Q3 2024 Voyager Therapeutics Inc Earnings Call
The New Year's Eve, [inaudible]
Thank you for watching!
Speaker Change: Good afternoon and welcome to the Voyager Therapeutics Third Quarter 2024 Financial Results Conference Call.
Speaker Change: At this time, our participants are in a listen-only mode. There will be a question and answer session at the end of this call.
Speaker Change: Please note that today's call is being recorded. A replay of today's call will be available on the investors section of the company website approximately two hours after completion of this call.
Speaker Change: I would now like to turn the call over to Trista Morrison, Chief Corporate Affairs Officer at Voyager.
Trista Morrison: 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.
Trista Morrison: Joining me on today's call are Dr. Alex Sandrock, our Chief Executive Officer, Dr. Toby Ferguson, our Chief Medical Officer, and Dr. Todd Carter, our Chief Scientific Officer.
Trista Morrison: We will also be joined for the Q&A portion of the call by Nathan Jorgensen, our Chief Financial Officer.
Trista Morrison: 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.
Trista Morrison: 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.
Now, I will turn the call over to Al.
Good afternoon, everyone, and thank you for joining us.
Please turn to slide 3.
Trista Morrison: At Voyager, we are leveraging the power of human genetics to discover and deliver transformative medicines that address the root cause of neurological diseases.
Trista Morrison: Our four pillars of value include, first, our pipeline of four wholly owned and 14 partnered programs.
Trista Morrison: 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.
Trista Morrison: We also recently saw encouraging third-party clinical data with another anti-Tau antibody for Alzheimer's disease, which Toby will talk about shortly.
Trista Morrison: Our second pillar of value is our industry leading tracer platform for the discovery of novel AAV capsids to enable CNS gene therapy.
Trista Morrison: 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.
Trista Morrison: Third, we have blue-chip partnerships with some of the world's experts in neurology and gene therapy, including Neuroquin, Novartis, and Nalexion.
Trista Morrison: We continue to progress these partnerships through the third quarter, with Novartis signing on for a fifth program partnership, and NeuroQuinn nominating a third development candidate.
Trista Morrison: Finally, we continue to explore the potential to leverage receptors we have identified to shuttle non-viral genetic medicines into the brain.
Trista Morrison: Ultimately, we aim to expand from gene therapy and antibodies into other modalities of neurogenetic medicine, broadening our impact.
Speaker Change: 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: Thanks Al, and good afternoon. Please turn to slide four. This slide summarizes the four wholly owned programs and 14 partner programs that Al mentioned earlier. Today we are going to focus on our TAO targeting programs for Alzheimer's disease.
Toby Ferguson: 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.
Toby Ferguson: As you can see in the image on the left of this slide, the spread of pathological Tau as identified on TauPAD imaging correlates closely to Alzheimer's disease progression as measured by Brock Clinical Pathologic Staging.
Toby Ferguson: Additionally, exploratory clinical data from Biogen's Bib-Adi-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.
Speaker Change: So 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 VY-7523 and our Tau silencing gene therapy
Speaker Change: On slide 6, I want to highlight how the team selected our anti-tau antibody.
Speaker Change: We started with more than 700 antibodies across the mid-domain and C-terminus of tau.
Speaker Change: We first focused on antibodies targeting pathological Tau. This was important with the anti-amyloid antibodies. Several that failed, such as solanuzumab or bapinezumab, were shown to have insufficient target engagement with aggregated forms of amyloid beta, while the approved anti-amyloid antibodies all target the aggregated species.
Speaker Change: 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.
Speaker Change: In a mouse feeding 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%.
Speaker Change: Based on these data and the specificity for pathological tau, we selected VY7523 as our clinical candidate.
Speaker Change: We also conducted a series of head-to-head studies in this same model against other anti-tetal antibodies. These data are summarized on slide 7.
Speaker Change: In the first head-to-head study, we evaluated murine 7523 against murine versions of Biogen's gosoneuromab and Lilly's zafigenimab. These antibodies both targeted the N-terminus of tau and both failed their primary endpoints in clinical trials.
Speaker Change: 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.
Speaker Change: In the second head-to-head study, we compared our C-terminal-targeted antibody to UCB's Brannanopab.
Speaker Change: 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 Vopanoprab clinical trial because we thought that if this antibody could impact tau in a clinical trial, then our model might also have a positive predictive value.
Speaker Change: Turning to slide 8, I want to summarize the recent propranomap 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.
Okay.
Speaker Change: Now I would like to note that propranolamab inhibited the accumulation of tau in human brain by 33 to 58 percent.
Speaker Change: 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.
Speaker Change: As I think that after the failure of the N-terminal anti-tau antibodies, there was uncertainty in industry as to whether an antibody approach could impact tau accumulation. As it turns out, it can.
Speaker Change: I also want to note that propranomab slowed cognitive decline by 21-25% versus placebo per ADES-CoG-14.
Speaker Change: 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.
Speaker Change: Finally, Bupenimab demonstrated an acceptable safety profile, with brain hemorrhagic and inflammatory changes similar to placebo.
Speaker Change: What does this mean for Voyager's VY7523? 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.
Speaker Change: 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.
Speaker Change: Slide 9 provides an overview of our Phase 1 clinical development plan for VY 7523.
Speaker Change: During the third quarter, we completed enrollment and dosing of healthy volunteers in our single ascending dose trial.
Speaker Change: 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 TauPAT imaging data in the second half of 2026.
Speaker Change: At this point, we don't see anything in the BrandMap data that would shift our thinking here. If anything, the data reaffirmed that TalPET imaging is the critical outcome we want to focus on, and we have planned a very efficient trial focused on that outcome.
Speaker Change: We found the safety profile of Pranimab encouraging and look forward to exploring the full range of dosing possibilities.
Speaker Change: 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.
Thanks Toby. Please turn to slide 10.
Todd Carter: In addition to our antibody-based approach, we are also advancing the tau silencing gene therapy program.
Todd Carter: This program deploys a Tau-targeted siRNA packaged in an IV-administered tracer capsid.
Todd Carter: Using this approach, we have demonstrated robust reductions in human tau from RNA and protein across the brain following a single ID administration in mice that express human tau, as shown on this slide.
Todd Carter: It is also important to note that the recent BIM-80 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.
Todd Carter: We view these data as supporting for a knockdown approach and believe that a one-time IVE therapy could provide benefits over repeated intrathecal therapy.
Todd Carter: This program remained on track for USIAD and Health Canada CTA filings in 2026.
I will now turn the call back over to Al.
Thanks, Todd.
al: 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.
al: 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.
al: This cash figure doesn't include the recent payments from Novartis or Neuroquin, which were received in October, nor does it contemplate any future potential milestones from our 14 partnered programs.
al: With a robust slate of clinical milestones expected into the next 12 to 24 months.
al: 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.
al: Finally, I'd like to thank all of our employees for their hard work and dedication to improving the lives of patients.
With that, we will open the call for questions. Operator?
Speaker Change: 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 1 1 on your telephone and wait for your name to be announced. To withdraw your question please press star 1 1 again. Please stand by while we compile the Q&A roster.
Our first question comes from Phil Nando at TD Cohen.
Speaker Change: Good afternoon. Thanks for taking our questions and congrats on the progress. I guess first, a follow-up to your comments on the talpin imaging.
Speaker Change: We're curious whether you have more insight as to how to translate the Taupo imaging results like we saw from Rosh UCB into cognitive improvements and any additional thoughts now that you've had a bit more time.
Speaker Change: to let the MISTI-TED data set in. Do you think it's a question of selecting the right patients, selecting the right endpoint, and any thoughts on how to get that TauPED imaging data to translate into a...
Clinical Improvement and Cognitive Benefits.
Maybe I'll start. I'll start that question. This is Toby.
Speaker Change: So I think fundamentally, I think that I'll reemphasize the point that the, or the top of the imaging, we saw clear data in the whole population that you did not, you slow the accumulation of tau. And then I think the other point I'd make is that when you looked in.
Speaker Change: and some of the other populations, particularly the lower health populations.
Speaker Change: You saw perhaps a slightly greater lesson of accumulation in that context. So do you think as we move forward, really understanding the population will be critical?
Speaker Change: in the terms of perhaps Talberton, which seems to be the main point.
Speaker Change: And then I think the other point I think is we 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 UCD moving forward.
Speaker Change: I would just add that, you know, this relationship between cow-pet effects and disease effects on clinical outcomes.
Speaker Change: are agnostic to the drug or to the approach, right? So there are more than one, there's 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?
Speaker Change: And I agree with Toby that selecting the right patients, particularly with respect to child burden, for example, may be very important.
Speaker Change: Perfect, that's helpful. And then a follow-up on the side one silencing gene therapy for ALS.
Speaker Change: You note in the press release and in your prepared remarks that the initial trial could generate proof of concept based on biomarkers.
Speaker Change: Is that something that we could possibly see in 2026? Is that something that's within 12 months of the USIND?
Speaker Change: So we have it guided to timing of the biomarker results.
Speaker Change: The points I can make is that one, we'll go into the SOG1 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
Regionally portable.
Speaker Change: and maybe I could add that certainly in the case of the person clinical development plan and the trials that have been published in the New England Journal you can start to see effects
Toby Ferguson: on SOD1 levels in spinal fluid in about, is it 12 weeks? 12 weeks, Toby, yeah. And then effects on plasma neurofilament, which is a surrogate outcome that's reasonably likely to predict clinical outcomes.
Toby Ferguson: and was the basis of approval by FDA up to Ferguson, 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.
Speaker Change: That's very helpful. Last question, an accounting question from us. The $15 million from Novaris and $3 million from NeuroCurrent, 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?
Speaker Change: It will be booked in the fourth quarter. Perfect. Thanks for taking our questions. Congrats again on the progress.
Thank you. Thank you. Thank you.
Thanks, Phil.
Our next question comes from Jack Allen at Baird.
Speaker Change: 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.
Speaker Change: 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 Abby's acquisition of Aliada and then also Roche providing some initial proof of concept data from their beta amyloid asset there as well.
to shuttle other sort of macromolecules across the BBB.
Speaker Change: And as you pointed out, you know, Trontinumab, the data with Trontinumab.
which leverages transferrin receptors, looking very promising.
Speaker Change: As an approach to get anti amyloid antibodies into the brain. And so we're very excited about that. We're still in the.
Todd Carter: preclinical stages. We haven't been, 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? Thanks, Al. So, Jack, as you do point out, we are excited by it. We know that these receptors, and we do have...
Todd Carter: different receptors in different capsid families that can mediate transcytosis 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.
Speaker Change: Hopefully in the future we'll be able to hear data on that. I think the other aspect is that we're seeing with
Speaker Change: 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.
Speaker Change: Great, that's great context. Maybe just one brief follow-up. You've been incredibly successful in partnering your gene therapy library of capsids.
Speaker Change: 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?
Speaker Change: Well, 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.
Speaker Change: to our shuttle program. So I'm always open to talking to potential partners about these kinds of things and really accelerate the program.
Great, thanks so much.
Thank you.
Our next question comes from June Lee at Truist Securities.
Speaker Change: Hey, congrats on the progress and thanks for taking our questions. Your plans for 7523 match study in 2025 imply that you may be
Speaker Change: May be 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 25, in addition to safety, what are you tracking that could give us some incremental conviction on the drug? Thank you.
Toby Ferguson: This is Toby. Thanks for the question. Just a reminder, the SAD Study is in Healthy Volunteers.
Toby Ferguson: And so really the data we're looking from the SAD study is PK, initial immunogenicity, and do we have the appropriate exposures to pick doses for the MAT study and some initial read-on safety. So really it's not in patients, and that's the key point.
Our next question comes from Jay Olson at Oppenheimer.
Jay Olson: Oh, hey, congrats on the progress and thanks for providing this update. We have a few questions.
Jay Olson: Based on the ParanetMap 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.
Jay Olson: Well, 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 that's, I look on that as positive, right? That an antibody approach could
Jay Olson: affect the biology of how spreading in the brain? We even before we knew about the Pranibat data, we did say that there could be read through because we had tested the UCB antibody, which
Jay Olson: binds to a mid-domain region versus our antibody which binds to the c-terminal region in an animal where we look for this we look at the spread of pathological tau
and a mouse expressing human tau where we inject
pathological tau from Alzheimer's brains into the animal.
Jay Olson: And we said before the CTAD, before we knew anything about the BRCANABAT data, that the UCB antibody was pretty comparable.
Jay Olson: to our antibody and 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.
Jay Olson: So, you know, and so we still believe that that there could be read through.
Jay Olson: And we also expect that the safety perhaps would also be similar in the sense that, you know, the antibody is binding.
Jay Olson: to extracellular tau. I would say the other differentiating feature of our antibody relative to the UCB antibody is the fact that our antibodies specific for pathological forms of tau
Jay Olson: 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?
Unknown Speaker Okay.
Speaker Change: I agree with everything you said, Al. The other thing to mention, there was a question about additional data.
Speaker Change: 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.
Speaker Change: As Alice pointed out, the relationship between reduction of tau accumulation and potential cognitive benefit that it appears
Speaker Change: is pretty interesting. And we see that as very encouraging. Those are in some groups, I think seeing more detail about target engagement in that relationship will really be important to interpret the results.
Speaker Change: Well, I would say that they're both high priorities. Am I allowed to say that two things are both high priorities? Yes. You know, look, we we've always said that was a pretty interesting, very important target that we think it's the next
Speaker Change: step in helping Alzheimer's patients that the anti-amyloid treatments got us started but we need to do better for patients.
Speaker Change: and so I think they're both high priority. They're very different approaches in many ways and so we'll find out which is the better approach.
Speaker Change: 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.
Speaker Change: If they have no response to the anti-amyloid antibodies, there's no sense in continuing the drug. If they've had a full response to anti-amyloid antibodies, which may be the case in some patients.
Speaker Change: If you're not progressing at all in your disease on anti-amyloid antibodies, there'd be no reason to add anything else.
so so I think time will will help us
Speaker Change: Time will tell what the heterogeneity of the treatment response is to the anti-amyloid antibody therapies in humans.
Speaker Change: 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.
Great. Thanks so much for taking all the questions.
Our next question comes from Lily Nfongo at LARINC.
Hi, good afternoon, and thank you for taking our question.
Speaker Change: So I guess two questions for me. So the first one, as we await for inpatient data for 2026 for the tau-segregated antibody,
Speaker Change: Has there any plans to potentially test previously developed T-terminal antibodies in preclinical models to try to further confirm the negative predictive values of the model you use in a more region-specific approach?
Well, if there's another antibody that's negative,
Speaker Change: then it might be interesting to do that experiment that you're proposing, Willie.
Yeah, because it was my understanding that both
Speaker Change: Hoffman, LaRoche, and then Lundbeck had some C-terminal input antibody. I think it could be really interesting, you know, technical data as we await. And I guess maybe segue into my second question. So regarding the UCB data and the challenges that they've had in the overall population,
Speaker Change: Would that compel you to potentially start the development in patient in maybe a smaller more targeted patient population?
Speaker Change: I guess my question is, does the result of the study compel you to maybe have more stringent inclusion criteria in the initial inpatient study for the antibody?
Speaker Change: Yeah, hi Lily, 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 that idea We would like to see if we can differentiate from the Pranabab if at all possible and it could be that the choice of patient population could be a way to boost the efficacy
Speaker Change: that we see, particularly on the clinical outcome measures, right, and get more clarity. As Toby noted in his comments, there were subgroups
Speaker Change: particularly those that were that were pre-specified. I think it was the APOE-4 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.
Speaker Change: 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, and to have a targeted treatment for a smaller population that's still quite large.
by the way, would be of interest. Toby?
Speaker Change: So the allele captures nicely. I think the only other comment I'd make is that when we did look at the probatum of data they had segregated their low and high tau populations. There really weren't that many low tau patients in the study overall about a
Toby Ferguson: 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.
Speaker Change: Thank you and maybe just a follow-up so we are you know 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 inpatient study
Speaker Change: I think she's interested in the design of the multiple ascending dose study.
Yes. Great. Thanks, Lily. So, so I think as we.
Speaker Change: Once we get closer to the start, which will start next year, we'll share the details of the design.
Speaker Change: Our next question comes from Patrick Trujillo at H. E. Wainworth & Co.
Patrick Trujillo: Good afternoon. Thanks very much. Just a couple of questions for me. The first is just a follow-up on earlier comment regarding the appropriate patient population for the TAL program.
Patrick Trujillo: for the Antibody Program, can you discuss what level of tau PEP burden do you think could be appropriate at baseline based on this learning from this recent data, and particularly as we approach that phase 1b trial with 7523?
Patrick Trujillo: 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.
Patrick Trujillo: And then secondly, what remains to be completed to ensure that the 2026 IND and CTA filings
Patrick Trujillo: remain on track for the Tau silencing gene therapy. 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.
Speaker Change: Wow, that's a lot of questions, Patrick, but we'll knock them off one by one here.
Speaker Change: 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
Speaker Change: The cutoff that UCB shared data with us was a pre-specified cutoff.
Speaker Change: But it was not the median. 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.
Speaker Change: 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.
Toby Ferguson: Toby, you can let me know if you disagree with that. I do not, Al. Okay. And then on the Tau KD, I think you were asking, how do we make sure that we stay, like,
Toby Ferguson: I'll be on track. And so maybe Toby and Todd, do you want to help me with those questions?
Toby Ferguson: 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 the molecule forward and then of course, I think the pivotal step will be doing the toxicology studies.
Todd Carter: All right, Standard IED Enabling Studies would be part of that whole process.
Todd Carter: You also asked about differentiation for the TEL knockdown versus the antibody.
Todd Carter: approach, I believe. And I think the BIV-80 data, which is an ASO delivered, that has shown some really interesting clinical data to date versus the antibody approaches. But what we've seen in the BIV-80 data are not only signs that you could reduce the accumulation of tau,
Todd Carter: But you may be able to reduce pathological child burden as measured by PET, in some cases below starting burden.
which is a pretty remarkable finding.
Todd Carter: When you look at those sorts of data, and even with the recent PANIMAB data, that also seem to suggest that an impact on how PET imaging results can impact
Todd Carter: clinically. I think there there is a accumulating evidence in the field that impacting tau accumulation can have a clinical benefit.
Todd Carter: with the gene therapy approach, of course. Here we're talking about a once-and-done approach. We can dose once.
Todd Carter: We know that our vectors, and this gets into a little bit of the Voyager platform question as well, that our captions can deliver quite broadly throughout the CNS. We can get delivery not only to the
Todd Carter: I'll call the shallower regions of the brain but also the deeper structures that single dose and so we think there are there could be some
Todd Carter: Substantial benefits for a cow knockdown approach. It is also an intracellular effect. The antibody has an impact presumably based on the prion spreading hypothesis.
Todd Carter: as the pathological tau spreads from cell to cell. So an intercellular reduction of tau could have an impact not only in reducing that cell to cell spread, but also in an intercellular way.
Todd Carter: So, those two approaches, I think, are both interesting, there are signs of both those mechanisms that they could work, and in the end, it's even possible there could be combination approaches.
Speaker Change: So Toby, do you want to add on potential clinical outcomes? So there I think the VIB-80 data in particular really emphasized, along with the recent ProPanelMap data, the importance of TalPAT and to Todd's PowerPoint.
and the
Toby Ferguson: We have a 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 time frames, six months or so, which is distinct from slowing accumulation. This is particular to the tau-knockdown approach.
Toby Ferguson: In addition, you can also see clear signals in the CSF biomarkers, a total tau, for example, and other tau species. And so there is a chance based on biomarkers to get a relative quick read on how the molecule is performing.
And what about the, do you think the effect size?
Speaker Change: It's hard. It's early data. I mean, if you look at the propensity score matching that Biogen performed,
They looked at a
Speaker Change: A comparison to another study called Tango, they looked at a natural history study.
Speaker Change: And there, that effect size was two to two and a half points on CDR-SIML boxes, as a reminder of the effects on the AMLET there, which are 0.4 to 0.9 points approximately on CDR-SIML boxes. So potentially a larger effect size as well, which gives you an additional opportunity to test the system, but we'll show you another smaller sample size.
Great. Very helpful. Thanks so much.
Speaker Change: I'm showing no further questions at this time. I would now like to turn it back to Al for closing remarks.
al: Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.
and their responsibilities.
Speaker Change: Ariana Grande 39 Man running Interstellar Ops Soldier Innoc binnen Skam U.s. male Countries President Dream Net
Speaker Change: Good afternoon and welcome to the Voyager Therapeutics 3rd Quarter 2024 Financial Results Conference Call.
Speaker Change: At this time, our participants are in a listen-only mode. There will be a question and answer session at the end of this call.
Speaker Change: Please note that today's call is being recorded. A replay of today's call will be available on the investors 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: 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.
Trista Morrison: Joining me on today's call are Dr. Alex Sandrock, our Chief Executive Officer, Dr. Toby Ferguson, our Chief Medical Officer, and Dr. Todd Carter, our Chief Scientific Officer.
Trista Morrison: We will also be joined for the Q&A portion of the call by Nathan Jorgensen, our Chief Financial Officer.
Speaker Change: 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.
Speaker Change: 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.
Now, I will turn the call over to Al.
Good afternoon, everyone, and thank you for joining us.
Please turn to slide 3.
Speaker Change: At Voyager, we are leveraging the power of human genetics to discover and deliver transformative medicines that address the root cause of neurological diseases.
Speaker Change: Our four pillars of value include, first, our pipeline of four wholly owned and 14 partnered programs.
Speaker Change: 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.
Speaker Change: We also recently saw encouraging third-party clinical data with another anti-Tau antibody for Alzheimer's disease, which Toby will talk about shortly.
Speaker Change: Our second pillar of value is our industry leading tracer platform for the discovery of novel AAV capsids to enable CNS gene therapy.
Toby Ferguson: 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.
Toby Ferguson: Third, we have blue-chip partnerships with some of the world's experts in neurology and gene therapy, including Neuroquin, Novartis, and Nalexion.
Toby Ferguson: We continue to progress these partnerships through the third quarter, with Novartis signing on for a fifth program partnership, and NeuroQuinn nominating a third development candidate.
Toby Ferguson: Finally, we continue to explore the potential to leverage receptors we have identified to shuttle non-viral genetic medicines into the brain.
Toby Ferguson: Ultimately, we aim to expand from gene therapy and antibodies into other modalities of neurogenetic medicine, broadening our impact.
Toby Ferguson: 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: 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 TauTargeting programs for Alzheimer's disease.
Toby Ferguson: 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.
Toby Ferguson: As you can see in the image on the left of this slide, the spread of pathological Tau as identified on TauPAD imaging correlates closely to Alzheimer's disease progression as measured by Brock Clinical Pathologic Staging.
Toby Ferguson: Additionally, exploratory clinical data from Biogen's Bib-Adi-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.
Speaker Change: So 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 VY-7523 and our Tau silencing gene therapy
Speaker Change: On slide 6, I want to highlight how the team selected our anti-tau antibody.
Speaker Change: We started with more than 700 antibodies across the mid-domain and C-terminus of tau.
Speaker Change: We first focused on antibodies targeting pathological Tau. This was important with the anti-amyloid antibodies. Several that failed, such as solanuzumab or bapinezumab, were shown to have insufficient target engagement with aggregated forms of amyloid beta, while the approved anti-amyloid antibodies all target the aggregated species.
Speaker Change: 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.
Speaker Change: In a mouse feeding model of human pathological tau spread, the C-terminal targeted antibody AB01, the murine version of VY7523.
Speaker Change: decreased the spread of injected pathological human tau by approximately 70 percent.
Speaker Change: Based on these data and the specificity for pathological tau, we selected VY7523 as our clinical candidate.
Speaker Change: We also conducted a series of head-to-head studies in this same model against other anti-Tau antibodies. These data are summarized on slide 7.
Speaker Change: In the first head-to-head study, we evaluated murine 7523 against murine versions of Biogen's gosoneuromab and Lilly's zathagenumab. These antibodies both targeted the N-terminus of tau and both failed their primary endpoints in clinical trials.
Speaker Change: Both were ineffective at reducing tau spread in the model, while our C-terminal-targeted antibody again blocked tau spread.
Speaker Change: This gave us confidence that the model had negative predictive value.
Speaker Change: In the second head-to-head study, we compared our C-terminal-targeted antibody to UCB's Brinanopab.
Speaker Change: 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 Vipraneprap clinical trial because we thought that if this antibody could impact tau in a clinical trial, then our model might also have a positive predictive value.
Speaker Change: Turning to slide 8, I want to summarize the recent propranomap 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.
Speaker Change: Now I would like to note that propranolamab inhibited the accumulation of tau in human brain by 33 to 58 percent.
Speaker Change: We saw this as establishing that an antibody can be used to inhibit the spread of pathological tau in the brain.
Speaker Change: This finding should not be underestimated, as I think that after the failure of the N-terminal anti-tau antibodies, there was uncertainty in industry as to whether an antibody approach could impact tau accumulation. As it turns out, it can.
Speaker Change: I also want to note that propranomab slowed cognitive decline by 21-25% versus placebo per ADES-CoG-14.
Speaker Change: 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.
Speaker Change: Finally, buprenoramab demonstrated an acceptable safety profile with brain hemorrhagic and inflammatory changes similar to placebo.
Speaker Change: What does this mean for Voyager's VY7523? I would say that these data give us increasing confidence that 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.
Speaker Change: 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.
Speaker Change: Slide nine provides an overview of our phase one clinical development plan for VY 7523.
Speaker Change: During the third quarter, we completed enrollment and dosing of healthy volunteers in our single ascending dose trial.
Speaker Change: 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 TauPET imaging data in the second half of 2026.
Speaker Change: At this point, we don't see anything in the program map data that would shift our thinking here. If anything, the data reaffirmed that TalPET imaging is the critical outcome we want to focus on. And we have planned a very efficient trial focused on that outcome.
Speaker Change: We found the safety profile of Pranimab encouraging and look forward to exploring the full range of dosing possibilities.
Speaker Change: 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.
Thanks Toby. Please turn to slide 10.
Todd Carter: In addition to our antibody-based approach, we are also advancing the Tau silencing gene therapy program.
Todd Carter: This program deploys a Tau-targeted siRNA packaged in an IV-administered tracer capsid.
Todd Carter: Using this approach, we have demonstrated robust reductions in human tau of RNA and protein across the brain following a single ID administration in mice that express human tau, as shown on this slide.
Todd Carter: It is also important to note that the recent BIM-80 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.
Todd Carter: We view these data as supporting for a knockdown approach and believe that a one-time IV etherapy could provide benefits over repeated intrathecal therapy.
Todd Carter: This program remained on track for USIAD and Health Canada CTA filings in 2026.
I will now turn the call back over to Al.
Thanks, Todd.
al: 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.
al: 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.
al: This cash figure doesn't include the recent payments from Novartis or Neuroquin, which were received in October, nor does it contemplate any future potential milestones from our 14 partnered programs.
al: With a robust slate of clinical milestones expected into the next 12 to 24 months.
al: 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.
al: Finally, I'd like to thank all of our employees for their hard work and dedication to improving the lives of patients.
With that, we will open the call for questions.
Operator.
Speaker Change: 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 1 1 on your telephone and wait for your name to be announced. To withdraw your question please press star 1 1 again. Please stand by while we compile the Q&A roster. Our first question comes from Phil Nando at TD Cohen.
Speaker Change: Good afternoon. Thanks for taking our questions and congrats on the progress. I guess first, a follow-up to your comments on the towel pen imaging.
Speaker Change: We're curious whether you have more insight as to how to translate the taupet imaging results like we saw from Rosh UCB into cognitive improvements and any additional thoughts now that you've had a bit more time.
Speaker Change: to let the CTAD data set in. Do you think it's a question of selecting the right patients, selecting the right endpoint, and any thoughts on how to get that TauPED imaging data to translate into a
Clinical Improvement and Cognitive Benefit.
So maybe I'll start that question, this is Toby.
Speaker Change: So I think fundamentally, I think that I'll reemphasize the point that the, for the TALPIT imaging, we saw clear data in the whole population that you did not, you slow the accumulation of TAL. And then I think the other point I'd make is that when you looked in
and some of the other populations, particularly the lower-top populations.
Speaker Change: You saw perhaps a slightly greater lesson of accumulation in that context. So do you think as we move forward, really understanding the population will be critical?
Speaker Change: in the terms of perhaps Tauberdin, which seems to be the main point.
Speaker Change: 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 PKPD. We look forward to that data from UCB moving forward.
Unknown Speaker
Speaker Change: I would just add that, you know, this relationship between cow-pet effects and disease effects on clinical outcomes.
Speaker Change: are agnostic to the drug or to the approach, right? So there are more than one, there's more than one drug targeting tau over the next couple of years. I think we'll learn this relationship better.
Speaker Change: What degree of tau PET imaging translates to what clinical outcome? And I agree with Toby that selecting the right patients, particularly with respect to tau burden, for example, may be very important.
Speaker Change: Perfect. That's helpful. And then a follow-up on the SOD1 silencing gene therapy for ALS. You note in the press release and 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 US IND?
Speaker Change: So we haven't gotten to timing of the biomarker results. The point I can make is that one, we'll go into the SOG1 population, of course, and two, we'll start at doses we think are potentially efficacious given the severity of the disease. In that context, we do think results would be significant.
I appreciate you coming.
Speaker Change: And maybe I could add that certainly in the case of the person clinical development plan and the trials that have been published in the New England Journal you can start to see effects
Speaker Change: on SOD1 levels in spinal fluid in about, is it 12 weeks? 12 weeks, Toby, yeah. And then effects on plasma neurofilament, which is a surrogate outcome that's reasonably likely to predict clinical outcomes.
Speaker Change: and was the basis of approval by FDA up to Ferguson. 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.
Speaker Change: That's very helpful. Last question, an accounting question from us. The $15 million from Novaris and $3 million from NeuroCurrent, 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?
https://www.youtube.com.au
Speaker Change: It will be booked in the fourth quarter. Perfect. Thanks for taking our questions. Congrats again on the progress.
Thank you.
Thanks, Bill.
Our next question comes from Jack Allen at Baird.
Speaker Change: 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.
Speaker Change: I was hoping you could just provide some context as to where those...
Speaker Change: 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 Abby's acquisition of Aliada and then also Roche providing some initial proof of concept data from their beta amyloid asset there as well.
to shuttle other sort of macromolecules across the BBB.
Speaker Change: And as you pointed out, you know, Troncinumab, the data with Troncinumab.
which leverages transferrin receptors, looking very promising.
as an approach to get anti-amyloid antibodies into the brain.
Speaker Change: And so we're very excited about that. We're still in the
preclinical stages. We haven't been
Todd Carter: 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? Thanks, Al. So, Jack, as you do point out, we are excited by it. We know that these receptors, and we do have...
Todd Carter: different receptors in different capsid families that can mediate transcytosis 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.
Speaker Change: Hopefully in the future we'll be able to hear data on that. I think the other aspect is that we're seeing with
Speaker Change: 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.
Speaker Change: 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 is that something you have an appetite for before moving this into the clinic?
Speaker Change: Well, 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. So I'm always open to talking to potential partners about these kinds of things and really accelerate the program.
Thank you. Thank you.
Our next question comes from June Lee at Truist Securities.
June Lee: Hey, congrats on the progress and thanks for taking our questions. Your plans for 7523 match study in 2025 imply that you may be
June Lee: May be seeing something positive in SAT study, or am I being too liberal with my interpretation? And for the SAT study due in first half of 25, in addition to safety, what are you tracking that could give us some incremental conviction on the drug? Thank you.
Toby Ferguson: This is Toby. Thanks for the question. Just a reminder, the SAD Study is in Healthy Volunteers.
Speaker Change: And so really the data we're looking from the SAD study is PK, initial immunogenicity, and do we have the appropriate exposures to pick doses for the MAT study and some initial read-on safety. So really it's not inpatients, that's the key point.
Our next question comes from Jay Olson at Oppenheimer.
Jay Olson: Hey, congrats on the progress and thanks for providing this update. We have a few questions. Based on the PRANIMAP data that you saw, what's your latest thinking on the potential
Speaker Change: 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.
Speaker Change: Well, look, I think, you know, Jay, this is Al, I mean...
Speaker Change: This is the first time we've seen that an antibody could have biological effects.
Speaker Change: In the brain in humans, right? And so that's I look on that as positive, right? That an antibody approach could affect the biology of how spreading in the brain.
Speaker Change: We, even before we knew about the Pranibat data, we did say that there could be read-through because we had tested the UCB antibody, which
Speaker Change: binds to a mid-domain region versus our antibody, which binds to the C-terminal region in an animal where we look for the, we look at the spread of pathological tau.
and a mouse expressing human tau where we inject
Speaker Change: pathological Tau from Alzheimer's brains into the animal. And we said before the CTAD, before we knew anything about the Burkina Faso data, that the UCB antibody was pretty comparable.
Speaker Change: 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.
Speaker Change: So, you know, and so we still believe that that there could be read through.
Speaker Change: And we also expect that the safety perhaps would also be similar in the sense that, you know, the antibody is binding.
Speaker Change: to extracellular tau. I would say the other differentiating feature of our antibody relative to the UCB antibody is the fact that our antibodies specific for pathological forms of tau
Speaker Change: 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?
um
Speaker Change: I agree with everything you said, Al. The other thing to mention, there is 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.
Speaker Change: As Alice pointed out, the relationship between reduction of tau accumulation and potential cognitive benefit that it appears
Speaker Change: 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.
Speaker Change: Great. Thank you for that. And then maybe just as a follow on, how are you thinking about prioritizing 7523 versus your tau silencing gene therapy and then the potential for combining either of your anti-tau approaches with anti-amyloid antibodies?
Speaker Change: Well, I would say that they're both high priorities. Am I allowed to say that two things are both high priorities? Yes. You know, look, we we've always said that.
Speaker Change: was a very important target that we think it's the next.
Speaker Change: step in helping Alzheimer's patients that the anti-amyloid treatments got us started but we need to do better for patients.
Speaker Change: and and so I think they're both high priorities. They're very different approaches in many ways and and so we'll find out which is the better approach.
Speaker Change: In terms of combining with the anti-amyloid antibodies, I do think that there could be a place for combining.
Speaker Change: I would say that it would be in those patients that seem to have a partial response to the anti-amyloid antibodies.
Speaker Change: If they have no response to the anti-amyloid antibodies, there's no sense in continuing the drug. If they've had a full response to anti-amyloid antibodies, which may be the case in some patients.
Speaker Change: 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.
Speaker Change: Time will tell what the heterogeneity of the treatment response is to the anti-amyloid antibody therapies in humans.
Speaker Change: 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.
Speaker Change: 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.
Great. Thanks so much for taking all the questions.
Our next question comes from Lily Nsongo at Lyrinc.
Hi, good afternoon and thank you for taking our question.
Speaker Change: So I guess two questions for me. So the first one, as we await for inpatient data for 2026 for the Tau-targeted antibodies, are there any plans to potentially test previously developed T-terminal antibodies in preclinical models to try to further confirm the negative predictive values of the model you use in a more region-specific approach?
Thank you. Thank you.
Well, if there's another antibody that's negative,
Speaker Change: 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,
Speaker Change: then it might be interesting to do that experiment that you're proposing, Willie.
Speaker Change: Yeah because it might be interesting that both Hoffman and Lundbeck had some C-terminal antibody. I think it could be really interesting, you know, technical data as we await. And I guess maybe segue into my second question. So regarding the UCB data and the challenges that they've had in the overall population.
Speaker Change: Would that compel you to potentially start the development in patient in maybe a smaller more targeted patient population?
Speaker Change: I guess my question is, does the result of the study compel you to maybe have more stringent inclusion criteria in the initial inpatient study for the antibody?
Unknown Speaker
Speaker Change: Yeah, hi Lily, 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.
Speaker Change: We would like to see if we can differentiate from the Pranibab, 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. We had Toby noted in his comments.
Speaker Change: 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.
Speaker Change: 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, and to have a targeted treatment for a smaller population, it's still quite large.
By the way, it would be of interest. Toby?
Speaker Change: So the allele captures nicely. I think the only other comment I'd make is that when we did look at the probatum of data they had segregated their low and high tau populations. There really weren't that many low tau patients in the study overall about a
Toby Ferguson: 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.
Speaker Change: Thank you and maybe just a follow-up so we are you know 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 inpatient study
Speaker Change: I think she's interested in the design of the multiple ascending dose study.
Yes. Great. Thanks, Lily. So, so I think as we.
Speaker Change: Once we get closer to the start, which will start next year, we'll share the details of the design.