Q4 2022 Voyager Therapeutics Inc Earnings Call
Speaker 1: The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 1-1.
Speaker 2: There will be a question and answer session at the end of this call. Please be advised this call is being recorded at the company's request. A replay of today's call will be available on the investor section of the company's website approximately two hours after completion of this call. I would like to turn the call over to Pete Frenshoe, Chief Financial Officer.
Speaker 3: Thank you and good morning.
Speaker 3: Joining me on today's call are Dr. Al Sandrock, our CEO , Dr. Todd Carter, our Chief Scientific Officer, and Alan Nunley, our Chief Business Officer.
Speaker 3: We issued our Q4 and year-end 2022 press release this morning.
Speaker 3: The Pressure lease in 10K are available on our website. We plan to provide a brief summary of key highlights from the quarter.
Speaker 3: and reserve the majority of time for your Q&A.
Speaker 3: In a moment, I will turn the call over to Al.
Speaker 3: Before I do this, I want to remind everyone that during this call, Voyager representatives may make forward-looking statements.
Speaker 3: regarding future expectations, plans, and prospects.
Speaker 3: All forward-looking statements are inherently uncertain and are subject to risks and uncertainties that may cause actual results to differ materially from those indicated by these forward-looking statements.
Speaker 3: You are encouraged to review and understand a number of the material risks and uncertainties.
Speaker 3: facing the company as described in the company's annual report on Form 10-K filed with the SEC this morning.
Speaker 3: All SEC filings are available on the company's website.
Speaker 3: Now it is my pleasure to turn the call over to Al.
Speaker 4: Thank you, Pete, and good morning, everyone.
Speaker 4: I'd like to start by acknowledging the transformation Voyager has undergone in 2022.
Speaker 4: Since I became CEO last March, we have advanced a pipeline focused on some of the most significant unmet needs in neurology.
Speaker 4: achieve breakthrough innovations in novel capsules discovery, including the identification of a receptor for one class of capsules.
Speaker 4: entered multiple high-value collaborations.
Speaker 4: Thanks to this progress, during a time when markets have been very difficult for much of the sector, we have created value for shareholders and we have made important steps toward creating value for patients.
Speaker 4: I believe we will continue to do so as we focus on the three pillars of our investment drive for now.
Speaker 4: Our first pillar of value is our Tracer CAPSID Discovery platform.
Speaker 4: The Voyager team evaluated multiple libraries, each with more than 20 million variants of AAV5 and AAV9 capsids to select those capsids that display increased transduction in the central nervous system following intravenous delivery.
Speaker 4: In preclinical studies, we have demonstrated more than 100-pole higher transgene expression in the brain compared to conventional AAV9 capsids. We have shown high levels of CNS expression at low doses, and we have demonstrated the ability to target specific cells such as neurons or glial cells.
Speaker 4: while detargeting the liver and dorsal root ganglion cells.
Speaker 4: This is why I came to Voyager. Our scientists never cease to impress me with their innovation.
Speaker 4: Last year, they identified the receptor for one of our capsid families, and I'm looking forward to seeing what they've accomplished this year.
Speaker 4: I'm not the only one impressed by Voyager's innovation.
Speaker 4: The data we have generated have allowed us to secure partnerships with gene therapy leaders like Pfizer and Novartis and with neurology leaders like Neuroprint.
Speaker 4: Our second pillar of value, which our recent transaction with Neuroc can brought into the spotlight, is our CNF pipeline.
Speaker 4: This is the result of combining Voyager's novel tracer capsid platform with our deep knowledge of neuropharmacology and payloads.
Speaker 4: We select diseases with high unmet need where the target is well validated by human genetics and human biology.
Speaker 4: and where biomarkers may enable a path to quickly and efficiently achieve proof of biology.
Speaker 4: We then design a payload, and our diverse payload capabilities allow us to access a wide variety of targets.
Speaker 4: We can use gene replacement to address loss of function mutations, vectorized siRNAs to address toxic gain of function mutations,
Speaker 4: and vectorized antibodies to address extracellular or cell surface CNS targets.
Speaker 4: As I mentioned, the value of our pipeline was recently illustrated through our strategic collaboration with Neuroprint Biosciences.
Speaker 4: This provided $175 million up front and up to $4.2 billion in potential milestones for rights to our GBA1 gene therapy program for Parkinson's disease and three additional gene therapy programs directed to rare CNS targets.
Speaker 4: And this leads me to our third pillar of value, partnerships.
Speaker 4: We have a sound balance sheet enabled by our track record of generating non-dilutive collaboration revenue.
Speaker 4: Allen and Pete will expand more on that in a minute.
Speaker 4: I will just note that the borders open to a wide variety of collaboration structures to enable neurogenetic medicine.
Speaker 4: We've executed strategic collaborations around our pipeline programs, such as with NeuroPrint.
Speaker 4: and completed crafted option and license agreements, such as with Pfizer and Novartis.
Speaker 4: And we are interested in and evaluating creative field structures, such as opportunities to combine our capsid and receptor technology with cutting edge payloads and biologics.
Speaker 4: It is important to note that we are advancing and we intend to continue to advance OLEOM program.
Speaker 4: The non-deludent financing from our partnerships is the key enabler of our wholly-owned program.
Speaker 4: Now, I will turn the call over to Allen to review the recent Novartis transaction.
Speaker 5: Thank you all. Please turn to slide 4.
Speaker 3: As Al said, Voyager is open to a variety of collaboration structures.
Speaker 5: Earlier this year, we announced the Strategic Collaboration with Neurokun to advance our GBA-1 gene therapy program as well as three new gene therapy programs directed to RhearCNF target.
Speaker 5: We received $175 million up front and are eligible for up to $1.5 billion in potential development milestones and up to $2.7 billion in potential commercial milestones, tiered royalties on net sales, program funding, and an option to elect 50-50 cost and profit sharing in the U.S. for the GBA I program following the GBA I program.
Speaker 5: to capsid against the CNS target. And earlier this month, Novartis exercised its options to capsids against two neurologic disease targets.
Speaker 5: As a reminder, Voyager received $54 million upfront from Novartis, with this option agreement with Signed in March 2022.
Speaker 5: For the last year, Novartis has been evaluating our captions.
Speaker 5: Their decision to license CAPSIDs for two CNS targets triggers $25 million in option exercise fees, and Voyager is eligible to receive up to $600 million in associated development, regulatory, and commercial milestone payments, as well as mid- to high-single-digit tiered royalties.
Speaker 5: based on the net sales of Novartis products incorporating the licensed capsid.
Speaker 5: Novartis also retains the right over the next 18 months to expand the scope of options to evaluate and license capsules for up to two additional CNS targets, subjects to their availability for $18 million per target and a $12.5 million fee per target upon exercise of the option.
Speaker 5: therapies for CNS diseases is very exciting.
Speaker 5: We look forward to continuing this relationship.
Speaker 5: Now, I will turn it over to Pete to review our balance sheet. Thank you, Alan. Please turn to slide five.
Speaker 3: Voyager is committed to maintaining a strong balance sheet that supports advancement of its platform and pipeline.
Speaker 3: As of December 31, 2022,
Speaker 3: We reported cash, cash equivalents, and marketable securities of $118.8 million.
Speaker 3: As Alan described, earlier this year we received $175 million from Neurocran.
Speaker 3: and we will now receive $25 million from the VARIS for the exercise of the options.
Speaker 3: On a pro forma basis, when you factor in neurocranial Novartis payments,
Speaker 3: The company has cash, cash equivalents, and marketable securities of approximately $320 million.
Speaker 3: Voyager is committed to maintaining a strong balance sheet in financial discipline.
Speaker 3: We expected our cash, cash equivalents and marketable securities.
Speaker 3: together with amounts expected to be received as reimbursements for development costs under the neurocranial collaborations.
Speaker 3: We'll be sufficient to meet our land operating expenses and capital expenditure requirements into 2025. This enables the advancement of our two wholly-owned programs.
Speaker 3: The Entite Chow antibody for Alzheimer's disease.
Speaker 3: and the SOD1 gene therapy for ALS into clinical trials.
Speaker 3: We expect the following of I&Ds for both programs in 2024.
Speaker 3: And Al will now expand on these and other programs in our pipeline.
Speaker 4: Thanks, Pete. And now on slide 6, you can see that Voyager has four programs advancing through late research.
Speaker 4: As Pete stated, two of these programs are wholly owned, are Humanized Antitouac about it for all climbers disease, and SOD1 gene violence in program for ALFs.
Speaker 4: Our anti-towel program is differentiated from others that have not demonstrated clinical efficacy in that we target the sea terminal rather than the intraminal region.
Speaker 4: Moreover, our antibody blocks the spread of pathological cow in animal models, whereas the antramural antibodies don't.
Speaker 4: We believe that both of these distinguishing features may prove to be very important as we attempt to block the spread of pathological tau in patients with Alzheimer's disease.
Speaker 4: In January , we selected a humanized development candidate to advance into IND enabling studies.
Speaker 4: Data that led to the selection of this candidate will be presented at the ADPD conference in Sweden later this month.
Speaker 4: Voyager expects to initiate a GLP toxicology study this year in order to enable a potential IND filing in the first half of 2024.
Speaker 4: Our SOB1 ALS program combines a potent SIRNA construct with a CNS trophic blood-brained barrier penetrant novel tracer derived captured.
Speaker 4: Proof of concept for the therapeutic hypothesis has been demonstrated by Tofersin, an investigational drug sponsored by Biogen and Ionis, as shown in a September 2022 New England Journal of Medicine publications.
Speaker 4: So, first end is currently under review by FDA, and if approved, could blaze the trail that we could then follow with a gene therapy solution.
Speaker 4: We are continuing to conduct non-human primate studies to select our lead candidate, which we expect will occur in the first half of this year. And we continue to expect to file an IND in 2024 for this program as well.
Speaker 4: Our other two preclinical programs, the GBA1 gene therapy for Parkinson's disease and other GBA1 mediated diseases, and the protection gene therapy program for Friedreich's ataxia are being advanced in collaboration with Neurocrisp. Thank you for listening.
Speaker 4: Narcindus fully funding both of these programs through phase one at which point the planning board has an option to co-develop and co-emerge the assets in the United States.
Speaker 4: We also continue to advance multiple early research initiatives, including a vectorized antibody for brain metastases associated with HER2-positive breast cancer and a vectorized siRNA approach to enable specific knockdown of mutant Huntington and MSH3 in Huntington's disease.
Speaker 4: Today, I'm all excited to introduce a new D-Therapy program for all finest disease.
Speaker 4: Slide 7 shows the rationale for our new research effort in Alzheimer's disease, which builds upon our COW expertise.
Speaker 4: This new program targets intracellular cow with a vectorized SIR and A gene silencing approach.
Speaker 4: We know that tau pathology closely correlates with Alzheimer's disease progression and cognitive decline. An siRNA gene therapy approach could enable us to knock down tau within neurons. This could be efficacious by itself and also has the potential to complement extracellular approaches.
Speaker 4: which is our anti-tow antibody effort. The unmet need in Alzheimer's disease is enormous.
Speaker 4: And while we're extremely encouraged by the recent advances with anti-amaloid antibodies, we believe that combination therapies may improve outcomes.
Speaker 4: much as they have in oncology. This could mean combining anti-amyloid and anti-tow approaches or combining extracellular and intracellular tau approaches.
Speaker 4: We are currently evaluating an siRNA tau gene silencing payload with our intravenous brain penetrant novel capsid.
Speaker 4: Turning to slide 8 in summary.
Speaker 4: Voyager has demonstrated our ability to execute and create value through 2022 and end to 2023.
Speaker 4: In addition to advancing our pipeline, we answered into multiple important collaborations and significantly strengthened our balance too.
Speaker 4: Looking towards 2023, we continue our work to break through the barriers constraining the field of gene therapy and neurology. We intend to identify a lead candidate for our SOD-1 ALS program, and we will advance our GBA-1 and protection programs.
Speaker 4: collaboratively with NERFEN. We will continue to share the exciting data we're generating at scientific conferences, including at the ADP-D conference later this month.
Speaker 4: And finally, we continue to engage in active discussions with potential partners around our platform and pipeline.
Speaker 4: I want to take a moment to thank everyone on the Voyager team for their incredible work in 2022. Together, I look forward to continuing to build Voyager in the next year, and we are off to a great start.
Speaker 4: With that, we are happy to take any questions you may have.
Speaker 4: to take any questions you may have. Operator.
Speaker 2: Thank you ladies and gentlemen. If you have a question or a comment at this time, please press star 11 on your telephone. If your question has been answered and you wish to move yourself from the queue, please press star 11 again. One moment for our first question. Our first question comes from Jack Allen with Baird. Your line is open.
Speaker 5: and you're guiding towards an IND in the first half of 2023. But do you expect that to be the first tracer casted to move towards an IND, or could it be a partnered program that progresses as well on a similar timeline or maybe even a more rapid timeline? How should we think about those gene therapy assets moving into the clinic? And then I have a few follow-ups as well, if I may.
Speaker 4: Hi Jack, this is Al Sandrock. So actually our IND for SOD1 ALS is planned for 2024. And it may very well be the very first cap in the clinic from TRACER platform. But it's hard to know because, you know, we have these multiple partner programs and of course the timeline.
Speaker 5: Great, and then if I made a few brief follow-up programs, there's been a lot of headlines around the procurement of non-human primates, particularly the supply coming out of Cambodia and Charles River Labs is slowing their imports. I wonder if you had any comments on your ability to get your hands on these non-human primates and what kind of conference you have on your pre-clinical time I was doing forward?
Speaker 6: targets revert back to you and if there's any work that you could leverage on those targets to rapidly advance assets towards the clinic.
Speaker 4: Thanks Jack. This is Al again. I'll answer the non-human primate question and I'll have Alan not only answer the Pfizer- Novartis question.
Speaker 4: But yeah, no, it's a real serious problem. You know, every company that I know of in this industry relies on non-human primates for one thing or another, and of course our tracer platform begins in the non-human primates.
Speaker 4: And so it's a serious problem. I'm not aware as of today of any delay in our programs, but I'm keeping my fingers crossed because anything can happen. And so I hope this gets resolved because there are a lot of patients waiting for drugs. And this is a pretty bad news for the whole industry, I think.
Speaker 4: And I'll just add that we do use multiple vendors to try to reduce that risk, but the risk we're looking at very close ones. Alan, you want to? Sure. Jack, this is Alan. Thanks for the question on Pfizer and Novartis. So in each of those relationships, there was one target that's for Pfizer and one target for Novartis, but they did not.
Speaker 5: rights in the programs. So we just simply have back the rights to do those targets ourselves or to partner on those targets with our tracer capsids with other parties.
Speaker 6: Great. Thank you so much for the multiple questions and congratulations again on the progress. One moment more next question.
Speaker 2: Our next question comes from June Lee with Truth. Your line is open.
Speaker 7: Hi, congrats on the progress and thanks for taking our questions.
Speaker 7: I have a question on the part of the receptor you identified. Is the receptor X sufficient for AAV delivery or is there a co-receptor or co-ligant that is necessary to complete the process of AAV delivery? And also with the identification of this receptor X, are you considering delivery with the delivery with values other than AAV such as coating the LMP?
Speaker 3: or using it to ASL or that's our only. And I have a follow-up question. Thank you. Hi, this is Todd. Thank you for the questions. I'm receptor-ex and the question of a coli-eggant. We have not identified a coli-eggant. We know and have shown that the receptor is...
Speaker 3: sufficient to increase transduction in vitro settings. So the increased expression of it alone can result in dramatically increased uptake and transduction. We have ongoing experiments to further elucidate that in the vivo setting.
Speaker 3: With regard to the question about delivery of other things, it's something we're actively exploring, delivery of other modalities. We have some early exploratory work right now that's ongoing.
Speaker 7: Great. And, you know, with this...
Speaker 7: With their capsules, by how much are you able to lower the systemic dosing achievements compared to, for example, so again, it's not which has a dosing about 10 to the 14.
Speaker 3: I'll talk again. So that's a great question, and it depends upon the target tissue and the amount of delivery you need. Our goal is to improve the therapeutic index and deliver sufficient or, hopefully, possibly more than sufficient. And so that's a great question.
Speaker 3: to the target tissues. You can do that in two ways. One, and given dose, you can deliver more to say the brain.
Speaker 3: which results in the ability to lower the dose and result in delivering less to the liver, for example, up off-target tissues.
Speaker 3: So it's this ratio of on targets to off target, that's the question. In addition, we have shown, for example, with some of our tasks that we can dramatically reduce the dose, attend...
Speaker 3: to 50 fold and still get dramatic delivery into the CNS-Apan human primates.
Speaker 3: So both of those goals are something we've seen with our capsids. I think at a minimum, what we're looking for is to go from the E14, a level that's seen quite often with the AAV9 and related capsids, and to get into the E13 per kilogram or lower doses. Great.
Speaker 7: And one final question for me, I know it's difficult to, with giving your potential milestones from your three collaborators, but curious if you're able to provide any cash fund or items based on the 320 million in performer cash and if you're planning for any capital expenditures related to in-house manufacturing scale-up borers that are in the next few years. Thank you.
Speaker 5: He had unanimous peace. So part of our actual presentation today, I think we did provide cash flow guidance with regards to runway. We said that we were going into 2025, which parts of the balance sheet and our ability there.
Speaker 5: I do want to highlight a couple things. I think we have a really strong balance sheet. We started this year with $320 million between our Nurekrand transaction as well as the Novars transaction. Our balance sheet cash flow projections I want to do say.
Speaker 5: They do not include the future potential milestones associated with the collaborations that are existing.
Speaker 5: So that actually can actually extend that one leg further beyond those projections. With regards to our burn for 2022, our burn was actually $78 million. And overall,
We were very capital efficient as an organization with regards to our expenditures and deployment of cash. Our cash flow projections for 2023, although we don't provide specific guidance with regards to that, we do anticipate those projections to actually go up year on year, although that's really the advancement of our wholly owned program.
I think as we described where you guys here today. I think for the most part, you know, it is our anticipation that as we move forward over the next couple of years, that our costs will increase somewhat meaningful associated with the development of our programs, especially as we get into clinical trials. However, with that being said,
One of the things that we've done really well as an organization is we've actually been able to do non-w financing associated with our programs.
As you can see over the last six months or so, we actually generated over $200 million in non-dilutive financings associated with the deals that we did. I think it is our overall goal and game plan to continue to be able to finance the company into the future based on additional non-dilutive deals that we can do, but also be able to mitigate costs.
through partnerships and other types of arrangements.
Great. Can you take our questions and then can grab from the execution I share. Looking forward to your progress.
Sure, thank you. One moment for our next question. Our next question comes from Dan Leon with Raymond James. Your line is open.
Thanks for taking the questions. Could you just maybe take us more specifically through the steps of the program. Focus on sadjone this year. That will help derisk the program getting into the I phase in the earlier part of next year.
You know, that differently, what you still need to do, experiment-wise, to get to that lead drug can't be a big thing. And then what do you need to do to actually finish the talk studies required to get the IND open? Thank you.
I am, Dean, this is Alc, and I'm going to turn it over to Todd in a minute. Yeah, I think that there's some key milestones here. First, it is nominating a development candidate. In other words, combining a trans gene with one of our caps, and then we have a cap to profile. So.
That we've already developed that we think we need in order to be effective in SOD1 ALS. I think an important thing to track for us is what's going on with the person. As you know, there's going to be an FDA Advisory Committee this month and the decision by FDA will come next month.
That'll give us a lot of insight into how to develop this drug and even how to get it approved and make it available to patients. And after the development candidate is identified, we'll have to start GLP talk studies.
And of course there's going to be important interactions with FDA as we approach the IND, which we plan for next year. It's still on track for next year. Todd, do you have anything to add to that? I think you've captured the bulk of it, Al. The next steps are the identification of the lead nomination that Al mentioned.
We're still tracking to the first half of this year on that and we're reasonably on track for our I&D pilot in 2024.
to the first half of this year on that, and we're reasonably on track for our IND filing in 2024. Thank you.
One moment for our next question. Our next question comes from Yun Zhang with VTIG. Your line is open. Hi. Good morning. Thank you very much for taking the questions. So I noticed that none of the pipeline program is actually using the vectorized anybody.
and developed here at Voyager over the years. And it's gonna be suitable for any target that is extracellular or on the cell surface of either neurons or glial cells or other kinds of cells, non-neuronal cells in the CNS. So, and so that actually is a pretty large number of targets and that's a pretty large number of targets.
And look, we are a lead program for Tau is the antibody. It's a passive immunotherapy as you pointed out. But we always have the options to vectorize it later. We feel like it's the shortest path.
very efficient cost effective and rapid path to get proof of concept just using it as a passive immunotherapy. After we get the proof of concept then we have multiple options available to us. And we see that a lot of potential value in our vectorized antibody platform and remain pretty excited about it.
Our VHIR2 program, where we're still interested and excited about that, it's an earlier stage, much like our HD program. We're hopeful that the data will continue to be generated and result in advancement of that program. And we're always interested in other approaches with the vectorized antibody platforms as well.
I believe the FA program and also some additional gene therapy programs were part of an older collaboration with Neurocran. So is it reasonable to assume that now they are also going to be based on a tracer technology platform? Yes, so I think that's a good question. I think that's a good question.
Yeah, this is Al Sandrock again. This is the original Narcran deal was signed before the availability of the tracer capsids.
But it's fair to say that we are both companies are now very interested in moving forward for the for pre-drikes and those other two programs that you mentioned with the novel capsules.
Okay, great. One moment before our next question.
The next question comes from Laura Chico with Wet Bus.
Hey, good morning guys. Thanks very much for taking the question. I guess I have one related to neurococollaboration as well. I'm wondering specifically for the Parkinson's, the GBA one program, if you could speak a little bit more to kind of the thought process leading to kind of exercising the co-development, co-commercialization option, obviously still.
just wondering how that might change or influence kind of the past forward here. Thanks very much.
Laura, this is out Sandrock again. Yeah, so, you know, for very common diseases like Parkinson's disease and Alzheimer's disease, it's hard to imagine the voidra would be able to go all the way to late stage clinical trials, which tend to be rather large or to commercialization. So it was never a question of whether we would.
partner, there was always a question of when. And our colleagues at Norfolkman was very excited about the program. I should say that it was a very competitive process. A lot of people were excited. We're excited about GBA1-CD because it makes so much sense, I think, it was highly validated target.
And so we decided to do the deal and it provided non-delutive revenue for us to pursue other programs and we just outlined one new one at this morning.
In terms of opt-in, it's after phase one. And you don't know what the phase one trial design is yet. It's just an earthquake and to tell us that it's very possible that after phase one, we'll see whether or not.
the gene therapy produces the enzyme, which we should be able to measure in the spinal fluid, and whether or not it reduces the substrates that build up abnormally in the spinal fluid in GBA1 carriers with Parkinson's disease.
So, after proof of biology perhaps, but again, it depends on what the phase one trial design is, and we don't know what that is yet, but that's a possibility, what I just outlined.
In terms of the approval of the drug by Riyada, the NRF2 activator, I think it's very, very exciting. This is a disease that had no treatment until last week and it's a terrible disease. And that...
I think it's very encouraging for the whole field. And so free drive state taxi is, I think, what happens typically is that after the first approval, other companies get involved and it just lifts all those. And so I think it's only a good news for us. And so free drive state taxi is, I think, a good news for the whole field.
Maybe just this is now not only one thing to add on the options for cross profit share. Is a good way for preserving optionality for Voyager is that we'll get to take a look at the data from that phase one trial. See how we're situated and we'll have an attractive option between the US 50 50 cost profit chair and really healthy milestone and loyalty track. So we're happy to be able to preserve that optionality after the phase one. Thank you.
I mean, a comment on the CFAE. In addition to what Al said, the mechanisms by which the riata drug and multiple oxalone works are different from our gene therapy approach. The two approaches are not exclusive at all. We're quite excited about the riata approval. Yeah. I should add.
that it gives us an idea of what the phase 3 trial needs to be. We now know what the outcome measure should be for a regulatory approval. We see what happens. We see the change in that outcome measure over the course of time, so we can now better power our studies.
I mean, it's just a huge, hugely positive event, I believe, for patients between the United States to be able to do it. Thank you very much. One moment for our next question.
Our next question comes from Sumat Gilkarni with the Kender Kord. Your line is open. Your line is open.
Hi, congrats on the quarter. This is actually Ross asking questions on behalf of SMAAT. I actually have two questions. In regards to receptor X that you've identified, given that you've been developing these novel capsules for some time now, what are your latest thoughts on the level of receptor expression and variability across primates and mice?
and non-human primates and in humans. We know that the capsids find the orthologs for all those species and that the orthologs, the protein versions from each of those species enhance transduction in our envitro studies. And so we're...
We think that the translation of the humans is greatly de-risked and there's a greater chance of success because of all of this data.
Okay, and then kind of a quick follow up is, is there any potential for these cap foods to effux out the brain? And so how might this concern be mitigated if this is kind of an area of concern?
Well, you know, we do check all the other organs when we, when we, the tracer platform allows us to actually look at messenger RNA, the expression of these caps into multiple organs simultaneously.
And what we find is actually if anything, decreased transduction in places like the liver. So many of our novel capsids, which are, you know, publicly get into the CNS, they tend to de-target the liver, for example. Have we looked at every single organ? No, not yet.
But so far, it doesn't look like there's significant e-flux, at least to the point where we get a transaction of organs in the periphery. Todd, do you want to add anything? Sure. There's opportunities in both directions to your question, actually. And one is, if we wanted to deliver to the CNS, which has been our focus.
Now looking for those caps that deliver better to the CNS and less well to the off target tissues. The novel caps are discovery team. There's a process that involves iteration. So there are initial screens and then there are secondary maturation screens. And what we found is we can identify caps that's with increased delivery to the CNS.
And then to the maturation process, we can identify variants that have similar or increased delivery to the CNS and then altered delivery to other tissues. So we can identify a panel of capsid variants and then select those that match our capsid profile for a given disease.
And that capsid profile that Al mentioned earlier is something that we do build for each of the diseases. And that includes the tissues we want to target and the tissues that we want to avoid for potential off-target risk.
Another opportunity side is that we have the potential to deploy tracer and other tissues as well. So if we're able to identify caps as a target muscle or other tissues, those present opportunities.
for licensing with others as well. So there's a lot of opportunity in the Tracer platform.
Thank you. One moment for our next question. Our next question comes from Yalyn Zuh with Wells Fargo. Your line is open.
I thank for taking the questions and congrats on the quarter. So first of the question on SOD1-AOS gene therapy development path, given the upcoming Toefersten adcom and Tadufa, I'm wondering if you could comment on the validity of neurofilament light chain as a surrogate marker for efficacy.
And if it turns out that FDA accepts this target marker, do you think that would be the same path for a gene therapy program as well?
And that's a great question and something I think we're all tracking. I do believe myself.
that neurofilament can be relied upon as a surrogate marker of efficacy. But I'm not a regulator, and whether FDA decides that it's a valid surrogate endpoint for approval, we'll find out very soon. Nevertheless, I think we can still use it. Thank you.
as a way to decrease risk. And we can use it even in the earliest clinical trials to track whether or not our gene therapy is affecting at least a neurofiber integrity as measured by neurofilement release. So I think it's a very useful surrogate marker of efficacy regardless of what the FDA decision is.
The FDA decision, if they do use it or consider it about an M.4 approval, that just makes the approval pathway even shorter from behalf of patients.
But in addition to NFL, Bayesian and IONUS have published in New England Journal that you can look at soluble SOB1 levels itself in this final fluid as sort of a target engagement biomarker.
and we could do the same thing as well. We should be reducing the expression of SOD1 in spinal fluid. So both of these measures are very useful to help us understand whether our gene therapy is on the right track and we plan to use all of it.
Another question on collaborating the partnership programs, the licensing with regard to TRACER. To what extent Pfizer and Novartis have studied the TRACER-CAF-STED in conjunction with their target? I don't think we have the valuable attributes in terms of people getting interviews, and other dice lagging examples too.
conducted any animal studies, for example, and then on the largest for the two additional targets that they may decide to pursue with some significant fees, is there a timeline that when they might have to make the decision to go with the option with $18 million per target payment?
So maybe this is Alan, I'll take the second piece first. So the ability for Novartis to expand to two additional targets, they have 18 months to decide whether they'd like to do that, to choose either to add one or two targets under the agreement.
If they do, it would be to attract the same terms as the original agreement, which is $18 million per target if they add a target, and then the same $12.5 million per exercise with the 300 million in potential milestones downstream and mid to high single digit royalties. So that's, they have 18 months to make that decision. And I'm sorry, what was the talk to
work before they opted into the the the the the crystal cap stain.
So in each instance both Pfizer and Novartis had a one year period to evaluate whichever of our capsules they wanted to look at to consider for exercise. So they conducted their own experiments on their end.
to help them decide which and whether they would like to exercise on which caps it. So at the end of that process Pfizer exercised an option for its neurologic target and no virus. It's just exercised for two of the CNS targets after their own evaluation. There's a subset of information that's shared back to us that is not...
intended to be specific to their targets, but to help Voyager understand the results of the experimentation with our capsids in the hands of our partners. So that information is valuable to us as we learn more and more about our own capsids.
Great, thanks for the color. And lastly, just wandering on the evolution of the Tracer capsids. So first of all, are you conducting additional experiments and have additional efforts?
for further reducing the capsules load, with IE with even more potent and more CNS selective cluster capsules. And when might we have some update on that? And also, how about...
targets outside the CNS. We will hear about some updates on that front. Thanks for taking all the questions.
Hi, this is Todd. So with regard to non-CNS application, our focus has been on the CNS. That's what we spend the bulk of our efforts on so far. So I can't commit to any timelines. It's certainly something that we're interested in exploring in the non-CNS side. With regard to the continued evolution of our tracer capsules.
That's absolutely something that we're seriously pursuing. We continue to mature our capsids and to develop. The team looks at different loops on the AED capsid surface. We use different starting capsids, different parental capsids.
and all those processes continue. We'll be presenting data at the upcoming ASGCT, I think the next conference that we'll be showing some new data, and we'll continue to share the work that comes out of our TRACER platform as it arises. Great, thank you. Looking forward to the ASGCT presentation.
talk about kind of lessons learned from your SOD1 chain therapy for ALS will inform your early recitements in Cal, siRNA and then
Since there are more interesting CNS targets, they could be targeted by SIR and A, you optimize genes, financing payloads, what sort of other new research initiatives are you considering, and I won't follow on this again, please.
Hi, Jay, I'll start and Todd will continue. Yeah, no, listen, I believe this ability to vectorize siRNAs is a huge...
You know, capability that we have a border honed over the years. It's not an easy thing to find at SIR and A's. And we published on some of the thinking that goes into it. How many versions we test, et cetera, and how we address things like overarnishing the potential. And so, yeah, I mean, I think that.
You know, the SIR and a vectorized SIR and a for SOD1, there'll be lessons learned there that we will apply to all of our future SIR and programs, including TAO. Todd? So one of the good things about...
Working here at Voyager is we can deploy different kinds of payloads to include the vectorized antibodies that we talked about, the gene replacement, and then the SIR and A that we're talking about here. Some of the hoating that we did that Al mentioned came through our first generation Huntington's program. We continue to pursue a Huntington's approach as well.
That was an early exploratory program that we announced earlier this year. That's a dual approach for looking to knock down both in a real specific way, the mutant form of Huntington and MSH3, which is a genetic modifier of Huntington's disease. We have a lot of efforts in the SIRNA approach.
We've honed that expertise over the years and we're looking forward to deploying these programs in addition to the other payload capabilities that we have. Yeah, and maybe I could add that the Huntington's program is a allele-specific SIRnet, which is also not straightforward to develop. And Voyager scientists have figured out how to do that.
I would also add that there's a lot of mutations that are taught to gain a function mutation for CNS disorders. So having this capability of knocking down gene expression is very, very helpful and opens up a large number of targets for us to pursue.
Actually, that's super helpful. And then if I could please ask one follow-on with the advancement of your anti-tau antibody, can you just talk about how that will fit in with your SIR and a tau gene silencing program and I guess how the two modalities could be potentially complementary and fit into it."
future treatment landscapes for Alzheimer's? Hi, this is Todd again. So thank you for the question. We're excited about how the target is a nerdy generative target scope. It's validated. We think that our.
antibody approach. So we mentioned earlier the antibody approach against Tau came out of the vectorized antibody program. We identified a series of antibodies that worked extremely well in our animal models and are differentiated by both the efficacy in our animal models and the epitope that the target. So we're continuing to move that forward.
That said, there are still other approaches that could be really effective potentially in TOW opportunities. And we think that vectorized SIRNA to reduce TOW is one of those. So the reduction of TOW, interestingly, is, while it still affects TOW, it's an independent mechanism of affecting TOW, then it's TOW antibodies. So I think those approaches are interesting as so-low approaches, but they're also potentially interesting in combination.
And of course, then there's the potential to combine with other Alzheimer's disease therapies as well, including the anti-amiloiites that have recently received accelerated approval. So I think I would say we're in a bit of a renaissance of neurodegeneration in Alzheimer's disease, and we're pretty excited about all of this progress. Thank you for taking the questions.
And I'm not showing any further questions at the time. I turn the call back over to Al Sanro to give any closing remarks.
Thank you everyone for joining us today. Please feel free to follow up with us directly with any other questions. Thanks again. Bye. Ladies and gentlemen, this concludes today's presentation. We now disconnect and have a wonderful day.
Again shortly. To raise and lower your hand during Q&A you can dial star 11.
I.
and answer session at the end of this call. Please be advised this call is being recorded at the company's request. A replay of today's call will be available on the investor section of the company's website approximately two hours after completion of this call. I would like to turn the call over to Pete Frenshu, Chief Financial Officer.
at the end of this call. Please be advised this call is being recorded at the company's request. A replay of today's call will be available on the investor section of the company's website approximately two hours after completion of this call. I would like to turn the call over to Pete Frenshue, Chief Financial Officer. Thank you and good morning.
Joining me on today's call are Dr. Al Sandrock, our CEO , Dr. Todd Carter, our Chief Sciences Officer, and Al Numley, our Chief Business Officer. We issued our Q4 and year end 2022 press release this morning. The press release in 10K are available on our website.
We plan to provide a brief summary of key highlights from the quarter and reserve the majority of time for your Q&A. In a moment, I will turn the call over to Al.
Before I do this, I want to remind everyone that during this call, what your representatives may make for looking statements regarding future expectations, plans and prospects.
All forward-looking statements are inherently uncertain and are subject to risk and uncertainties that may cause actual results to differ materially and those indicated by these forward-looking statements. You are encouraged to review and understand the number of the material risks and uncertainties facing the company as described in the company's annual report.
on form 10K followed with the SEC this morning. All SEC filings are available on the company's website.
Now it is my pleasure to turn the call over to Al. Thank you Pete and good morning everyone. I'd like to start by acknowledging the transformation Bozer has undergone in 2022.
Since I became CEO last March, we have advanced at pipeline, both at some of the most significant unmet needs in neurology. Achieve breakthrough innovations in novel capsules discovery, including the identification of a receptor for one class of capsules, and entered multiple high-value collaborations.
continue to do so as we focus on the three pillars of our investment rationale.
Our first killer value is our Tracer Capsid Discovery platform. The Voyager Team evaluated multiple libraries, each with more than 20 million variants of AAD5 and AAD9 Capsid, so like those Capsids, it displayed increased transduction in the central nervous system following intravenous delivery.
In preclinical studies, we have demonstrated more than 100-fold higher transgene expression in the brain compared to conventional A89 capsids.
We have shown high levels of CNF expression at low doses, and we have demonstrated the ability to target specific cells, such as neurons or glial cells, while detargeting the liver and dorsor root ganglion cells.
This is why I came to Voyager. Our scientists never see to impress me with their innovation. Last year, they identified the receptor for one of our Capsid families, and I'm looking forward to seeing what they accomplished this year. I'm not the only one impressed by Voyager's innovation.
The data we have generated have allowed us to secure partnerships with gene therapy leaders like Pfizer and Novartis and with neurology leaders like Naraprin.
Our second pillar of value, which our recent transaction with Narrow can brought into the spotlight, is our CNF pipeline. This is a result of combining Goaier's novel, tracer-capsid platform with our deep knowledge of neuropharmacology and payloads. We select diseases with high on that need.
where the target is well validated by human genetics and human biology. And where biomarkers may enable a path to quickly and efficiently achieve proof of biology. We then design a payload in our diverse payload capabilities allow us to accept the wide variety of targets. We can use gene replacement to address loss of function mutations.
for the program by Ops Sciences. This provided $175 million upfront and up to $4.2 billion in potential milestones for rights to our GBA-1 gene therapy program for Parkinson's disease and three additional gene therapy programs directed to rare CNS targets. And this leads me to our third killer of value.
partnerships. We have a sound balance sheet enabled by our track record of generating non-delative collaboration revenue. Allen and Pete will expand more on that in a minute. I will just note that Voyager's open to a wide variety of collaboration structures to enable neurogenetic medicine. We've executed strategic collaborations around our pipeline program.
It is important to note that we are advancing and we intend to continue to advance all the own programs.
The non-dilutive financing from our partnerships is a key enabler of our wholly owned program.
Now I will turn the call over to Alan to review the recent Novartis transaction.
Thank you, Al. Please turn to slide four. As Al said, Voyager is open to a variety of collaboration structures. Earlier this year, we announced a strategic collaboration with NURKRIN to advance our GBA-1 gene therapy program, as well as three new gene therapy programs directed to Rhearcy and F-target.
We received $175 million up front and are eligible for up to $1.5 billion in potential development milestones and up to $2.7 billion in potential commercial milestones, tiered royalties on net sales, program funding, and an option to elect 50-50 cost and profit sharing in the U.S. for the GBA I program following the Phase I readout.
This type of cost and risk sharing structure provides transformational value for Voyager, and it is one of a variety of structures we have executed. We have also entered Capsid option in license agreements with Pfizer and Novartis.
Last year, Pfizer exercised its option to a capsid against the CNF target. And earlier this month, Novartis exercised its option to capsid against two neurologic disease targets. As a reminder, Voyager received $54 million upfront from Novartis when this option agreement was signed in March 2022.
For the last year, Novartis has been evaluating our capsules. Their decision to license capsules for 2CNF targets, triggers $25 million in option exercise fees, and Voyager is eligible to receive up to $600 million in associated development, regulatory, and commercial milestone payment, as well as mid to high single digit tiered royalties.
based on the net sales of Novartis products incorporating the license capsules. Novartis also retains the right over the next 18 months to expand the scope of options to evaluate and license capsules for up to two additional CNS targets, subjects to their availability for $18 million per target and to $12.5 million fee per target upon exercise of the option to license the capsules as well as milestones and royalties.
It's important to note here that we avoid your view Novartis is one of the current leaders in gene therapy fields. Their decision to license our novel, intravenous AAB capsules to enable gene therapies for C&S diseases is very exciting.
It's important to note here that we avoid your view Novartis is one of the current leaders in gene therapy fields. Their decision to license our novel, intravenous AAD capsules to enable gene therapies for C&S diseases is very exciting. We look forward to continuing this relationship. Thank you.
Now I will turn it over to Pete to review our balance sheet. Thank you, Ellen. Please turn to flood 5. What is your commitment to maintaining a strong balance sheet that supports advancement of its platform and pipeline? As of December 31, 2022, we reported cash, cash, click on some marketable securities.
of $118.8 million. Does that all describe earlier this year we received $175 million from NURRICRAN?
and we will now receive $25 million from Novartis for the exercise of the options. On a pro-formal basis when you factor in neurocranin Novartis payments,
The company has cash, cash equivalents and marketable securities of approximately $320 million. Voyager is committed to maintaining a strong balance sheet in financial discipline. We expect that our cash, cash, equivalents and marketable securities, together with the amounts expected to be received as reimbursements.
for development costs under the Neurotrim Collaborations will be sufficient to meet our planned operating expenses and capital expenditure requirements into 2025. This enables the advancement of our two wholly owned programs.
The anti-chow antibody for Alzheimer's disease and the sub-1 gene therapy for ALS and two clinical trials. We expect a following of INDs for both programs in 2024, and ALO now expand on these and other programs in our pipeline. Thanks Pete, and now on slide 6, you can see that Voyager has four programs advancing through late research.
As Pete stated, two of these programs are wholly owned, our Humanized Antitouac about it for all climbers disease, and SOD-1 gene silencing program for ALS. Our Antitouc program is differentiated from others that have not demonstrated clinical efficacy.
in that we target the sea terminal rather than the intraminal region. Moreover, our antibody blocks the spread of pathological power in animal models, whereas the intraminal antibody don't.
We believe that both of these distinguishing features may prove to be very important as we attempt to block the spread of pathological tau in patients with Alzheimer's disease.
In January , we selected a humanized development candidate to advance into IND enabling studies. Data that led to the selection of this candidate will be presented at the ADPB conference in Sweden later this month.
Voyager expects to initiate a GLP toxicology study this year in order to enable a potential IND filing in the first half of 2024. Our SOV-1 ALS program combines a potent SIR-9 construct with a CNS-trophic blood-brain barrier penetrant novel tracer derived captured.
Proof of concept for the therapeutic hypothesis has been demonstrated by so person an investigational drug sponsored by biogen and ionus as shown in a September 2022 New England Journal of Medicine publication.
So, first one is currently under review by FDA, and if approved, could blaze a trail that we could then follow with a gene therapy solution. We are continuing to conduct non-human primate studies to select our lead candidate, which we expect will occur in the first half of this year.
and we continue to expect to file an IND in 2024 for this program as well. For other two preclinical programs, the GBA-1 gene therapy for Parkinson's disease and other GBA-1 mediated diseases, and the protection gene therapy program for a free-dry-state taxi are being advanced in collaboration with Neuropran.
Narakrindas fully funding both of these programs through phase one at which point the county board has an option to co-develop and co-meritialize the assets in the United States.
We also continue to advance multiple early research initiatives, including a vectorized antibody for brain metastases associated with HER2-positive breast cancer.
and a vectorized siRNA approach to enable specific knockdown of mutant Huntington and MSH3 in Huntington's disease. Today, I'm also excited to introduce a new gene therapy program for Alzheimer's disease.
Slide 7 shows the rationale for our new research effort in Alzheimer's disease, which still upon our cow expects for teeth.
This new program targets intracellular cow with a vectorized SIR and A gene silencing approach.
We know that tau pathology closely correlates with Alzheimer's disease progression and cognitive decline. An siRNA gene therapy approach could enable us to knock down tau within neurons. This could be efficacious by itself and also has the potential to complement extracellular approaches, such as our anti-tau antibody effort. The unmet need in Alzheimer's disease is enormous.
And while we're extremely encouraged by the recent advances with anti-amoloid antibodies, we believe that combination therapies may improve outcomes, much as they have in oncology. This could mean combining anti-amoloid and anti-tile approaches or combining extracellular and intracellular tile approaches. We are currently evaluating an SIR-Nate-Tao-Gene-Filemsing payload.
and significantly strengthens our balance sheet.
Looking towards 2023, we continue our work to break through the barriers constraining the field of gene therapy and neurology. We intend to identify a lead candidate for our SOD-1ALS program and we will advance our GBA-1 in protection programs collaboratively with Narcron.
We will continue to share the exciting data we are generating at scientific conferences, including at the ADP-D conference later this month. And finally, we continue to engage in active discussions with potential partners around our platform and pipeline. I want to take a moment to thank everyone on the Boisier team.
gentlemen, if you have a question or a comment at this time, please press star 11 on your telephone. If your question has been answered and you wish to move yourself from the queue, please press star 11 again. One moment for our first question. Our first question comes from Jack Allen with Baird. Your line is open.
Great, thank you so much and congratulations to the team on all the progress made over the course of the quarter. I guess to start, I'm hoping we could talk broadly about the tracer capsids and then move towards the clinic. I know that you have your ALF-SOD 1 program that's wholly owned and you're guiding towards an IND in the first half of 2023.
But do you expect that to be the first tracer cast to move towards an IND or could it be a partner program that it progresses as well on a similar timeline or maybe even more rapid timeline? How should we think about the other student therapy assets moving in the clinic and then KivaPee call-ups as well? I may. I jack this is Al Sandrock. So actually our IND for SOD1 ALF is planned for 2024. And it may very well be the very first capture in the clinic from the tracer platform.
But it's hard to know because we have these multiple partner programs and of course the timelines for these partner programs are in their hands. And so it will be neck and neck likely. But I think that roughly in the 2024, 2025 timeframe is when a lot of these IMBs will come into play. Todd, do you have anything to add to that? It sounds right, Al. Thank you. Yes, yes, absolutely absolutely. Yes.
Great. And then if I made a few brief follow-up programs, there's been a lot of headlines around the procurement of non-human primates, particularly the supply coming out of Cambodia and the Charles River Labs is slowing their imports. I wonder if you had any comments on your ability to get your hands on these non-human primates and what kind of conference you have on your pre-clinical time I was moving forward. And then maybe outside of that question, I wanted to touch on just the Pfizer and Novartis relationships. It's really great to see the two major leaders in GDPRB into some programs.
industry relies on non-human primates for one thing or another. And of course, our tracer platform begins in the non-human primates. And so it's a serious problem. I'm not aware as of today of any delay in our programs, but you know, I'm keeping my fingers crossed because anything can happen.
And so I hope this gets resolved because there are a lot of patients waiting for drugs. And this is a pretty bad news for the whole industry, I think. Todd. And I'll just add that we do use multiple vendors to try to reduce that risk, but it's a risk we're looking at very close ones. Alan, you want to? Sure. And Jack, this is Alan. Thanks for the question on Pfizer and Novartis. So in each of those relationships, there was one target that's for Pfizer and one target for Novartis, that they did not exercise an option to attach it.
So the rights with respect to our capsits for those targets do revert to Voyager, but because the programs are being prosecuted entirely on the partners that Pfizer and Novartis, we don't have information about the program or any rights in the programs. So we just simply have back the rights to do those targets ourselves or to partner on those targets with our Tracer Tapsits with other parties. Great. Thank you so much for the multiple questions and congratulations again on the progress.
One moment more next question. Our next question comes from June Lee with Truist. Your line is open. Hi, congrats on the progress and thanks for taking our questions. I have a question on the part of the receptor you identified. Is the receptor X sufficient for a V delivery or is there a co-receptor or co-likeant that is necessary to complete the process of a V delivery?
And also with the identification of this receptor X, are you considering delivering mobalities other than AAB such as coding the LNP or fusing it to ASO or SRN? And I have a follow-up question. Hi, this is Todd. Thank you for the questions. I'm receptor X and the question of a coli-Li-Ga-F. We have not identified a coli-Ga-F.
We know and have shown that the receptor is sufficient to increase transduction in vitro settings. So the increased expression of it alone can result in dramatically increased uptake and transduction. And we have ongoing experiments to further reduce the data in the NABBO setting. With regard to the question about delivery of other things, it's something we're actively exploring. And with regard to the question about delivery of other things, it's something we're constantly exploring.
delivery of other modalities and we have to early exploratory work right now.
of other modalities and we have some early exploratory work right now. Put it on the note. Great.
And, you know, with this, with your capsules, by how much are you able to lower the systemic dosing achievements compared to, for example, Sorgasmout, which has a dosing about 10 to 14? Todd, again, so that's a great question. And it depends upon the target tissue and the amount of delivery you need.
Our goal is to improve the therapeutic index and deliver sufficient or hopefully, if possible, more than sufficient to the target tissues. You can do that in two ways. One, and a given dose, you can deliver more to say the brain.
which results in the ability to lower the dose and result in delivering less to the liver, for example, the off-target tissues. So it's this ratio of on-targets to off-target, that's the question. In addition, we have shown, for example, with some of our cassids, that we can dramatically reduce the dose of 10 to 50 fold and still get dramatic delivery into the CNS-Athon human primates.
with giving your potential milestones from your three collaborators. But curious if you're able to provide any cash fund or items based on the 320 million in performer cash. And if you're planning for any capital expenditures related to in-house manufacturing skill up for us that are in the next few years.
with giving your potential milestones from your three collaborators. But curious if you're able to provide any cash fund or items based on the 320 million in performer cash. And if you're planning for any capital expenditures related to in-house manufacturing scale up for us that are in the next few years. Thank you.
So part of our actual presentation today, I think we did provide cash flow guidance with regards to runway. We said that we were going into 2025, which parts of the balance sheet and our ability there. I do want to highlight a couple things. I think we have a really strong balance sheet. We started this year with $320 million between our Nurekrand transaction as well as the Nurekrand transaction. Our balance sheet cash flow projections I want to do say they do not include the future potential milestones.
associated with the collaborations that are existing. So that actually can actually extend that runway further beyond those projections. With regards to our burn for 2022, our burn was actually 78 million dollars and overall we were very capital efficient as an organization with regards to our expenditures and deployment of cash. Our cash flow projections for 2023, although we don't provide specific guidance with regards to that.
We do anticipate those projections to actually go up year on year. Although that's really in the advancement of our fully owned programs. I think as we described where you guys here today. I think for the most part, you know, it is our anticipation that as we move forward over the next couple of years, that our costs will increase somewhat meaningful associated with the development of our programs, especially as we get into clinical trials. However, with that being said, one of the things that we've done really well as an organization is we've actually been able to do non-dolluted financing associated with our programs.
And as you can see over the last six months or so, we actually generated over $200 million to not that with the financing associated with the deals that we did. So I think, you know, it is our overall goal and game plan to continue to be able to finance the company into the future based on additional, non-dialuted deals that we can do, but also be able to mitigate kind of costs through partnerships and other types of arrangements. Thank you.
Great. Thanks for taking our questions and congrats on the execution. I'm not sure. Looking forward to your progress. Sure. Thank you. One moment for our next question. Our next question comes from Dan Leon with Raymond James. Your line is open. Thanks for taking the question. Could you just maybe take us more specifically through the steps?
of the program focused on SOD1 this year that will help de-risk the program getting into that IND phase in the earlier part of next year. You know, it's that differently, what do you still need to do experiment wise to get to that lead drug candidate? And then what do you need to do to actually finish the talk studies required to get the IND open? Thank you.
I am, Dean, this is Alf. I'm going to turn it over to Todd in a minute. But yeah, I think that there's some key milestones here. First is nominating a development candidate. In other words, combining a trans gene with one of our caps, and then we have a capsule profile that we've already developed that we think we need in order to be effective in SOD1AOS. So, I'm going to turn it over to Todd in a minute.
I think an important thing to track for us is what's going on with Tilferson. As you know, there's going to be an FDA Advisory Committee this month, and the decision by FDA will come next month. That will give us a lot of insight into how to develop this drug and even how to get it approved and make it available to patients.
So, and you know, actually the development candidate is identified. We'll have to start GLP talk studies. And, of course, there's going to be important interactions with FDA if we approach the IMD, which we pointed up for next year. So on track for next year. Todd, do you have anything to add to that? I think you've captured the bulk of it now. I mean, the next steps are the identification of the...
The lead nomination that I'll mention, we're still tracking to the first half of this year on that and we're reasonably on track for our IND filing in 2024. One more for our next question. Our next question comes from Yoon-Zong with BTIG or Lyon is open. Hi. Good morning. Thank you very much for taking the question. So I noticed that none of the pipeline program is actually using the vectorized anybody.
or any target that is extracellular or on the cell surface of either neurons or glial cells or other kind of cells, non-eronal cells in the CNF. So that actually is a pretty large number of targets.
And look, we are a lead program for Tau is the antibody. It's a passive immunotherapy, as you pointed out. But we always have the options to vectorize it later. We feel like it's the shortest path, very efficient, cost-effective, and rapid path to get proof of concept, just using it as a passive immunotherapy.
After we get the proof of concept, then we have multiple options available to us. Todd? We see that a lot of potential value in our vectorized antibody platform and remain pretty excited about it. Our VHIR 2 program, where we're still interested and excited about that, it's an earlier stage, much like our HD program.
We're hopeful that the data will continue to be generated and result in advancement of that program. We're always interested in other approaches with the vectorized antibody platforms as well.
Okay, so my next question is on the collaboration with Neurocran. I believe the FA program and also some additional gene therapy programs were part of an old collaboration with Neurocran. So is it reasonable to assume that now they are also going to be based on a tracer technology platform? Yeah, this is Al Fendrock again.
Okay, great. Thank you very much. One moment before our next question. Our next question comes from Laura Chico with Wedbush. Your line is open. Hey, good morning, guys. Thanks very much for taking the question. I guess I have one related to neurococollaboration as well. Wondering specifically for the Parkinson's, the GBA1 program, if you could speak a little bit more to kind of the thought process leading to kind of exercising the co-development, co-commercialization option.
Yeah, so you know for very common diseases like Parkinson's disease and Alzheimer's disease.
we would partner those. It was always a question of when. And our colleagues at Norfolkon was very excited about the program. I should say that it was a very competitive process. A lot of people were excited. We're excited about GBA1TD because it makes someone sense. I think it was highly validated target.
And so we decided to do the deal and it provided non-delutive revenue for us to pursue other programs and we just outlined one new one at this morning. In terms of opt-in, it's after phase one and you don't know what the phase one trial design is yet. It's just an earthquake to tell us, but it's very possible that after phase one we'll see whether or not...
the gene therapy produces the enzyme, which we should be able to measure in the spinal fluid, and whether or not it reduces the substrates that build up abnormally in the spinal fluid in GBA1 carriers with Parkinson's disease. So, that's a proof of biology, perhaps, but again, it depends on what the phase one trial design is, and we don't know what that is yet, but that's a possibility, what I just outlined.
In terms of the approval of the drug by Riyada, the NRF2 activator, I think it's very, very exciting. This is a disease that had no treatment until last week and it's a terrible disease. And I don't think it's very encouraging for the whole field. And so free drive state taxi is, I think, what happens typically is that after the first approval,
other companies get involved and it just lists all those and so I think it's only a good news for us.
Thank you very much. This is now only one thing to add on the options for cross-profit share. It's a good way for preserving optionality for Voyager. It's also that we get to take a look at the data from that phase one trial, see how we're situated and we'll have an attractive option between the US 5050 cost-profit share and really healthy milestone and royalty track. So we're happy to be able to preserve that optionality after the phase one. Thank you very much.
I think you know, coming on the SFA in addition to what else that the mechanisms by which the Riyada, the Dragon of the Lots, along works are different from our gene therapy approach. And so the two approaches are not exclusive at all. So we're quite excited about that Riyada. Yeah. And I should add that, you know, it gives us, say, an idea of what the Phase 3 trial needs to be. We now know what the outcome measure should be for regulatory approval.
We see what happens, you know, we see the change in that outcome measure over the course of time, so we can now better power our studies. I mean, it's just a huge, hugely positive event, I believe, for patients with recently seen taxing. Thank you very much. One moment for our next question.
Our next question comes from Sumat Kilkarni with the kindergarten line is open Hi, um congrats on the quarter. This is actually Ross asking questions on behalf for some not say I have two questions In regards to receptor acts that you've identified Given that she's been developing these novel capsules for some time now or your latest thoughts on the level of receptor expression and variability across primates and mice and What's your conference level on how that might translate to humans?
Hi, this is Todd. So we know that receptor X is expressed in the right cells and in the right places in all of those species and mice and non-human primates and in humans. We know that the capsids find the orthologs for all those species and that the orthologs, the protein versions from each of those species enhance transduction in our and vitro studies
And so we think that the translation of the humans is greatly de-risk and is a greater chance to success because of all of those data.
Okay, and then kind of a quick follow-up. Is there any potential for these cat foods to efflux out of the brain? If so, how might this concern be mitigated if this is kind of an area of concern? Well, you know, we do check all the other organs when we...
are, you know, publicly get into the CNS, it tends to de-target the liver, for example. Have we looked at every single organ? No, not yet, but so far, it doesn't look like there's significant e-flux, at least to the point where we get transduction of organs in the periphery. Todd, do you want to add anything?
involves iteration. So there are initial screens and then there are secondary maturation screens. And what we found is we can identify capsids with increased delivery to the CNS. And then through the maturation process, we can identify variants that have similar or increased delivery to the CNS and then altered delivery to other tissues. And so we can identify a panel of capsid variants.
and then select those that match our capsid profile for a given disease. That capsid profile that I'll mention earlier is something that we do build for each of the diseases. That includes the tissues we want to target and the tissues that we want to avoid for potential off-target risk. Another opportunity side is that we have the potential to deploy tracer and other tissues as well. If we're able to identify capsids that target muscle or other tissues, those present opportunities.
for licensing with others as well. So there is a lot of opportunity in the TREASURE platform. Thank you. One moment for our next question. Our next question comes from Yalan Zhu with Wells Fargo. Your line is open. Hi. Thanks for taking the questions and congrats on the quarter. So first of the question on SOD1, AOS, Gene therapy, development path given the upcoming Tofersten adcom and TREASURE.
I'm wondering if you could comment on the validity of neurofilament light chain as a surrogate marker for efficacy. And if it turns out that FDA accepts this surrogate marker, do you think that would be the same path for gene therapy program as well? Thank you. And that's a great question and something I think we're all tracking. I do believe myself.
that neurofilament can be relied upon as a surrogate marker of efficacy. But I'm not a regulator, and whether FDA decides that it's a valid surrogate endpoint for approval, we'll find out very soon. Nevertheless, I think we can still use it. selected by dhina
as a way to decrease risk. And we can use it even in the earliest clinical trials to track whether or not our gene therapy is affecting at least a neurofiber integrity as measured by neurofilament release. So I think it's a very useful surrogate marker of efficacy, regardless of what the FDA decision is. The FDA decision, if they do use it, or consider it valid. The FDA decision is valid.
end point for approval, that just makes the approval pathway even shorter on behalf of patients. But, you know, in addition to NFL, Biogen and Ionis have published in a New England journal that you can look at soluble SOD1 levels itself in the spinal fluid as sort of a target engagement biomarker. And we could do the same thing as well. We should be reducing the expression of SOD1 in the spinal fluid. So both of these measures are very useful.
to help us understand whether our gene therapies on the right track and we plan to use all of it. Got it. And another question on the collaborating, the partnership programs, the licensing with regard to tracing. To what extent, Pfizer and Novartis have studied the tracing capacity in conjunction with their targets. Happy.
conducted any animal studies, for example. And then on the vortices for the two additional targets that they may decide to pursue with some significant fees, if there are a timeline that when they have to make the decision to...
to go with the option with $18 million per target payment. Yes, so maybe this is Alan. I'll take the second piece first. So the ability for Novartis to expand to additional targets. They have 18 months to decide whether they'd like to do that.
to choose either to add one or two targets under the agreement. If they do, it would be, you would track the same terms as the original agreement, which is $18 million per target if they add a target. And then the same $12.5 million per exercise with the $300 million and potential milestones downstream and the high single-digit royalties.
So that's the 18 months to make that decision. And I'm sorry, what was the, now I've talked too long and missed the first part of the question if you could just repeat that. Right, so thanks for those answers. And have the, have Fiverr and Novartis studied the traits or corpses together with their specific targets in animal models? So what extent have they done work before they opt?
up to the crystal cap state. Right apologies. So in each instance both Pfizer and Novartis had a one year period to evaluate whichever of our capsids they wanted to look at to consider for exercise. So they conducted their own experiments on their end to help them decide which and whether they would like to exercise on which capsids. So at the end of that process Pfizer exercised an option for its neurologic target.
Great, thanks for the color. And lastly, just wondering on the evolution of the tracer capsids. So first of all, are you conducting additional experiments and having additional efforts for further reducing the capsid load?
with more even more potent and more CNS selective And when might we have some update on that? And also how about targets outside the CNS? Will we hear about some update on that front? Thanks for taking all the questions. And behind this is Todd.
So, with regard to non-CNS application, our focus has been on the CNS. That's what we spend the bulk of our efforts on so far. So, I can't commit to any timelines. It's certainly something that we're interested in exploring in the non-CNS site. With regard to the continued evolution of our tracer capsids, it's absolutely something that we're...
We're seriously pursuing. We continue to mature our capsids and to develop. The team looks at different loops on the AEDV capsid surface. We use different starting capsids, different parental capsids, and all those processes continue. We'll be presenting data at the upcoming ASGCP, because I think the next conference that we'll be showing some of your data, and we'll continue to share.
The work that comes out of our Tracer platform as it arises. Great. Looking forward to the ASGC-T presentation. One moment for next question. So, it can graph on all of the progress. Thank you for taking that question. Thank you.
Can you talk about how the lessons learned from the ASOD 1 change their for ALS will turn your early research into Cal, ASI RNA, and then since there are more interesting TNS targets that could be targeted by ASI RNA, you optimize genes, financing, payloads, what sort of other new research initiatives are you considering and then I won't follow it
I'll start and Todd will continue, but yeah, now listen to this, I believe this ability to vectorize SIR needs a huge capability that we have at Boerger honed over the years. It's not an easy thing to find SIR needs and we published on some of the thinking that it goes into it. I'm in here.
how many versions we test, etc., and how we address things like over harnessing the potential. And so, yeah, I mean, I think that, you know, the SIRNA vectorized SIRNA for SOD1, there'll be lessons learned there that we will apply to all of our future SIRNA programs, including TAO. Todd? So one of the good things about SIRNA
Working here at Voyager, we can deploy different kinds of payloads. Those include the vectorized antibodies that we talked about, gene replacement, and then the siRNA that we're talking about here. Some of the honing that we did that Al mentioned came through our first generation Huntington's program. We continued to pursue a Huntington's approach as well. That was an early exploratory program that we announced earlier this year. That's a dual approach where we're looking to knock down both in an allele specific way, the mutant form of Huntington, and MSH3, which is a genetic modifier of Huntington's disease. We have a lot of effort in the siRNA approach. We've honed that expertise over the years and we're looking forward to it.
Actually, it's super counts.
And then if I can please ask one follow on with the advancement of your anti-tile antibody. Can you just talk about how that will fit in with your SIR and Natal chain silencing program? And I guess how the two modalities could be essentially complementary and fit into the future treatment landscape for Alzheimer's?
Hi, this is Todd again. So thank you for the question. We're excited about Tile's target. Is a nerdy generative target scope validated? We think that our antibody approach, we mentioned earlier, the antibody approach against Tile came out of the vectorized antibody.
program. We identified a series of antibodies that worked extremely well in our animal models and are differentiated by both the efficacy in our animal models and the epitope that we target. So we're continuing to move that forward. That said, there's still other approaches that could be really effective potentially in tauopathies. And we think that vectorized...
SIRNA to reduce tau is one of those. So the reduction of tau, interestingly, is, while it still affects tau, it's an independent mechanism of affecting tau, then it's tau antibodies. So I think those approaches are interesting as so low approaches, but they're also potential interesting in combination. And of course, then there's the potential to combine with other Alzheimer's disease therapies as well, including the anti-amolites that have recently received accelerated approval. So I think, I would say we're in a bit of a renaissance.
of neurodegeneration and Alzheimer's disease, and we're pretty excited about all of this progress. Thank you for taking the questions. I'm not showing any further questions at the time. I turned the call back over to Al Sandrock for any closing remarks.
Thank you, everyone, for joining us today. Please feel free to follow up with us directly with any other questions. Thanks again. Bye. Ladies and gentlemen, that's conclude today's presentation. We're now disconnected.