Q4 2023 Voyager Therapeutics Inc Earnings Call
Operator: Good day. Thank you for standing by.
Good day, Thank you for standing by welcome to the Q4 2023, Voyager Therapeutics earnings Conference call. At this time all participants are in a listen only mode. After the speaker's presentation, there will be a question and answer session.
Operator: Welcome to the Q4 2023 Voyager Therapeutics Earnings Conference Call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during the session, you'll need to press star one one on your telephone; you'll then hear an automated message advising your hand is raised.
To ask a question during the session you will need to press star one on your telephone.
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Operator: To withdraw your question, please press star one one again. Please be advised that today's conference is being recorded. I would now like to hand the conference over to your first speaker today, Peter Pfreundschuh, Chief Financial Officer. Please go ahead. Thank you, and good afternoon.
Draw. Your question. Please press star one again.
Please be advised that today's conference is being recorded I would now like to hand, the conference over to your first speaker today, Peter Frank <unk> Chief Financial Officer. Please go ahead.
Peter Frank: Thank you and good afternoon.
Peter P. Pfreundschuh: Joining me on the call today are Dr. Alsan and Dr. Todd Carter. We issued our Q4 and year-end 2023 financial results. Press release this, Press Release in 10K, are available on our website. In a moment, I will turn the call over to Dr. Alsan.
Peter Frank: Joining me on the call today is Dr Al Sandrock, our CEO.
Peter Frank: And Dr. Todd Carter, our Chief Scientific Officer.
Peter Frank: We issued our Q4 and year end 2023 financial results press release this afternoon.
The press release and 10-K are available on our website.
Peter Frank: In a moment I will turn the call over to al.
Peter P. Pfreundschuh: Before I do this, I want to remind everyone... During this call, Voyager representatives may make forward-looking statements, as noted in slide two of today's presentation. These forward-looking statements include future expectations. Transcribed by https://otter.ai, All forward-looking states are inherently uncertain and are subject to risk. Uncertainty that may cause actual results to differ materially from those indicated by these forward-looking states. You are encouraged to review and understand the various material recipes facing the company as described and the company's most recent annual report, Form 10-K, filed with the FCC this afternoon. All SEC filings are available on the company's website.
Speaker Change: Before I do that I want to remind everyone that during this call Voyager Representatives may make forward looking statements as noted on slide two of today's deck.
Speaker Change: These forward looking statements include future expectations.
Alfred W. Sandrock: Lance and prospects.
Alfred W. Sandrock: All forward looking statements are inherently uncertain and are subject to risks and uncertainties.
Alfred W. Sandrock: That may cause actual results to differ materially from those indicated by these forward looking statements.
You are encouraged to review and understand the various material risks.
Alfred W. Sandrock: Uncertainties facing the company as described in the Companys. Most recent annual report Form 10-K filed with the SEC. This afternoon.
Alfred W. Sandrock: <unk> SEC filings are available on the company's website now it is my pleasure to turn the call over to al. Thank you Pete and good afternoon, everyone. Please turn to slide three.
Alfred W. Sandrock: Now it is my pleasure to turn the call over to you, Pete. Thank you, Pete, and good afternoon, everyone. Please turn to slide three. I'd like to start by defining Voyager's position as an emerging leader in neurogenetic medicine. First, our pipeline. We anticipate having at least four wholly owned and partnered CNS programs in the clinic by the end of 2025, with the potential to generate clinical data in 2025 and 2026. Our most advanced programs are anti-tau antibody for Alzheimer's disease and our SOD1 gene therapy program for amyotrophic lateral sclerosis or ALS. I will talk more about both programs in a few minutes.
Alfred W. Sandrock: I'd like to start by defining voyages position as an emerging leader in neuro genetic medicine.
Alfred W. Sandrock: First our pipeline.
Alfred W. Sandrock: We anticipate having at least four wholly owned and partnered CNS programs in the clinic by the end of 2025 with the potential to generate clinical data in 2025 and 2026.
Alfred W. Sandrock: Our most advanced programs, our anti Tau antibody for Alzheimer's disease, and our <unk> gene therapy program for amyotrophic lateral sclerosis or ALS.
I will talk more about both programs in a few minutes.
Alfred W. Sandrock: Second, our platform. Voyager is working to solve the delivery challenges inherent to CNS gene therapy with our Tracer Capsid Discovery Platform. We have demonstrated high transduction in multiple brain areas at relatively low doses, with Detargeting of the Liver and Dorsal Root Ganglia Across Multiple Stomachs.
Alfred W. Sandrock: Second our platform.
Alfred W. Sandrock: Voyager is working to solve the delivery challenges inherent to CNS gene therapies with our tracer capsid discovery platform.
Alfred W. Sandrock: We have demonstrated high transduction in multiple brain areas at relatively low doses with <unk> targeting of the liver and dorsal root ganglia across multiple species.
Alfred W. Sandrock: We have also shown blood-brain barrier penetrance across multiple animals, and we have identified a receptor that is expressed in humans. Third Partnership In January of 2024, we received $100 million from Novartis in a combination of upfront payment and equity investment to develop gene therapies for Huntington's disease and spinal muscular atrophy. This brings our total of partnered programs to 13, with the potential to generate $8.2 billion in longer-term milestone payments. Whereas this is a quote, BioBucks is an unquote number.
Alfred W. Sandrock: We have also shown blood brain barrier penetrant across multiple animal species and we have identified a receptor that is expressed in humans.
Alfred W. Sandrock: Third partnerships.
Alfred W. Sandrock: In January of 2024, we received $100 million from Novartis in a combination of upfront payment and equity investment to develop gene therapies for huntington's disease and spinal muscular atrophy.
Alfred W. Sandrock: This brings our total of partnered programs to 13 with the potential to generate $8 $2 billion and longer term milestone payments.
Alfred W. Sandrock: Whereas this is a quote bio bucks unquote number it is not factored into our cash runway guidance.
Alfred W. Sandrock: It is not factored into our cash runway, guys, but I will note that some of it is becoming real. Earlier this week, we triggered a $5 million milestone payment upon selection of a lead development candidate for our Neurocrine-partnered Friedreich's ataxia program. All of this has given us a strong balance, which we expect to provide runway into 2027. Removing our financial overhang and enabling us to potentially generate value-creating clinical data in 2025 and 2026. Finally, the potential.
Alfred W. Sandrock: I will note that some of it is becoming real.
Alfred W. Sandrock: Earlier this week, we triggered a $5 million milestone payment upon selection of our lead development candidate for our Neurocrine partnered Friedrichs ataxia program.
Alfred W. Sandrock: All of US all of this as giving us a strong balance sheet, which we expect to provide runway into 2027.
Alfred W. Sandrock: Removing our financial overhang, and enabling us to potentially generate value, creating clinical data in 2025 and 2026.
Alfred W. Sandrock: Finally potential.
Alfred W. Sandrock: We have already demonstrated our strengths as a leader in CNS capsid technology. We now aim to expand from gene therapy and antibodies into other modalities of neurogenetic medicine, potentially broadening our impact. We continue to explore the potential to leverage Receptor X to shuttle non-viral genetic medicines across the blood-brain barrier and look forward to sharing data on this in the future. On slide 4, I want to take a moment to acknowledge just how much Voyager has achieved recently. Following the Novartis collaboration, we closed a $100 million public offering. We will close 2023 with approximately $231 million in cash.
Alfred W. Sandrock: We have already demonstrated our strength as a leader in CNS capsid technology.
Alfred W. Sandrock: We now aim to expand from gene therapy, and antibodies into other modalities of narrow genetic medicine potentially broadening our impact.
Alfred W. Sandrock: We continue to explore the potential to leverage receptor acts to shuttle non viral genetic medicines across the blood brain barrier and look forward to sharing data on this in the future.
On slide four I want to take a moment to acknowledge just how much Voyager has achieved recently.
Following the Novartis collaboration we closed a $100 million public offering.
Alfred W. Sandrock: We closed 2023 with approximately $231 million in cash when.
Alfred W. Sandrock: When you add the $100 million from Novartis and the $100 million from the offering, that brings us to a pro forma cash number of approximately $431 million as of December 31st, 2023. We are also progressing our GLP toxicology work with our anti-tau antibody VY-Tau-01 for Alzheimer's disease and remain on track for an IND filing in the first half of this year. We achieved two development candidate selections with gene therapy programs. One, our wholly-owned SOD1 ALS gene therapy, and one with our Neurocrine-partnered Friedreich's Ataxia Program. We also generated data with our wholly owned Tau Silencing Gene Therapy Program showing robust reductions in human tau mRNA and protein in a mouse model, which Todd will share more on later. All of these milestones are helping us build a robust pipeline, as you can see on slide 5. I do want to note that the wholly owned programs at the top of this slide, denoted in orange, are the only programs we fund.
Alfred W. Sandrock: When you add the $100 million from Novartis in the $100 million from the offering that brings us to a pro forma cash number of approximately $431 million as of December 31 2023.
We are also progressing our GOP toxicology work with our anti Tau antibody <unk> zero, one for all timers disease and remain on track for an IND filing in the first half of this year.
We achieved two development candidates selections with gene therapy programs.
Alfred W. Sandrock: One our wholly owned <unk> AOS gene therapy, and one with our Neurocrine partnered Friedrichs ataxia program.
Alfred W. Sandrock: We also generated data with our wholly owned tower silencing gene therapy program, showing robust reductions in human Tau mrna and protein in a mouse model, which Todd will share more on later.
Alfred W. Sandrock: All of these milestones are helping us build a robust pipeline as you can see on slide five.
Alfred W. Sandrock: I do want to note that the wholly owned programs at the top of the slide the noted in Orange are the only programs we fund.
Alfred W. Sandrock: The rest of our pipeline is funded by our partners. While I won't go into detail on all of these today, I do want to dig into some of our wholly owned programs, particularly our anti-tau antibody, our tau knockdown gene therapy, and our SOD1 ALS gene therapy. Moving to slide six.
Alfred W. Sandrock: The rest of our pipeline is funded by our partners.
Alfred W. Sandrock: While I won't go into detail on all of these today I do want to dig into some of our wholly owned programs, particularly our anti Tau antibody archived knockdown gene therapy, and our <unk>, one alpha gene therapy.
Alfred W. Sandrock: Moving to slide six when.
Alfred W. Sandrock: When I look at the Alzheimer's space, I'm encouraged by the progress, particularly the approval of two anti-amyloid antibodies. I view Tau as the next exciting target in this... Why? We've long known that the spread of pathological tau correlates to the progression of Alzheimer's. In fact, Alzheimer's disease progression is characterized by Brock staging, which is based on the spread of pathological tau. Our anti-tau antibody, VY-Tau-01, is differentiated from other approaches based on the epitope it targets, which is located in the C-terminal rather than the N-terminal or mid-domain and which has been shown to inhibit the spread of pathological tau by more than 70% in a pre-clinical study.
Alfred W. Sandrock: When I look at the Alzheimers space I am encouraged by the progress, particularly the approval of two anti amyloid antibodies.
Alfred W. Sandrock: I view Tau as the next exciting targeted in this field.
Alfred W. Sandrock: Why.
Alfred W. Sandrock: We've long known that the spread of pathological correlates to the progression of Alzheimer's disease. In fact, all timers disease progression is characterized by broad staging which is based on the spread of pathological tab.
Alfred W. Sandrock: Our anti Tau antibody <unk> zero, one is differentiated from other approaches based on the epitope it targets, which is located in the <unk> terminal rather than the end terminal or mid domain, and which has been shown to inhibit the spread of pathological tau by more than 70% preclinical study.
Alfred W. Sandrock: We are currently progressing through IND-enabling studies and remain on track to file an IND in the first half of this year. We plan to initiate a single ascending dose study this year in healthy volunteers, and we plan to initiate a multiple ascending dose study next year in patients with early stages of Alzheimer's. We hope to generate proof-of-concept data for slowing the spread of pathological tau via PET imaging in 2020.
Alfred W. Sandrock: We are currently progressing through IND, enabling studies and remain on track to file an IND in the first half of this year.
Alfred W. Sandrock: We plan to initiate a single ascending dose study this year in healthy volunteers and we plan to initiate a multiple ascending dose study next year in patients with early stages of Alzheimer disease.
Alfred W. Sandrock: We hope to generate proof of concept data for slowing the spread of pathological Tau pet.
Pet imaging in 2026.
Todd Carter: I'll now turn it over to Todd to talk about another approach we are developing to target talent. Thank you. Please turn to slide 7.
Alfred W. Sandrock: I'll now turn it over to Todd to talk about another approach, we're developing to target tower.
Todd Carter: Thank you ma'am, please turn to slide seven.
Todd Carter: In addition to our anti-child antibody approach, we are also working on a child-sized... This approach leverages a tracer-derived BDD, Deliver, Vectorize, How Targeted. As shown, the single intravenous administration of our Tile Silent NG Therapy... This was observed across multiple... In some regions, we have seen up to a 90%...
Todd Carter: <unk> our <unk> antibody approach we are also working on it.
Todd Carter: This approach leveraging the trickier derived adv and it shrinks.
Todd Carter: Yes.
Todd Carter: To deliver Victor.
Todd Carter: Okay.
Todd Carter: As shown a single intravenous administration of our titles and gene therapy.
Todd Carter: Humanized mouse model cluster robust reductions in humans have marni encouraging.
Todd Carter: This was observed across multiple regions and in some regions. We have seen also a 90% reduction in California.
Todd Carter: This work will be presented at the 2024.. Given these, Voyager has prioritized this program and advanced it to lead. We anticipate an I&E file. I'll just echo what Al said, https://www.youtube.com. So much so that we are pursuing multiple modalities, both an antibody and We are encouraged by the early data for both of these and look forward to continuing to share. In addition, I want to share a little data from our SOD1 ALS gene therapy program. Finally, we announce the selection of the developer. I'm in December.
Todd Carter: This work will be presented at the 2024.
Todd Carter: Yes.
Todd Carter: Given these promising data wagers prioritizes program.
Todd Carter: Research.
Todd Carter: Anticipated 90 filed in 2026.
Speaker Change: I will just echo without sitting here, we see now is an incredibly important target for Alzheimer's disease.
Speaker Change: So that we are pursuing multiple modalities, both antibody and gene therapy.
Speaker Change: We are encouraged by the early data from both of these programs.
Speaker Change: Forward to continuing to share.
Speaker Change: Yes.
Speaker Change: In addition, I want to share it with data from our SMB, one gene therapy program.
Speaker Change: We announced the selection of a development candidate for this program in December 2012.
Todd Carter: Some of the data behind this decision. As you can see, a single IV dose of our development candidate in non-U.S. www.youtube.com cervical and lumbar spinal cord Unknown Speaker 0, Some of the key cell types affected by... Additionally, we think it added, is that the effect is not. When you look at approaches to injecting in medicine... You often see steep gradients of effects dropping off once you move away from them. But because our IV approach leverages... to deliver across the blood-brain barrier, not only The Bulletproof Executive 2013,. ... This program continues to progress. Violin.
Speaker Change: All of the data behind the decision are shown on slide eight.
Speaker Change: As you can see a single IV dose of our development candidate in nonhuman primates.
Speaker Change: 73% and 82% redemptions initially one MRV.
Speaker Change: Cervical and lumbar spinal cord motor neurons, respectively.
These are quite significant reductions in some of the key cell types affected by the disease.
Speaker Change: Additionally, we take an added benefit is that the effect is not limited to the spinal cord.
Speaker Change: When you look at approaches and injecting in medicine.
Speaker Change: The occupancy decrease dropping off wishing to delinquent.
Speaker Change: But because our IV approach leveraging the vascular system to deliver across the blood brain barrier, we see not only strong knockdown along the spinal cord.
Speaker Change: The lowering of the brainstem and motor cortex, which we believe will be important to addressing ngls.
Speaker Change: This program continues to progress toward a 90 filing mid 2025.
Alfred W. Sandrock: Now I'll turn the call back down. Thank you, Todd. Turning to slide 9, you can see Voyager has started the year off strong, and we continue to execute on our milestones. We began the year with our second Novartis collaboration, this time to advance gene therapies for Huntington's disease and Spinal Muscular Atrophy.
Speaker Change: Now I will turn the call back to al.
Alfred W. Sandrock: Thank you Todd.
Alfred W. Sandrock: Turning to slide nine you can see Voyager has started the year off strong and we continue to execute on our milestones.
Alfred W. Sandrock: We began the year with our second Novartis collaboration this time to advance gene therapies for Huntington's disease and spinal muscular atrophy.
Alfred W. Sandrock: We then raised $100 million through a public offering in January of 2024, providing runway into 2027. Just this week, we announced the selection of a development candidate for our Neurocrine Partnered Freedrich's Ataxia Gene Therapy Program, which triggered a $5 million Milestone. I want to close by acknowledging all of the hard work of the Voyager team, which has allowed us to progress as much as we have. Looking forward, Voyager is well-capitalized to advance at least four wholly owned and partnered CNS programs into the clinic this year and next. And with our financial overhang removed, we look forward to potentially generating value-creating clinical data in 2025 and 2026. With that, we're happy to take any questions you may have. Operator.
Alfred W. Sandrock: We then raised $100 million.
Alfred W. Sandrock: Through a public offering in January of 2020 for providing runway into 2027.
Alfred W. Sandrock: Just this week, we announced the selection of a development candidate for our Neurocrine partnered Friedrichs ataxia gene therapy program, which triggered a $5 million milestone.
Alfred W. Sandrock: I want to close by acknowledging all of the hard work of the Voyager team, which has allowed us to progress as much as we have.
Alfred W. Sandrock: Looking forward Voyager is well capitalized to advance at least four wholly owned and partnered CNS programs into the clinic this year and next.
And with our financial overhang removed, we look forward to potentially generating value, creating clinical data in 2025 and 2026.
Speaker Change: With that we're happy to take any questions you may have.
Operator.
Operator: Yes, thank you. As mentioned, at this time, we'll conduct the question and answer session. As a reminder, to ask a question, you'll need to press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again.
Speaker Change: Thank you.
Speaker Change: As mentioned at this time, we will conduct a question and answer session.
Speaker Change: Reminder, to ask a question you will need to press star one on your telephone and wait for your name to be announced to withdraw. Your question. Please press star one again, please stand by while we compile the Q&A roster.
Operator: Please stand by while we compile the Q&A roster. Our first question comes from the line of Jack Allen with Baird. Your line is now open.
Our first question comes from the line of Jack Allen with Baird. Your line is now open.
Alfred W. Sandrock: All right, thanks for taking my question, and congratulations to the team on all the progress made throughout the quarter. My question is fairly high level, but it relates to all three of the assets that you anticipate moving forward towards clinical studies here, be it the ALS program, the Frederickson-Taxia program externally, and then the internal Alzheimer's program that you're prioritizing. How should we think about vector selection across all three of these assets? Do they feature the same vector, or are they each using novel vectors? And as you move towards a clinic, I guess, to what degree can you translate preclinical results across these programs and clinical results from early, you know, early clinical data to the later pipeline assets that are going to move forward as well? Hi Jack, this is Al.
Jack Kilgannon Allen: Alright, Thanks for taking my question and congratulations to the team on all the progress made throughout the quarter.
Jack Kilgannon Allen: My question is sort of a high level, but it relates to all three of the assets that you anticipate moving forward towards clinical studies therapy at the ALS program. The <unk> ataxia program externally and then the internal Alzheimers program that Youre prioritizing how should we think about the vector selection across all three of these assets.
Jack Kilgannon Allen: They feature the same vector or are they each using novel vectors and as you move towards the clinic.
Jack Kilgannon Allen: To what degree can you translate preclinical results across these programs and clinical results from an early.
Jack Kilgannon Allen: Early clinical data to the <unk> pipeline assets that are going to move forward as well.
Alfred W. Sandrock: Hey, Jack this is al I'll start and then I'll turn it over to Todd for his comments.
Alfred W. Sandrock: I'll start and then I'll turn it over to Todd for his comments. So, with respect to the CAHPSID, we haven't disclosed which CAHPSID we will be using. Every one of these programs will use one of our novel CAHPSIDs discovered through the TRACER platform. They will be delivered IV, and we anticipate we will use doses. Well below E14 VGs per kg because that's where and those are the doses that have shown some safety issues with other AAV programs.
Todd Carter: So with respect to the capsid, we haven't disclosed which cap said.
We will be you every one of these programs will use one of our novel cap since discovered to the trades for platform they will be delivered IV.
Todd Carter: And we anticipate we will use doses.
Todd Carter: Well below <unk> vg per kg, because thats, where so those are the doses that have jumped in safety issues with other AAV programs. So.
Alfred W. Sandrock: So, and, you know, we select these capsids based on a capsid profile that we create for every single disease and every single target, based on the fact that these diseases reside in different parts of the nervous system. And also, we want to be sure that we target the cells that are necessary while de-targeting the cells that may cause toxicities. That leads us to these capsid profiles, and luckily, we have an array of capsids we can choose from and our partners can choose from. Todd?
Todd Carter: We select these caps.
Todd Carter: Based on end caps and profile that we create for every single disease and every single target based on the fact that these diseases reside in different parts of the nervous system and also.
Todd Carter: We want to be sure that we target themselves that are necessary well be targeting themselves.
Todd Carter: It may cause toxicity that leads us to these capture profiles and Luckily we have an array of capsid, we can choose from and our partners can choose from.
Todd Carter: I don't have a lot to add to your comments, Al. You hit the major points. As Al mentioned, we identify a profile for the capsids that are specifically oriented to each disease that we're going after. Of course, it's a different payload in each case.
Todd Carter: Todd.
Speaker Change: I don't have a lot to add to your car.
Todd Carter: It does.
Todd Carter: The major points as Al mentioned, we identify a profile for the cabinets specifically.
Todd Carter: Detroit each disease that were calling after of course, it's a different payload in each case can you talk a little bit sure attempted to capture that as effectively.
Alfred W. Sandrock: You're talking about the serotype with the capsid that is effectively the envelope that delivers that payload. And we really try to hit each of those components that Al mentioned to give us the best opportunity for success and to reduce any potential risks of tolerance issues. You know, Jack had a question about predictability of preclinical models. And, you know, we don't really, Jack. We choose targets that we think are validated, based on human genetics or human studies of other types, including controlled clinical trials. And then what we aim to do is to do pharmacology in animals. And, you know, for us.
Todd Carter: The envelope it delivers the payload.
Todd Carter: And we really try to hit each of those components that al mentioned gives us the best opportunity for success at.
To reduce any potential risks.
Todd Carter: Our ability issues.
I think Jack had a question about <unk>.
Todd Carter: Stability I think of preclinical models.
Todd Carter: And.
Todd Carter: We don't.
Todd Carter: We chose targets Jack that we think are validated.
Todd Carter: Based on human genetics.
Todd Carter: Our human studies of other types, including control clinical trials and then what we aim to do is to do pharmacology in animals and for us.
Alfred W. Sandrock: Doing clear pharmacological studies in non-human primates, where you don't have the availability of so-called models of disease, we think that may be just as informative, or perhaps more informative, to help us choose the right capsid. Because the size of the animals is obviously different from mice, and the delivery characteristics may be more similar to humans. I hope that helps with that part of the question, outside of the building.
Todd Carter: Doing clear pharmacological studies in non human primates, where.
Todd Carter: You don't have the availability of the so called models of disease.
Todd Carter: We think that may be just as informative or perhaps perhaps more informative.
Todd Carter: US choose the rate caps because.
Todd Carter: The size of the animals are obviously different from mice and the delivery characteristics may be more similar to humans.
Speaker Change: I hope that helps with that part of the question.
Speaker Change: The only thing.
Alfred W. Sandrock: Thanks, Jack. Thank you. Operator. Yes, excuse me.
Speaker Change: Thanks Jack.
Jack: Thank you.
Operator.
Jack: Thank you.
Jack: Okay.
Yes, excuse me.
Operator: The next question comes to the line of David Hong with Citi. Your line is now open. Hey, this is Sam back on for David.
Jack: The next question comes from the line of David Hong with Citi. Your line is now open.
Jack: Hey, this is Sam back on for David Congrats on the progress and thanks for taking the question.
Peter P. Pfreundschuh: Congratulations on the progress. And thanks for taking the question. Just if you could provide any color on how we should think about collaboration revenues for 2024. Are there any significant potential near-term milestones for partners that can lead to any lumpiness in quarterly revenues? Would you like to take that?
Sam: Just if you could provide any color on how we should think about collaboration revenues for 2024, there are any significant potential near term milestones for partners.
Sam: That could lead to any lumpiness in quarterly revenues.
Sam: Steve do you want to take that sure. So we don't provide specific guidance with regards to <unk>.
Peter P. Pfreundschuh: Sure, Al. So, you know, we don't provide specific guidance with regard to collaboration revenue, especially new collaborations per se. You know, we have been very fortunate, and as part of today's announcement and what came out earlier this week, there was further validation that the collaborations that we already have in place, specifically, Collaboration around the FAA program with NeuroCren is advancing and moving forward, and so that continues to validate the science in the organization and also bring additional cash flow revenues that we had not previously kind of projected as part of our overall cash runway. That's an additional five million I do think, you know, as you look at our financials for the close of 2023, we do have pretty significant revenues this year.
Steve: Collaboration revenue.
Steve: Especially new collaborations per se.
Steve: We have been very fortunate in that as part of <unk> now spent and what came out earlier. This week was further validation that the collaborations that we already have in place specifically.
Steve: Collaboration around PFA program with Neurocrine is advancing moving forward and so on.
Steve: It continues to validate the science in the organization and also bring to the company additional cash flow revenues that we had not previously kind of projected as part of our overall cash runway.
Steve: Additional $5 million as we've discussed in todays conference call I do think.
Steve: As you look at our financials for the close of 2023.
Steve: You had a pretty significant revenues this year and that was largely driven through originally the first deal that we did with Merck trend at the beginning of 'twenty three.
Peter P. Pfreundschuh: And that was largely driven by the first deal that we did with Nurocrin at the beginning of 23, the subsequent option to license agreement with Novartis earlier in the year, and then, of course, the final collaboration or the second collaboration with Novartis around the VFMA program as well as the VHD program. So, you know, 23 was a banner year for us, I think, from a revenue generation and cash flow perspective.
Steve: The subsequent option to license agreement.
Steve: With Novartis earlier in the year and then of course the final collaboration number the second collaboration with Novartis.
Steve: Around.
Steve: The SMA program as well as the HD program. So.
Steve: 23 was a banner year for us I think from a revenue generation and cash flow perspective.
Peter P. Pfreundschuh: You know, obviously, moving forward, we're going to be very open to business development discussions and always open to conversations. And there could be further revenue generation associated with our CAHPSA platform. As you think about 2024, and definitely milestones for our existing 13 programs, so I think it's important to just be mindful that, you know, we don't provide guidance here, but we do believe that there could be further revenue generation as we move forward in 2024. Great, thank you.
Steve: Obviously, we're.
Speaker Change: We're going to be very open to business development discussions and are always open to conversations.
Speaker Change: And there could be further revenue generation associated with our capsid platform as you think about 2024 and definitely milestones.
Speaker Change: For our existing 13 partner program. So I think it's important to just be mindful that we don't provide guidance here, but we do believe that there could be further revenue generation as we move forward 'twenty four.
Okay.
Speaker Change: Great. Thank you.
Operator: Thank you. One moment for our next question. This question comes from the line of Jay Olson with Oppenheimer.
Speaker Change: Thank you.
Speaker Change: One moment for our next question.
This question comes from the line of Jay Olson with Oppenheimer. Your line is now open.
Alfred W. Sandrock: Your line is now open. Oh, hey guys, congrats on all the progress, and thank you for providing the update. We have a question about the Tau-01 program. There are some near-term readouts for competing Tau-targeted therapies. Phase II readouts from an anti-Tau mid-domain antibody from Roche and UCB and an OGA inhibitor from Lilly. Can you just talk about the potential read-across to your own Tau-01 program and maybe more broadly to the Tau targeting strategy? And then I have a follow-on question if I could. Well, that's a great question. I mean, yes, we are aware that there are multiple antibodies against various epitopes on the tau molecule, and there could be some reunification.
Jay Olson: Hey, guys. Congrats on all the progress and thank you for providing the update we have a question about the <unk> zero one program since Theres, some near term readouts for competing <unk> targeted therapies, including phase III Readouts from an anti Tau mid domain antibody from Roche and UCB.
Speaker Change: And OGA inhibitor from Lilly can you just talk about the potential read across to your own <unk> zero, one program and maybe more broadly to the tower targeting strategy and then I have follow on if I could please.
Speaker Change: Well, that's a great question I mean, yes, we are aware that there is multiple antibodies against various epitopes on the Tau molecule and.
Speaker Change: There could be some read through.
Alfred W. Sandrock: I would say that we believe that epitope matters a lot. It certainly did in the case of the amyloid antibodies, and because all the ones that work are N-terminal, it turned out. The C-terminal and mid-terminal anti-amyloid antibodies were not as effective. In the case of tau, we chose the C-terminal based on animal experiments where we inject human pathological tau into the animal, and we look at the blockade of spread to other brain regions. And we chose the C-terminal because it was the most robust antibody in blocking that spread. We actually had a number of antibodies against other epitopes, and they were highly specific for pathological tau. So we had to We had about half a dozen of those. We had to choose one of them.
Speaker Change: I would say that we believe that epitope matters a lot.
Speaker Change: That in the case of the amyloid antibodies.
And because all of the ones that work and terminal.
Speaker Change: Terminal turned out.
Speaker Change: The C terminal in mid terminal MTM, alright antibodies were not as effective.
Speaker Change: In the case of Tau, we chose the C terminal based on.
Speaker Change: Animal experiments, where we inject human pathological talent to the animal and we look at this the blockade of spread to other brain regions.
Speaker Change: And we chose the C terminal because it was the most robust antibody and blocking that spread we actually had a number of antibodies against other epitopes.
And highly specific for pathological Tao. So we had we had about a half a dozen of those we have to choose one of them and we decided that we would use this spreading assay bio assay in animals.
Alfred W. Sandrock: And we decided that we would use this spreading assay bioassay in animals to make our decision on which epitope. It's a long answer to say that. I think a positive result just underscores, I think, that the tau is a great target to go after, but a negative result, maybe because it was the wrong epitope. Now, if it's a C-terminal antibody, then we have to take notice there. But again, even within the same region, some antibody blocks spread better than others, so even that we can't take too seriously either. Todd, do you want to add anything? I think he captured it well.
Speaker Change: To make our decision on which up until so.
Speaker Change: No.
Speaker Change: So long answer to say that.
Speaker Change: A positive result, just underscores I think.
Speaker Change: Tau is about is a great target to go after but a negative result, maybe because it was the wrong epitope.
Speaker Change: But the six terminal antibody that we have to take notice there.
Speaker Change: But again, even within the same region, some antibody blocks spread better than others. So even that we can't pick can't take too seriously either.
Todd do you want to add anything.
Alfred W. Sandrock: And the point at the end there that Al made was, we can identify, and through our studies, we did antibodies that targeted epitopes very close to one another on cross the tau protein. And some of those antibodies would work quite well in our screening assay, and others would not, and it really depended upon a particular epitope.
Todd Carter: I think you captured it and the point at the end there that al made was we can identify and through our studies, we did antibodies that targeted epitopes very close to one another on cross the Tau protein.
Todd Carter: And some of those antibodies.
Todd Carter: Worked quite well and are screening assay and others would not really dependent upon the particular epitope and I'll just reiterate that our assays the intermodal antibodies.
Todd Carter: And I'll just reiterate that in our assays, the interminal antibodies that have failed in the clinic to date failed in that assay as well. So we're taking something forward that is quite robust and targets pathological pathology. Great, thank you so much.
Todd Carter: The sale of the clinic to date sales in that assay as well. So we're taking something forward that was quite robust and targets pathological specifically.
Speaker Change: Great. Thank you so much and if I could squeeze in a follow up question about.
Alfred W. Sandrock: And if I could squeeze in a follow-up question about recent discussions at the FDA. Can you just comment on their plans to more broadly use biomarkers for the accelerated approval of gene therapy? Yeah, no, that was, we read that with great interest, and, you know, I applaud the use of surrogate markers, if you will. These are diseases with such terrible consequences for patients.
Speaker Change: Recent discussions with the FDA could you just comment on.
Speaker Change: There.
Speaker Change: Plans to more broadly use biomarkers for the accelerated approval of gene therapies.
Speaker Change: Yes, no that balanced we read that with great interest and.
No.
Speaker Change: I applaud the use of.
Speaker Change: Surrogate markers if you will.
Speaker Change: These are diseases with such terrible consequences for patients.
Speaker Change: And.
Alfred W. Sandrock: And if we can use a surrogate biomarker to get accelerated approval and then confirm it in a confirmatory trial, I think patients get access to the drugs earlier. And you know, I think it's a good approach. And I personally think that for the right disease and the right surrogate marker, this is exactly the right approach for patients. Thank you. And maybe just looking at regulators outside the U.S., any takeaways from the positive CHMP opinion for TOEFLers? Well, yeah, that's another great example.
Speaker Change: If we can use the surrogate biomarker to get accelerated approval.
Speaker Change: And then confirm in a confirmatory trial I think the patients get access to the drugs earlier.
Speaker Change: I think it is.
Speaker Change: It's a valid approach and I personally think that for the right disease and the right surrogate marker. This is exactly the right approach for patients.
Speaker Change: Great. Thank you and maybe just looking at regulators outside the U S any any.
Speaker Change: <unk> from the positive <unk> opinion for <unk>.
Alfred W. Sandrock: I mean, as we all know, a person did not meet the primary endpoint, which was a clinical outcome measure, the pre-specified outcome measure of the ALS functional rating scale, but it did have a strong effect, a clear-cut effect on neurofilament. The U.S. approved it based on that as a surrogate biomarker reasonably likely to predict clinical efficacy. And we now just saw last week that Europe essentially followed suit and allowed for a person to be approved, I assume, again, specifically based on the use of neurofilament as a surrogate biomarker. We'll have to wait for the regulatory, you know, the EPAR, to know exactly what their thinking was. But it's important to note that the only outcome measure that was, well, the main outcome measure that was positive was the NFL.
Speaker Change: Well, yes, that's another Great example.
Speaker Change: As we all know to a first time did not meet the primary endpoint, which was the clinical outcome measure.
Speaker Change: The pre specified.
Speaker Change: Outcome measure of ALS functional rating scale, but it did have a strong effect clear kind of effect on neuro settlement.
Speaker Change: The us approved based on that as a surrogate biomarker reasonably likely to predict clinical efficacy efficacy and we know just saw last week. The Europe, essentially followed suit and allowed for a person to be approved.
Speaker Change: I assume again, specifically based on the use of nerf element as the surrogate biomarker, we'll have to wait for the.
Speaker Change: The regulatory par.
Speaker Change: No exactly what their thinking was but it's important to note that the only outcome measure that was passed well.
Speaker Change: The main outcome measure that was positive.
Alfred W. Sandrock: There was a lot of strong support from the other clinical outcome measures, but the one that was statistically significant was NFL. So Europe may be thinking along the same lines, I guess, is the point. Great, super helpful. Thank you so much for taking the questions and congratulations again on all the progress. Thank you. Our next question comes from the line of Frye-Forseth with Guggenheim Securities. Your line is now open.
Speaker Change: Does the NFL.
Speaker Change: But a lot of strong support from the other clinical outcome measures, but the one that was statistically significant with NFL. So Europe may be thinking along the same lines I guess is the point.
Great Super helpful. Thank you so much for taking the questions and congrats again on all the progress.
Speaker Change: Thank you.
Thank you.
Speaker Change: Okay.
Speaker Change: Our next question comes from the line of price comes from the line of Ryan <unk> with Guggenheim Securities. Your line is now open.
Alfred W. Sandrock: Hey, this is Ry Forseth from Debjit's team at Guggenheim. Two questions from us: One, could you highlight the features of your VY Tau 01 Phase 1B clinical plan that you would point to as competitive advantages relative to historical or ongoing Tau clinical efforts? And our second question is, what lessons from Lecanumab and other A-beta targeting therapies would you point to as most informative for the design of a Tau targeting clinical program, and specifically your VY-Tau-01 program? Yeah, so the BY Tau phase, the phase two program that we hope to get proof of concept based on Tau PET imaging, our current plan, and you know, we still have more work to do to actually get input from investigators and FDA, obviously, but the current plan is to enroll early stage Alzheimer's patients, probably at Brock stage 2, perhaps 3, but, you know, early stage by Brock staging as well, and look for the spread of tau to other regions in The great thing about Alzheimer's disease is that it has a very stereotypical spreading pattern.
Speaker Change: Hey, This is Ryan <unk> from <unk> team at Guggenheim two questions from US one could you highlight the features of your D Y <unk> zero, one phase one b clinical plan.
I'd point to as.
Competitive advantages relative to historical or ongoing.
Speaker Change: <unk> clinical efforts.
Ryan: And our second question is what lessons from La <unk> and other <unk> targeting therapies would you point to as most informative for the design of a tau targeting clinical program and specifically <unk> one program.
Ryan: Yes, so the <unk>.
Ryan: Tao phase.
Ryan: The phase III program that we hope to get proof of concept based on Tau pet imaging.
Ryan: Our current plan and we still have more work to do to actually get input from investigators and the FDA obviously, but.
The current plan is to enroll early stage Alzheimer's patients.
Ryan: Probably a broad stage two.
Ryan: Perhaps III, but early stage.
Ryan: Barack staging as well and look for the spread of Tau to other other regions in the brain by their cortical regions that we know.
Ryan: Todd will spread to the great thing about Alzheimer's disease is that it's a very stereotypical spreading pattern. So we can look at regions of interest in the brain and see whether or not we.
Alfred W. Sandrock: So we can look at regions of interest in the brain and see whether or not we're reducing the spread. And in some ways, we want to recapitulate the data we saw quite robustly in the animals that we just talked about earlier, where we used human pathological tau and looked at the spread. So whether that's a competitive advantage or not, you know, I mean, we chose the program because we like the fact that we can get proof of concept on the spread of Tau very efficiently. We think we can do it with, you know, on the order of 25 or so patients per group in a one-year duration, and then we have proof of concept, and proof of principle on the spread. So that's our current plan. As I said, it's still kind of, you know, we're still a couple of years away.
Ryan: Reducing this spread.
Ryan: And in some way and we want to recapitulate. The data we saw quite robustly in the animals that we just talked about earlier, where we use human pathological Tom look at the spread.
Ryan: So whether thats, a competitive advantage or whether it's.
Ryan: I mean, we chose the program because we like the fact, we can get proof of concept on the on the spread of Tau very efficiently. We think we can do it.
Ryan: On the order of 25, or so patients per group and a one year duration and <unk>.
Ryan: Proof of concept proof of principle on the spread so that's our current plan is as I said, it's still kind of.
Ryan: A couple of years away, so that may change, but that's our current plan.
Alfred W. Sandrock: So that may change, but that's our current plan. In terms of lessons from Leucanumab, Well, you know, in a way, I mentioned earlier that the epitope matters a lot, that early stage patients are probably where you need to go, and that you need to have a robust effect. I mean, you know, the other distinguishing feature of aducanumab and licanumab and endonanumab is that you have a very robust effect on the amyloid PET image in one year. And so we hope to see a robust, clear-cut effect on TILEPAD imaging. And if we don't see that, we're not going to move forward.
Ryan: In terms of lessons from Mccann <unk>.
Ryan: Well in a way I mentioned that earlier that epitope matters a lot.
Ryan: Early stage patients are probably where you need to go and that you would need to have a robust effect I mean, the other distinguishing feature of <unk> Mab at Mccann and Donana. Matt is that you have a very robust effect on the amyloid pet imaging.
Ryan: In one year and so we hope to see a robust credit kind of effect on Tau pet imaging and if we don't see that we're not going to move forward, we need to see the fact that we've got not only target engagement, but a clear pharmacodynamic effect on the tile spreading a hypothesis. If you will if you don't see that we're going to.
Alfred W. Sandrock: We need to see the fact that we've got not only target engagement but a clear pharmacodynamic effect on the TILE spreading hypothesis, if you will. If we don't see that, we're not going to move forward with that program. But as we talked about earlier, we still have the TILE silencing program behind that, which takes a different approach to a very important target. Very helpful, thank you.
Ryan: We're not going to move forward with that program.
Ryan: As we talked about earlier, we still have the top silencing program behind that which takes a different approach.
Ryan: A very important target.
Ryan: Okay.
Speaker Change: Very helpful. Thank you.
Alfred W. Sandrock: Thank you. One moment for our next question. This question comes from the line of Phil Nadeau with T.D. Cowan.
Thank you.
Speaker Change: One moment for our next question.
Speaker Change: This question comes from the line of Phil Nadeau with TD Cowen. Your line is now open.
Operator: Your line is now open. Good afternoon. Thanks for taking our questions. A couple from us.
Philip M. Nadeau: Good afternoon, Thanks for taking my questions.
Philip M. Nadeau: First on the SOD1 program. In the past, you'd got it towards starting GOP1 talks for the program in the first half of 2024. We see that you're getting towards an IND next year. Are the GOP1 talks on schedule?
Philip M. Nadeau: A couple from US first on the <unk> one program in the past you had guided towards starting GOP talks.
Philip M. Nadeau: For the program in the first half of 2024, we see that you're guiding towards an IND next year.
Philip M. Nadeau: GOP talks on schedule any any changes to the timelines.
Alfred W. Sandrock: Any changes to the timelines ahead of the IND final? Actually, no, there's been no change in the timing. This is exactly the timeline that we had planned from the very beginning, Phil.
Philip M. Nadeau: Ahead of the IND filing.
Speaker Change: Actually no there's been no change in our.
Speaker Change: And the timing and this is exactly the timeline that we had planned from the very beginning Phil.
Alfred W. Sandrock: Perfect. And then second, on VY-TIL-01, a follow-up to the prior question on Phase 1a and 1b, acknowledging that proof of concept will be generated by PET scans. What PD markers will you be able to look at from phase 1a and 1b in advance of getting the PET scan data to make sure you're on the right track? Will it simply be pharmacokinetics? Will you have good data on target engagement or any other?
Philip M. Nadeau: Perfect and then second on.
Taylor I wanted to follow up to the prior question.
Philip M. Nadeau: Phase one a one b appreciating that proof of concept will be generated by the pet scans.
Taylor: What PD markers that we'll be able to look at from the phase <unk> b in advance of getting the pet scan data.
Taylor: To make sure Youre on the right track will it simply be pharmacokinetics.
Taylor: Have good data on target engagement or any other.
Alfred W. Sandrock: PD biomarkers that you'll be able to look at to make sure or to ensure that you're on the right track towards producing them. The Pet Proof of Concept, Yana. Yeah, that's a good question, Phil.
Taylor: PD biomarkers that you'll be able to look at to make sure.
Taylor: To ensure that you are on.
Taylor: On the right track towards producing the.
Taylor: The pet proof of concept data.
Speaker Change: Yes, that's a good Craig good question, Phil So on the phase one.
Alfred W. Sandrock: So in Phase 1a, that's going to be a single ascending dose study in normal healthy volunteers, so we're not going to get any pharmacodynamic or target engagement data. We will be getting data on safety and PK and try to get to the point where we identify the optimal doses to move into the Phase 1b trial based on safety and PK. And then in the Phase 1b, or I may have called it, Phase 2 trial, we will be There is a whole pamphlet of Tau-related biomarkers we could look at. The primary one that we're going to pay attention to is Tau PET imaging because, as I said earlier, we'll take advantage of the stereotypical spread of Tau and look at regions of interest in the brain to test the spreading hypothesis, if you will.
Speaker Change: That's going to be a single ascending dose study in normal healthy volunteers. So we're not going to get any pharmacodynamic target engagement data, we will be getting data on safety and PK.
Speaker Change: And trying to get to the point, where we identify the.
Speaker Change: The optimal doses to move into the phase one b trial based on safety and PK.
Speaker Change: And then in the phase one I may have called US phase two trial, we will be.
Speaker Change: There are a whole panoply of Tau related Biomarkers, we could look at the primary one that we're going to pay attention to as Tau pet imaging because as I said earlier, we will take advantage of the stereotypical spread of Tau and look at regions of interest in the brain to test the <unk>.
Speaker Change: Spreading hypothesis, if you will.
Alfred W. Sandrock: There are a number of additional biomarkers we will be looking at, in addition to CSF biomarkers for Tau. We're lucky to have some blood biomarkers of covalently modified forms of Tau that we can look at, such as P-Tau, you know, various phosphorylated forms of Tau. And people have seen efficacy in those, certainly in the anti-amyloid trials, but also in some of the Tau trials as well.
Speaker Change: But there are a number of additional biomarkers, we will be looking at in addition to CSF Biomarkers for Tao.
Speaker Change: We'll also we're lucky to have some blood biomarkers.
Speaker Change: <unk>.
Speaker Change: Covalently modified forms of Tau that we can look at.
Speaker Change: Such as P Tau various phosphorylated forms of Tau.
Speaker Change: And people have asked.
Speaker Change: We've seen efficacy on those certainly in the anti amyloid trials, but also in some of our.
Alfred W. Sandrock: For example, VIV-80, the Tau ASO that Biogen is pursuing. So I think that, you know, we'll look at all of them, but our decision-making, Phil, is going to be primarily based on the Tau PET imaging for the reasons I stated earlier. That's very helpful. Thanks again for taking our questions. Uh huh.
Speaker Change: Tao trials as well for example, debating the Tao.
Speaker Change: So that Biogen is pursuing so so I think that.
Speaker Change: We will look at all of them, but our decision making is going to be primarily based on the Tau pet imaging for the reasons I stated earlier.
Speaker Change: That's very helpful. Thanks, again for taking our questions.
Speaker Change: Okay.
Operator: Thank you. One moment for our next question. This question comes from the line of Joon Lee with Truist Securities. Your line is now open.
Speaker Change: Thank you.
Speaker Change: One moment for our next question.
Speaker Change: This question comes from the line of Joon Lee with <unk> Securities. Your line is now open.
Todd Carter: Hi, good afternoon. This is Mehdi for June. Congratulations on the quarter and thanks for taking our questions. So could you please elaborate on the choice of artificial microRNAs over vectorized siRNA or shRNA for your TauCell Lensing candidate of yours? And I have a follow-up. Todd, do you want to take that?
Joon So Lee: Hi, Good afternoon. This is maybe on for June and congrats on the quarter and thanks for taking our questions.
Joon So Lee: So could you. Please elaborate on the choice of artificial micro Rnas over <unk> already made for household Lansing candidate of yours and I have a follow up.
Joon So Lee: Todd do you want to take that.
Todd Carter: Sure. Of course, our payloads are vectorized siRNAs, or technically a vectorized form of the prior artificial microRNAs. We have a lot of experience. We've been doing this for many, many years at Voyager on how to vectorize these things.
Todd Carter: Sure of course, our payloads are that Victor I SA RNA or technically <unk> pharma the prior artificial micro Rnas.
Todd Carter: Have a lot of experience we've been doing this for many many years.
Todd Carter: At Voyager and added vector as these things.
Todd Carter: You identify the siRNA. It sits within a particular cassette. When expressed, it will give the process, is processed in the nucleus and exported into the cytoplasm, with a single dose to deliver a constitutive level of expression. And this is a catalytic type of approach where the sRNA continues to be used by the processing. Mechanisms of the Cell to Knock Down the mRNA
Todd Carter: We identify the SA RNA it sits within a particular cassette.
Todd Carter: Expressjet will get the process.
Todd Carter: It's processed in the nucleus and export it into the cytoplasm, we think characterizing the SA RNA as we can.
Todd Carter: The single dose deliver stitching.
Todd Carter: The level of expression and these are.
Todd Carter: Catalytic type of approach, where the SA RNA continues to be used by the processing.
Todd Carter: Mechanisms in the cell to knockdown the mrna.
Todd Carter: We know we can get quite specific in targeting the mRNAs involved. And our whole process of selecting these things involves careful attention to things like processing, the lack of off-targets, and that sort of thing. So we're comfortable and actually very enthusiastic about the siRNA approach we take. Does that answer your question?
Todd Carter: We know we can get quite specific in targeting of the mrna is involved.
Todd Carter: And our whole process of selecting lead treatments involves careful attention to things like the processing.
Todd Carter: The lack of off targets.
Speaker Change: Thanks.
Speaker Change: Were comfortable and actually very enthusiastic about the Saturday approach we take.
Speaker Change: Does that answer your question.
Todd Carter: Thank you. So, a quick addition to this question. Is it different from shrna backbone or an artificial RNA backbone? So, the type of promoters that you use? I heard SHRNA, what was your other...
Speaker Change: Thank you so a quick.
Speaker Change: Addition to this question is it different from SHR had made backbone.
Speaker Change: Or.
Speaker Change: RNA backbones so Bob.
Speaker Change: Promoters like us.
Speaker Change: I heard Fsh RNA what was your artificial micro are part of it. It is effectively an artificial micro RNA, but is entirely artificial in that.
Todd Carter: Artificial microRNA. Artificial... It is effectively an artificial microRNA, but it is entirely artificial in that those that we choose do not exist in the endogenous expression, but it is an artificial microRNA. It is different from an shrna, where those hairpins are involved in other types of processing that result in reductions in mRNA. So it is. Thank you. And lastly, there have been multiple N-terminal targeting antibodies for Tau and several for the microtubule binding domain, and it seems that you are the only one with the C-terminal targeting. Can you please provide some insight on how selection of C-terminal has been like less... You know, let's put it out there.
Speaker Change: Those that we choose do not exist in the endogenous expression.
Speaker Change: But it is an artificial micro RNA it is different from an S. H RNA.
Speaker Change: Those hairpins are involved in other types of processing.
Speaker Change: We don't.
Speaker Change: She's an mrna so it is the state.
Speaker Change: Thank you and lastly.
Speaker Change: There have been multiple anti <unk> targeting antibody antibodies for Tau and several.
Speaker Change: Before that.
Speaker Change: Mark marketable binding domain.
Speaker Change: It seems that you are the only one with the <unk> targeting can you. Please provide some insight on how.
Speaker Change: Selection of CFM at all.
Speaker Change: Less.
Alfred W. Sandrock: Well, thank you. Yeah, so it turns out that there are two other companies that are also targeting the C-terminal. We're aware of, that we're aware of, there could be more, but Merck, for example, is in phase one with a C-terminal monoclonal antibody, and Lumbeck is also in phase one with a C-terminal targeting antibody. And you're right that there are a couple of other, at least two other, maybe three other companies targeting the microtubule binding region. You know, again, I think many of us select these antibodies that are specific for pathological forms of Tau, and we have a number against various regions as well. How do you pick which one of those?
Speaker Change: Let's talk about it.
Speaker Change: Thank you, yes, so it turns out that there is.
Speaker Change: There are two other companies that are also targeting the C terminal.
Speaker Change: Where that we're aware of there could be more but.
Speaker Change: Merck for example is in phase one with the C terminal monoclonal antibody and <unk> is also in phase one with the C terminal targeting antibody and Youre right that there are a couple of them, but these two other maybe three other companies targeting the microtubule binding region.
Speaker Change: Again.
Speaker Change: I think many of US we select these antibodies that are specific for pathological forms of Tau and we had a number against various regions as well how do you pick which one of those that are also active for pathological forms of Tau.
Alfred W. Sandrock: They're all selective for pathological forms of tau, and so some have chosen, for example, cellular uptake assays or cellular toxicity assays. We happen to choose the in vivo spreading assay, where you inject human pathological tau into the brain of mice, and we look at the spread. Who knows which of these assays is the right one to use?
Speaker Change: So some have chosen for example, cellular uptake assays or cellular toxicity assay, we happen to choose the in vivo spreading assay, where you inject human pathological tow into the brain of mice and we look at the spread.
Speaker Change: Which one of these assays is the right one to use.
Alfred W. Sandrock: I mean, you know, it's hard to know until we see the human data to be able to say, ah, that's the one that was most predictive. But we like the fact that it's biological, you know, that it's a spreading assay in vivo. It starts with human pathological tau, and so that's why we chose the C-terminal directed antibody, but we're not the only ones that chose the C-terminal theme. Go ahead, Todd.
Speaker Change: It's hard to know until we see the human data to be able to say that's the one that was most predictive.
Speaker Change: But we like the fact that it's a biological.
Speaker Change: That it's a spreading assay in vivo.
Speaker Change: It starts with humans pathological tower and so thats why we chose the C terminal directed antibody, but we're not the only ones who chose the C terminal themes.
Todd Carter: Go ahead Todd.
Todd Carter: Just a couple of other points. You mentioned the N-terminal antibodies, and those have, I think, almost without fail, they have not succeeded in the clinic. And in, and I mentioned this earlier, in the in vivo model that Al described, those antibodies do not work in that model, and so our antibodies are different from those that, to date, have failed in the clinic. We've also chosen the epitope, and when we say C-terminal, these other antibodies that target the C-terminal region target distinct epitopes in the C-terminal region. So even different antibodies in what we might call the C-terminal region are likely to be distinct from one another as well. So, so far, when you look at the N-terminal antibodies, it seems that the animal has a negative predictive value. What we don't know is whether it also has a positive predictive value, but that's the point I think you were trying to make about the N-terminal antibody.
Todd Carter: Just a couple of thoughts.
Todd Carter: Couple of other points you mentioned the in terminal antibodies and those have.
Todd Carter: I think almost without fail.
Todd Carter: Have not succeeded in the clinic.
Speaker Change: And I mentioned this earlier in the in vivo model that al described.
Speaker Change: Those those antibodies do not work in that model and so our antibodies are different from those two data sales in clinic.
Speaker Change: We've also chosen the epic Hilton when we say see terminal is other antibodies that target the C terminal.
Speaker Change: Region, they target distinct episodes in the C terminal region, so even different antibodies and what we might call. The C terminal region are likely to be distinct from one another as well. So so far when you look at the <unk> terminal antibody. It seems that the animal had negative predictive value, but we don't know is whether also has positive predictive.
Speaker Change: But thats the point I think you were trying to make on the N terminal.
Operator: Thank you. Very helpful. I appreciate it.
Speaker Change: Okay.
Speaker Change: Thank you very helpful. I appreciate it.
Operator: Okay, thank you. One moment for our next question. This last question comes in line with Sumant Kulkarni with Canaccord.
Speaker Change: Okay. Thank you.
Speaker Change: Yes.
Speaker Change: Our next question.
Speaker Change: Okay.
Speaker Change: This last question comes from the line of Sumac Kulkarni with Canaccord. Your line is now open.
Sumant Satchidanand Kulkarni: Your line is now open. Good afternoon. Thanks for taking my question. It's actually a follow-up to a question that I asked during the last quarterly update, and it relates to GLP talks on the anti-tau antibody. You mentioned that there were some nuances to running those studies, and your slides today say you still expect to complete these studies in the first quarter. So could you share any specifics on what more needs to be done so you can hit your timeline for an IND submission in the first half of this year? Uh, well, the nuances are that it's an antibody that binds... Specifically to human pathological Tau. And typical stocks, you know, so typical tox studies are done in wild-type animals. But to look at on-target toxicity, there is no animal, wild-type animal, that can be used to evaluate on-target toxicity.
Sumant Satchidanand Kulkarni: Good afternoon. Thanks for taking my question, it's actually a follow up to a question that had asked on the last quarterly update and it relates to GMP talks on the anti Tau antibody.
Sumant Satchidanand Kulkarni: You had mentioned that there were some nuances to running those studies and your slides today, you say you still expect to complete these studies in the first quarter. So could you share any specifics on what more needs to be done. So you can hit your timeline for 90 submission in the first half of this year.
Speaker Change: Well the nuances are that it's an antibody that binds to <unk>.
Speaker Change: Specifically to humans pathological tower.
Speaker Change: And the typical stocks.
Speaker Change: So typical tox studies are done in wild type animals.
Speaker Change: And to.
Speaker Change: To look at on target toxicity, there is no animal wild type animal that.
Speaker Change: That can be used to evaluate on target toxicity.
Alfred W. Sandrock: The nuance is that you have to do studies in animals that are, www.youtube.com.uk But we've been, but we have a lot of confidence in the, in the toxicology package we chose. You'll recall that we did have a pre-IND meeting last year. I think it was almost a year ago; I think it was March of last year; we had an interaction with FDA. A lot of our work is, actually, all of our work is based on that interaction. And look, we're on track to achieve our goal of filing the IND in the first half of this year, so sometime in the next couple of months or so.
Speaker Change: The nuances that you have to do studies in animals that are expressing human pathological Tau otherwise. There is there is no target and the problem is that those animals are sick.
Speaker Change: Because they carry human pathological tower. So it's very hard to do long lasting studies in animals that are sick.
Speaker Change: But we have been but we have look we have a lot of confidence in the <unk>.
Speaker Change: Toxicology package, we chose Youll recall that we did have a pre IMD meeting last year.
Speaker Change: Almost a year ago. It becomes March of last year, where we had an interaction with FDA.
Speaker Change: All of our work is actually all of our work is based on.
Speaker Change: That interaction and look we are on track to achieve our goal of filing the IND.
Speaker Change: In the first half of this year.
Speaker Change: So sometime in the next couple of months or so.
Alfred W. Sandrock: And, and, you know, and, and we hope to start the first in human studies shortly thereafter. Thank you. So at this time, I'm showing no further questions and would now like to turn the call back to Dr. Sandrock for closing remarks. Well, I just wanted to say thank you to everyone for joining us today and please feel free to follow up directly with any questions. Yeah, thank you. And thank you for your participation in today's conference. This does conclude the program, and you may now disconnect. Goodbye. Thank you for watching!
Speaker Change: And.
Speaker Change: And we hope to start the first in human studies shortly thereafter.
Speaker Change: Thank you.
Speaker Change: Thank you.
Speaker Change: So at this time Im showing no further questions and would now like to turn the call back to Dr. <unk> for closing remarks.
Dr. <unk>: Well I just wanted to say thank you to everyone for joining us today and please feel free to follow up directly with any questions. Thank you.
Speaker Change: Yes. Thank you.
Speaker Change: And thank you for your participation in today's conference. This does conclude the program and you may now disconnect.
Speaker Change: Goodbye.
Speaker Change: Okay.
Speaker Change: [music].
Speaker Change: Okay.
Speaker Change: Yes.
Speaker Change: Yes.
Speaker Change: Yes.
Speaker Change: [music].
Speaker Change: Thanks.
Speaker Change: Okay.
Speaker Change: Okay.