of 2019. The release is available at voyagertherapeutics.com. Before we begin, just a reminder that the forward-looking statements included in this call represent the company's views as of today, August 9, 2019. Voyager disclaims any obligation to update these statements to reflect future events or circumstances, except as required by law. Please refer to today's press release as well as Voyager's filings with the SEC for information concerning risk factors that could cause actual results to differ materially from those expressed or implied by such statements. With that, I'll pass the call over to Andre.

Thank you, Allison, and good morning, everyone. Welcome to our Q2 earnings and corporate highlights call. Today, I'll discuss selected elements of our portfolio evolution, including the recent restructuring of our gene therapy relationship with Sanofi Genzyme. Next, Omar Khwaja, our Chief Medical Officer and Head of R&D, will comment on our existing programs and new discovery efforts. Allison will wrap up the call with a discussion of our second quarter results. Mat Ottmer, our Chief Operating Officer has also joined us for the Q&A after our prepared remarks. We entered 2019 with the focused strategic vision of becoming a leading fully integrated biopharmaceutical company focused on AAV gene therapy for severe neurological disease. And in the second quarter, we continued to take steps in achieving that goal. As we've outlined previously, under our plan, we will pursue new program opportunities with 3 distinct approaches. The first approach is to advance novel discovery programs with a partner, up to an earlier point, typically the IND stage, when the partner takes on full development and future commercial responsibility. Our partners provide an upfront payment and fund the research activities through cost reimbursement and where typically eligible for near-term development milestones, later-stage milestones and royalty payments, all of which can be funneled back into our operations. Both programs with AbbVie as well as the discovery programs with Neurocrine follow this approach. We're currently eligible for up to more than $300 million in preclinical milestone payments over the coming years across these programs. Under the second approach, we advance existing development programs and candidates with the support of partners' funding and resources, but retain co-development and co-commercialization rights. Our Parkinson's and Friedreich's ataxia programs with Neurocrine align with this approach. Working with selected partners in this way allows us to do more while…

Thank you, Andre. I want to start by saying that I'm excited to be part of Voyager's next sail. Building on a solid scientific foundation is the company's innovative gene therapy for severe neurological disease with a wealth of knowledge and discovery and developments of AAV-based therapeutics. Importantly, that includes robust expertise in gene delivery to the human brain and the learnings from several years of direct clinical experience. I was drawn to Voyager by the scientific rigor of the company and the potential of this modality to help people affected by severe neurological diseases. I'm even more enthusiastic as I've come to understand at a deeper level, the outstanding knowledge and experience of the team, and the opportunity to work with such a deep bench of expert scientists at the convergence of AAV gene therapy and neuroscience. Together with our collaboration partners as well as in our own wholly owned asset, Voyager is now poised to even more fully explore the potential role for gene therapy in addressing the enormous unmet need in neurological diseases as well as opening up the addressable target space for these disorders and overcoming the challenge of therapeutic delivery to the nervous system. First, I'll focus on our collaboration with Neurocrine. On the Parkinson's program, our teams are well integrated in collaborating on the execution of the first pivotal trial, including the activation of new trial sites and advancing enrollment. We're also progressing on the regulatory front with the finalization of our statistical analysis plan for RESTORE-1. On the Friedreich's program, we've made much progress having agreed on the development plan. We're now executing against that plan and working toward selecting our lead clinical candidate. We've also taken important steps toward our 2 new discovery programs with Neurocrine. The planning process has been highly…

Thanks, Omar. Voyager reported net income of $11.2 million for $0.30 per basic share for the second quarter ended June 30, 2019 compared to net loss of $25.5 million or $0.80 per share for the second quarter of 2018. Collaboration revenues of $46.1 million for the second quarter ended June 30, 2019 compared to collaboration revenues of $2.6 million for the second quarter of 2018. These revenues reflect the recognition of noncash amounts for research services that we performed for various programs under the Sanofi Genzyme, AbbVie and Neurocrine collaboration agreements, in addition to amounts expected to be reimbursed by Neurocrine as per that collaboration agreement. Amounts can vary based on quarterly assessments of our efforts under each of those collaborations. In the second quarter ended June 30, 2019, collaboration revenues also included the onetime recognition of $28.7 million previously deferred amount related to the termination of the Sanofi Genzyme collaboration agreement. Under the termination agreement, we paid $10 million upfront to Sanofi Genzyme and will pay an additional $10 million upon the filing of an IND for the Huntington's program. We also agreed to pay low single-digit royalties to Sanofi Genzyme on net sales of Huntington's disease product and entered into an amended capsid agreement with Sanofi Genzyme at the same time. Under this capsid agreement, Sanofi Genzyme can evaluate 6 of our capsids and can opt to exclusively license up to 2 for use in 2 specified non-CNS indications. The revenue recognized in the quarter included $48.7 million, which was remaining a deferred revenue at the termination date, offset by the $10 million upfront payment and the $10 million we expect to pay upon the filing of an IND. Additionally, we revised our collaboration agreement with Neurocrine and received $5 million from Neurocrine to facilitate the transfer of…

[Operator Instructions] And our first question comes from Dane Leone with Raymond James. Your line is now open.

Hi. Thank you so much. Thank you for the updates. I just wanted to maybe get more color, if you could, on what the blocking and tackling needs to be done on the Huntington's IND? What's still needed to do internally, whether it's more on bench work or work with the transitional models or more on the manufacturing side? That be great.

Right. Thanks, Dane. I'll ask Omar to answer the question.

Yes. Thanks, Dane, for the question. So currently, I should say that we are focused on really vetting for potential IND filing if things line up toward the end of the year. So we're finishing up the in life phases of some of the non – at the preclinical GLP toxicology studies and collecting that data, including the bioanalytics and knockdown information that will be necessary to support the IND filing. The second activity is, we've built out the clinical team led by Steve Hersch. He's our Vice President of Translational Medicine and Huntington's disease expert. We've held 2 scientific advisory boards for planning for the entry into patients, and in the last pages of finalizing the protocol for that Phase 1/Phase II study. And then the third aspect is the development of the biomarker modeling as well as the biomarkers that will be used in the clinic themselves, so as well as wild type of mutant Huntington protein and biomarkers – the neurodegeneration biomarker suite that will also put around that as well as potential imaging biomarkers as well. And then we are also in the final stages of our rodent efficacy model – mouse model study that will be used to support the IND filing as well as help us build the translational model to ensure that we are starting with clinically efficacious doses that are predicted to be clinically efficacious with our first entry into the clinic.

Great. And just one follow-up on that and this probably isn't a fair question, as you speculated. But do you – have there been any learnings from what you've seen, I guess, specifically where we all looked at during AAN this year in terms of biomarkers and maybe specifically, NfL in terms of disease response or disease control with this type of therapy?

Yes. I mean, I think the data that was presented from the Roche Ionis program as well as in the – that was published in The New England Journal of Medicine earlier this year, I think the NFL findings are still – is unclear why either there was an increase rather than the decrease. We will be measuring – plan to measure NfL in our own clinical study. I think one of the key things that the community generally and we are leveraging our close collaboration with CHDI on this is really trying to understand the relationship of these biomarkers with clinical progression from natural history cohorts. And we hope that that data is going to be informative as we start to interpret these biomarkers in our clinical program.

Excellent thank you so much.

Thank you. And our next question comes from Phil Nadeau with Cowen and Company. Your line is now open.

Company thanks for taking my questions. First, one question on RESTORE-1. It seems like from your prepared remarks there may have been a change in the design and specifically, the statistical analysis plan. Is that accurate or did we misinterpret your comments?

Thanks, Phil. So – This is Andre and Matt and Omar can also add to this. So we shared with everyone earlier this year that we had a plan for 75- to 100-patient size trial in RESTORE-1. And we shared also at that point that we would look to finalize our SAPT to determine – predetermine the precise target number of patients that we will look to enroll. So that was prior to entering into relationship with the Neurocrine. So now we're working with them to define that target number of patients that we're going to look to enroll. And we may look as we do that to make also any potential minor amendments to the protocol. But these I would say are more of the standards. So there is not a revisit of the protocol at a higher level than that. If there are some amendments that are meaningful, we will, of course, let – we'll inform every one of these changes. But one thing that, as Omar alluded to, that we are clearly looking to do as we had planned as to finalize at SAPT in that target number of patients.

Perfect. And do you have any updated guidance on the time lines for RESTORE-1, in terms of when we could see the data?

So we expect we will be able to give further clarity around that once we do have a target number of patients and then taking into account the enrollment rate. So again, we'll work with our partner to be able to give that guidance, and that will follow naturally the determination of how many patients we're going to aim for in that range.

Thanks for taking my questions.

Thanks.

Thank you. And our next question comes from Debjit Chattopadhyay with H.C. Wainwright. Your line is now open.

Hey guys. Good morning. This is Aron Welch on for Debjit. So I just had a question about the AAV records being used for the Huntington's disease program. Would you – I saw in your corporate deck that you've mentioned that there – it looks like there is going to be a passenger strand or that you're cognizant of the passenger to guide strand ratio. So could you tell us anything about how much of a ratio there may be?

Yes. Thanks, Aron, for your question. I'll ask Omar to touch on this. We've not shared in our prior publication the precise ratio, but as we develop these primary microRNA programs in these cassettes, we have some guiding rules as we apply our expertise from one program to the other, as to what looks to be an optimal amount of guide to passenger ratio. So that's informed from prior work we've done and what others have done. But – so these are minimum thresholds that we look to have as the screening criteria to select our candidates for each program. But we don't have a precise disclosure here on neither the Huntington nor the ALS to share. But that's the approach of how we look at this across our programs.

Yes, I don't think there's a lot to talk about. The key factors that we look at obviously, that affect the potency itself of the transgene including the guide to passenger ratio. We do have some broad rules that help us optimize this. But I don't think we're going to disclose the precise ratio as it relates to the Huntington's program.

Okay. All right. And real quick, do you guys – I know you haven't disclosed the axon that are being targeted, but would you be able to tell us, if there's any consideration for immune oligospecificity or oligospecificity when considering which axons to go after?

That is a good question. So we are taking a non-oligospecific approach. Considerations around oligospecificity was really to have a gene therapy that will be able to cover the broad Huntington's population and the challenges of developing SNPs with really a broad coverage of the Huntington's population that would allow us to really ensure that our gene therapy would be accessible to the broad majority of patients with – as we might benefit from it. The other way of addressing oligospecificity is to target the actual repeated cell. We have stayed away from that approach because of the fact that there are other genes that contain that repeat and the risk of off target or unwanted effects by targeting other genes with an siRNA to that region. So that together with the data that exists on the safety of non-oligospecific approach, we've decided to stick with the non-oligospecific approach.

Okay great. Thanks for the clarity.

Thank you. And our next question comes from Tom Shrader with BTIG. Your line is now open

Good morning. Thanks for taking the question. You just answered some of them. But one sort of broad survey question, AAV capsid development is incredibly crowded right now. And I'm just kind of – from a survey point of view, what's your sense of how good primate data are? Are they quantitatively predictive? Is there a sense share? I know there've been some negative surprises from mice, but your sense of how much confidence we should have from primate readouts would be helpful.

Yes. That's a good question. I think just from a – just at a very high level, we feel that the composition of the primate blood-brain barrier, the nonhuman primate is likely to be more translatable to the human situations than mouse. And particularly, I think, if you see, the surprises which have come where even – where the genetic background of these very inbred mice lines seems to affect the potency of the capsid to achieve, for examples, blood-brain barrier penetration. So I think it's yet to be – they – the hypothesis that the nonhuman primate selection of capsids will more optimally translate in human situation is yet to be validated. But I think what we're confident now, particularly using the TRACER system is that we can at least use tissue that's closer to the human situation for evolution and selection of capsids, that we can do that efficiently and in quite a fast way to select for the characteristics that we're looking for. And we're looking forward to bringing these forward into the clinic and really being able to confirm the hypothesis that this is a superior approach than selection in rodent species.

Okay great. Thank you.

Thank you. And our next question comes from Christopher Marai with Nomura. Your line is now open.

Hey good morning. Thank you for taking the question. Just thinking about the upcoming INDs and specifically Huntington's, how should we think about or where are you guys on manufacturing product? And would you be planning on going into the clinic with your commercial product process? Or do you expect to be making changes after the initial trial has run?

Thanks, Chris. I'll ask Matt Ottmer to answer your question.

Chris, so I think as we've covered before our manufacturing strategy with the group led by Luis Maranga is to really focus on the baculo platform, which gives us a lot of flexibility and confidence as we make the jump from preclinical into the clinic, with the productivity of that process and the robustness of moving to something that we feel we could move across scales and to different manufacturers. Our intent, as we move into clinical, is that it's a process that would be very, very similar to what we would eventually commercialize. We would not want to have to make changes that would require any step back in the future. So when we select that final process, it has to meet that standard. There is, of course, always the opportunity to optimize the conditions in the way you run it in the future, and again the investment we've made at the preclinical stage across multiple programs gives us confidence that we can do that within the defined process space. And so as we prepare for the IND filing, I think we're executing against that plan, similarly to what we did actually with a higher hurdle on the Parkinson's program where we made a change from one process to another. It's very dependent on your analytical capability, which we've also invested in, so that we have high confidence in the characterization, in the process parameters, and so making good progress on that phase.

Okay. So are you thinking that you're going to change it after moving into the clinic, I mean on the Huntington's program specifically or not?

We would not anticipate any changes that we would need to make. There's always the possibility, as you advance in the clinic, that you can do process optimization within narrow parameters that would not be considered so significant they would have any clinical impact. That's part of when you validate your process, demonstrating that when you move toward your BLA. And so you have to have a process, you have high confidence and as you go into the clinic, that it is going to be within a manageable range of what you would then validate for your BLA. And we have that confidence at this point.

Got it. Thank you.

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

Thanks for taking the questions. For Huntington's, you've said that greater than 40% knockdown of HTT results in a significant functional benefit in mice. So what magnitude of knockdown do you think you need to see in humans that translate into a clinically meaningful benefit?

Yes. Thanks, Jeff. Omar will answer your question.

Yes. Again, I think it's for most of us unknown. I mean the limitation really in the field is that the preclinical efficacy data is based on the heritable readouts from transgenic animals, particularly transgenic rodents. One of their challenges has been that many of these transgenic models don't show neurodegeneration in the same way that it's seen in the human situation. And so I think what we're focused on is using the best evidence based on nonclinical, behavioral experiments on efficacy and then modeling those forward from essentially determining what level of knockdown is necessary to get the clinical benefit in these transgenic species and then making sure that, that sets the minimum threshold for the degree of knockdown as based on the mRNA and protein levels in the nonhuman primate and then model that forward to what doses we think are necessary to achieve similar levels of knockdown in the human brain. I think that we'll be watching the field very closely, particularly data that's emerging from competitive programs in both gene therapy as well as other modalities such as the antisense program, and making sure that we adjust to that. In our Phase I that we plan to explore at a good range of doses really dose starting with what we believe will be at least minimally clinically efficacious dose as the first dose that's taken into patients.\

Great. And you mentioned the nonhuman primates, so maybe if I can ask a little more on that. So you've shown the HTT lowering in different parts of the brain in nonhuman primates. So does threshold for HTT lowering translate into a clinically meaningful benefit vary by location in the brain?

Yes, it seems so. I think again it comes back to the challenge of the actual progression of the [indecipherable] in animal models. So obviously, the nonhuman primate studies are animals that don't – that essentially were just taking down that at wild-type Huntington. They don't have these in Huntington. Since that we're really looking at knockdown that at least is going to be safe, and that's achievable based on the knockdown that's necessary for recovery in the rodent species and the transgenic rordent species. So that's really the best we can do. It does seem, however, that from the combination of preclinical models that there is variability in the degree of knockdown depending on the – which parts the brain you're focusing, inner cortex versus striatum for example, and that either probably higher levels of knockdown are necessary in the striatum than in the cortex, but that both are needed.

Thank you.

Thank you. And our next question comes from Sumant Kulkarni with Canaccord. Your line is now open.

Morning thanks for taking the questions. My question is specifically on what you've termed your TRACER program capsids that cross the blood-brain barrier with mainfold improved transaction and potentially better cell specificity. What might be the first program that gets into the clinic that uses this TRACER technology? And how far way is that? And are these capsids part of the AbbVie Vectored antibody program or further down the line?

Thanks, Sumant. The – as we said in the earlier parts of the call that we are – the TRACER program that we've already started to present data from that and that's proceeding apace. We're using it to select vectors and define vectors with different characteristics both cell type specificity as well as other characteristics, for example, degree of blood-brain barrier penetration and how that can be achieved by root. Likely, vectors that are emerging from our capsid evolution strategy, perhaps, one of the first programs that we may see deployed is on Friedreich's ataxia program. And then as we also said, we're considering a number of new targets, both with Neurocrine as well as Voyager own targets, and we'll be definitely using the results of the capsid evolution from the TRACER program to take those target forward and look forward to talking about that at a later date.

Thank you.

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

Thanks, operator, and thank you, everyone, for joining our call today. Just before we wrap up, I'd like to thank Perry Karsen and Dinah Sah. As we noted in this morning's release, Perry has provided us notice that he is resigning from our Board of Directors, effective August 31. Perry is joining The Stanford Distinguished Careers Institute as a fellow, and given the time constraints of that will no longer serve on our Board, effective at the end of the month. And as also noted previously, Dinah has retried as our Chief Scientific Officer, but will continue to consult with us and advise us, including as part of our SAB. So I just wanted to again thank them and wish them both the best of luck. And I look forward to updating all of you on our progress again next quarter and as we see between now and then. Thank you.

Ladies and gentlemen, thank you for participating in today’s conference. This concludes today’s program and you may all disconnect. Everyone have a wonderful day.