Voyager Therapeutics Inc
NASDAQ:VYGR
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Voyager Therapeutics Inc
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Good morning, and welcome to the Voyager Therapeutics Second Quarter 2023 Conference Call. [Operator Instructions] Please be advised that this call is being recorded at the company's request. A replay of today's call will be available on the Investors section of the company website approximately 2 hours after completion of this call.
I would now like to turn the call over to Pete Pfreundschuh, Chief Financial Officer. Please go ahead.
Thank you, and good morning. Joining me on the call today are Dr. Al Sandrock, our Chief Executive Officer; Dr. Todd Carter, our Chief Scientific Officer. We issued our Q2 2023 financial results press release this morning. The press release and the 10-Q are available on our website.
In a moment, I will turn the call over to Al. Before I do this, I want to remind everyone that during this call, Voyager representatives may make forward-looking statements as noted in Slide 2 of today's deck. These forward-looking statements include future expectations, plans and prospects. All forward-looking statements are inherently uncertain and subject to risks and uncertainties that may cause actual results to differ materially from those indicated by these forward-looking statements. You are encouraged to review and understand the various material risks and uncertainties facing the company as described in the company's most recent annual report on Form 10-K filed with the SEC.
As of the following of today's quarterly report on Form 10-Q, there have been no material changes to the risk factors described in our annual report. All SEC filings are available on the company's website.
Now it is my pleasure to turn the call over to Al.
Thank you, Pete, and good morning, everyone. Please turn to Slide 3. I'd like to start by recognizing the incredible innovation happening right now in neurotherapeutics and in gene therapy. I talked about this on our last call. And since then, we continue to see tremendous progress.
On the neurotherapeutics front, just last month, lecanemab received full FDA approval for Alzheimer's disease as well as Medicare coverage. This follows other recent FDA approvals in the neurotherapeutic space, including approvals of medicines for Friedreich's ataxia and amyotrophic lateral sclerosis. The gene therapy field also continues to advance, with recent FDA approvals of the first gene therapies for Duchenne's muscular dystrophy and hemophilia A.
Voyager sits at the intersection of neurotherapeutics and gene therapy. We believe we are uniquely positioned to leverage the advancements in both fields and importantly, to combine them. To date, the delivery of gene therapies into the central nervous system, or CNS, has proven challenging. Approaches to inject these therapies into the brain parenchyma or various cerebral spinal fluid spaces generally have not been successful and continue to result in setbacks for other companies. Voyager recognized this back in 2021. That's why we pivoted to intravenous delivery, leveraging the vasculature to penetrate the CNS, something we have enabled through our innovative capsid design.
Moving to Slide 4, I will briefly review our investment rationale, platform, pipeline, partnerships and potential.
First, the platform. Voyager uses our TRACER capsid discovery platform to generate multiple families of novel capsids with robust CNS tropism following IV delivery. We have presented data demonstrating strong transduction to multiple areas within the brain, and activity across multiple species. Our most recent data at the American Society for Gene and Cell Therapy, or ASGCT, 2023 Conference showed greater than 50% transduction in multiple brain areas at the relatively low dose of 2E12 VGs per kilogram in marmosets.
Second, our pipeline. We are advancing 4 CNS programs through late-stage research and towards IND filings, including our wholly-owned anti-tau antibody for Alzheimer's disease and SOD1 gene therapy program for ALS. We currently have 3 wholly-owned assets targeting Alzheimer's disease, including a new early research initiative just announced today to advance a vectorized anti- A-beta antibody. We'll talk more about this in a minute.
Third, partnerships. Voyager has generated more than $200 million this year alone in non-dilutive partnering revenue. In Q2, we executed a license agreement with Sangamo around prion disease, bringing our total number of partnered programs to 11. These programs provide opportunities for additional milestones and/or royalty revenue to Voyager as well as opportunities to generate data with our capsids and most importantly, to help patients.
Finally, potential, specifically the potential to expand from gene therapy into other approaches of neurogenetic medicine. As those of you who attended our standing room only talk at ASGCT know, we are making good progress in our receptor program. After identifying a receptor for one of our capsid families, we have now also identified a ligand for this receptor, which has many of the characteristics required for transport of macro molecules across the blood-brain barrier or BBB.
We are exploring the potential to leverage the receptor to shuttle nonviral genetic medicines across the BBB. We have also preliminarily identified 2 receptors for additional families of our TRACER capsids, and we are conducting confirmatory research to further validate these discoveries. While this program is early, I am increasingly excited about the potential here to expand the reach of our technology into other approaches of neurogenetic medicine.
Moving to Slide 5. As you can see, Voyager is advancing quite a robust pipeline. However, we are doing so efficiently. The 4 programs depicted in blue at the bottom of the slide are funded and executed by partners. They do not require significant investment of time or money from Voyager.
Moving up to slide, the 7 programs depicted in yellow represent our collaborative programs with Neurocrine. For these programs, Voyager is fully reimbursed for our collaborative research. The 6 programs depicted in orange at the top of the slide represent our wholly-owned pipeline. This is where I will focus today.
Turning to Slide 6. You can see that our wholly-owned pipeline now includes 3 programs for Alzheimer's disease. Our lead program is our humanized anti-tau antibody, which is advancing towards initiation of IND-enabling studies this year. We continue to expect to file an IND in the first half of 2024. Additionally, we continue to conduct early research on our to tau gene silencing program, which we introduced earlier this year. This program utilizes a vectorized siRNA delivered with a TRACER capsid to reduce tau expression in the brain.
Today, we are introducing another early research program in our Alzheimer's disease franchise. In this program, we are combining a vectorized anti-A-beta antibody with a TRACER capsid.
I will turn the call over to Todd, who will talk more about this program momentarily. But first, I want to explain why Voyager has chosen to focus 3 of our 6 wholly-owned programs on Alzheimer's disease.
On Slide 7, a glance across the top row highlights some of the recent progress with anti-amyloid antibodies. These represent tremendous first steps towards modifying the course of Alzheimer's disease.
Turning to the second row of milestones on this slide, there's an increasing body of data demonstrating the role of tau in Alzheimer's disease. I think of amyloid as the trigger and tau as the bullet. There's a tipping point at which increasing amounts of amyloid caused tau to spread, and that spread of tau is what causes neurodegeneration. The Lilly data reinforced this, demonstrating that anti-amyloid treatment showed greater clinical benefit in patients with lower tau burden.
Ultimately, we need to better understand the clinical efficacy of anti-amyloid treatments by stage and subtype. We may already be starting to see evidence of complete responders, partial responders and nonresponders to anti-amyloid treatment based on recent Phase III data. Complete responders may not need any further treatment than anti-amyloid, but partial responders may be appropriate for a combination of anti-amyloid and anti-tau therapies, and nonresponders to anti-amyloid might be candidates for switching to anti-tau monotherapy.
In short, this is a disease that affects millions of people. The field is making great progress against multiple targets, and there's still much work to be done.
Now I'll turn the call over to Todd to talk about our new anti-amyloid gene therapy program.
Thank you, Al. Please turn to Slide 8. As Al mentioned, there are now multiple FDA-approved anti-amyloid antibodies for Alzheimer's disease. We think a vectorized anti-amyloid gene therapy may offer the benefit of providing similar disease-modifying efficacy with a single dose. Additionally, while more research is needed, there is biologic rationale to suggest that a gene therapy approach to targeting amyloid may reduce the risk of amyloid-related imaging abnormalities or ARIA.
In the gene therapy approach, the anti-amyloid antibodies are steadily secreted by cells in the central nervous system. And thus, we would be avoiding high antibody concentrations that necessarily follow intravenous antibody infusions. Moreover, the antibody would first engage the beta amyloid deposited in and around amyloid plaques rather than the beta amyloid deposited around blood vessels. Both mechanisms may reduce the risk of ARIA.
Voyager has a long history of antibody expertise. Our lead program is our anti-tau antibody, VY-TAU01. Although VY-TAU01 is not a gene therapy, we previously shared data at the Alzheimer's Association International Conference in 2022, demonstrating that we had vectorized antibodies from this program and achieved substantial anti-tau antibody expression in hippocampus, cortex and CSF of mice, which was sustained 7 months after a single administration.
In addition, we have also vectorized an anti-HER2 antibody for the potential treatment of brain metastases from breast cancer. So this gives you a flavor for Voyager's working antibodies as a whole and in vectorizing antibodies specifically. In this new program, we have vectorized an anti-A-beta antibody and delivered it using a novel capsid. Preliminary data in mice has shown target engagement with amyloid plaques following a single IV administration of the vectorized antibody with a BBB [indiscernible] capsid.
We have shown this using vectorized murine antibodies and vectorized humanized antibodies, and we are currently evaluating antibody payloads with our TRACER capsids.
I'll now turn the call back to Al.
Thank you, Todd. Turning to Slide 9. As you can see, Voyager continues to execute on our milestones. We secured partnerships with Pfizer, Neurocrine, Novartis and now Sangamo, and the company is well capitalized with approximately $273 million in cash on our balance sheet. We selected a development candidate for our anti-tau antibody program for Alzheimer's disease. And we launched 3 new early-stage gene therapy programs, one for Huntington's disease and 2 for Alzheimer's disease.
We also continue to add incredible talent to our team. Last quarter, we welcomed George Scangos to our Board of Directors. Earlier this month, we appointed Jacquelyn Fahey Sandell as our Chief Legal Officer, and she is already adding tremendous value.
Looking forward, we continue our work to break through the barriers constraining the fields of gene therapy and neurology. We expect to identify a lead candidate for our wholly-owned SOD1 ALS gene therapy program by the end of this year. As we look towards 2024 and 2025, we anticipate the potential for multiple IND filings across our wholly-owned and collaborative and/or licensed programs. This translates into multiple opportunities to earn milestone payments, and even more importantly, once clinical trials begin, several shots on goal to establish human proof-of-concept for our TRACER capsids.
Furthermore, there is potential to see early biomarker-based evidence of disease impact in some of these very difficult CNS indications. We continue to engage in active discussions with potential partners regarding collaboration and licensing arrangements around our platform and pipeline.
In summary, it's a very exciting time at Voyager, and we look forward to continued execution this year and next.
With that, we're happy to take any questions you may have. Operator?
[Operator Instructions] Your first question comes from the line of Joon Lee of Truist Securities.
On the Alzheimer's program, are you able to share any information regarding the choice of the antibody that you plan to vectorize? And how do you plan to mitigate risks associated with ARIA, for example? And I know you mentioned specifically plaques that are not on vessels. I'm curious if there are certain antibodies you're aware that can do that.
And lastly, would you be able to fit an RNAi in the same contract? I'm thinking maybe a vectorized tau RNAi for a dual-pronged strategy. And I have a quick follow-up.
Thanks, Joon. This is Al Sandrock. But we haven't disclosed which of the anti-amyloid antibodies we're going to vectorize yet. As you know, we have a choice of a few, but -- and we're doing experiments to -- on several of them now or at least more than one anyway. We will disclose that at the right time in the future.
The risk of ARIA is real, and Todd nicely pointed out the reasons why we think we're going to minimize the risk of ARIA with our vectorized antibody. Nevertheless, it's something to keep in mind. There's 2 things I would say here. One is that the risk of ARIA is mostly in the first 6 months to 1 year of treatment. And so if ARIA were still a concern, we may wait until most of the risk has passed and therefore, use the gene therapy as more of a maintenance after the initial treatment for 6 to 12 months.
And then the second thing is that we are -- we have some preliminary experiments regulating gene expression with a small molecule, which we may be able to then turn on or turn off or adjust the dose in the future. So both are things we are actually contemplating at this point.
In terms of RNAi, you're right that we have a vectorized RNAi tau knockdown program. At the present time, we don't plan on combining the 2 into the same vector.
Got it. And your deal with Sangamo, it's really interesting because they got to license your capsids or the prion disease yet. Just a month later, Prevail, a subsidiary of Eli Lilly, announced an agreement with Sangamo to develop a novel capsid for Prevail's Parkinson's program. I mean it's confusing and amusing at the same time. We would appreciate if you could elaborate a little bit on the deal, given your competitive position on a similar gene therapy program for Parkinson's.
Yes. Thanks, Joon. Well, I really can't speak to Prevail's strategy here. However, I can verify that Sangamo did come to us seeking the capsid for the prion disease program.
Right. Just a quick follow-up. I mean, obviously, are you concerned at all? Or are there mechanisms in place to ensure that whatever they may learn from your path, it is not safe within Sangamo or maybe with between you and Sangamo, but not to leak to competitors?
Well, we trust Sangamo. I know the scientists and the CEO there very well. We think they'll take good care of our capsid as well as any of the intellectual property around them.
Your next question comes from the line of Laura Chico of Wedbush.
This is [ Ingrid ] on for Laura Chico. One question for Pete. Pete, how should we be thinking about R&D expense trajectory as you're heading into 2024? You'll be in a position to file an IND. And so how much of a pickup should we be expecting here?
Ingrid, I appreciate the question. And we don't really provide tremendous guidance with regard to forward-looking burn or R&D expenses going forward into 2024 at this point. I would say this, if you do look at our R&D burden for the first 6 months of this year and in the most recent quarter, our burn is up about 50-plus percent on the R&D side. Overall, from a financial perspective, you see that that's from an OpEx perspective.
From a cash flow perspective, our overall burn is kind of tracking and tracing to about 15% higher. That's on a 6-month basis. So if you look at last year in 2022, our burn was $78 million for the full year. Our first 6 months of this year is $45 million on a net basis. That translates to that 15% increase. So hopefully, that helps you.
Ingrid, May I add that your concern, I guess, about burn, it's a good concern. I would say that we will continue to exercise financial discipline that these early-stage programs are relatively -- they're not very intensive in terms of resource requirements for early-stage programs. And I also say that we choose programs based on our ability to rapidly achieve proof of concept and to derisk as quickly as possible in the clinic. And so -- but I want to end by saying reiterating that we will continue to exercise financial discipline and maintain a healthy cash runway.
And [ no ] I agree with you wholeheartedly. I think that really shows in the cash balance that we had at the close of the quarter $273 million on the balance sheet, a good runway going forward, and we continue to reiterate that, that carries us into 2025.
Your next question comes from the line of Jack Allen of Baird.
Congratulations to the team and all the progress made over the quarter. I guess the one key question I have is around the tau antibody IND in the first half of next year. I guess any additional color you can provide as it relates to pre-IND activities that need to be completed to get that IND done and submitted?
Yes. So Jack, this is Al. We did have feedback from the FDA in the form of a pre-IND interaction earlier this year. And so our time lines are based on what we learned on that feedback and what more needs to be done to get to an IND. The main thing, of course, is the toxicology study, the GLP tox studies that we will be initiating shortly as well as, of course, [ skewing ] our manufacturing so we can start dosing patients. And I'm happy to say that we're on track on all these fronts. And we continue to believe we'll file an IND in the first half of next year.
Your next question comes from the line of Phil Nadeau of TD Cowen.
First, on the SOD1 ALS gene therapy program, can you discuss in a bit more detail the work you're doing to identify the lead candidate? What experiments in particular do you think will differentiate among the candidates that you have in development currently?
Good question. I'm going to ask Todd to answer that.
So thanks for the question. We're really excited about our capsids and their ability to cross the BBB. We're in the process of finding the optimal -- combining the optimal transgene with the optimal capsid. And so, we're doing experiments in non-human primates to find the combination.
And I mean, he might be asking about how did you choose the particular siRNA.
So our process, we have a long history of vectorizing siRNAs at Voyager. We have a process in which we first screen, identify siRNAs then begin screening the vectorization components of that. We look at a whole variety of different characteristics. So if you look at specificity for the gene, we look at the ability to knock it down with the -- that represents specificity, making sure that we don't have a substantial off-target effects. And all of those things come together to identify the optimal transgene.
And if I remember correctly, Todd, we've used a mouse-specific capsid with one of these vectorized siRNAs and we got some very nice data in mouse models of SOD1 ALS.
That's true. On the G93A SOD1 animal model, we saw great leads into the lifespan and motor capacity retained, and we presented that at conferences as well.
That's really helpful. And then one last question from us. The slides note that there are discussions ongoing for potential partnerships. Can you give us some sense of what type of partnerships you're interested in? What do you think would create value for the company and shareholders?
Yes. So thanks. Well, as you can see, we have a history of doing a variety of different types of deals. I'd say on one end of the spectrum, we have the deal that we did with Pfizer and Novartis, where we -- where it's basically a capsid licensing agreement. We do very little work after they choose the capsid. They have all the capabilities in-house to prosecute those programs and they run with it.
On the other extreme, I would say, we have the Neurocrine collaboration where it's more of a program collaboration around GBA1 and 3 undisclosed neuro targets as well as the prior arrangements around Friedreich's ataxia. And for these, we're much more sort of research collaborators, if you will. They reimburse us for our expenses, but we're working hand-in-hand with them. And -- but the programs are there, they make all the decisions. We try to be as collaborative and helpful as possible.
And then we have other -- we have -- those I would say are the 2 extremes, and where we can do anything in between those. And we're -- look, we want to help patients, and we want to grow shareholder value over time. And we'll do whatever makes sense for both.
Your next question comes from the line of Yanan Zhu of Wells Fargo Securities.
This is Kuan-Hung for Yanan. So I have a 2-part question for the new anti-A-beta program. So first, I know you don't want to disclose the asset, but may I ask would you be targeting like monomer -- A-beta monomer, oligomer or fibril? And I think Todd mentioned engagement with the plaque. Does that mean it's targeting fibril? And the second part is, I assume the tissue concentration you want to achieve might be different from the naked antibody strategy. So what would be the tissue concentration you are targeting? And also speculation on how would be the dose level that would be required to achieve that tissue concentration?
Yanan, I'll take the first question, and I'll ask Todd to answer the second one. In terms of the antibody, we will not be targeting -- we will not be using antibodies that target the monomer. Those don't work actually. Solanezumab is a clear example that just hasn't worked. We will be targeting -- we will be using antibodies that favor the soluble oligomers as well as insoluble fibrils. And examples of that would include, for example, aducanumab and lecanemab, both of which are selective for aggregated forms of A-beta, either the large soluble oligomers, including protofibrils, or -- and as well as the fibrillar amyloids that's present in the amyloid plaques.
And the reason why we choose those is that there's very good validation, obviously, in human clinical trials. And of course, they have been FDA approved. One of them has even been fully approved recently. So I think the presence is there for that. And Todd, do you want to take the second one?
I think so. I want to confirm that I heard the second one correctly. It's a question about the vectorized antibody and how it differs from the straight antibodies. Is that right?
Right. And the tissue concentration you plan to achieve and probably the dose level that might be required?
So I can't comment specifically on the tissue concentrations and the doses we'll be going into. Clearly, we can take what the learnings are from the field on the antibody concentrations needed for efficacy. We think a potential advantage of the vectorization is beyond the single dose, which, of course, could have implications for being able to treat a large number of patients. But as we talked about in the call, we hope to avoid the potential reactions as ARIA that you get when you infuse an antibody, you necessarily get a peak of delivery, a peak of antibody exposure in the vascular system.
We'll be secreting in a constitutive fashion. So we hope to avoid that high exposure, and we hope that the -- we expect to encounter the plaques on the brain before it's encountered in the blood vessels. We hope to have some advantage there as well.
Yes. So I guess a summary of that would be that we're sort of targeting the AUC side of things rather than the Cmax that we achieve with antibodies because Cmax is more related to ARIA, and AUC is more related to efficacy. I would also say that we know the concentrations in spinal fluid we would have to achieve with both of those antibodies. And they're in the typical range, 0.1% to 0.5% brain-to-plasma ratio. So -- and then there's a lot of published information from animals as to what antibody concentrations are needed for removal of amyloid.
So the nice thing is this is a derisked program in many ways. We're going after a highly validated target. We have a lot of quantitative information that we can use for drug development. We understand the major side effects and thought about how to mitigate those. And that's the kind of thing that we like to go after, highly validated targets with efficient path to proof of concept.
Your next question comes from the line of Matthew Hershenhorn of Oppenheimer.
Congrats on all the progress. This is Matt on for Jay. So we were wondering if you had any thoughts following Biogen's acquisition of Reata, which obviously reflects a pretty high value for the Friedreich's ataxia opportunity. So how are you thinking about any differentiating factors for your FA gene therapy program, obviously, pros and cons potentially versus Skyclarys, which you have collaborated with Neurocrine? And any advantages as a potential later follower?
And then for Pete, if you could just please remind us any timing on the potential for milestones from that FA program, that would be very helpful.
I'll start, and I'll ask Pete to talk about the milestones. But yes, so I'm excited to see that Biogen acquired Reata. Reata's drug, bardoxolone, was the very first drug ever approved for FA. It shows evidence of disease modification in the sense that it slows the worsening. This was all published in Annals of Neurology, and I thought that the data were pretty convincing when I first saw that on the paper that was published. And so I think it's a breakthrough. And I'd love for us to also continue on that trend and make further progress.
I think that with FA, the complexity -- the slight complexity here is that it involves the central nervous system, but also the heart. And the Reata drug really targets the CNS side of things because the outcome measure that they looked at was more oriented towards neurological outcomes. And so obviously, this is a program that is in the hands of Neurocrine. It's their decision. But I -- it can't hurt to have regulatory precedents established by another company, outcome measures that work and that have been accepted by regulators.
And look, but here's -- we want to replace the gene. It's autosomal recessive. So the patients who have a disease basically aren't making frataxin. We need to replace frataxin in some way, well, and our approach, of course, is to use gene therapy. And you have to get the dose right here because too much frataxin is probably not good either. So this is all in the capable hands of our colleagues at Neurocrine, and I'll let them answer the question more specifically with respect to the program.
Matt, with regards to specific guidance on milestones associated with the FA program, which I think was the second part of your question. So what we've provided in the past is kind of a full summary of what the 2019 Neurocrine agreement looks like in terms of future milestones. The milestones, they're about $1.4 billion approximately. We have not guided or provided detailed guidance with regards to what the specific next milestones are on that program. But I do think what I would highlight, not just for Neurocrine, but also for some of our other partnerships, we do have a number of milestones that potentially could come due in the next couple of years here on all those partnerships.
As Al alluded to earlier, we've got 11 partnered programs now, 7 with Neurocrine alone, 3 in the original 2019 agreement, which includes FA. Those milestones have not been factored into our cash runway as of yet and potentially could benefit us greatly as we move forward here. So that would be what I would say with regards to that.
And our next question comes from the line of Ross Fladeland of Canaccord Genuity.
Ross on for Sumant Kulkarni. I had a question in regards to the antibiotic programs that you have going on. Given that you now have an anti-tau antibody and also vectorized anti-tau antibody program, what does this mean in context for prioritizing spend levels on relatively expensive Alzheimer's programs versus the other programs in your pipeline?
Yes. Thanks for the question. So actually, we do -- we do not have a vectorized antibody against tau program. We have essentially a passive intravenously administered antibody, monoclonal antibody, not vectorized. After we achieve proof of biology, hopefully, we will achieve that. And if we do, we have the choice then of moving forward with either continuing with the passive antibody or going to vectorization. So that's -- so I just wanted to clarify that.
And the whole approach here is to choose programs where we can get proof of biology very efficiently. For example, the antibody, the tau, we think we can do a proof of biology experiment in humans with about 25 patients per dose group in a 1-year study. And with tau PET imaging, we think we can determine whether we block the spread of pathological tau. And so we like that because it's a rapid path to derisking and proof of biology.
And then after that, as I said, we have a choice of vectorizing or not. I hope that clarifies or answers your question.
And presenters, there are no further questions at this time. I would now like to turn the conference back to you for closing remarks.
Well, thank you very much for all the great questions. And if you have any further questions, obviously, we're ready to -- please call us, and we'll do our best to answer them. But thank you very much for your interest in Voyager.
Thank you, presenters. And this concludes today's conference call. Thank you for participating, and you may now disconnect. Have a good day.