Q1 2024 Voyager Therapeutics Inc Earnings Call
Operator: Good afternoon, and welcome to Voyager Therapeutics' first quarter 2024 financial results conference call at this time. All participants are in listen only mode.
Operator: There will be a question and answer session at the end of this call. Please note that today's conference is being recorded. A replay of today's call will be available on the vendors section of the company's website approximately two hours after the completion of this call. I'd like to turn the call over to Trista Morrison, Chief Corporate Affairs Officer. Thank you, and good afternoon.
Yeah.
Speaker Change: Good afternoon, and welcome to the Voyager Therapeutics first quarter 2024 financial results Conference call. At this time all participants are in listen only mode there'll be a question and answer session. At the end of this call. Please note that today's conference is being recorded and a replay of today's call will be available on investors section of the company's website approximately two hours after completion.
Speaker Change: This call I'll now turn the call over to Mr. Morrison, Chief Corporate Affairs Officer.
Trista Morrison: We issued our first quarter 2024 financial results press release this afternoon. The press release and 10 Q are available on our website. Joining me on today's call are Dr. Al Sandrock, our Chief Executive Officer; Dr. Toby Ferguson, our Chief Medical Officer; and Dr. Todd Carter, our Chief Scientific Officer. We will also be joined for the Q&A portion of the call by our Chief Operating Officer and Principal Financial Officer, Robin Swartz. 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 two of today's deck. These statements are based on our current expectations and beliefs. They are subject to risks and uncertainties, and our actual results may differ materially.
Morrison: Thank you and good afternoon, we issued our first quarter 'twenty 'twenty or financial results press release this afternoon.
Mr. Morrison: Yes release, and 10-Q are available on our website.
Morrison: Joining me on today's call are Dr. Al Sandrock, our Chief Executive Officer, Dr. Toby Ferguson, our Chief Medical Officer, and Dr. Tom Carter, our Chief Scientific Officer.
Speaker Change: We'll also be joined for the Q&A portion of the call by our Chief operating Officer, and principal financial Officer Robin Sweat.
Speaker Change: Before we get started I would like to remind everyone that during this call wager Representatives may make forward looking statements as noted in slide two 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.
Trista Morrison: I encourage you to consult the risk factors discussed in our SEC filings, which are available on our website. Now, I will turn the call over to Al. Thank you, Trista, and good afternoon, everyone. Please turn to slide three.
Speaker Change: And now I will turn the call over to al.
Alfred W. Sandrock: <unk> good afternoon, everyone.
Alfred W. Sandrock: I'd like to start by thanking the Voyager team for their dedication to creating transformative genetic medicine. We made tremendous progress advancing these medicines in the first quarter. We just announced that we have obtained IND clearance for our anti-Tau antibody VY-Tau-01 for Alzheimer's disease, and we expect to announce the dosing of the first subject in a single ascending dose trial in healthy volunteers in the coming week or so. Our gene therapy pipeline also advanced during the quarter, with development candidates selected in the GBA-1 and Friedreich's ataxia programs partnered with Neurocrin. These programs, along with our wholly owned SOD1ALS program, are advancing toward IOD filings in 2025. In March, we appointed Dr. Toby Ferguson as our chief medical officer.
Alfred W. Sandrock: Please turn to slide three.
Alfred W. Sandrock: I'd like to start by thanking the Voyager team for their dedication to creating transformative genetic medicine.
Alfred W. Sandrock: We made tremendous progress advancing these medicines in the first quarter.
Alfred W. Sandrock: We just announced that we've obtained RMB clearance for our anti Tau antibody <unk> zero, one for all timers disease, and we expect to announce the dosing of the first subject in this.
Alfred W. Sandrock: Single ascending dose trial in healthy volunteers in the coming week or so.
Alfred W. Sandrock: Our gene therapy pipeline also advanced during the quarter with development candidate selected in the GBA, one and <unk> ataxia programs partnered with Neurocrine. These.
Alfred W. Sandrock: These programs along with our wholly owned <unk> AOS program are advancing toward our IND filings in 2025.
In March we appointed Dr. Toby Ferguson as our Chief Medical Officer Toby.
Alfred W. Sandrock: Toby is an exceptional biotech executive with deep experience advancing novel therapies for CNS diseases. This includes TOFERSEN, the first genetically targeted therapy to be FDA approved for SOD1 ALS, and the first treatment to receive accelerated approval based on plasma neurofilament light chain response. Toby has hit the ground running, and we look forward to his leadership of our emerging clinical portfolio. In January, we announced an expansion of our relationship with Novartis through a new strategic collaboration and CAHPSID license agreement to advance potential gene therapies for Huntington's disease and spinal muscular atrophy. This agreement, together with the public offering we completed in January, brought $200 million of total consideration to Voyager in the first quarter.
Alfred W. Sandrock: Tobey is an exceptional biotech executive with deep experience advancing novel therapies for CNS diseases.
Alfred W. Sandrock: This includes top person the first genetically targeted therapy to be FDA approved for <unk> and the first treatment to receive accelerated approval based on plasma neuro Covenant light chain response.
Alfred W. Sandrock: He has hit the ground running and we look forward to his leadership of our emerging clinical portfolio.
Alfred W. Sandrock: In January we announced an expansion of our relationship with Novartis through a new strategic collaboration and perhaps it license agreement to advance potential gene therapies for Huntington's disease and spinal muscular atrophy.
Alfred W. Sandrock: This agreement together with the public offering we completed in January brought $200 million of total consideration to <unk> during the first quarter.
Alfred W. Sandrock: This bolstered our balance sheet and extended our runway into 2027, and we expect that it will enable us to achieve multiple clinical data readouts. Finally, we presented a robust set of data at the recent ADPD and ASGCT meetings, including data on our multiple TAL targeting programs in our second generation CAHPS system. Given this significant progress, we believe Voyager is emerging as a leader in neurogenetic medicine. Our pillars of value are summarized on slide four.
Alfred W. Sandrock: This bolstered our balance sheet and extended our runway into 2027, and we expect that it will enable us to achieve multiple clinical data readouts.
Alfred W. Sandrock: Finally, we presented a robust set of data at the recent ADP D and ASP TCT meetings, including data on our multiple car targeting programs and our second generation capsid.
Alfred W. Sandrock: Given the significant progress we believe Voyager is emerging as a leader in neuro genetic medicine.
Alfred W. Sandrock: Our pillars of value are summarized on slide four.
Alfred W. Sandrock: First, we have a strong pipeline of four wholly owned and 13 partnered programs, with the first expected to enter clinical trials in the coming weeks and the potential for three more to follow next year. Second, we have an industry-leading platform designed to overcome the delivery challenges inherent to CNS gene therapy. Our tracer platform enables us to create novel capsids that, following IV delivery, harness the extensive cerebrovasculature to enable widespread payload distribution across multiple brain regions and cell types. These capsids have demonstrated translatability in multiple species and have enabled the selection of multiple development candidates in our wholly owned and partnered gene therapy program.
Alfred W. Sandrock: First we have a strong pipeline of four wholly owned and 13 partnered programs with the first expected to enter clinical trials in the coming weeks and the potential for three more to follow next year.
Alfred W. Sandrock: Second we have an industry leading platform designed to overcome the delivery challenges inherent to CNS gene therapies.
Alfred W. Sandrock: Our tracer platform enables us to create novel capsid that following IV delivery harness the extensive three Boe vasculature to enable widespread payload distribution across multiple brain regions and cell types.
Alfred W. Sandrock: These capsules have demonstrated demonstrated translate ability in multiple species and have enabled a selection of multiple development candidates in our wholly owned and partnered gene therapy programs.
Alfred W. Sandrock: Third, we have Blue Chip Partnerships, anchored by Tracers Potential, to transform the treatment of CNS diseases. In addition to Neurocrine, our partners include Novartis and Alexion. In total, our partnered programs could generate up to $8.2 billion in longer-term milestone payments.
Alfred W. Sandrock: Third we have blue ship Blue chip partnerships anchored by tracers potential to transform the treatment of CNS diseases. In addition to Neurocrine. Our partners include Novartis and Alexia on in total our partnered programs could generate up to $8 2 billion.
Alfred W. Sandrock: Longer term milestone payments.
Toby Ferguson: Finally, we continue to explore the potential to leverage receptors we have identified to shuttle non-viral genetic medicines into the brain. Ultimately, we aim to expand from gene therapy and antibodies into other modalities of neurogenetic medicine, broadening our impact. With that, I'll turn the call over to Toby. Thank you, Al, and good afternoon. Please turn to slide five.
Alfred W. Sandrock: Finally, we continue to explore the potential to leverage receptors, we have identified to shuttle non viral genetic medicines into the brain.
Alfred W. Sandrock: Ultimately, we aim to expand from gene therapy and antibodies into other modalities of narrow genetic medicine.
Alfred W. Sandrock: <unk> our impact.
Alfred W. Sandrock: With that I'll turn the call over to Tobi.
Tobi: Thank you al and good afternoon, please turn to slide five.
Toby Ferguson: This slide summarizes the four wholly owned programs and our 13 partner programs that Al mentioned earlier. Part of what attracted me to Voyager is that these programs are focused on targets validated by human biology and human genetics, as a drug developer and former practicing neurologist. I've dedicated my career to improving the lives of people living with neurologic disease, and while our understanding of the genetic and biological basis of CNS diseases has advanced considerably.
Tobi: This slide summarizes the four wholly owned programs and our 13 partner programs that al mentioned earlier.
Tobi: Part of what attracted me to Voyager.
Tobi: These programs are focused on targets validated by human biology is human genetics.
Tobi: As a drug developer and former practicing urologist I've.
Tobi: I've dedicated my career to improving the lives of people living with neurologic diseases.
Tobi: And while our understanding of the genetic and biological basis, a CNS diseases has advanced considerably.
Toby Ferguson: Translating that understanding to new therapies has been hindered by challenges with crossing the blood-brain barrier. I believe that the progress that Voyager has made in this regard is transformative and provides an unprecedented opportunity to redefine the treatment of CNS diseases. I'm delighted to join the company as we prepare to enter the clinic and realize the full potential of our pipeline of neurogenetic medicine. Turning to slide six, I want to focus for a moment on two of our wholly owned programs at Target.
Tobi: I think that understanding to new therapies has been hindered by challenges with crossing the blood brain barrier.
Tobi: I believe that the progress that <unk> has made in this regard is transformative.
Tobi: It provides an unprecedented opportunity to redefine the treatment of CNS diseases.
Speaker Change: Im delighted to join the company as we prepare to enter the clinic and realize the full potential of our pipeline of neuro genetic medicines.
Speaker Change: Okay.
Speaker Change: Turning to slide six I want to focus for a moment on two of our wholly owned programs at target Com.
Toby Ferguson: We believe tau is a critically important target for the treatment of Alzheimer's disease. The presence of tau pathology in the brain is a cardinal feature of AD. Further, the spread of tau pathology through the brain closely correlates with clinical decline, and can be visualized with tau pathology.
Speaker Change: We believe Tau is a critically important target for the treatment of Alzheimer's disease.
Speaker Change: The presence of Tau pathology in the brain as a cardinal feature of <unk>.
Speaker Change: Further the spread of Tau pathology through the brain closely correlates with clinical decline.
Toby Ferguson: Importantly, recent third-party clinical data generated using an intrathecally administered tau ASO have shown that reducing tau was associated with favorable trends in clinical outcomes. As I'll mention, we're excited to announce that BY-Tau-01, our anti-tau monoclonal antibody, has obtained INE clearance. And we look forward to announcing in the coming weeks the initiation of a single-setting dose trial in healthy volunteers. I'll talk more about that trial in a moment. First, a bit of background on this.
Speaker Change: Can be visualized with Tau pet imaging.
Speaker Change: Importantly, recent third party clinical data generated using it particularly administer.
Speaker Change: So I've shown that reducing tao with associated with favorable trends on clinical outcomes.
Speaker Change: As Al mentioned, we're excited to announce that <unk>.
Speaker Change: Anti Tau monoclonal antibody obtained IV clearance.
Speaker Change: We look forward to announcing in the coming weeks initiation of a single ascending dose trial in healthy volunteers.
Speaker Change: I'll talk more about that trial in a moment.
Speaker Change: First a bit of background on this program.
Toby Ferguson: DUI Tau O1 aims to inhibit the cell-to-cell spread of the exoskeleton's pathological tau in the brain. In contrast to third-party anti-Tau antibody approaches that have targeted the N-terminus of Tau and have been unsuccessful in the clinic, BY Tau O1 targets the C-terminal epitope of pathological tau.
Speaker Change: <unk> aims to inhibit the cell to cell spread for the ACA silicones pathological Tau in the brain.
In contrast to third party anti Tau antibody approaches that are targeted the interim in this hotel and have been unsuccessful in the clinic.
Speaker Change: One part is the <unk> epitopes pathologic hotel.
Toby Ferguson: We believe the epitope matters; in a preclinical in vivo model of tau spread, the murine surrogate of VY tau O1, inhibited tau spread by approximately 70%. However, N-terminally directed antibodies had no significance, indicating the negative predictive value of this.
Speaker Change: We believe the epitope matters.
Speaker Change: In a preclinical in vivo model of <unk> spread.
Speaker Change: <unk> target of <unk> one.
Speaker Change: Inhibited tell spread where approximately 70%.
Speaker Change: Well internally directed antibodies had no significant.
Speaker Change: This indicates the negative predictive value of this model.
Toby Ferguson: We look forward to establishing whether or not it has positive predictive value as we advance into clinical trials. Importantly, and in parallel, we are progressing a tau silencing gene therapy approach intended to inhibit the production of tau proteins. This program deploys a Tau-targeted sRNA package and an IV-administered tracer cap. Using this approach, we've demonstrated robust reduction.
Speaker Change: We look forward to establishing whether or not it has positive predictive value.
Speaker Change: We advanced into clinical trials.
Speaker Change: Importantly, and in parallel.
Speaker Change: <unk> silencing gene therapy approach intended to inhibit the production of Tau protein.
Speaker Change: This program deploys, a tau targeted RNA packaged into an IV administered tracer capsid.
Speaker Change: Using this approach we have demonstrated robust reductions.
Toby Ferguson: Tau mRNA and Protein Across the Brain on a Single IV Administration in Mice Expressing Human Tau. We believe this program has the potential to provide a transformative... Single Dose Treatment for Alzheimer's Disease. We anticipate filing an IND in 2020. Turning to slide 7, as I mentioned, we anticipate the announcement of the dosing of the first subjects in our single ascending dose trial, VY Tau O1, in the coming weeks. This will be a single-site study in which we expect to enroll approximately 48 participants.
Speaker Change: And Tau mrna and protein across the brain find a single IV administration and mice expressing human talent.
Speaker Change: We believe this program has the potential to provide a transformative.
Speaker Change: Single dose treatment for Alzheimers disease, and we anticipate filing an IND in 2026.
Turning to slide seven as I mentioned, we anticipate the announcement dosing of the first subjects in our single ascending dose trial of <unk> in the coming weeks. This.
Speaker Change: This will be a single site study.
And which we expect to enroll approximately 48 participants.
Toby Ferguson: The primary aim of the trial is to generate initial safety and PK data that will inform a subsequent multiple ascending dose trial for participants with early Alzheimer's disease. Expect to conduct the multiple ascending dose trial for participants with early Alzheimer's disease next year and generate initial TALPAT imaging data in 2026 that has the potential to show slowing of calcium. Turn to slide 8.
Speaker Change: The primary end of the trial is to generate initial safety and PK data outlook.
Speaker Change: That will form a subsequent multiple ascending dose trial.
Speaker Change: We expect to conduct the multiple ascending dose trial participants with early Alzheimer's disease.
Speaker Change: <unk> initiated this trial next year.
Speaker Change: And general initial Tau pet imaging data in 2026.
Speaker Change: That has the potential to show a slowing of Carlsbad.
Toby Ferguson: In addition to our programs targeting Tau, we are also advancing three gene therapy programs for which we expect to file INDs next year. They include our wholly owned SOD1 silencing program targeting the genetic cause of SOD1 ALS. The Neurocrine Partnered Protaxin Gene Replacement Program targeting the JETA cause of predilects ataxia and the Neurocrine Partnered GBA1 Gene Replacement Program. Mutations in GBA1 represent both one of the most common genetic causes of Parkinson's disease, as well as the cause of other GBA1-related diseases.
Speaker Change: Turning to slide eight.
Speaker Change: In addition to our programs targeting Tau we are.
Speaker Change: Also advancing three gene therapy programs, which we expect to file our IND next year.
Speaker Change: They include our wholly owned <unk> program targeting the genetic cause of sideline AOS.
Speaker Change: The Neurocrine partnered for tax engine replacement program targeting the <unk> cost of freight Electrotaxis.
Speaker Change: The Neurocrine partnered GBA gene replacement program mutation.
Speaker Change: Mutations in GBS GBA one.
Speaker Change: Both one of the most common genetic causes of Parkinson's disease as well as the cause of other GBA one related diseases.
Toby Ferguson: Each of these programs leverages an IV-administered blood-brain barrier penetrator, Tracer-Cava, and has the potential to provide a single-dose disease-modifying... I look forward to advancing this promising suite of programs in the clinic. With that, I'll turn the call over to Todd. Thanks, Toby. Please turn to slide 9.
Speaker Change: Each of these programs Leverages, an IV administered blood brain barrier penetrant tracer capsid.
Speaker Change: Has the potential to provide a single dose disease modifying treatment.
Speaker Change: We look forward to advancing promising suite of programs in the clinic.
Speaker Change: Is that I will turn the call over to Tom.
Todd Carter: Thanks Tobey.
Todd Carter: In support of our advancing gene therapy pipeline, we were pleased to present a robust set of data on the potential clinical translatability, manufacturing, and overall performance of our tracer cap at the American Society of Gene and Cell Therapy Annual Meeting on Wednesday. Voyager scientists presented a total of 12 abstracts of, and I'd like to review a few highlights first. We presented new data on our second-generation IV-delivered tracer capsules. This session was standing room only, with a line out of the door and down the hall, which I think speaks to the high level of interest in novel capsids engineered to cross the blood-brain barrier.
Todd Carter: Please turn to slide nine.
Todd Carter: And supported by our advancing gene therapy pipeline.
Todd Carter: Pleased to present, a robust set of data on the potential clinical translate ability manufacturing and overall performance of our tracer captions at the American Society of gene and cell therapy annual meeting last week.
Todd Carter: Wade your scientists presented a total of 12 abstracts at the meeting.
Todd Carter: And I'd like to review a few highlights.
Todd Carter: First we presented new data on our second generation IV delivered tracer cabinets.
Todd Carter: This session with standing room, only with a line out of the door down the hall.
Todd Carter: Which I think speaks to the high level of interest in novel Capsid is engineered to cross the blood brain barrier.
Todd Carter: Our second-generation capsids showed further enhanced blood-brain barrier penetrance and reduced liver expression, compared to our own first-generation tracer-derived cats. These second-gen capsids demonstrated robust transduction of 50 to 75 percent of cells across diverse brains, with upwards of 95% transduction, and certain T cell types, such as Purkinje neurons, at a clinically relevant dose of three times 10 to the 13 vector genome This also included the transduction of 98% of dopaminergic neurons of the substantia nigra and over 80% of spinal motor neurons.
Todd Carter: Our second generation capsid should further enhance split brain barrier penetrates and reduced liver expression.
Todd Carter: Third to our own first generation tracer derive catches.
Todd Carter: These second Gen <unk> demonstrated robust transduction of 50% to 75% of sales across diverse bringing regions with upwards of 95% transduction.
Todd Carter: Certain key cell types, such as purkinje neurons.
Todd Carter: At a clinically relevant dose of three times 10 to the 13 vector genomes per kilogram.
Todd Carter: This also included transduction of 98% of dopaminergic neurons at the substantial Niagara.
Todd Carter: And over 80% of spinal motor neurons.
Todd Carter: Importantly, our tracer capsids have enabled selection of development candidates for the three lead gene therapy programs that Toby just reviewed. We presented data at ASGCT on VYA 9323, our wholly owned shot one silencing gene therapy, which uses a second generation tracer cast. The data demonstrated that a single IV dose of UI-9323, which had the 3E13 specter genomes per kilogram dose, reduced SOD1 mRNA by up to 80% in spinal cord motor neurons in non-human primates.
Todd Carter: Importantly, our tracer captains have enabled selection of development candidates for the three lead gene therapy programs that Toby just reviewed.
Todd Carter: We presented data at <unk> 93 to three.
Todd Carter: Our wholly owned <unk> silencing gene therapy.
Todd Carter: Which uses the second generation tracer capsid.
The data demonstrated that a single IV dose of <unk> 93 to three <unk>.
Todd Carter: The <unk> 13 vector genomes per kilogram dose reduced.
By up to 80% and spinal cord modern competence in nonhuman primates.
Todd Carter: Finally, as part of our strategy to mitigate the risks of developing tracer capsid-derived product candidates and maximize the probability of success in the clinic, Voyager has been working to identify the receptors that mediate the delivery of these capsids into the CNS and confirm their expression here. At ASGCT, we identified tissue-nonspecific alkaline phosphates, or ALPL, formerly known as ReceptorX, as the highly conserved receptor expressed on the brain vasculature that mediates the delivery of tracer capsids VCAP 101 and 102 across the blood-brain barrier.
Todd Carter: Finally, as part of our strategy to mitigate the risks of developing tracer captured derived product candidates.
And maximize their probability of success in the clinic.
Todd Carter: <unk> been working to identify the receptors that mediate to deliver at least cap since into the CNS.
Todd Carter: And confirm their expression in humans.
And ESG ECT, we identified tissue nonspecific alkaline phosphatase or LPL, formerly known as <unk> receptor acts as the highly conserved receptor expressed on brain vasculature that mediates the delivery of <unk> 101, and 102 across the blood brain barrier.
Todd Carter: These capsids bind human, primate, and murine ALPL isoforms, further strengthening our confidence in the clinical potential of tracer capsid. More broadly, these data establish ALPL as a novel brain delivery shuttle, and we're exploring the opportunity to leverage this receptor to deliver multiple therapeutic modalities across the blood-brain barrier. We look forward to sharing these data in the future.
Todd Carter: These captured by human Primate and <unk> farms.
Todd Carter: Further strengthening our confidence in the clinical potential of <unk> capex.
Todd Carter: More broadly these data established LPL as a novel brain delivery channel.
And we are exploring the opportunity to leverage this receptor to deliver multiple therapeutic modalities across the blood brain barrier.
Todd Carter: We look forward to sharing these data in the future.
Todd Carter: Collectively, the data package we presented today as GCT represents the most extensive validation to date of the potential clinical translatability of our tracer capsid, and we look forward to evaluating its ability to transform the course of a broad range of neurological diseases. I will now turn the call back over to Al. Thanks, Todd.
Todd Carter: Collectively the data package, we presented today <unk> represents the most extensive validation to date of.
Todd Carter: The potential clinical translate ability of our tracer captives.
Todd Carter: And we look forward to evaluating their ability to transform the course of a broad range of neurological diseases.
Todd Carter: I will now turn the call back over to al.
Alfred W. Sandrock: Thanks Todd.
Alfred W. Sandrock: Turning to slide 10, you can see Voyager has had an incredibly strong start to the year.
Alfred W. Sandrock: As I mentioned before, this would not be possible without the hard work and dedication of our employees. I know many of them are listening, so I want to say again, thank you. With a robust slate of upcoming clinical milestones, a maturing partnership portfolio, and cash runway into 2027, we believe Voyager is poised to drive significant value over both the near and long term. With that, we will open the call to questions. Operator.
Alfred W. Sandrock: As I mentioned before this would not be possible without the hard work and dedication of our employees.
Alfred W. Sandrock: I know many of them are listening so I want to say again. Thank you.
Alfred W. Sandrock: With a robust slate of upcoming clinical milestones are maturing partnership portfolio and cash runway into 2027, we believe Voyager is poised to drive significant value over both the near and long term.
Speaker Change: With that we will open the call for questions operator.
Operator: Thank you. At this time, we'll conduct a 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.
Speaker Change: Okay.
Speaker Change: Thank you at this time, we will conduct a question and answer session.
Speaker Change: I wanted 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 standby, 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 Joon Lee of True Securities. Your line is now open. Hi. Good afternoon and congratulations on the great progress. This is Mahdi on for June.
Speaker Change: Our first question comes from the line of Joon Lee of true Securities. Your line is now open.
Joon So Lee: Hi, good afternoon, and congrats on the great progress. This is maybe on for June.
Joon So Lee: Last week at ASGCD, you showed great data related to receptor X ALPL. So, could you please elaborate on the ways that you are planning to use this knowledge for delivery of the other modalities to the CNS? Specifically, do you think antisense oligos and LMPs could see similar levels of transcytosis seen with AAVs?
Joon So Lee: Last week.
Joon So Lee: And specifically you showed great data related to a receptor ex <unk>. So could you. Please elaborate on the ways that you are planning to use this knowledge for delivery of the other modalities.
Joon So Lee: CNS, specifically do you think.
Antisense Oligos and LNP could see similar levels of psychosis.
Joon So Lee: Sin.
Speaker Change: With <unk>. Thank you.
Alfred W. Sandrock: Thank you. Yeah, thanks for the question. This is Al Sandrock.
Alfred W. Sandrock: Hi, yes. Thanks for the question. This is al Sandrock. So briefly we know that these receptors mediate the transport of these very large AAV capsid across the BBB.
Alfred W. Sandrock: So, briefly, you know that these receptors mediate the transport of these very large AAV capsids across the BBB. And what we're going to do now is to make ligands against the receptors, conjugate them to various macromolecules to see if we can get them to cross the BBB, we believe by transcytosis. And the range of molecules we could look at includes protein therapeutics as well as oligonucleotides, and we're progressing those experiments as we speak. Thanks, Al.
Speaker Change: And where.
Alfred W. Sandrock: We're going to do now is to make a lot of gains against the receptor conjugate them to various macro molecules to see if we can get them to cross the BBB hope.
Alfred W. Sandrock: We believe by Trans Cytosis.
Alfred W. Sandrock: And the range of molecules, we could look at include protein therapeutics as well as oligonucleotides and we're progressing those experiments as we speak.
Alfred W. Sandrock: So we are looking at a variety of different modalities. As Al indicated, we're looking at antibodies, oligos, other sorts of proteins. Al mentioned that we're in the process of identifying ligands, and we have identified some ligands. And we're looking forward in the future to hopefully sharing some of those data when we're ready.
Speaker Change: Thanks Al. So we are looking at a variety of different modalities as al indicated we're looking at antibodies all of those other sorts of proteins.
Speaker Change: Al mentioned that we're in the process of identifying ligands and we have identified some ligands and we're looking forward in the future to hopefully sharing some of those data when we're ready to.
Speaker Change: I appreciate it thank you.
Operator: Thank you. Thank you one moment for our next question. Our next question comes from the line of Jack Allen of Baird. Your line is now open. All right, thanks so much for taking the questions and congratulations on the progress. I wanted to ask about some of the work you presented at ASJCT around the optimization of manufacturing.
Speaker Change: Thank you for our next question.
Speaker Change: Okay.
Speaker Change: Our next question comes from the line of Jack Holland of Baird. Your line is now open.
Jack Kilgannon Allen: How are you thinking about optimizing manufacturing before you bring candidates into the clinic with your gene therapies? And what do you expect the benefits will be as it relates to COGs of your more potent gene therapies as well? Well, I'll start, and I'll ask Todd to help here. So we're going to be planning to use HEK-293 cells to manufacture these products. We have a very robust internal technical operations team, and as part of the development candidate selection, we assess manufacturability, both in the downstream as well as upstream processes. And, of course, we're going to be verifying the percentage of full capsids, partially full capsids, as well as empty capsids. And so we assess manufacturability as part of the development candidate selection. Todd?
Jack Kilgannon Allen: Alright, thanks, so much for taking the questions and congratulations on the progress I wanted to ask about some of the work you presented at Ias JCT around the optimization of manufacturing how are you thinking about optimizing manufacturing before you bring candidates in the clinic with our gene therapies and what do you expect the benefits will be as it relates to cargo gear more potent gene therapy.
Jack Kilgannon Allen: These as well.
Speaker Change: Well I'll start and I'll ask Todd to help here. So we're going to be planning to use <unk> hundred 93 cells to manufacture these products we have.
Speaker Change: Have a.
Speaker Change: A very robust internal tech technical operations team and part of the development candidate selection, we assess manufacturer ability.
Speaker Change: Both both as well as the.
Todd Carter: Downstream as well as upstream processes.
Todd Carter: And of course, we're going to be verifying percentage of full capsid, partially full capsid as well as empty capsid and so we assess manufacturer ability.
Todd Carter: As part of the development candidate selection.
Alfred W. Sandrock: So, as Al mentioned, we do have that manufacturability is a key component. It's actually part of our whole assessment of our novel capsids as we identify them. In each case, the payload can make a difference, so for any given program, we have to establish the manufacturability of the capsid in question and the particular payload for the disease indication as well. All that goes into our assessment, and we begin with research-grade material.
As Al mentioned, we do have that manufacture ability is a key component, it's actually part of our whole assessment of our novel capsid as we identify them.
Todd Carter: In each case the payload can make a difference so that for any given program. We have to establish the manufacturer ability with the capsid in question and the particular payloads for the disease indication as well.
Todd Carter: And then once we develop the development candidate, then we proceed to the process development to move that into manufacturability. You also asked a question about COGS, and, of course, it's not exactly necessarily a one-to-one tradeoff, but you can imagine, as we're looking with our novel capsids that have a potency approximately about an order of magnitude greater than what the dose is currently used in the clinic, we expect to see substantial savings because we need much less material to deliver the same level, or actually greater levels of delivery to the CNS than the conventional capsid.
Todd Carter: All of that goes into our assessment and we begin with research grade material and then once the once we developed the development candidate and we proceed to the process development to move that in the manufacturer ability. You also asked a question about Cogs and of course, it's not exactly necessarily a one to one.
Todd Carter: Trade off but you can imagine as we're looking with our novel capsid that have a potency approximately about an order of magnitude greater than one.
Todd Carter: The dose is currently used in the clinic, we expect to see substantial savings because we need much less material to deliver the same level or actually greater levels of delivery to the CNS and the conventional catchwords.
Todd Carter: Yeah, and I would just add, Jack, that in addition to the lower doses, you know, what we note is that we're going to transfer the process to a CDMO for manufacturing. And the CDMO world has really come up to speed in terms of scalability.
Todd Carter: And I would just add Jack that in addition to the lower doses.
What we note is that we're going to we're going to transfer the process to a CMO for manufacturing and the CMO World has really come up to speed in terms of scalability. We're now seeing scale and every time you increase the scale.
Alfred W. Sandrock: We're now seeing scale, and every time you increase the scale, you actually reduce the cost. So, and at the pace that it's going, we expect to see continued advancement in that area as well. That's great.
Todd Carter: We actually reduce the cost so.
Todd Carter: And at the pace that it's growing we expect to see continued advancement in that area as well.
Jack Kilgannon Allen: Can I just ask one final question on that? I know we haven't really gotten this far in the gene therapy space, but how does, you know, shelf life of these products play a role when you think about the commercial applicability of this manufacturing scale here? Shelf life.
Speaker Change: Alright, Thats, great can I just ask one final question on that.
Speaker Change: I know, we haven't really gotten thus far in the gene therapy space. So how does it.
Speaker Change: Shelf life of these products play a role when you figure out the commercial I'll talk about these manufacturing scale here.
Speaker Change: Shelf life, while that's a question I hadn't thought about yet but anybody.
Todd Carter: Wow, that's a question I hadn't thought about yet. But anybody here has an answer to that? So we do assess the shelf life. And of course, for gene therapy, we typically would need to require it to be held at particular cold temperatures; all that is part of the evaluation for stability, both short-term and long-term. So that's an important part of our manufacturability and our process development. Thank you, Todd. Thanks so much.
Speaker Change: <unk>.
Speaker Change: Either the answer to that so.
Speaker Change: We do assess the shelf life and of course for a gene therapy.
We typically would be required to be held at particular cold temperatures all that is part of the evaluation for stability.
Speaker Change: Yes.
Speaker Change: For both short term and long term, so thats, an important part of our manufacture ability and our process development.
Speaker Change: Thanks, Todd got it.
Todd Carter: Thanks, so much congrats on the progress.
Speaker Change: Thank you.
Speaker Change: For next question.
Speaker Change: Okay.
Jack Kilgannon Allen: Congratulations on the progress. Thank you. Thank you one more for the next question. Our next question comes from the line of Patrick Trucchio of HC Wainwright & Co. Your line is now open.
Speaker Change: Our next question comes from the line of Patrick <unk> of <unk>.
Patrick: We were and co. Your line is now open.
Patrick Ralph Trucchio: Thanks. Good afternoon, and congrats on all the progress. Just a couple of follow-up questions from me. The first is, I'm wondering if you can discuss any potential read-through that you'll be looking for from the Advisory Committee meeting on June 10 regarding donetimab and Alzheimer's disease with your Alzheimer's programs. And then, separately, just to follow up on the ASGCT data, specifically the data in the human tau mouse model that showed reduction in tau mRNA levels up to 90 percent and 50 to 70 percent reduction in tau protein. Can you tell us how this data compare with prior generation capsids and how the data may support advancement of tau silencing gene therapy, IND, in 2026? Thanks, Patrick.
Patrick: Thanks, Good afternoon, and congrats on all the progress just a couple of follow up questions from me.
Patrick: The first is I'm wondering if you can discuss any potential read through that youll be looking for from the Advisory Committee meeting on June 10 regarding Donana mob in Alzheimer's disease to your Alzheimer's programs.
Patrick: And then separately just to follow up on the <unk> data specifically the data in human talent mouse model that showed reduction in tau mrna levels up to 90% and 50% to 70% reduction in Tau protein can you tell us how this data compare with prior generation capsid.
Patrick: How the database support advancement of Tau gene.
Patrick: Silencing gene therapy IND in 2026.
Alfred W. Sandrock: I'll answer the first question, and maybe I'll ask Todd to answer the second one. On the first question, well, it will be a very interesting advisory committee. We do have a vectorized anti-amyloid program in our pipeline as well, so we're watching that advisory committee with interest. I think a lot of the questions might be unique to Donanimab. It may not pertain very much to our program, but nevertheless, there might be some important features. For example, what are the outcome measures that are going to be important for approval? And, of course, that's always something that we need to keep an eye on. But that's down the line for us.
Speaker Change: Thanks, Patrick I'll answer the first question and maybe I'll ask Todd to answer the second one.
Todd Carter: The first question, while it will be a very interesting Advisory committee. We do have a vector is empty amyloid program in our pipeline as well. So we're watching that advisory committee with interest.
Speaker Change: <unk>.
Todd Carter: I think a lot of the questions.
Todd Carter: Questions might be unique to Donana mab it may not pertain very much to our program.
Todd Carter: The less there might be some important features for example, what are the outcome measures that are going to be important for.
Todd Carter: For approval.
Todd Carter: And of course, that's always something that that we need to keep an eye on but.
Alfred W. Sandrock: We have to get into the clinic first. But so that's the kind of thing we may be paying attention to, but it'll be an interesting meeting. Todd?
Todd Carter: That's down the line for us.
Todd Carter: We have to get into the clinic first but.
Todd Carter: So that's the kind of thing we may be paying attention to but it'll be an interesting meeting thought.
Todd Carter: So on our COW Knockdown program, the data that you're referring to, we showed some at ADPD and also at ASGCT. The knockdown in the mouse was with a mouse-capable capsid, so we used that really to assess the payload and also to hopefully demonstrate, and we feel that we did, that it has the ability to knock down Tau, both mRNA and protein, at a clinically relevant dose. So we think that that's what we showed in those mouse studies.
Todd Carter: So on Martell knockdown program the data that you're referring to we showed some at ADP D and also at <unk>.
Todd Carter: <unk>.
Todd Carter: The knockdown in the mouse was with a mouse capable capsid. So we use that really to assess the payload and also to hopefully demonstrate and we feel that we did that it's the payload has the ability to knockdown tau mrna and protein.
Todd Carter: And the clinically relevant dose.
Todd Carter: With regard to the payload, we were able to see at a well-tolerated and safe dose in those animals delivering sufficient vector to the brain that we saw quite a remarkable knockdown of the mRNA in those animals. So it's building that proof of concept for the knockdown.
Todd Carter: So we think that that's what we showed in those now studies with regard to the payload, we were able to see well tolerated and safe dose in those animals delivering sufficient vector to the brain that we saw quite remarkable knockdown of the mrna in those animals.
Todd Carter: It's building that proof of concept for the knockdown and we're moving forward now and evaluating the <unk>.
Patrick Ralph Trucchio: And we're moving forward now and evaluating the novel capsids for non-human primates and humans with the payloads in question. So we're looking forward to sharing more of that in the future. Great. Thanks so much.
Todd Carter: <unk> for non human primates and humans with the payloads in question. So we're looking forward to share more of that in the future.
Speaker Change: Great. Thanks, so much.
Operator: Thank you. One moment for the next question. Our next question comes from the line of Philip Nadeau of T. Cowan. The line is now open. Good afternoon.
Speaker Change: Thank you Juan for next question.
Speaker Change: Our next question comes from the line of Phil Nadeau of Cowen. Your line is now open.
Philip M. Nadeau: Congratulations on the progress. And thanks for taking our questions. First couple on VY Tau O1.
Philip M. Nadeau: Good afternoon, congrats on the progress and thanks for taking our questions first a couple on <unk>.
Philip M. Nadeau: Have you disclosed what doses you are going to be exploring in the single ascending dose trial and can you talk a little bit how youre going to use the pharmacokinetic data that you.
Toby Ferguson: Have you disclosed what doses you are going to be exploring in this single ascending dose trial? And can you talk a little bit about how you're going to use the pharmacokinetic data that you gather to determine what doses should be explored in the MAD trial? How will you extrapolate from the single dose to the multiple doses, and particularly for peripheral versus maybe crossing the blood-brain barrier? Thanks for the call. This is Toby.
Speaker Change: So you gather to determine what doses should be fixed.
Speaker Change: Gordon.
Speaker Change: Trial.
<unk>.
Speaker Change: Yes.
Speaker Change: Extrapolate from the single dose to the multiple doses and particularly for Brian.
Speaker Change: Peripheral versus maybe crossing the blood brain barrier.
Speaker Change: Great. Thanks for the call this is Toby.
Toby Ferguson: We haven't disclosed our doses, but broadly speaking, we've examined our candidates in our preclinical model of tau spread, where we've shown that we see a reduction by about 70% of the spread of pathologic tau in our mouse models. In addition, we've done preclinical work in primates. I think, fundamentally, this is a single ascending dose study in about 48 patients over multiple cohorts. We expect, based on that data, to get both, of course, safety information, as well as PK information on the periphery that we think we can appropriately translate into doses for the MAD in mid-2025.
Speaker Change: We haven't disclosed our doses, but broadly speaking we've examined our multiple candidates in our preclinical model of <unk> spread but we've shown that we see reduction by about 70% of the splitter project how in our mouse models.
Speaker Change: In addition, we have.
Speaker Change: We've done preclinical work in primates I think fundamentally this is a single ascending dose study in about 48 patients over multiple cohorts. We expect based on that data to get both of course safety information as well as PK information I'll quickly that we think we can appropriately translates into doses for the mad in mid 2020.
Toby Ferguson: Broadly, we want to aim to estimate the sort of the underlying exposures needed to get appropriate exposure in the brain to treatment. Yeah, and so I may want to add that, based on our preclinical studies, including an NHP, we don't anticipate any major surprises. This is likely to be very similar to other monoclonal antibodies, and therefore the brain to plasma ratio will be in the 0.1 to 0.5 percent range.
Speaker Change: Broadly we want to aim to estimate sort of.
Speaker Change: The underlying exposures needed to get appropriate exposure in the brain.
Speaker Change: Yes, Phil I may want to add that.
Speaker Change: I mean based on our preclinical studies, including <unk> and Hps.
Speaker Change: We don't anticipate any major surprises this is likely to be very similar to other monoclonal antibodies and therefore, the brain to plasma ratio will be in the 1% to 5% range.
Toby Ferguson: And as Toby said, we know the exposures we need to get into the brain to inhibit tau spreading in the model that we use to choose the antibodies. So that'll give you some idea. And of course, we do expect that trial to inform the dose range in the upcoming multiple ascending dose trial. That's really helpful.
Speaker Change: And as Toby said.
Speaker Change: No the exposures that we need to get into the brain to inhibit tau spreading in the model that we use to choose the antibody. So so that'll give you some idea.
Speaker Change: Of course, we do expect that trial to inform the dose range in the upcoming multiple ascending dose trial.
Alfred W. Sandrock: And then secondly, on the taxidermy candidate, would you be able to disclose anything new about the candidate that was chosen and anything? Anything notable that you'd be willing to tell us about what differentiated that candidate from the others? Well, so, you know, that's a neurocrime program. And so we're, you know, we don't want to disclose these things.
Speaker Change: That's really helpful and then second on the.
Speaker Change: Protection candidate would you be able to disclose anything new about the candidate that was chosen.
Speaker Change: And anything.
Speaker Change: Taking notable that you'd be willing to tell us about what differentiated that candidly from the others.
Speaker Change: Well, so neurocrine program and so were.
Alfred W. Sandrock: Suffice it to say that for the development candidate, we had a set of criteria for the Capsid as well as the Capsid plus payload combination, both in terms of its mechanistic effects in animals as well as its manufacturability. And, you know, we'll ask Neurocrin to answer your question. Fair enough.
We don't want to disclose these things, but suffice it to say that the development candidate we.
Speaker Change: We had a set of criteria for the capsid as well as the cap surplus payload combination.
Speaker Change: Both in terms of its mechanistic.
Speaker Change: FX in animals, as well as manufacturer ability and.
Speaker Change: Well I will ask Eric.
Speaker Change: Two.
Eric: Answer your question.
Eric: Fair enough. Thanks for taking my questions. Congrats again on the progress.
Speaker Change: Thank you.
Speaker Change: Thank you William for next question.
Philip M. Nadeau: Thanks for taking our questions. Congratulations again on the progress. Thank you. Thank you one moment for the next question. Our next question comes from the line of Ry Forseth of Goulahan Security. Your line is now open. Hi, this is Ry from Debjit's team at Guggenheim. From the ASGCT data, now with Gen 3 technology maturing, where you're able to navigate pre-existing neutralizing antibodies, how are you framing the market opportunity expansion given the preclinical profile you're seeing today? I'll start, and maybe Toby or Todd can add.
Speaker Change: Our next question comes from the line of Ryan <unk> of Guggenheim Securities. Your line is now open.
Ryan: Hi, This is derived from <unk> team at Guggenheim from the ESG data now with Gen three technology maturing.
Ryan: Where youre able to navigate preexisting neutralizing antibodies, how you're framing the market opportunity expansion given the preclinical profile year is seen to date.
Ry Roger Forseth: But yes, so you notice that one of our posters that we are looking at, we're leveraging tracer to see whether we can make modifications to capsids that affect immunogenicity. And by that, what we're doing is we're looking to see whether pre-existing antibodies in humans can bind to the capsids, actually, and therefore affect how they perform in the clinic. And so, obviously, if we can find novel capsids that can evade, if you will, the pre-existing antibodies, more patients would be available for treatment.
Speaker Change: Well I'll start and maybe Toby or Todd can can add but yes, so you'd notice that our one of our posters that we are looking we're leveraging tracer to see whether we can make modifications to the capsid that effect immunogenicity and by that what we're doing is we're looking to see.
Speaker Change: And whether pre existing antibodies.
Speaker Change: Humans can.
Speaker Change: <unk> combined with the cabinets actually and therefore affect how they perform in the clinic and.
So obviously, if we can find.
Speaker Change: Our novel Capsid that.
Speaker Change: Curt can evade if you will the preexisting antibodies more patients would be available for treatment.
Ry Roger Forseth: In addition, I would note that we and others are going to be evaluating ways in which we can lower pre-existing antibody levels. And as you know, several other companies are investigating the use of various enzymes that can degrade pre-existing antibodies. So that would be another way to achieve essentially the same thing, which is to try to get more patients to be eligible for our treatment. Toby?
Speaker Change: In addition, I would note that we and others are going to be evaluating ways in which we can lower <unk> usage.
Speaker Change: The antibody levels.
Speaker Change: And as you know several other companies are investigating the use of various enzymes that can degrade pre existing antibodies that would be another way to achieve essentially the same thing which is to try to get more patients to be eligible for our treatment.
Alfred W. Sandrock: I would agree with Alan. I think the only point I would make in addition is that this may be particularly important in adult populations. There may be select pediatric populations, which is not as much of a concern.
Speaker Change: Tobey I.
Tobey: I would agree with all I think the only point I would make in addition is that this may be particularly important in adult populations. There may be select pediatric populations with is not as much of a concern that may represent some opportunities.
Speaker Change: Fascinating work thanks.
Speaker Change: Thank you. Thank you and one for next question.
Speaker Change: Yes.
Toby Ferguson: That may represent some opportunities. Fascinating work, thank you. Thank you one more for next question. Our next question comes from the line of David Hoang of Citigroup. Your line is now open. Hi there.
Speaker Change: Our next question comes from the line David Hong of Citigroup. Your line is now open.
David Timothy Hoang: Congratulations on the progress. And thanks for taking my question. I guess first, I just want to ask about how you think about the anti-tau antibody fitting into the treatment landscape of Alzheimer's as compared to the tau silencing gene therapy that you also have. What could be the advantages versus maybe disadvantages of each of those modalities? And then maybe just a second question.
David Hong: Hi, there congrats on the progress and thanks for taking my question.
David Hong: First I just wanted to ask about how you think about the anti tau antibody fitting into the treatment landscape.
David Hong: Altzheimer's as compared to the Tau silencing gene therapy that you also have what could be the advantages versus maybe disadvantages in each of those modalities.
Alfred W. Sandrock: Have you interrogated or to what extent have you interrogated other transporters besides ALPL for crossing the blood brain barrier? And if you've done that work, how did ALPL compare to other potential transporters? Thanks. I'll start with the first question, and then Toby, I'll ask Toby to help with that one, and then Todd, maybe you can answer the second question. So, anti-tau versus tau silencing. So, very different approaches.
Speaker Change: Then maybe just a second question have you.
Speaker Change: Interrogated or to what extent have you targeted other transporters. Besides LPL for crossing the blood brain barrier and if you've done that work how does <unk> compare to other potential transporters.
Speaker Change: So I'll start on the first question and then Toby I'll ask Toby to help with that one and then Bob.
Alfred W. Sandrock: Anti-tau antibody, we expect to bind to extracellular forms of tau, and as Todd said earlier, what we're trying to do is to block the spread of pathological tau, which we demonstrated quite nicely in an animal model where we injected human pathological tau into animals and looked at its spread. The tau knockdown is very different, so that's an antibody that will need to be given, you know, on a regular basis, probably on the order of every month or so, every four weeks, we anticipate. The tau knockdown is gene silencing that will be done by gene therapy. So that will be a once and done job, essentially.
Toby Ferguson: Maybe you can answer the second question, so anti Tau versus tower financing, so very different approaches anti Tau, we expect to bind the extra cellular forms of Tau and as Todd said earlier, what we're trying to do is to block the spread of pathological tower, which we demonstrated quite nicely in an animal.
Toby Ferguson: Model, where we inject human pathological tower into the animals and look at spreads.
Tayo knockdown is very different.
So that's an antibody that will need to be given.
Toby Ferguson: On a regular basis, probably on the order of every month or so every four weeks we anticipate.
Toby Ferguson: <unk>.
Toby Ferguson: The tower knockdown as gene silencing that will be done by gene therapy, So that would be a once and done essentially.
Alfred W. Sandrock: And it decreases the expression of all forms of tau. It's akin to, you know, others have used an antisense approach to decrease the expression of tau. So it's a different mechanism of action. And we'll have to see which one works best, and then we'll see whether or not it can be done once and for all or whether it'll need to be regular infusions. Toby?
Toby Ferguson: And it decreases the.
Toby Ferguson: Expression of all forms of Tau.
Toby Ferguson: It's akin to others have used an antisense approach to decrease the expression of Tau.
Toby Ferguson: So it's a different mechanism of action and we will have to see the first thing is which one works the best.
Toby Ferguson: And then we'll see whether or not it can be done once and done or whether it'll need to be regular infusions Tobey.
Toby Ferguson: Thank you. I think what I would add is that, in concert, we fundamentally, at this point, don't have enough clinical data to understand the potential completeness of treatments with any of these modalities. I think, first and foremost, the most important point is determining which ones work.
Speaker Change: Hey, Joe I think what I would add is.
Joe: In concert we fundamentally at this point don't have enough clinical data to other <unk>.
Joe: Potential completeness of treatments of either any of these modalities I think first and foremost the most important point is determining which ones work Amit.
Toby Ferguson: And we're excited to test, have two opportunities to test how, for our programs, both the antibody program and the knockdown. I do think moving forward, we'll need to look at and try to understand the combination as well, and that is a potential to be investigated in the future. And Todd, do you want to take the second question?
And we're excited to test have two opportunities to test how.
Joe: For our programs, both antibody program and the knockdown program.
Joe: I do think moving forward, we will need to look and try to understand the accommodation as well.
Joe: As a potential be investigated in the future.
Todd Carter: Sure. The second question, just to recap, would be the evaluation of ALPL and others in the context of other potential shuttles or shuttle targets for BBV delivery. So we absolutely would need to evaluate ALPL in the context of other receptors, such as transferrin, and there are a few others. While we're not in a position to share any data today, you can imagine that anything we would choose to move forward would need to perform at least as well as the existing BBB transporters.
Joe: And Todd you might take a second question for a second question just to recap with devaluation of LPL and other in the context of other potential shuttles are several targets for BBB delivering so we absolutely.
Todd Carter: Would need to evaluate <unk> in the context of other other receptors such as transparent and there are a few others.
Not in a position to share any data today.
Todd Carter: You can imagine that anything we would choose to move forward, we need to perform at least as well as the existing BBB transporters.
Alfred W. Sandrock: And so that would be part of our assessment and our evaluation, and I look forward to, hopefully, in the future, being able to share more about our work in that area. And then, Todd, I think maybe David was also asking whether we have other receptors as well, and how we're looking at those, perhaps, you know, in comparing them to ALPL. So we have identified some other receptors. We have multiple capsid families that target different receptors. And so it goes.
Todd Carter: And so that that will be part of our assessment and our evaluation is looking.
Speaker Change: Looking forward to hopefully in the future being able to share more about our work in that area and then Todd I thought I think maybe David was also asking whether we have other receptors as well.
Todd Carter: And how we're looking at those perhaps.
Todd Carter: And comparing them to LPL.
Speaker Change: So we have identified some other receptors, we have multiple capsid families.
Speaker Change: Target different receptors and sell.
Todd Carter: In terms of our novel receptor discovery, we have identified a few, and we are in the process of evaluating all of them for non-viral delivery. Thank you one moment for the next question. Our next question comes from the line of Jay Olson of OpCo. Your line is now open. Oh, hi, this is Chong on the line for Jay.
Speaker Change: In terms of our novel receptor discovery, we have identified a few and we are in the process of evaluating all of them for non viral delivery.
Speaker Change: Okay.
Speaker Change: Okay.
Speaker Change: Thank you Juan <unk> for next question.
Speaker Change: Our next question comes from the line of Jay Olson of Opco. Your line is now open.
Chong: Thanks for taking the question and congrats on the progress. Maybe a two-part question on the ALPR target you disclosed. Just first, I'm just wondering if you can talk about the expression, Cerebrity of ALPL in humans and, maybe whether the expression may change over time with aging or with some underlying diseases, and secondly for the development of other therapeutics. Are you planning to do that internally or through collaborations?
Speaker Change: Oh, Hi, this is Charles on the line for J. Thanks for taking my question and congrats on the progress.
Charles: Maybe a two part question on the <unk>.
Speaker Change: <unk> targets.
Speaker Change: <unk>.
Charles: Just first I was just wondering if you can talk about the expression.
Charles: <unk> in humans.
Charles: <unk>.
Charles: Maybe whether the expression may change over time with aging where with some underlying diseases.
Charles: And secondly for the development of other therapeutic.
Charles: Modality or delivery modality.
Speaker Change: Are you planning to do that.
Speaker Change: Finally, we're through collaborations thank you.
Alfred W. Sandrock: Thank you. So, Todd will answer the first question, and I'll answer the second one.
Speaker Change: So Todd ill answer the first question I'll answer the second one.
Todd Carter: So, on the first question, differences or changes in ALPL expression. So, we can look at different genetic variations of ALPL, and we're in the process of doing that. In terms of the expression level, we know that ALPL is expressed at a quite robust level starting at birth, from the databases and also from internal work on preclinical models. And that expression goes up a bit with age.
Todd Carter: So on the first question.
Todd Carter: Differences or changes of LPL expression so.
Todd Carter: So we can look at different genetic variation of LPL.
Todd Carter: And we are in the process of doing that in terms of the expression level. We know that <unk> is expressed at a quite robust level.
Todd Carter: Starting at birth from the databases and also from internal work on in preclinical models.
Alfred W. Sandrock: So, if anything, we might expect even better delivery in older populations, but all the evidence to date suggests that the level of expression in the vasculature is quite robust, even starting at a very early age. Yeah, in terms of the second question, we do expect to be doing a lot of the work internally. And we have already started to do that.
Todd Carter: That expression those up a bit with age.
Todd Carter: So if anything we might expect even better delivery in older populations, but all the evidence to date suggests that at the level of expression in the vasculature is quite robust even starting at a very early age.
Alfred W. Sandrock: But we're always looking for collaborations that can enhance these discovery and development efforts. So stay tuned. Yes, thank you so much. Thank you, Bomoy, for the next question. Our next question comes from the line of Sumant Kulkarni of Cancord, January.
Speaker Change: And in terms of the second question.
Speaker Change: We do expect to be doing a lot of the work internally.
Speaker Change: And we have already started to do that but we're always looking at FERC.
Speaker Change: Collaborations that can enhance that debt.
Speaker Change: That discovery and development efforts so stay tuned.
Speaker Change: Yes. Thank you so much.
Thank you Omar for next question.
Speaker Change: Our next question comes from the line of <unk> Kulkarni of Canaccord Genuity. Your line is now open.
Sumant Satchidanand Kulkarni: Good afternoon, nice to see all the progress, and thanks for taking our questions. I guess these are welcome questions for Dr. Toby Ferguson. So on your SARD-1 ALS program, given the limited patient population and because Toverson is on the market already, do you expect to involve Toverson in preclinical work? And how do you expect eventual trial recruitment to play out for Voyager's SARD-1 ALS program? Thanks for the question.
Kulkarni: Good afternoon, and nice to see all the progress and thanks for taking our questions. I guess these are welcome questions for Dr. Toby Ferguson.
Kulkarni: On your <unk> program, given the limited patient population and because 2% is on the market already or do you expect to involve two person in preclinical work and how do you expect eventually trial recruitment to play out for a while just start when the Atlas program.
Toby Ferguson: So I think fundamentally, I think at first I'd iterate, so first of all, it's obviously approved, and I think it's approved on the basis of biomarkers, particularly neurofilament, and it is indeed a disease modified therapy for ALS administered once intrathecally. I think what I'd point you in our programs, once a month, correct. What I'd point you in our programs is that we did I think I will highlight that to start.
Speaker Change: Thanks for the question.
Speaker Change: First I would iterate. So first of all obviously approved and I think it's approved on the basis of biomarker of particularly of our filament.
Speaker Change: It is indeed, a disease modifying therapy for ALS administered once interest equally.
Speaker Change: I think what I'd point to in our program once a month excuse me.
Speaker Change: Correct Yep.
Speaker Change: What I'd point to in our programs is that.
Toby Ferguson: In motor neurons, we saw 80 to 93% transduction and up to 68% in cortex when we looked at second-gen VCAP capsid. So that's really quite important, and that was with an intravenous administered dose.
We did.
Speaker Change: Discussed recently <unk> really the transaction data I think I would highlight that to start motor neurons, we saw 80%, 93% transduction in up to 68% and cortex. When we looked at second Gen recap cabinets. So that's really quite important and that was administered with an intravenous administered dose and.
Toby Ferguson: In the context of our VOA 9.3.2.3 program, we saw a 73% reduction in mRNA and SOD1 mRNA and 82% in motor neuroneurasthetic. So I think fundamentally, we'll take some lessons learned from Tuferson, particularly around the biomarkers, and we'll apply these to our clinical development program. We think this provides an opportunity to understand not only the potential proof of concept for our tracer platform as a whole but also the potential importance for our tracer platform as a whole.
Speaker Change: In the context of our <unk> three program, we saw 73% reduction of mrna in southern mrna and 82% in motor neurons in the quarter.
Speaker Change: I think fundamentally.
Speaker Change: We will take some lessons learned from the FERC.
Speaker Change: Particularly around the Biomarkers will apply these to our clinical development program. We think this provides us an opportunity to understand not only the potential.
Proof of concept and people will start with AOS, but also.
Speaker Change: Potential importance for our tracer platform as a whole.
Toby Ferguson: And Suman, maybe I'll add that, you know, if we look forward to the potential approval of our SOD1 gene therapy, I'll note that, in the case of SMA, Spinraza was approved a couple of years prior to Zolgensma, and the two are used sort of in some ways concurrently in the real world.
Speaker Change: And <unk>, maybe I'll add that if we look forward to the potential approval of our <unk> gene therapy I will note that in the case of SMA.
Speaker Change: <unk> was approved a couple of years prior to <unk>.
Speaker Change: And the two are used.
Speaker Change: Sort of in some ways concurrently in.
Alfred W. Sandrock: So, for example, we're aware that many patients can get treated with Zolgensma right after birth, and then, if necessary, they add Spinaraza. And so, you know, taking a gene therapy doesn't preclude continued treatment with the person when necessary. And so, I think if we take a page from the SMA story, we could see both products first and, hopefully, our SOD1 gene therapy being used together essentially by physicians to treat their patients optimally. And as a quick follow-up, what percentage reduction on NFL is considered clinically relevant in the SARD-1 ALS context?
Speaker Change: In the real World. So for example, we're aware that many patients get treated with Xeljanz from right. After birth and then if necessary.
Speaker Change: Spin Raza.
Speaker Change: So.
Speaker Change: Taking a gene therapy doesn't preclude continued treatment with the person when necessary and so I think if we take a page from the SMA story we.
Speaker Change: Could see both.
Speaker Change: <unk> the first one as well as hopefully our <unk> gene therapy being used together essentially by physicians to treat their patients optimally.
Toby Ferguson: We've seen the data that Biogen has, but what would be considered clinically relevant, I guess, for what's out there already and for a gene therapy? So I think we've all seen the reductions that Biogen is highlighting with neurofiltration reductions. I think fundamentally what a clinically relevant reduction is not clear, but I guess the points I would highlight are it has to be substantially greater than.
Speaker Change: Got it and as a quick follow up.
Speaker Change: What percentage reduction on NFL is considered clinically relevant and disarmed one analyst context, you've seen the data that biogen head, but what would be considered clinically relevant I guess from what's out there already and for the gene therapy.
Speaker Change: So I think we.
Speaker Change: We've all seen the reductions that biogen's highlighted with ortho reductions I think fundamentally.
Speaker Change: What a what a clinically relevant reduction is not clear, but I guess the points I would highlight is it has to be substantially greater than that.
Speaker Change: Very good as your assay and biologic variability and that the <unk> data doesn't form.
Speaker Change: The magnitude of needs of reduction.
Speaker Change: Thank you.
Toby Ferguson: Thank you. Thank you. One moment for the next question. Our next question comes from the line of Yanan Zhu of Wells Fargo Security. Your line is now open.
Speaker Change: Thank you <unk> for next question.
Speaker Change: Our next question comes from the line of Ian Sue at Wells Fargo Securities. Your line is now open.
Yanan Zhu: Great. Thanks for taking our questions, and congrats on the progress. So first, I'm wondering about the ALPL receptor. Is there expression of this receptor in any other tissue, and how does that potentially impact or not impact a brain delivery drug in terms of delivery into other tissues? Thanks. Sure, this is Todd. I can take that question.
Ian Sue: Great. Thanks for taking our questions and congrats on the progress. So first of all I was wondering about the <unk>.
Ian Sue: Receptor.
Ian Sue: <unk> expression.
Ian Sue: And receptor on any other tissue and how did that.
Ian Sue: Potentially in <unk>.
Ian Sue: Perhaps they will not impact.
Ian Sue: Brain delivery driver in terms of delivery into other tissues.
Todd Carter: So thank you for that. ALPL is expressed across the vasculature and the entire body and in some other cell types. However, what we think is going on is that AEV capsids, AEV gene therapies do not need to harness these other mechanisms to get into other tissues. But the blood-brain barrier is preventing most conventional capsids or all conventional capsids from getting into the brain.
Ian Sue: Sure. This is Tom I can take that question. So thank you for it.
So the LPL is expressed across the vasculature and the entire body and in some other cell types. However, what we think is going on is that right.
Todd Carter: AAV capsid AAV gene therapies do not need to harness these other mechanisms to get into other tissues, but the blood brain barrier is blocking for most conventional capsid youre all conventional capsules to get into the brain. So the harnessing of LPL to cross the blood brain barrier is really only important to get into the brain.
Todd Carter: So the harnessing of ALPL to cross the blood-brain barrier is really only important to get into the brain. But what we also see is that the use of ALPL is giving us some significant cross-species activity. So this provides us not only with in vitro evidence of cross-species activity in transcytosis assays but also in vivo cross-species activity, which we see in multiple species. So we have examples of four species, African green monkeys, and Sonomogus macaques. Marmosets, and Mike.
Todd Carter: But we also see is that.
Todd Carter: The use of LPL is giving us some significant.
Todd Carter: Cross species activity. So it provides us not only with in vitro evidence across species activity and translate ptosis assays, but also in vivo cross species activity, which we see in multiple species. So we have examples of four species African green monkeys Southern <unk>.
Todd Carter: <unk>.
Todd Carter: And ultimately, what we're able to see is that at relatively low doses, we're able to achieve these kinds of high delivery and transduction that Toby mentioned, 80% of motor neurons in the spinal cord, 95% of Purkinje neurons, and 98% of dopaminergic neurons in the substantia nigra. And then, finally, I'll just comment that with regard to tissue and cell delivery, what we're That's probably not specifically driven by ALPL or any hypothesis, as that's based on other characteristics of the capsid.
Todd Carter: Marmosets and mice.
Todd Carter: And ultimately what we're able to see is that at relatively low doses were able to achieve these kinds of high delivery and transduction that Toby mentioned, 80% of motor neurons in the spinal cord, 95% and purkinje neurons, 98% of dopaminergic neurons in the substantial lycra.
Speaker Change: And then finally I will just comment.
Speaker Change: With regard to the tissue and cell delivery, what we're seeing is a significant deep targeting from the liver.
Speaker Change: That's probably not specifically driven by LPL. Our hypothesis is that based on other characteristics of the capsid, but we see a quite substantially targeting from the liver with the simultaneous increase in delivery into the CNS.
Yanan Zhu: But we see quite a substantial de-targeting from the liver with the simultaneous increase in delivery into the CMC. Great, that's very nice to hear. And also, at ASGCT, there are quite a few presentations on BBB penetrating.
Speaker Change: Great Thats very nice here.
Speaker Change: And also at the <unk> key.
Speaker Change: There are quite a few presentations.
Alfred W. Sandrock: BBB Capsid works from different industry players, and some of them have begun to touch upon receptors. I think you might have started a trend. Just wondering, after taking a survey of the landscape, how do you feel about your BBB Capsid and where it stands in the landscape? Thanks. Maybe I'll start and Todd will complete the answer. But, listen, it's great to see that a lot of people are finding what we found years ago.
Speaker Change: BBB penetrating.
Speaker Change: Capsid work.
Speaker Change: From different industry players and.
Speaker Change: Some of them also begin to touch upon receptors I think you might have started to trend.
Speaker Change: Just wondering after either taking a survey of the landscape how do you feel your BBB.
Speaker Change: Capsid, Larry stance in the landscape. Thanks.
Speaker Change: Maybe I'll start and Todd will complete the answer but.
Todd Carter: So listen it's great to see that.
Alfred W. Sandrock: And that, you know, yeah, I mean, I think what we're seeing is that I think the world appreciates the need for new capsids that cross the blood-brain barrier so as to improve delivery. And look, the competition is heating up, you know, I would say that we're very proud of our capsids. As Todd said, we get the key cells that are relevant for the diseases of interest, we get 80-90%, as Todd just mentioned, of cells transduced at relatively low doses of 3E13 VGs per Kg, and we have demonstrated in vivo, multiple cross-species experiments have been done with three different non-human primate species as well as mice, and knowing the receptor is also very helpful.
Todd Carter: A lot of people are finding what we found years ago.
Speaker Change: And that.
Todd Carter: Yeah, I mean I think it.
Todd Carter: What we're seeing is that I think the world depreciates the need for new capsid across the blood brain barrier, so as to improve delivery and look the competition is heating up.
Todd Carter: I would say that we're very proud of our capsid.
Todd Carter: As.
Todd Carter: Todd said, we get.
Todd Carter: The key cells that we that are better irrelevant further diseases of interest.
Todd Carter: Get 80%, 90% as Todd just mentioned.
Todd Carter: <unk> transducer at relatively low doses of $3 13, Vg per kg and we have demonstrated in vivo.
Todd Carter: Multiple cross species experiments have been done with three different nonhuman primate species as well as mice now knowing the receptor.
Alfred W. Sandrock: So, and then, look, we have already selected three development candidates, two with our partners at Neurocrin and one wholly owned, and we expect to be in the clinic soon. So, you know, Todd? I think you've captured everything that I was going to say, Alan, and I do think the important point, in addition to the cross-species activity, is that over the past quarter or so, those three candidates that we're moving into the clinics. We think the next step is really the. Yep. Yep. I got it.
It is also very helpful. So so and then look we have already selected three development candidates to with our partners at Neurocrine in one of our wholly owned and we expect to be in the clinic soon so.
Todd Carter: Sure.
Todd Carter: Scott.
Scott: Thank you captured everything that I was going to say Alan and I do think the important point in addition to the.
Speaker Change: Crosspieces activity is over the past quarter or so of those three candidates that we're moving into the clinics. We think the next step is really in the clinic.
Speaker Change: Got it.
Speaker Change: Alright, Thank you very helpful.
Speaker Change: Thank you Ron for next question.
Yanan Zhu: Thank you. Very helpful. Thank you one more for the next question. Our next question comes from the line of Laura Chico of Wedbush. Your line is now open. Good afternoon, and thanks very much for taking the questions. Just one housekeeping question.
Speaker Change: Our next question comes from the line of Laura Chico of Wedbush. Your line is now open.
Laura Kathryn Chico: I believe there was one milestone payment that was triggered in the second quarter, but I'm curious if you could just kind of elaborate or if you've disclosed any additional milestones that we should be watching out for over the remainder of 2024. And then I have a quick follow-up for you. Hi, this is Robin.
Laura Kathryn Chico: Good afternoon, and thanks very much for taking the questions.
Laura Kathryn Chico: One housekeeping question I believe there is one milestone payment that was triggered in the second quarter, but curious if you could just kind of elaborate or have you disclosed any additional milestones that we should be watching out for over the remainder of 2024, and then I have a quick follow up for you.
Robin Swartz: Thank you for the question. We were very pleased with the advancement of our NURC and programs and the achievement of the DC milestone. However, we don't provide guidance on potential future milestone payments across the 13 partner programs. It is also important to note that further milestone payments are not included in our cash guidance, which is into 2027.
Laura Kathryn Chico: Hi, This is robin. Thank you for the question. So we were very pleased with the advancement of Byron American programs.
Robin Sweat: And the achievement of the DC milestone. However, we don't provide guidance on potential future milestone payments across the 13 partner program.
Robin Sweat: It is also important to note that further milestone payments are not included in our cash guidance, which is into 2027.
Laura Kathryn Chico: Okay, thank you very much. And then, in terms of follow-up, obviously, there's a lot of discussion about the ALPL receptor data from ASGCT, but I'm wondering if you could perhaps, Al, perhaps strategically, what would happen in terms of the direction of focus for Voyager with the VY-TAL1 data? You know, if that reads out positively in the patients, what does that mean strategically in terms of the focus? Obviously, that's as an antibody right now, but how does that shift or change the focus on other traits or programs, assuming success?
Speaker Change: Thank you very much and then in terms of a follow up obviously theres a lot of discussion on the LPL receptor data from <unk>, but I am wondering if you can just talk perhaps al strategically what would happen in terms of the direction of focus for Voyager with.
Speaker Change: The <unk> one data.
Speaker Change: That reads out positively in the patients what does that mean strategically in terms of the focus obviously that's in as an antibody right now, but how does that shift or change the focus on other traits are programs assuming success there.
Laura Kathryn Chico: Well, Laura, thanks for the question. You know, I think what you're implying is that we would have a choice of whether we proceed with the BY-Tau-01 program as an intravenous antibody or whether we could vectorize the antibody. We actually do have that option.
Speaker Change: Well Laura Thanks for the question.
Speaker Change: What.
Speaker Change: What you are implying is that we would have a choice of whether we proceed with the <unk> program.
Laura Kathryn Chico: As an intravenous antibody.
Laura Kathryn Chico: Or whether we could <unk> the antibody, we actually do have that option, we may actually do both in fact.
Alfred W. Sandrock: We may actually do both, in fact. But I've always been thinking, though, that strategically, it wouldn't make sense for Voyager, a small company like us, to try to go into phase three or commercialize an Alzheimer's disease. It's too large, too expensive.
Speaker Change: I've always been thinking, though that strategically what makes sense for a voyage or a small company like us to try to go into phase III or commercialize and Alzheimers disease, it's too large too expensive.
Alfred W. Sandrock: So we've always thought we will likely get a partner if the BY-Tau-01 program is positive. But I do think that the option to potentially vectorize a once-and-done antibody could be of high interest to us, and we'll make that decision when the time comes. Thanks very much.
Speaker Change: So we've always thought we will likely get a partner.
Speaker Change: If the <unk> program is positive, but we are but I do think that the option to potentially bacterize, a once and done.
Speaker Change: Antibody.
Speaker Change: Could be of high interest to us and we will make that decision when the time pumps.
Speaker Change: Thanks very much.
Laura Kathryn Chico: Thank you. One moment for our next question. Our next question comes from the line of Joon Lee of True Securities. Your line is now open.
Speaker Change: Thank you ma'am for next question.
Speaker Change: Our next question comes from the line of John Lee of True Securities. Your line is now open.
Joon So Lee: Following Laura's question, last week in ASGCT, Bregeron suggested in some of the presentations that compared to cathode-inserted vectorized antibodies, the expression of vectorized antibodies had a lower expression. Do you expect the same for your vectorized antibody platform in general, and specifically for the Alzheimer's vectorized antibody? You know, could you share any plans that you have for preclinical data in this program? Yeah, let me start, and I'll ask Todd to help.
Speaker Change: Hi.
Speaker Change: Following.
Joon So Lee: His question.
Joon So Lee: Last week.
Joon So Lee: <unk>.
Joon So Lee: Suggest that.
Joon So Lee: And some of the presentation.
Joon So Lee: Compared to cast it inserted.
Joon So Lee: Victor I was asking about the expression of <unk>.
Speaker Change: <unk> sorry.
Speaker Change: So the inserted antibodies the VIX rice.
Speaker Change: Antibodies have lower expression do you expect the same for your <unk> antibody platform in general and specifically for them.
Speaker Change: Alzheimers Victoria's lines worthy and if.
Speaker Change: Could you share.
Speaker Change: Any plans.
Speaker Change: You have four.
Speaker Change: Preclinical data opted in this program.
Alfred W. Sandrock: So, when we vectorized an antibody, we did show at a meeting, I think it was last year or two years ago, that we could vectorize an anti-amyloid antibody and get enough expression to bind to amyloid plaques in transgenic mice. And correct me if I'm wrong on that, Todd. So, we can get enough expression to bind to amyloid plaques in animals. We'll have to see.
Speaker Change: Yes, let me start and I'll ask Todd to help.
Todd Carter: So the so when we backed horizon antibody, we did show at a meeting I think it was last year or two years ago that we come back to horizon anti amyloid antibody and get enough.
Todd Carter: Expression to bind to amyloid plaques in transgenic mice and correct me if I'm wrong on that Todd. So so we can get enough expression to bind to amyloid plaques in animals.
Alfred W. Sandrock: My view is that a lot is going to change relative to IV. So we're going to lose the C-maxes, if you will, the high concentrations that you get immediately after IV dosing. We expect to have more constitutive expression from within the central nervous system. So we expect that we'll have mainly glial cells producing the antibody, as we've shown in the past, and so it'll be sort of an inside-out, if you will, approach, rather than giving it IV and having it cross the vasculature to get into the brain. It'll be made in the brain directly.
Speaker Change: We will have to see my view is that a lot's going to change relative to IV. So we're going to lose the.
Speaker Change: The C. Max is if you will the high concentrations that you get immediately after IV dosing, we expect to have more constitutively expression from within the central nervous system. So we.
Speaker Change: We expect that we will have mainly glial cells producing the antibody.
Speaker Change: As we've shown in the past and that we will.
And so it will be sort of an inside.
Speaker Change: If you will approach rather than giving it IV and having across the vascular to get into the Brian. It will be made in the brain directly and then we would be able to look in animal models at the not only binding amyloid plaques, but we will be assessing whether or not we can lower amyloid plaques and theres. Some precedents we can.
Alfred W. Sandrock: And then we would be able to look in animal models at not only binding to amyloid plaques, but we would be assessing whether or not we can lower amyloid plaques. And there are some precedents we can follow from in vivo studies that have been done with anti-amyloid antibodies. And then, of course, we'll have to see whether or not we affect any adverse events. One concept would be that the rates of ARIA may be affected by the fact that we don't get the C-maxes, and we have constitutive expression from within the brain. We'll have to see if that's true. And there are some animal models that mimic ARIA, whether they truly are ARIAs or not.
Speaker Change: Follow in vivo studies that have been done with the anti amyloid antibodies.
Speaker Change: And then of course.
Speaker Change: We'll have to see whether or not we effect.
Speaker Change: Any adverse events, one concept would be that ARIA.
Speaker Change: The rates of <unk> may be affected by the fact that we don't get the <unk> and we have constituent of expression from within the brain will have to see if thats true.
Speaker Change: There are some animal models that mimic ARIA, whether they truly are already or not.
Speaker Change: I'm not certain but.
Alfred W. Sandrock: I'm not certain, but we can even assess that. And finally, I would say that one of the things we're investigating right now is whether or not we can regulate the expression of the antibody with a small molecule. And so a regulatable vectorized antibody program would, I think, be ideal. And so those are the kinds of things we're thinking about in terms of preclinical experiments that would help us get to a development candidate. Todd, did you want to add anything? I can add a little bit.
Speaker Change: We can even assess that and finally I would say that.
Speaker Change: One of the things we're investigating right now is whether or not we can regulate the expression of the antibody with a small molecule.
Speaker Change: And so our regulator Bowl Bacterize antibody program I think the ideal.
Speaker Change: And so those are the kinds of things we're thinking about in terms of preclinical experiments that would help us get to a development candidate Todd did you want to add anything I can add a little bit so while the <unk>. The focus there is on the antibody itself not on to Victor is farm, we do have substantial experience going back several.
Todd Carter: So while VY Tau O1, the focus there is on the antibody itself, not on a vectorized form. However, we do have substantial experience going back several years on vectorization of antibodies in general, including Tau antibodies and the amyloid that Al mentioned and others. And we found that the payload can matter quite a bit. The structure of the vector payload, the vector genome, and, of course, the promoter. So there are a lot of things that we can do, some of which Al mentioned, to tweak the expression level, not just on the promoter but by the kinds of cells, the specific cell types that you target as well.
Todd Carter: Here's an <unk> antibodies in general, including Tau antibodies and.
Todd Carter: The amyloid that al mentioned and others and.
Todd Carter: And we found that the payload to matter quite a bit of the structure of the vector payload the vector genome.
Todd Carter: And of course, the promoter. So there are a lot of things that we can do some of which al mentioned two.
Todd Carter: To tweak the expression level.
Speaker Change: Not just on the promoter, but by the kinds of cells that the specific cell types that you target as well and so we'll be looking at all of those characteristics.
Todd Carter: And so we'll be looking at all of those characteristics when we move any vectorized form of an antibody, a gene therapy-based antibody, forward. You know, I would just add that in the real world, being able to give it a vectorized anti-amyloid once IV and not have to give it every other week or every month could really relieve the strain on the healthcare system that I think we're witnessing now with antibody treatments for Alzheimer's disease.
When we move any vector is form of an antibody of gene therapy based antibody forward.
I would just add in the.
Speaker Change: In the real world being able to give it.
Speaker Change: <unk> anti amyloid once IV.
Speaker Change: And not have to give it every other week or every month could really relieve the strain on the health care system that I think we are witnessing now with antibody treatments for Alzheimer's disease.
Todd Carter: Very helpful. And if I can sneak in one last question, So between now and the second half of 2026 when you hopefully present, like PET imaging data for WEY-TAS, how should we think about the cadence of any interim data release related to your findings along the way? [inaudible] I think what we've highlighted for the SADD program will inform the MADD program, and I think really the key data readout in that timeframe really is the MADD data in the latter half of 2026. Yep.
Speaker Change: Very helpful and if I can sneak in one last question so between now and second half of 2006.
Speaker Change: Hopefully our present.
Speaker Change: Imaging data, where we why comps how we should think about the cadence of comp.
Speaker Change: Interim data release related to your findings along the way.
Speaker Change: Toby.
Speaker Change: Okay.
I think what we've highlighted for the.
Toby Ferguson: SaaS program it will inform the map program and I think really the key data readout next in that time frame really has demanded an allowed us 22 races.
Joon So Lee: Thank you very much. Thank you. I'm showing no further questions at this time. I would now like to turn it back to Alessandra for a closing remark. Thank you everyone for joining us today, and feel free to follow up directly with any questions. Thanks again. Ladies and gentlemen, this concludes today's presentation. Thank you once again for your participation. You may now disconnect.
Toby Ferguson: Yes.
Thank you Robert.
Robert: Thank you I'm showing no further questions at this time I would now like to turn it back to Alessandra for closing remarks.
Alessandra: Thank you everyone for joining us today and feel free to follow up directly with any questions. Thanks again.
Speaker Change #100: Ladies and gentlemen. This concludes today's presentation. Thank you once again for your participation you may now disconnect.
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Operator: Copyright 2020 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. Copyright 2019 Mooji Media Ltd. All Rights Reserved. No part of this recording may be reproduced without Mooji Media Ltd.'s express consent. Thank you for watching!
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Speaker Change #100: Okay.
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Yes.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: Okay.
Speaker Change #100: Yes.
Speaker Change #100: [music].
Speaker Change #100: No.
Speaker Change #100: Dan.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: Okay.
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Yes.
Speaker Change #100: Okay.
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Yes.
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Yes.
Speaker Change #100: Yes.
Speaker Change #100: [music].
Speaker Change #100: Yeah.
Speaker Change #100: No.
Speaker Change #100: Dan.
Speaker Change #100: [music].
Speaker Change #100: Yes.
Speaker Change #100: [music].
Speaker Change #100: Yeah.
Speaker Change #100: Yes.
Speaker Change #100: Okay.
Speaker Change #100: [music].
Okay.
Speaker Change #100: Yes.
Speaker Change #100: [music].
Speaker Change #100: Yes.
Speaker Change #100: Okay.
Okay.
Speaker Change #100: [music].
Speaker Change #100: Sure.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Yes.
Okay.
Speaker Change #100: [music].
Speaker Change #100: Yes.
Dan.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].
Speaker Change #100: Okay.
Speaker Change #100: [music].