Voyager Therapeutics Q3 2024 Earnings Call Transcript

Quartr
Provided by Quartr
November 12, 2024

Key Takeaways

  • Voyager’s anti-tau antibody program VY7523 has completed single ascending dose dosing in healthy volunteers, with top-line safety and PK data expected in H1 2025, a multiple ascending dose trial in early Alzheimer’s patients next year, and initial tau PET imaging data in H2 2026.
  • Third-party data on propranumab showed a 33–58% reduction in pathological tau accumulation and a 21–25% slowing of cognitive decline, reinforcing confidence that antibodies targeting the appropriate tau epitope can meaningfully impact Alzheimer’s disease progression.
  • The tau silencing gene therapy program, which uses an IV-administered tracer capsid carrying tau-targeted siRNA, has demonstrated robust reductions in tau mRNA and protein in preclinical models and remains on track for U.S. IND and Health Canada CTA filings in 2026.
  • Voyager’s industry-leading tracer platform for discovering novel AAV capsids underpins all 4 wholly owned and 14 partnered CNS gene therapy programs, with INDs for three new capsid-mediated therapies expected next year.
  • With $345 million in cash at end-Q3 (excluding October milestone payments from Novartis and Neurocrine) and blue-chip partnerships with Neurocrine, Novartis, and Alexion, Voyager’s financial runway extends into 2027 to support multiple upcoming clinical milestones.
AI Generated. May Contain Errors.
Earnings Conference Call
Voyager Therapeutics Q3 2024
00:00 / 00:00

Transcript Sections

Skip to Participants
Operator

Good afternoon, and welcome to the Voyager Therapeutics third quarter 2024 financial results conference call. At this time, all participants are in a listen-only mode. There will be a question-and-answer session at the end of this call. Please note that today's call is being recorded. A replay of today's call will be available on the investor section of the company website approximately two hours after completion of this call. I would now like to turn the call over to Trista Morrison, Chief Corporate Affairs Officer at Voyager.

Trista Morrison
Trista Morrison
Chief Corporate Affairs Officer at Voyager Therapeutics

Thank you, and good afternoon. We issued our third quarter 2024 financial results press release this afternoon. The press release and 10-Q are available on our website. Joining me on today's call are Dr. Al Sandrock, our Chief Executive Officer, Dr. Toby Ferguson, our Chief Medical Officer, and Dr. Todd Carter, our Chief Scientific Officer. We will also be joined for the Q&A portion of the call by Nathan Jorgensen, our Chief Financial Officer. Before we get started, I would like to remind everyone that during this call, Voyager representatives may make forward-looking statements as noted in Slide 2 of today's deck. These statements are based on our current expectations and beliefs. They are subject to risks and uncertainties, and our actual results may differ materially. I encourage you to consult the risk factors discussed in our SEC filings, which are available on our website for additional detail.

Trista Morrison
Trista Morrison
Chief Corporate Affairs Officer at Voyager Therapeutics

Now, I will turn the call over to Al.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Good afternoon, everyone, and thank you for joining us. Please turn to Slide 3. At Voyager, we are leveraging the power of human genetics to discover and deliver transformative medicines that address the root cause of neurological diseases. Our four pillars of value include: first, our pipeline of four wholly owned and 14 partnered programs. During the third quarter, we completed enrollment and dosing in the single ascending dose trial of VY7523, our anti-Tau antibody for Alzheimer's disease. We also recently saw encouraging third-party clinical data with another anti-Tau antibody for Alzheimer's disease, which Toby will talk about shortly. Our second pillar of value is our industry-leading TRACER platform for the discovery of novel AAV capsids to enable CNS gene therapy. These IV-delivered CNS-targeted capsids underlie all of our wholly owned and partnered gene therapy programs, and we expect INDs for three of these programs next year.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Third, we have blue-chip partnerships with some of the world's experts in neurology and gene therapy, including Neurocrine, Novartis, and Alexion. We continue to progress these partnerships through the third quarter, with Novartis signing on for a fifth program partnership and Neurocrine nominating a third development candidate. Finally, we continue to explore the potential to leverage receptors we have identified to shuttle non-viral genetic medicines into the brain. Ultimately, we aim to expand from gene therapy and antibodies into other modalities of neurogenetic medicine, broadening our impact. With that, I'll turn the call over to Toby to talk more about our anti-Tau antibody and some of the recent third-party data in the space.

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

Thanks, Al, and good afternoon. Please turn to Slide 4. This slide summarizes the four wholly owned programs and 14 partner programs that Al mentioned earlier. Today, we are going to focus on our Tau targeting programs for Alzheimer's disease. Turning to Slide 5, the point I want to make here is that we view Tau as a critically important target for the treatment of Alzheimer's disease. As you can see in the image on the left of this slide, the spread of pathological Tau, as identified on Tau PET imaging, correlates closely to Alzheimer's disease progression as measured by Braak clinical pathologic staging. Additionally, exploratory clinical data from Biogen's BIIB080 Tau knockdown program showed a reduction in pathological Tau, as well as potentially greater slowing of clinical disease progression than seen with anti-amyloid antibodies.

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

In short, we think targeting Tau has the potential to impact Alzheimer's disease progression and do so in a significant way. This is why Voyager is pursuing two approaches to targeting Tau: our anti-Tau antibody VY7523 and our Tau silencing gene therapy. On Slide 6, I want to highlight how the team selected our anti-Tau antibody. We started with more than 700 antibodies across the mid-domain and C-terminus of Tau. We first focused on antibodies targeting pathological Tau. This was important with the anti-amyloid antibodies. Several that failed, such as solanezumab or bapineuzumab, were shown to have insufficient target engagement with aggregated forms of amyloid beta, while the approved anti-amyloid antibodies all target the aggregated species. We narrowed the funnel through further in vitro and in vivo studies. We evaluated antibodies targeting various epitopes across Tau, including in the mid-domain and the C-terminus.

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

In a mouse seed model of human pathological Tau spread, the C-terminal targeted antibody AB01, the murine version of VY7523, decreased the spread of injected pathological human Tau by approximately 70%. Based on these data and the specificity for pathological Tau, we selected VY7523 as our clinical candidate. We also conducted a series of head-to-head studies in the same model against other anti-Tau antibodies. These data are summarized on Slide 7. In the first head-to-head study, we evaluated murine 7523 against murine versions of Biogen's gosuranemab and Lilly's zagotenemab. These antibodies both targeted the N-terminus of Tau and both failed their primary endpoints in clinical trials. Both were ineffective at reducing Tau spread in the model, while our C-terminal targeted antibody again blocked Tau spread. This gave us confidence that the model had negative predictive value.

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

In the second head-to-head study, we compared our C-terminal targeted antibody to UCB's bepranemab, which targets the mid-domain. In our models, both antibodies inhibited Tau spread. Based on these data, we were eager to see the results from the bepranemab clinical trial because we thought that if this antibody could impact Tau in a clinical trial, then our model might also have positive predictive value. Turning to Slide 8, I want to summarize the recent bepranemab data shared at the 2024 CTAD meeting. I want to start by noting that the primary endpoint, CDR Sum of Boxes, was not met in the full study population. This is important to acknowledge. Now, I would like to note that bepranemab inhibited the accumulation of Tau in the human brain by 33%-58%.

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

We saw this as establishing that an antibody can be used to inhibit the spread of pathological Tau in the brain. This finding should not be underestimated, as I think that after the failure of the N-terminal anti-Tau antibodies, there was uncertainty in the industry as to whether an antibody approach could impact Tau accumulation. As it turns out, it can. I also want to note that bepranemab slowed cognitive decline by 21%-25% versus placebo per ADAS-Cog14. Additionally, in subgroup analyses, it seems that patients with the greatest reduction in Tau burden had more consistent clinical benefit, although we will need to see more detailed PK/PD and PD clinical correlation analyses. Finally, bepranemab demonstrated an acceptable safety profile with brain hemorrhagic and inflammatory changes similar to placebo. What does this mean for Voyager's VY7523?

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

I would say that these data give us increasing confidence that an antibody targeting the appropriate epitope of Tau can slow the accumulation of Tau in the brain of Alzheimer's patients and that this slowing may offer a clinically significant benefit in some patients. This was a top-line data presentation, and there is certainly more work to be done here, and we look forward to seeing the additional data. Slide 9 provides an overview of our phase I clinical development plan for VY7523. During the third quarter, we completed enrollment and dosing of healthy volunteers in our single ascending dose trial. We expect to report top-line safety and pharmacokinetic data in the first half of next year. We expect to initiate a multiple ascending dose trial in patients with early Alzheimer's disease next year and generate initial Tau PET imaging data in the second half of 2026.

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

At this point, we don't see anything in the bepranemab data that would shift our thinking here. If anything, the data reaffirm that Tau PET imaging is the critical outcome we want to focus on, and we have planned a very efficient trial focused on that outcome. We found the safety profile of bepranemab encouraging and look forward to exploring the full range of dosing possibilities. I mentioned earlier that we are advancing two approaches to targeting Tau for Alzheimer's disease. We focused a lot on the antibody approach today in light of the recent third-party data, but I will now turn the call over to Todd to touch on our other approach.

Todd Carter
Todd Carter
Chief Scientific Officer at Voyager Therapeutics

Thanks, Toby. Please turn to Slide 10. In addition to our antibody-based approach, we are also advancing the Tau silencing gene therapy program. This program deploys a Tau-targeted siRNA packaged in an IV-administered TRACER capsid. Using this approach, we have demonstrated robust reductions in human Tau from RNA and protein across the brain following a single IV administration in mice that express human Tau, as shown on this slide. It is also important to note that the recent BIIB080 data that Toby mentioned showed that reducing Tau expression was associated with favorable trends on clinical outcomes and pathological Tau as measured by PET imaging. We view these data as supportive for a knockdown approach and believe that a one-time IV gene therapy could provide benefits over repeated intrathecal therapy. This program remains on track for U.S. IND and Health Canada CTA filings in 2026.

Todd Carter
Todd Carter
Chief Scientific Officer at Voyager Therapeutics

I will now turn the call back over to Al.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Thanks, Todd. As you can see on Slide 11, Voyager continues to deliver on expectations for 2024. We have advanced our pipeline, our platform, and our partnerships. Our strong cash position of $345 million at the end of the third quarter is expected to provide runway into 2027, enabling multiple data readouts. This cash figure doesn't include the recent payments from Novartis or Neurocrine, which were received in October, nor does it contemplate any future potential milestones from our 14 partnered programs. With a robust slate of clinical milestones expected into the next 12 to 24 months, a maturing partnership portfolio with top-tier collaborators, and cash runway into 2027, we believe Voyager is poised to drive significant value creation over both the near and long term. Finally, I'd like to thank all of our employees for their hard work and dedication to improving the lives of patients.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

With that, we will open the call for questions. Operator?

Operator

Thank you. At this time, we will conduct the question-and-answer session. As a reminder, to ask a question, you will need to press star one one on your telephone and wait for your name to be announced. To withdraw your question, please press star one one again. Please stand by while we compile the Q&A roster. Our first question comes from Phil Nadeau at TD Cowen.

Phil Nadeau
Phil Nadeau
Managing Director and Senior Research Analyst at TD Cowen

Good afternoon. Thanks for taking our questions and congrats on the progress. I guess first, a follow-up to your comments on the Tau PET imaging. We're curious whether you have more insight as to how to translate the Tau PET imaging results like we saw from Roche UCB into cognitive improvements. Any additional thoughts now that you've had a bit more time to let the CTAD data set in? Do you think it's a question of selecting the right patients, selecting the right endpoint? Any thoughts on how to get that Tau PET imaging data to translate into a clinical improvement and cognitive benefits?

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

Maybe I'll start that question. This is Toby. I think fundamentally, I think I'll reemphasize the point that the Tau PET imaging, we saw clear data in the whole population that you did not slow the accumulation of Tau. And then I think the other point I'd make is that when you looked in some of the other populations, particularly the lower Tau populations, you saw perhaps a slightly greater lessening of accumulation in that context. So I do think as we move forward, really understanding the population will be critical in terms of perhaps Tau burden, which seems to be the main point. And then I think the other point, I think, is we'll look forward to understanding the full dose response in terms of sort of the Tau reduction in the context of PK/PD. We look forward to that data from UCB moving forward.

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

I think those are my initial thoughts.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

I would just add that this relationship between Tau PET effects and disease effects on clinical outcomes are agnostic to the drug or to the approach, right? There are more than one drug targeting Tau. Over the next couple of years, I think we'll learn this relationship better, what degree of Tau PET imaging translates to what clinical outcome. I agree with Toby that selecting the right patients, particularly with respect to Tau burden, for example, may be very important.

Phil Nadeau
Phil Nadeau
Managing Director and Senior Research Analyst at TD Cowen

Perfect. That's helpful. And then a follow-up on the SOD1 silencing gene therapy for ALS. You note in the press release in your prepared remarks that the initial trial could generate proof of concept based on biomarkers. Is that something that we could possibly see in 2026? Is that something that's within 12 months of the U.S. IND?

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

We haven't guided to timing of the biomarker results. The points I can make is that, one, we'll go into the SOD1 population, of course, and two, we'll start in at doses we think are potentially efficacious given the severity of the disease. In that context, we do think results would be reasonably forthcoming.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Maybe I could add that certainly in the case of the first clinical development plan and the trials that have been published in the New England Journal, you can start to see effects on SOD1 levels in spinal fluid in about, is it 12 weeks?

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

About 12 weeks.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Toby, yeah. And then effects on plasma neurofilament, which is a surrogate outcome that's reasonably likely to predict clinical outcomes and was the basis of approval by FDA of tofersen. That measurement should also yield data in the first, say, six months or so. So if that's any precedent, that gives you an idea of the timing that it takes to see both biological effect and the outcomes on clinically relevant surrogate outcomes like NfL.

Phil Nadeau
Phil Nadeau
Managing Director and Senior Research Analyst at TD Cowen

That's very helpful. And last question, a coming question from us. The $15 million from Novartis and $3 million from Neurocrine, how will those be booked? Are those going to be booked in the fourth quarter of this year, or will they be spread out over the life of those agreements?

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

It will be booked in the fourth quarter.

Phil Nadeau
Phil Nadeau
Managing Director and Senior Research Analyst at TD Cowen

Perfect. Thanks for taking our questions. Congrats again on the progress.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Thanks, Phil.

Operator

Our next question comes from Jack Allen at Baird.

Jack Allen
Jack Allen
Senior Research Analyst at Baird

Great. Thanks so much for taking the questions and congrats on the progress. I wanted to ask about an aspect of the Voyager story that's more in its infancy and that being the blood-brain shuttle programs. I was hoping you could just provide some context as to where those programs sit and when you maybe could look to bring an asset into the clinic. I know there's been a lot of activity in the space with AbbVie's acquisition of Aliada and then also Roche providing some initial proof of concept data from their beta amyloid asset there as well.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Jack, I'll start and I'll ask Todd to provide more color, but I would say that we're very excited about the potential of leveraging the receptors we identify through our capsids to shuttle other sort of macromolecules across the BBB. And as you pointed out, the data with trontinemab, which leverages a transferrin receptor, is looking very promising as an approach to get anti-amyloid antibodies into the brain. And so we're very excited about that. We're still in the preclinical stages. We're not close enough to the clinic yet to guide on when we would enter the clinic. Todd, do you want to provide more color on that?

Todd Carter
Todd Carter
Chief Scientific Officer at Voyager Therapeutics

Thanks, Al. So, Jack, as you do point out, we are excited by it. We know that these receptors, and we do have different receptors in different capsid families, they can mediate transcytosis or delivery across the blood-brain barrier for a large molecule, the AAV capsid. So there's reason to believe that they should be able to deliver other things. Hopefully, in the future, we'll be able to hear data on that. I think the other aspect is that we're seeing with receptors such as transferrin that there's the opportunity for additional receptors to have an impact because we expect that each receptor could have its own profile, both for pharmacokinetics and safety, that could really give an opportunity for different receptors for different diseases and indications.

Jack Allen
Jack Allen
Senior Research Analyst at Baird

Great. That's great context. Maybe just one brief follow-up. You've been incredibly successful in partnering your gene therapy library of capsids, even in the context of using preclinical assets. Any comments as it relates to potential partnerships around the blood-brain shuttle programs and something you have an appetite for before moving this into the clinic?

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Jack, this is Al. Yeah, I mean, I'm always interested and willing to talk to potential partners. This is exactly the kind of thing where there could be expertise in other companies that could really be very complementary to our shuttle program. Always open to talking to potential partners about these kinds of things and really accelerate the program.

Jack Allen
Jack Allen
Senior Research Analyst at Baird

Great. Thanks so much.

Operator

Our next question comes from Joon Lee at Truist Securities.

Joon Lee
Joon Lee
Managing Director and Senior Biotech Analyst at Truist Securities

Hey, congrats on the progress, and thanks for taking our questions. Your plans for 7523 MAD study in 2025 imply that you may be maybe seeing something positive in SAD study, or am I being too liberal with my interpretation? And for the SAD study due in first half of 2025, in addition to safety, what are you tracking that could give us some incremental conviction on the drug? Thank you.

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

Thanks, Toby, thank you for the question. Just to remind, the SAD study is in healthy volunteers, and so really the data we're looking for from the SAD study is PK, initial immunogenicity, and do we have the appropriate exposures to pick doses for the MAD study and some initial read on safety, so really it's not in patients, and that's the key point.

Operator

Our next question comes from Jay Olson at Oppenheimer.

Jay Olson
Jay Olson
Managing Director and Senior Analyst at Oppenheimer

Oh, hey, congrats on the progress, and thanks for providing this update. We have a few questions. Based on the bepranemab data that you saw, what's your latest thinking on the potential read across to your own 7523 program? And is there any additional data from UCB that you would be interested in seeing? And then I have a follow-up.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Look, I think, you know, Jay, this is Al. I mean, this is the first time we've seen that an antibody could have biological effects in the brain in humans, right? And so I look on that as positive, right, that an antibody approach could affect the biology of how spreading in the brain. Even before we knew about the bepranemab data, we did say that there could be read-through because we had tested the UCB antibody, which binds to a mid-domain region, versus our antibody, which binds to the C-terminal region in an animal where we look at the spread of pathological Tau in a mouse expressing human Tau, where we inject pathological Tau from Alzheimer's brains into the animal.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

We said before the CTAD, before we knew anything about the bepranemab data, that the UCB antibody was pretty comparable to our antibody in blocking the spread and actually distinguishable from the N-terminal-directed antibodies that did not block the spread in that same model and which also failed in the clinic. So you know, and so we still believe that there could be read-through. And we also expect that the safety perhaps would also be similar in the sense that the antibody is binding to extracellular Tau. I would say the other differentiating feature of our antibody relative to the UCB antibody is the fact that our antibody is specific for pathological forms of Tau. We don't know how important that is. We'll find out, but that is another distinguishing feature. So that's where we stand, Jay. Todd, do you want to add anything?

Todd Carter
Todd Carter
Chief Scientific Officer at Voyager Therapeutics

I agree with everything you said, Al. The other thing to mention, there was a question about additional data from UCB, and I think it will be important for us to see what additional data come out on some of the PK and PD, that PK/PD relationship. As Al has pointed out, the relationship between reduction of Tau accumulation and potential cognitive benefit that it appears is pretty interesting, and we see that as very encouraging. Those are in some groups. I think seeing more detail about target engagement and that relationship will really be important to interpret the results.

Jay Olson
Jay Olson
Managing Director and Senior Analyst at Oppenheimer

Great. That's great. Thank you for that. And then maybe just as a follow-on, how are you thinking about prioritizing VY7523 versus your Tau silencing gene therapy and then the potential for combining either of your anti-Tau approaches with anti-amyloid antibodies?

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

I would say that they're both high priorities. Am I allowed to say that two things are both high priorities?

Jay Olson
Jay Olson
Managing Director and Senior Analyst at Oppenheimer

Yes.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

You know, look, we've always said that Tau was a pretty very important target, that we think it's the next step in helping Alzheimer's patients, that the anti-amyloid treatments got us started, but we need to do better for patients, and so I think they're both high priorities. They're very different approaches in many ways, and so we'll find out which is the better approach. In terms of combining with the anti-amyloid antibodies, I do think that there could be a place for combining. I would say that it would be in those patients that seem to have a partial response to the anti-amyloid antibodies. If they have no response to the anti-amyloid antibodies, there's no sense in continuing the drug.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

If they've had a full response to anti-amyloid antibodies, which may be the case in some patients, if you're not progressing at all in your disease on anti-amyloid antibodies, there'd be no reason to add anything else. So I think time will help us. Time will tell what the heterogeneity of the treatment response is to the anti-amyloid antibody therapies in humans as we see the drugs being rolled out. And then by the time we're ready to think about that combination approach, I think we'll have more data on how many patients respond fully, how many respond not at all, and how many respond partially. But I would say that we would want data initially as monotherapy too first to see that make sure that our drug is active and then have some understanding of the doses that we would want to use.

Jay Olson
Jay Olson
Managing Director and Senior Analyst at Oppenheimer

Great. Thanks so much for taking all the questions.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

You're welcome, Jay.

Operator

Our next question comes from Lili Nsongo at Leerink.

Lili Nsongo
Lili Nsongo
Analyst at Leerink

Hi, good afternoon, and thank you for taking our question. So I guess two questions for me. So the first one, as we await for in-patient data, so in 2026, for the Tau-targeted antibody, are there any plans to potentially test previously developed C-terminal antibodies in preclinical models to try to further confirm the negative predictive value of the model you use in a more region-specific approach?

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

If there's another antibody that's negative, I think that would be a pretty interesting study to do, particularly if it's not N-terminal, right? So I'm not sure doing any more N-terminal-directed antibodies would add much, but if there's an antibody targeting a different epitope that fails, then it might be interesting to do that experiment that you're proposing, Lili.

Lili Nsongo
Lili Nsongo
Analyst at Leerink

Yeah, because it was my understanding that both Hoffmann-La Roche and then Lundbeck had some C-terminal antibody. I think it could be really interesting preclinical data as we await. I guess maybe segue into my second question. So regarding the UCB data and the challenges that they've had in the overall population, would that compel you to potentially start the development in patients in maybe a smaller, more targeted patient population? So I guess my question is, does the result of the study compel you to maybe have more stringent inclusion criteria in the initial in-patients study for the antibody?

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Yeah, hi, Lili, this is Al, and I'll start, and I'll ask Toby to add his comments, but I would say that we would be very open to that idea. We would like to see if we can differentiate from the bepranemab, if at all possible, and it could be that the choice of patient population could be a way to boost the efficacy that we see, particularly on the clinical outcome measures, right, and get more clarity. As Toby noted in his comments, there were subgroups, particularly those that were pre-specified. I think it was the APOE4 non-carrier, low Tau burden patients who seemed to do better, and those were exactly the patients where the effect on Tau accumulation was more pronounced, so I'd be open to that. Even though it's a smaller population, we're talking about a gigantic population overall, the Alzheimer's disease patients.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

And to have a targeted treatment for a smaller population that's still quite large, by the way, would be of interest. Toby?

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

So I think Al, you captured it nicely. I think the only other comment I'd make is that when we did look at the bepranemab data, they had segregated their low and high Tau populations. There really weren't that many low Tau patients in the study overall, about an 80/20 ratio approximately. And so I think more data there, that is suggestive data, but we want to see sort of the breakdown of those data.

Lili Nsongo
Lili Nsongo
Analyst at Leerink

Thank you. And maybe just a follow-up. So we will be waiting for initial safety and PK data in healthy volunteers in the first half of 2025. But I was wondering maybe if you could give a little more granularity in terms of when we should expect an update on the potential design of the in-patient study?

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

I think she's interested in the design of the multiple ascending dose study.

Lili Nsongo
Lili Nsongo
Analyst at Leerink

Yes, exactly.

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

Thanks, Lili. So I think as we get closer to the start, which we're going to start next year, we'll share the details of the design.

Lili Nsongo
Lili Nsongo
Analyst at Leerink

Thank you.

Operator

Our next question comes from Patrick Trujillo at H.C. Wainwright & Co.

Patrick Trujillo
Patrick Trujillo
Associate Analyst at H.C. Wainwright

Good afternoon. Thanks very much. Just a couple of questions for me. The first is just a follow-up on the earlier comment regarding the appropriate patient population for the Tau program, for the antibody program. Can you discuss what level of Tau PET burden do you think could be appropriate at baseline based on these learnings from this recent data, and particularly as we approach the phase I-B trial with VY7523? And then separately, as we think about or as we look ahead to the Tau silencing gene therapy, I'm wondering if you can talk about the advantages or differences we should expect from the Tau silencing gene therapy as compared to these Tau targeting antibodies. And then secondly, what remains to be completed to ensure that the 2026 IND and CTA filings remain on track for the Tau silencing gene therapy?

Patrick Trujillo
Patrick Trujillo
Associate Analyst at H.C. Wainwright

And then lastly, if you could just talk about the anticipated capsid and advantages of the Voyager platform as compared to some of these others in the field developing a similar approach?

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Wow, that's a lot of questions, Patrick, but we'll knock them off one by one here. So I'll take the first one, and then maybe Toby can take the second, and Todd, you can take the third one. But anyway, on the appropriate patients, the cutoff that UCB shared data with us was a pre-specified cutoff, but it was not the median. You know, in fact, there were many fewer patients, I think, in the low Tau burden subgroup versus the high Tau. I think that was because it was pre-specified. Hopefully, we'll see more data on the full range of Tau burden and to understand better what the cutoff needs to be. And so right now, I mean, all we have is that one piece of data to go on. I think we would need more to be more specific about the Tau burden.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Toby, you can let me know if you disagree with that.

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

I do not, Al.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Okay. And then on the Tau KD, I think you were asking how do we make sure that we stay like we'll be on track. And so maybe Toby and Todd, do you want to help me with those questions?

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

Sure, maybe I'll start and ask Todd to fill in. So the preclinical development is proceeding. I think the key next steps are sort of moving them all through forward, and then, of course, I think the pivotal step will be doing the toxicology studies.

Todd Carter
Todd Carter
Chief Scientific Officer at Voyager Therapeutics

Right. Standard IND enabling studies would be part of the whole process. You also asked about differentiation for the Tau knockdown versus the antibody approach, I believe, and I think the BIIB080 data, which is an ASO delivered that has shown some really interesting clinical data to date versus the antibody approaches. What was seen in the BIIB080 data are not only signs that you could reduce the accumulation of Tau, but you may be able to reduce pathological Tau burden as measured by PET, in some cases below starting burden, which is a pretty remarkable finding. When you look at those sorts of data, and even with the recent bepranemab data that also seem to suggest that an impact on Tau PET imaging results can impact clinically, I think there is accumulating evidence in the field that impacting Tau accumulation can have a clinical benefit.

Todd Carter
Todd Carter
Chief Scientific Officer at Voyager Therapeutics

With the gene therapy approach, of course, here we're talking about a once-and-done approach. We can dose once. We know that our vectors, and this gets into a little bit of the Voyager platform question as well, that our capsids can deliver quite broadly throughout the CNS. We can get delivery not only to the, I'll call it the shallower regions of the brain, but also the deeper structures with that single dose, and so we think there could be some substantial benefits for a Tau knockdown approach. It is also an intracellular effect. The antibody has an impact, presumably based on the prion-spreading hypothesis, as the pathological Tau spreads from cell to cell. So an intracellular reduction of Tau could have an impact not only in reducing that cell-to-cell spread, but also in an intracellular way, so those two approaches, I think, are both interesting.

Todd Carter
Todd Carter
Chief Scientific Officer at Voyager Therapeutics

There are signs for both those mechanisms that they could work, and in the end, it's even possible there could be combination approaches.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

So Toby, do you want to add on potential clinical outcomes?

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

I think the BIIB080 data in particular really emphasized, along with the recent bepranemab data, the importance of Tau PET. To Todd's prior point, in the BIIB080 knockdown-based approach or a knockdown-based approach, you can see the removal of both pre-existing pathological Tau and prevention of further accumulation in somewhat earlier timeframe, six months or so, which is distinct from slowing accumulation. This is particular to the Tau knockdown approach. In addition, you can also see clear signals in the CSF biomarkers, total Tau, for example, and other Tau species. There is a chance based on biomarkers to get a relatively quick read on how the molecule is performing.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

What about the, do you think the effect size? I mean, it's hard, right?

Toby Ferguson
Toby Ferguson
Chief Medical Officer at Voyager Therapeutics

It's early data. I mean, if you look at the propensity score matching that Biogen performed, they looked at a comparison to another study called TANGO, and they looked at a natural history study, and there, that effect size was 2.0-2.5 points on CDR Sum of Boxes. As a reminder, the effects on the amyloid therapies were 0.4-0.9 points approximately on CDR Sum of Boxes, so potentially larger effect size as well, which gives you an additional opportunity to potentially see a clinical signal with smaller sample size.

Patrick Trujillo
Patrick Trujillo
Associate Analyst at H.C. Wainwright

Great. Very helpful. Thanks so much.

Operator

I'm showing no further questions at this time. I would now like to turn it back to Al for closing remarks.

Al Sandrock
Al Sandrock
CEO at Voyager Therapeutics

Thank you, everyone, for joining us today, and we look forward to speaking with you again soon.

Operator

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

Executives
    • Trista Morrison
      Trista Morrison
      Chief Corporate Affairs Officer
    • Al Sandrock
      Al Sandrock
      CEO
    • Todd Carter
      Todd Carter
      Chief Scientific Officer
    • Toby Ferguson
      Toby Ferguson
      Chief Medical Officer
Analysts
    • Jay Olson
      Managing Director and Senior Analyst at Oppenheimer
    • Jack Allen
      Senior Research Analyst at Baird
    • Patrick Trujillo
      Associate Analyst at H.C. Wainwright
    • Lili Nsongo
      Analyst at Leerink
    • Phil Nadeau
      Managing Director and Senior Research Analyst at TD Cowen
    • Joon Lee
      Managing Director and Senior Biotech Analyst at Truist Securities
Powered by Quartr