Voyager Therapeutics Inc (VYGR) 2020 Q4 法說會逐字稿

Good afternoon, and welcome to the Voyager Therapeutics Fourth Quarter and Full Year 2020 Financial Results Conference Call. (Operator Instructions) This call is being webcast live on the Investor & Media section of Voyager's website at voyagertherapeutics.com. This call is the property of Voyager Therapeutics, and recording, reproduction or transmission of this call without the express written consent of Voyager Therapeutics is strictly prohibited. Please be advised that this call is being recorded.

I would now like to introduce Allison Dorval, CFO 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; and Omar Khwaja, Chief Medical Officer and Head of R&D.

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 2020. 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 view as of today, February 25, 2021. 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 turn the call over to Andre.

Great. Thank you, Allison, and good afternoon, everyone. Welcome to our Q4 earnings and corporate update call. I'll begin by walking through the highlights from 2020 and expectations for 2021. 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 questions in a Q&A session.

In 2020, we remain focused on moving our pipeline and our key platform activities forward. Among the key highlights, we made significant progress in readying our Huntington's disease program for clinical trial. Based on our preclinical data, we believe that the VY-HTT01 has the potential to be a best-in-class therapy for this devastating disease. We achieved highly promising results using our TRACER platform to identify capsids with a much better ability to cross the blood-brain barrier than current serotypes. The implication of these advances could be profound for both our own pipeline and for the field of gene therapy through collaborations. We also advanced our overall pipeline and platform and provided updates on the progress through 18 presentations at scientific conferences and 4 publications and peer-reviewed journals. And finally, we made key additions to our team at the board level, at the SAB level and also at the senior management level.

While we made very good progress, the past year wasn't without its challenges. Our Huntington's IND was placed on clinical hold pending resolution of additional device- and CMC-related requests from the FDA. The Parkinson's IND was also placed on clinical hold, in that case pending follow-up imaging and clinical assessments requested by the DSMB and a risk-benefit assessment requested by the FDA. And Neurocrine recently notified us of its intent to terminate the portion of our collaboration related to the VY-AADC program.

The work we do is challenging, but the potential rewards for patients and their families are enormous. Voyager was founded on a commitment to applying gene therapy to some of the most life-limiting and disabling disorders in medicine, and our resolve is unwavering. We've built a world-class team of experts at the intersection of gene therapy and neuroscience. On the back of the pioneering work we've done to date and our most recent advances, we're now poised to enter a new phase in our mission to deliver transformative therapies for people suffering from severe neurological diseases.

Before I turn it over to Omar, I'd like to point out some of our upcoming highlights for 2021. For the Huntington's program, we expect to provide our response to the FDA on our IND in the first half of the year and to initiate our first-in-human trial upon IND acceptance. For the novel capsids, we plan to present nonhuman primate data on our lead capsids at a scientific conference in the first half of 2021. For the Parkinson's program, we expect to provide an update on the potential path forward based on the additional information being collected by Neurocrine in response to the DSMB request. And lastly, for the preclinical pipeline, including our innovative vectorized antibodies, we expect to announce new programs and provide updates at scientific meeting and other presentations in the first half of the year.

With that, I'll turn the call over to Omar.

Thanks, Andre. I'll walk through our program updates in more detail. Today, we'll start with VY-HTT01, our wholly owned program for Huntington's disease.

Huntington's disease affects approximately 40,000 people in the United States and is the most common monogenic neurological disorder in the developed world. It's a relentlessly progressive and ultimately fatal disorder that strikes people in the prime of life. It's a disease characterized by a toxic gain of function mutation in the Huntington gene. This leads to abnormal Huntington protein aggregates that cause neuronal cell death. For patients, their families and care partners, it's a devastating disease that results in a progressive decline of motor skills and cognitive functions.

Our therapeutic candidate, VY-HTT01, is an AAV1 gene therapy encoding a novel microRNA designed to potentially reduce human HTT messenger RNA. We've developed our candidates and route of administration to safely deliver the highly potent gene-silencing microRNA where it can impact the neuropathology of the disease in the core structures of the striatum and cortex. The canonical RNA interference pathway used in VY-HTT01 is a well-characterized and highly precise mechanism that's been validated in the clinic. And since the caudate has significantly atrophied and striatal to cortical connections are compromised in early Huntington's disease, we plan to deliver VY-HTT01 directly to the putamen and thalamus, targeting the primary site of disease pathology and leveraging the thalamus' extensive neuronal projections to the cortex.

We've previously presented data demonstrating that delivery of VY-HTT01 into the putamen and thalamus of nonhuman primates was well tolerated. The investigational gene therapy results in a widespread distribution of VY-HTT01 vector genomes across the striatum and cortex. This leads to robust reductions of HTT messenger RNA and proteins in these key brain structures. These reductions stabilize between 6 and 12 months following a single injection of the gene therapy.

VY-HTT01 treatment also demonstrated potent reduction of HTT mRNA and proteins in the YAC128 and BACHD transgenic mouse models of Huntington's disease, with significant improvements in motor function, allowing us to select doses that we predict to be clinically efficacious. We're very pleased with these results, and as Andre mentioned, we plan to present preclinical data from the IND-enabling studies later this year.

We submitted our IND application for VY-HTT01 in September and were placed on clinical hold by the FDA, pending resolution of questions on CMC-related items. These include drug device compatibility and drug substance and product characterization. Our team is working hard to complete the information request and expects to provide our complete response to the agency in the first half of 2021.

While we work to gain IND acceptance, our clinical team has been actively engaging with investigators, trial sites as well as the patients and clinician communities to ensure a smooth transition to our first-in-human trial. We're focused on having our trial active and positioned to enroll patients quickly upon IND acceptance.

There's currently no available disease-modifying treatments to help people with Huntington's disease, and we believe VY-HTT01 has the potential to change that.

Andre also mentioned our vectorized anti-tau program. Tauopathies are progressive neurodegenerative disorders defined by toxic aggregates of tau protein in the brain. These are in conditions such as Alzheimer's disease, frontotemporal dementia and progressive supranuclear palsy. Current treatments address symptoms only.

We had originally started this program under a collaboration with AbbVie where we not only developed our process of vectorizing antibodies but also worked on antibody discovery. When AbbVie terminated the collaboration last summer, we retained the right to the vectorization technology and certain novel vectorized antibodies that had been developed. The vectorized anti-tau program is now included in our wholly owned pipeline. We believe that the delivery of vectorized antibodies can overcome many of the limitations of passive immunization, including the amount of antibody reaching the brain. The advances we've made to date validate our belief that we have a better method for delivering antibodies to the brain.

We continue to drive these efforts forward. In 2021, we plan to select our development candidate and begin dose-range finding and buyer distribution studies on this program. We're also advancing our work in vectorizing novel payloads, including innovative antibody and other biotherapeutic formats.

I'd like to spend the next few minutes discussing our progress on novel capsid discoveries, an area Voyager is conducting groundbreaking work and is a leader in the field of gene therapy. We're using our TRACER functional screening technology, a directed evolution approach, in nonhuman primates to find novel capsids with improved abilities to cross the blood-brain barrier. Without better capsids, the field will remain limited to relying upon either direct delivery to the brain or systemic dosing with high doses that carry immune and safety risk. Capsids with better biodistribution allow not just an improved route of administration for patients but significantly open up the number and types of neurological disorders that could be realistically addressed by AAV gene therapy. We believe our novel capsid discoveries have the potential to support a significant number of programs, including current programs and those yet to be named.

We recently had a publication in Molecular Therapy - Methods & Clinical Development entitled Rapid Evolution of Blood-Brain Barrier-Penetrating AAV Capsids by RNA-Driven Biopanning, which describes the foundational rodent proof-of-concept experiment, or the TRACER platform. This platform has allowed us to advance our efforts working directly with nonhuman primates.

The data we're seeing from the experiments using nonhuman primates suggests these novel capsids could have significant potential for blood-brain barrier penetration and that these capsids could be effective for a number of neurological diseases where optimal treatment would be IV delivery of AAV gene therapy. Treatment of diseases such as Friedreich's ataxia, Alzheimer's disease and certain childhood disorders could benefit from these efforts. We've characterized capsids from our first proprietary library with notable results so far and continue to work on several others. We hope to share our NHP data from these novel capsid assets at a scientific conference in the first half of this year.

Lastly, let's move to the VY-AADC program for Parkinson's disease with Neurocrine. As Andre mentioned, the RESTORE-1 trial was placed on clinical hold by the FDA in December 2020. This followed Neurocrine, the study sponsor and IND holder, filing a safety report regarding the observation of MRI abnormalities in some study participants. The DSMB met most recently in January and requested additional clinical and imaging data. Neurocrine has committed to provide these data to the DSMB.

We intend to support Neurocrine on ongoing matters related to the completion of imaging and clinical assessments as requested by the DSMB as well as the provision of other information requested by the FDA. The clinical implication of these radiological findings remains unknown and is being evaluated.

We'll work to determine the potential path forward for the VY-AADC program based on the additional information being collected by Neurocrine in response to the DSMB request. We plan to continue to provide updates across all our pipeline initiatives in 2021.

I'll now pass the call on to Allison.

Thanks, Omar. I'll review the highlights of our financial results and guidance.

We ended 2020 with $174.8 million in cash, cash equivalents and marketable debt securities, compared to $281.5 million at the end of 2019.

We booked collaboration revenues of $6.5 million in Q4 2020 and $171.1 million for the year, compared to $32.7 million and $104.4 million for the same periods of 2019. The quarter-over-quarter decrease reflects the reduction of revenue related to research services and cost reimbursements from the collaborations with Neurocrine and AbbVie.

Full year 2020 revenue includes $105.2 million related to the recognition of the remaining deferred revenue for AbbVie upon the collaboration termination in the summer. All research services related to the AbbVie collaborations were completed prior to the fourth quarter of 2020.

Net loss was $15.9 million for Q4 2020 and net income was $36.7 million for the full year, compared to net losses of $12.6 million and $43.6 million for the same periods of 2019.

R&D expenses were $22 million for Q4 2020 and $108.8 million for the full year, compared to $36.6 million and $119.7 million for the same periods of 2019. The decrease in R&D expenses was primarily related to lower external costs for services supporting our clinical and preclinical pipeline programs.

G&A expenses were $8.3 million for Q4 2020 and $35 million for the full year, compared to $9.9 million and $36.3 million for the same periods of 2019. The decrease in G&A expenses was primarily related to legal and professional fees.

Turning now to our financial guidance. Excluding any potential financing or business development activities in 2021, we expect to end the year with cash, cash equivalents and marketable debt securities between $50 million and $60 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 the Neurocrine collaboration, will continue to be sufficient to meet our needs for projected operating expenses and capital expenditures into mid-2022.

We've consistently demonstrated a disciplined financial approach and strategic partnering strategy, and we'll continue to evaluate opportunities to thoughtfully fund our business. We look forward to continuing our progress through multiple milestone events across our programs in 2021.

And with that, we'd like to now open the call up for questions.

(Operator Instructions) Our first question comes from the line of Phil Nadeau with Cowen.

Just 2 questions from us. First, on the HTT clinical hold, are you able to give us any more information about what it is you have to accomplish and what's going to be in your complete response that's submitted to the FDA in the first half of the year?

Yes. Thanks, Phil, for the question. Omar, I'll turn it to you for this.

Yes, thanks, Phil. So the FDA's concerns are limited to CMC issues, and just to emphasize that, there's been no concerns with the preclinical safety or toxicity. Really, the request from the FDA relates to sort of 2 pieces of data. One is information regarding devices, and we're seeking that from the third parties that have been involved in the manufacture or licensing of those devices. So I mean, that's almost a pure information request. And then the second relates to the biocompatibility of the gene therapy product, not just with the cannula that's used to infuse the gene therapy, but also the entire fluid pathway, so the tubing and syringes which are used as well. And so we're generating that biocompatibility data, and that will be the other significant piece of the information that we'll submit to the FDA in response to the clinical hold.

Yes, that's very helpful. And then second, on the RESTORE trial, what do you hope to learn over the next few months that could better elucidate either the causes or consequences of the MRI abnormalities? Are you watching the patients to see if those abnormalities cure themselves or is there other information that's particularly important that you'd like to submit to the FDA?

Yes. So thanks, Phil. So there are some imaging data that we're going to get from a -- at a later time point for the patients that were enrolled in the Phase I. And for the RESTORE study, there are a couple of additional clinical assessments that they're going to be guiding on for those patients as well as additional PET scan for the patients that were in the RESTORE-1. So these are the -- that's the information that Neurocrine is working, and we're supporting them to collect over the coming months.

And our next question comes from the line of Laura Chico with Wedbush Securities.

It's Ken Shields on for Laura Chico. So the first is, how are you guys prioritizing the pipeline with respect to cash position? Will you guys still plan to develop VY-AADC independently at this point?

Yes. So we have a number of programs that we've been advancing. As we've said, we'll look to announce some of these programs at scientific meetings and throughout our presentations in the first half of the year.

At this point, on the VY-AADC program, what we're focused on is getting the additional information that the DSMB has requested. And based on that, we're going to be able to make an informed portfolio decision as to the best path forward for the program. But at the moment, the key priority for us portfolio-wise is on the Huntington's program, to submit the complete response, and then advancing some of the earlier-stage program, including some of the novel payloads and some of the programs that are enabled by the novel capsids that we've been working on. So we'll look forward for an opportunity in the first half of the year to provide updates on the full portfolio.

Okay, thanks. And then I guess just one more. I mean, you mentioned the novel capsid program. And it looks like you guys have been exploring them in nonhuman primates, and you're going to be sharing data later this year. But could you provide an update on what the next steps or the overall strategy will be there going forward? Thank you.

Sure. Omar, do you want to address this?

Yes, of course. So in terms of the next steps, from the first series of capsids that we're getting from the first library that (technical difficulty) in nonhuman primates. So those capsids that look very promising in terms of their performance characteristics versus AAV9, for example. Those capsids are now in advanced stages of characterization, including understanding the manufacturability of the capsids as well as the -- identifying potentially the receptors that are involved in the apparent improvements in transfection that we're seeing with these capsids. So there's the sort of detailed characterization from the first tranche of capsids that are emerging from the libraries.

We then have a significant number of libraries from a number of different parental capsid serotypes that are now going through the TRACER, somewhere in late stages of the TRACER screening. Others are in earlier stages, and we plan to advance those through the TRACER process and then begin to characterize the promising capsids that emerge from those as well.

The second part of the strategy will relate to deploying the TRACER platform for other capsid characteristics that would be beneficial for neuro AAV gene therapy, including cell-specific tropisms for the different cell types in the nervous system as well as potential other tissue systems as well.

And our next question comes from the line of Jay Olson with Oppenheimer.

This is Matt on for Jay. We were wondering, I guess, generally, how is your view for gene therapy in Parkinson's, if that's changed at all, as a result of the clinical hold on VY-AADC? And also, in general, maybe just given the recent setbacks for others who have gene therapies, including Bluebird and UniQure, obviously different, but what would you just say to investors who may now perceive gene therapy generally in kind of a negative light? Definitely appreciate the color. Thank you.

Yes. Thanks, Matt. Omar, if you want to start, I may add to your comments.

Yes. I think, obviously, the patient safety is our top priority. And so in terms of the VY-AADC program, our goal is to really determine whether the radiological findings that we -- have been reported had any clinical significance. And so that's the immediate focus in understanding that. And then as we get that information and can prepare those requests to the DSMB and also respond to the FDA's request for more detailed assessment of the risk-benefit of the product, we'll, in parallel, determine the next steps for the VY-AADC program.

I think -- in terms of the field of gene therapy, I think one of the things, too, that's probably important to differentiate from, is the actual type of viral vector that's used. And so in AAV it's generally a nonintegrating virus, and that's somewhat different to lentivirus, which is an integrating virus. And so the safety liabilities from AAV are quite different from lentivirus. So we anticipate limited readthrough from the challenges that maybe, for example, Bluebird are seeing. Andre, do you want to add anything to that?

I'll only add that part of our endeavor with novel capsids is to be able to lower the doses, too, when we deliver systemically, and that maybe, like most other therapeutics, where there could be some liabilities that start surfacing with the higher doses. So that's part of the benefit of getting improved capsids with better properties. It may allow for lower doses to be administered with the benefit on both the safety and the efficacy front.

Got it. That's helpful, thank you. And looking forward to the novel capsid data. I appreciate the time. Thanks.

(Operator Instructions) Our next question comes from the line of Jeff Hung with Morgan Stanley.

This is Hannah on for Jeff. So just 2 quick questions. So for Parkinson's, what kind of protocol amendments are you thinking might be necessary? Is it more for monitoring, or are there other ways to change the administration to reduce the risk of the MRI abnormalities?

And then just second, any read-through to the Huntington's program since the drug candidate is also injected directly into the brain? Thank you.

Yes. Thanks for your questions, Hannah. Omar?

Yes. In terms of the protocol amendments, the most immediate protocol amendments are really focused on adding the additional imaging as well as clinical assessments that the DSMB have requested. So we're not anticipating otherwise any significant change in the route of administration or the infusion procedure. But really, the protocols are being amended right now to implement the additional assessments that are being requested, so MRI and clinical assessment.

The -- in terms of potential read-through, I mean, I think it's important to understand that the 2 programs are quite different. And so they both utilize intraparenchymal administration; however, the vectors are different between the 2 programs. So in the VY-AADC program, it's AAV2, whereas in the Huntington's program, we're using AAV1. Also, the Parkinson's program is a protein that's an enzyme that's being replaced. That's quite different to the Huntington's, where we're delivering a microRNA to knock down the toxic Huntington's species. And the third thing is that the doses are quite different between the 2 programs because the microRNA that we're using in Huntington's is extremely potent, and so we're using significantly lower doses. And the fourth thing is that we've got a very extensive nonhuman primate safety package with data up to 1 year after dosing in nonhuman primates at a range of doses. And so we believe that's also going to be important in understanding the safety profile of VY-HTT01 program.

So we're looking forward to submitting our response to the FDA and anticipating moving forward with the clinical trial once the dosing is lifted.

And our next question comes from the line of Brian Skorney with Baird.

Jack, dialing in for Brian. The first one is a bit more of a housekeeping question. We're wondering if you could provide some comments about the financial implications of the Neurocrine dissolution of the partnership.

And then the second question is more -- quite early, but the novel capsids are very interesting. And you did mention some potential indications, but we were wondering if you could provide some more color as to what areas you'd be looking to move these assets into? Thank you so much.

Yes, thanks for your questions. Allison, on the financials?

Sure. So on the financial side, we've projected that we'll end 2021 with $50 million to $60 million of cash and cash equivalents on hand and that we continue to have cash on hand to reach mid-2022, which is consistent with what we've said in the past. We continue to execute on a strategy with financial discipline and evaluating strategic alternatives for additional financing to run our business. So at this point, I think, no real impact from the termination of the Neurocrine program.

Thanks, Allison. And on your second question around the targets for novel capsids, so this -- the early campaigns that have read through and that are in various stages of characterization, these are for IV delivery to enable a good transduction of target cells, different regions of the brain. So we have an opportunity with different capsids that have different distribution to be able to marry the neuropathology with the distribution of a given capsid. So that's the process that we have gone through and we'll continue to go through as we read through additional capsids. And that's the type of information that we want to provide an update on in the first half of the year.

And our next question comes from the line of Aydin Huseynov with Benchmark.

The first question is about the Parkinson's program. So you have 23 patients that were treated in Phase I study so far. Did you see any MRI abnormalities in those 23 patients? And did DSMB request the MRI images from the Phase I trials as well?

Yes. Thanks, Aydin. Omar?

Yes. So a couple of things to note. So I mean, just -- the DSMB have requested MRI scans to be reviewed from the Phase Ib patients. One of the differences between the imaging that was collected in the Phase I studies and in RESTORE-1 is the timing of the imaging. So in RESTORE-1, there was imaging out to 1 year, whereas in the Phase I studies, the imaging went out to 6 months. So one of the things that the DSMB are requesting is to get longer-term imaging from those Phase I patients as well as a review of the imaging already collected to date. The -- so it's not really possible because there's not an -- it's not an apples-to-apples comparison on the imaging front yet, until we've had longer-term imaging data from the Phase I patients.

Okay. Thank you for that.

So that…

Yes, that's helpful. And for Huntington, I have another question. So you mentioned that this is -- this could be a potential best-in-class therapy. Could you give us some more color? Why do you think it could be the best-in-class? And do you have any specifics from the preclinical data other than the safety? Thank you.

Yes. Thanks for that. So what we know from our preclinical work is that we have a very potent construct. We know also that through the work we've done to optimize the delivery, that we get some good transport of the vector genomes through retrograde and anterograde travel. So we're -- the route of administration that we've chosen, to target the putamen and the thalamus, from the preclinical work, suggests that we should be able to get a broad distribution of HTT knockdown. And we have the results, as Omar mentioned, from our transgenic rodent models showing that we get some strong phenotypic rescue in these HD disease models, transgenic models.

So it's the totality of the evidence that we've developed to date that give us some confidence about the profile of the program, and we'll look to present additional preclinical results later this year on the program so that we can show the longer-term results that we've had in nonhuman primates, where we've studied the knockdown up to 12 months. We'll be able to provide updates on these longer-term NHP experiments.

Thank you. And I'm showing no further questions at this time and I would like to turn the conference back over to Andre Turenne for any further remarks.

Okay. Well, thanks, everyone, for joining us today, and we look forward to keeping you updated on our progress through the rest of the year. Thanks very much.

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