Great. Thank you all for taking the time to join us for another session on day two of Baird's Healthcare Conference. My name is Jack Allen, and I cover the cell and gene therapy subset of the biotech sector here at Baird, and today I'm joined by the Voyager Therapeutics team. We've got Nate Jorgensen, the CFO, Trista Morrison, Head of IR and External Communications, and Todd Carter, the Chief Scientific Officer. Thank you all for taking the time to join us.
Thanks for having us here. We're excited to tell this Voyager story.
Yeah. So Voyager, a very topical conference, you know, fireside here. You've had some great news in the last couple of days. Maybe we can start with the Novartis expansion of the collaboration.
Yeah. So even before I joined, I've only been here a few months. There's been a very strong relationship with Novartis, which of course is one of the leaders in gene therapy and in neuro, right? They have a product out there, and it's great to see them have confidence in us, in our capsids, and continue to expand that relationship. Right now, there's five partnerships and collaborations. One of them is disclosed, the target. The recent one we just announced, we didn't disclose the collaboration, but it was great to get, you know, extra money into the company, $15 million, and then continue to build that relationship, and so we could have additional milestones coming along the way.
Yeah, it's great-
Maybe I can also add, one of the things we like most about it is, somebody like Novartis, who's one of the leading experts in gene therapy in the world. They've taken our capsids, they've evaluated them in their own hands, in their own house, and they're coming back to us for more deals. So we see that as really substantial validation of our platform.
Yeah.
Just to clarify, that's our fifth partnered program just with Novartis. We actually have 14 partnered programs across our TRACER capsid technology, and then we have multiple internal wholly-owned programs as well.
Yeah, it's great. We're going to be touching on all of those various aspects. And Todd, I very much agree, Novartis, a leader in gene therapy with a billion-dollar product in Zolgensma. You know, another key partner of yours has been Neurocrine. They've come back multiple times. How has that deal developed over time?
Do you want to talk about that?
Sure. I mean, the Neurocrine partnership has been fantastic. So we have seven partnered programs with them. The most advanced are gene therapies for Friedreich's ataxia and for GBA1 Parkinson's disease and other GBA1-mediated diseases. Those two programs are moving towards an IND in 2025, and what's great about those two programs is that they're true collaborations. We have our own employees working on the science, working on the programs. We work very closely with the Neurocrine teams. We have joint steering committees, so that's. It's a very productive partnership. And then behind that, we have a number of other partner programs with them for which the targets are undisclosed, and stay tuned as everything moves forward.
Yeah. Trista, I think you mentioned 14 partnered programs.
Mm-hmm.
How do you balance partnering in these assets while also maintaining the ability to capitalize on the strong technology internally as well?
Our cost to capital is a little different than some of our partners. Obviously, it's much higher, and when we're thinking about keeping something in-house, we want to have it well validated. Like, so as a neurogenetic validation of that specific target, we also would like to get to clinical endpoints that are meaningful with biomarkers sooner than later. Those are the type of assets that historically we've kept in-house. There's a lot of other opportunities in the CNS space, which may, you know, fit more appropriately with our partners and some of their interests, and those are the ones that then we move outside.
That makes a lot of sense. And I guess, are you still active then, in the context of the, the balancing here?
Yeah, definitely. We just announced one.
Yeah.
There's a lot of opportunity in the CNS space, so we're going to continue to develop things internally and to look for partners. So there'll be more of this. Historically, you know, Voyager's been funded a lot. It's been over $400 million has come in through these BD transactions, and we'll continue that.
Yeah-
Yeah.
It might be worth adding that across those 14 partner programs, right, some of them are capsid licenses. So in those cases, we're a passive partner. We don't have any FTEs or internal effort against that. We just get to sit back and collect milestones and royalties. In other cases, where there's an active collaboration and we do have FTEs, those FTEs are completely reimbursed by the partner. So all of that is actually fueling our ability to then fund, advance, and put FTEs against our own internal pipeline.
That's great. Maybe now is a good time also to touch on the cash position at Voyager, which I think is differentiated compared to some peers. Nate, I'll let you take it away.
Yeah, so we have $371 million as of last quarter, which gets us into 2027. So it's a pretty nice pipeline or cash runway, so we can get beyond some of these clinical readouts.
Right.
And then if we start to add in some of these milestones that aren't actually in that cash runway forecast, I mean, we can extend it even further.
Yeah, I mean, that's across those 14 partnerships, we have $8.2 billion in potential milestones. Now, we know this is biotech, and that may not all become real, but some of it's already becoming real. Earlier this year, we had our development candidate selections on the FA and the GBA1 programs partnered with Neurocrine, and both of those triggered actual milestone payments. So it is starting to become real. It should become increasingly material and important as the programs advance. And as Nate said, none of that is baked into the runway. That is all on top.
... And we're still. Sorry, I just wanna make this comment, 'cause this gets lost sometimes for some investors. We still actually maintain meaningful upside to a lot of these deals. It's decent or hefty royalties, I would say, in these single digits to double digits. And then with two of the programs, we have opt-ins, where we'll co-promote this. So these are substantial economics still left in Voyager in these with these deals.
Yeah, it's great. We'll have to keep an eye out for early January, the next deal. Don't you have a trend where you do that in progressive fashion each year?
It's difficult to predict, but I think there's opportunities out there that we're pursuing, so they'll hopefully keep coming.
That's great. Todd, did you have something to add on?
I was just gonna make the point that Nate did, that GBA and FA are both those where we've got co-co option rights in the future, so there's significant upside potential for us.
That's great. I don't mean to jump around too much, but there's a lot going on at Voyager. I also wanted to touch on the news as it related to the tau program, and that an external tau mid-domain candidate is potentially looking at having data later this year, I understand. How do you think that could read through to Voyager?
Yeah. So our antibody, our lead antibody program-
Yeah
... it's against tau, and we, through our discovery process, we identified a number of antibodies, hitting epitopes, different regions of the protein. We used a particular model, with a variety of other assays, but a particular mouse model to select our candidate, and this is based on taking pathological tau from an Alzheimer's patient brain, injecting it into a mouse, and then looking at the spread of that pathological tau to try to do the best that we can to mimic what we know happens in the clinical setting and in a human with Alzheimer's disease. So what we've-- what we did, was we found that the antibody we selected gave us the most robust reduction of that spread of tau. It was a remarkable 70% reduction.
What we also saw was that as we looked at these different antibodies, many, many of these epitopes do not reduce tau at all in this model, and a few did, of which we chose the one that gave us the most robust signal. What we also saw is that historically, there are antibodies that have failed in the clinic for Alzheimer's disease that target tau. Those antibodies that have failed, these N-terminal, what we call them pan-tau, they're not pathologically specific, they failed in this model as well. So, this animal model appears to negatively predict, to predict what won't work. The question at hand is, will it positively predict what will work? We have optimism for our own antibody. This particular readout that you bring up, it's the UCB antibody. It hits a particular, domain in the mid-domain.
This actually works in this model as well. So if that trial turns out to have a positive outcome, we think that would read very well for our antibody as well. And that could happen, you know, anytime in Q4.
What kind of data are we expecting from that external readout? I know we've got a lot of internal things to keep our eye on as it relates to Voyager, but as it relates to this external update, are they at the clinical efficacy stage of development, or how far along?
It's a sizable trial, so it does look like it's reasonably well powered for a Phase II type of trial. But, what I think we can expect and hope to see, again, this is out of our control-
Yeah
... would be signals, perhaps on Tau PET and maybe some cognitive endpoints.
Yeah. And we have seen positive data from even the beta-amyloid targeted antibodies, and that tau is implicated in progression. Patients with lower, you know, greater, greater reduction in tau in those studies saw a greater benefit as well. Is that fair to say?
That's right. And the biology of what we understand of how tau works, of how Alzheimer's disease progresses, is that beta-amyloid, those plaques come on early, maybe start accumulating twenty years before the onset of symptoms or diagnosis. And then later on, beta-amyloid appears to trigger the tau misfolding, which then spreads and causes the neurodegeneration. So beta-amyloid, it's pretty clearly validated, both genetically and now clinically. Tau is incredibly well validated from this context, and that correlation of the spread of tau with the pathology and progression of the disease, now we can track that with these Tau PET markers.
That's one of the reasons, and Nate touched on this earlier, we do a lot to pick our indications carefully, so we can use that Tau PET signal to identify evidence that our therapeutics are working at a relatively early stage, so we don't spend a lot of money to get the right answer.
Yeah. As it relates to your internal program, I believe it's in a healthy volunteer study, and we're gonna get some PK, PD, PD data next year. How should we think about that readout? And then, as you alluded to, getting the tau, biomarker data, I believe that's the following year, though. How-
That's exactly right.
So, what's the readout take?
The single ascending dose study, I mean, we expect and hope this is pretty routine. We're getting PK data, we're confirming that it's safe, et cetera, in healthy volunteers, and really, what we're trying to do is make sure that that's the case, and also determine the dose and able to deliver the kind of exposure that we think we need to get to see efficacy based on all of our preclinical work. As soon as we have that, and we expect to have that top-line data in early next year, then we'll move to that multiple ascending dose, which will be in Alzheimer's patients, so we'll move straight into Alzheimer's patients and hopefully aiming for a relatively early readout on some of these signals, the Tau PET and other factors.
That's great.
So we're very excited about this antibody, but I don't think we're getting a lot of credit from investors right now, and I think it's just the overhang of some of those failed tau antibodies. But with that UCB data on the fourth quarter, I think it could actually reinvigorate tau and then help validate this preclinical model that we used. And so I think hopefully, that'll get more interest in, and so we're super excited about that program.
Yeah-
That's why we released that new data just last week, right? Because we had done these two internal head-to-head studies in the mouse model, the mouse spreading model. We'd done one against the N-terminal antibodies that had failed in the clinic, and they failed in the model, and then we did another. Our antibody performed and did work. Then we did a second head-to-head against the UCB antibody, and both ours and theirs worked in the model. So we felt like it was important to share that data with investors so you guys could all understand how we're thinking about that and how we're looking at that UCB data as potentially a de-risking event.
... Yeah, that makes a lot of sense. I guess the one last question on the tau program is how you think to progress it forward after you have this proof of concept data, be it externally or internally? You know, Alzheimer's studies can be quite expensive, and large, and take many years to run. You know, what is Voyager's appetite for prosecuting this internally and funding that?
I mean, we realize that Alzheimer's is, trials are massive, right?
Yeah.
And so this probably will make more sense in the hands of some of these other large biopharma companies who are interested in this space. So it's something we're interested in, but of course, we're not going to commit to that yet.
Yeah.
Let's keep all our options open, 'cause who knows, a year or two from now, our stock price could be in a whole different, you know, zip code. Our cash position could be in a different place, even from here.
Yeah.
And so I don't want to shut any doors, but we realize the challenges here. I also think there's a lot of probably interest from external parties in this asset.
Yeah.
So once we have that, you know, clinical proof of concept, or as we get there, I think they'll be coming to us. So that's the most likely path, but we're going to keep it open.
Yeah, lots of great avenues, and you've obviously shown a great appetite for partnering and a great ability to execute on those deals. I say it not jokingly, that every January, it seems like you come out with a larger and larger deal around the gene therapy business. Maybe one day we'll see a deal around the tau monoclonal antibody in January.
It's a lot of pressure for every January.
All right, well, keep up the good work. I guess, maybe it would make sense to shift gears now to the three gene therapies that are going to move into the clinic next year. I guess, but before we jump into those three programs, let's talk about the TRACER capsid at a portfolio at a high level. Could you just provide a, I guess, an overview of your iteration on first generation gene therapy to the second generation TRACER capsid-derived gene therapy?
So if I think about kind of original generation gene therapy, it was with pre-existing capsids, not novel, but naturally occurring capsids. And what Voyager learned, a bit the hard way, was those don't sufficiently deliver. And so in 2021, we pivoted. We had data coming out of our novel capsid discovery team, showing that we could get thousands of fold better delivery into the CNS if we use the right capsid that's been engineered and identified using the vascular system, using IV delivery. And it makes sense in the context of thinking about how highly vascularized the brain is. Every cell in the brain needs to be fed, and so the vascular system evolved to do that. The trick is, how do you harness that? And so what our team did...
The field had identified capsids that worked quite well, say, in a mouse. But translating that into monkeys, it didn't work, so then we changed and began doing our experiments in non-human primates, which was a significant investment and a bit of a risk at the time. What we also did was we made sure we weren't only looking at a single species of monkey, because we want to make sure that we have cross-species activity to give us the best chance of actually working in humans, so we have multiple families of capsids now. All of them are cross-species, or we wouldn't have moved them forward. Some of them are cross-species, not only across multiple monkey species, but also into rodents.
On top of that, for some of them, we've now identified the receptor responsible for delivering across the blood-brain barrier. What that has enabled us to do is a couple of things. One, we can do kind of an SAR, a structure activity relationship, of targeting the receptor with different capsid isoforms to really hone in on the activity. The other thing we can do is confirm and identify, okay, it works in these species because it binds the receptors, that the version of the receptors from those species, and we can confirm that it will work in humans too. It works against the human receptor, and so that gives us really dramatically increased confidence that our capsid should work in human beings as well.
All of that was really based around moving into non-human primates, and also, I will say, not just looking at the delivery of the genome of the virus, but also functional delivery. So we don't only get the vector there, we get it there in a functional state that actually shows really dramatic increased expression in the right tissues.
Yeah, I mean, it's incredible science that you've really developed with TRACER, and that's obviously attracted the attention of a number of your peers with the significant partnership portfolio. Maybe before we get into the three assets that are going to move into the clinic next year, which I think is a huge catalyst for the business, potential proof of concept data from the TRACER capsid portfolio, can we just talk again, high-level picture about the benefits of having these highly tropic vectors and that, you know, 1,000 times fold tropism for certain tissues could have as it relates to lower doses, lower cost of goods, and potential also safety, detargeting the liver?
Absolutely, and you're hitting on the key points. So what we can do with these novel capsids is we can, of course, deliver many orders of magnitude increased levels into the target tissues, the brain, and we actually look at very specific regions of the brain. For any given indication, we actually build a capsid profile for what we want to do to target for that particular disease, which is one of the reasons why we have multiple capsid families. The other aspect is we want to detarget to reduce delivery to these off-target tissues. One of the classic is the liver, that's a driver for substantial dose therapeutic issues that we see with therapies such as AAV9-based therapies.
When we increase delivery to the on-target tissues, different regions of the brain, and then we decrease delivery to the liver, in both cases, we're increasing that therapeutic index. We see that in our non-human primate studies, greatly improved kind of response on or lack of an effect on the liver enzymes when we dose these things, and we expect that to have translatability into the humans based on everything we know.
... That's great. And the lower total dose also reduces cost of goods substantially as well, is that correct?
That's right. So there's kind of a huge knock-on effect that you impact manufacturing, you impact safety, and you impact efficacy by all the things that we're doing.
That's great. Maybe at this point, we can step into the three programs that are going to move into the clinic next year. I don't know where you guys want to start. Maybe the internally owned SOD1-ALS program?
So we can obviously talk more definitively about our own SOD1 program. What we've guided to externally is we're going to file in the second half of next year, and so that will set that trial up to potentially have readouts not that far after. And so the initial readout could be this SOD1 knockdown, which will be the first clinical proof of concept for a capsid, which is going to read through to the rest of this pipeline. So that's it's a very exciting readout, and then beyond that, we can get into patient outcomes, which is going to be, you know, not that far behind it, but then those will obviously be huge inflection points for that particular therapeutic goal. And so that's that's our SOD1.
Yeah.
Then the other ones are controlled by our partner, as you know, and they plan to file next year, and so we have to defer to them, unfortunately.
Yeah.
But, we're super excited because, again, we own a lot of the economics, or potentially, because we have opt-ins there. And so anything else you guys want to add?
No, other than that, I mean, the key is, over the past several months, we've identified three gene therapy-based development candidates, including the wholly owned, the FA and GBA1 programs. All of them are using next generation TRACER-derived capsids, using IV delivery and BBB penetrance, and, we're continuing to see progress across our whole portfolio with these capsids.
When will we find out more about the actual construction of these capsids and whether they all utilize the same specific capsid that is a TRACER capsid? Because I know you have a whole or capsid family. How should we think about that as it relates to disclosures?
Yeah. So as it relates to disclosures, obviously, with our partnered programs, it's up to them, right? And they'll drive a lot of that. For our own internal, I think you can expect to see more and more data come out at kind of the classic, classically, we present at scientific and therapeutic area conferences. So certainly keep your eye out for that. I will say that I mentioned earlier that we build a capsid profile, and we do this with our partners as well, to try to make sure that we're hitting the tissues and cells and regions that we want to. We're not hitting potential risky areas.
I think you can expect to see perhaps an overlap in some cases, but also differences in the capsid and capsid families that are chosen to really hone in on what's the best case for each individual disease.
That's great.
So what we have disclosed, right, is that the wholly owned SOD1 program, which we intend to file an IND for mid-next year, that one, we have said, utilizes one of our second-generation TRACER capsids. And so those were evolved off of our, we'll call them first generation, but still TRACER capsid family, the VCAP-101, -102 family, which does bind ALPL, which is the receptor that we have disclosed. And so we have put that much out into the public domain. We haven't specifically named which one. But as Todd noted, I think it's important to point out we have multiple families of capsids, and they do not all bind ALPL. There are other receptors that we have identified and are characterizing and have not yet disclosed.
So, I think what you're getting to is, right, like, how much read-through from the first flip of the card on capsids are you going to get? I think if it's positive, I think that would be great to see that the TRACER platform generated something that works, right?
Yeah.
But I think you do have to bear in mind that there are different receptors and different capsids, and the way that we structure our business development deals, it's specific to the target, but not the capsid. So it is certainly possible that the same capsid could be chosen by multiple of our partners across multiple of their programs, and we could choose for some of our own internal programs as well.
Mm.
But there are many options there, so you can't assume that everything is using the same capsid.
That makes a lot of sense. And then, as it relates to SOD1, I know there is an approved product. How do you think about that approved product? I believe it's an RNA derived product, but how do you think about the approved product that's on the market, if patients on that product will be allowed in your studies, and what we can derive from the regulatory precedent from that product? I think it was a pretty rapid, accelerated approval.
It was, and actually, I think it's incredibly promising because that approved product is, it validates the mechanism and the target for our own program. So that takes much of that target-based risk out. We know that knocking down SOD1 has an effect and a pretty incredible effect as well. I'll just give a little shout-out. We've just hired Dr. Toby Ferguson, who actually led that work at Biogen, to get that development. So we've got the best people in the world at Voyager now-
Yeah
... along with Al Sandrock, our CEO, to drive that, all that work forward. That work paved the way for that accelerated approval by identifying what you need to do, what kind of trial you need to build, the size of the trial, and the use of NfL as a biomarker endpoint, all of which was very well received by the FDA, and I think really puts us in a great place to know exactly what to do. So now it's a matter of getting our drug into the clinic and executing.
Yeah, and that, that's an intrathecal injection, though, so you'd have a huge advantage as it relates to convenience. How would you see the two competing in the marketplace?
It-
Should you drive similar clinical effects?
Right. And so I think that there are a couple of aspects of that. One is that I think there is a bit of a convenience play, but it's not only a convenience play. It is a burden on those patients to get into the clinic for monthly injections intrathecally. That's not just convenience, that is a substantial burden.
Yeah.
ALS patients are understandably willing to do that, but it is a challenge. So ours would be a one-time intravenous dose. The other aspect is what we've seen, when you dose intrathecally, you can have limited distribution through the cerebrospinal fluid. But we've demonstrated, and we showed some of these data at ASGCT this year, is that we're able to get delivery 80% knocked down into 80%-90% of motor neurons in the spinal cord, but we also deliver to the brainstem, we also deliver into the motor cortex, into these important cells that... Motor neurons are important at the beginning of ALS, and they're important for survival.
But these other regions of the CNS are important for later stages of the disease as well, and we know that we can deliver to them.
They ultimately could play together, and I think SPINRAZA and Zolgensma set a good precedent, where, like, you could start with one therapy and not get the effect that you wanted, and then layer on the other therapy.
Yeah, that's great. And then, just to go full circle on the other two programs, it's GBA1 in Parkinson's disease, and then also frataxin in Friedreich's ataxia as well. Those are in the hands of Neurocrine, but they're both advancing into the clinic, with INDs expected next year. How should we think about those moving forward, and how quickly you get proof of concept data from your partner there?
Yeah, we really can't give a whole lot more-
Yeah
... granularity there. They have said that they're tracking towards INDs next year. So, other than that, I think we just have to kind of stay tuned.
I guess, is it fair, though, to think about three INDs, three potential shots on goal for clinical data in 2025, 2026, within the cash runway? Nate, how do you think about that?
Yeah.
We can't actually be that explicit about when we're gonna get that data.
Right.
But for certain, we're gonna have some good, solid Phase I data on our side. We're gonna have some of our anti-tau antibody data, you know, within that window, and then we're gonna also potentially have some more BD deals, which have been catalyst, you know, for the stock previously. So there's a lot of stuff going on, and then there's this other potential readout, you know, in the fourth quarter with UCB, where it should also have readout read through to us. So there's a lot of stuff over the next, you know, six to 18 months within that cash runway window.
Yeah, and then the last piece I wanted to touch on was this blood-brain barrier shuttle program that you're also developing. When is the deal expected around the partnerships- ... on that asset?
Yeah, and I'll tell you what the upfront is gonna be, too. No. No, but it's, that's interesting that, you know, they identified, you know, this receptor. They've actually, it's a revolution in AAV delivery, with being IV to get to the brain, and now they're going to develop delivery or non-viral delivery to potentially other modalities. So I'll let Todd-
Right
... comment on that.
So we're absolutely exploring that. We know that ALPL is the example, this novel receptor that we know is expressed in humans as well. We know it can deliver macromolecules across the blood-brain barrier because it does that for AAV. So the question is, can it be used for others as well? And so we are absolutely pursuing that. But the whole platform actually extends beyond just ALPL. ALPL's critical and important, but with our ability to use capsids, we can deploy TRACER to identify additional receptors, right? And so we have an engine that can be deployed not only for capsids, but also for other blood-brain barrier-penetrant shuttles. So we have a lot of work ongoing. We hope to be able to share a lot of that in the future.
Yeah, I think that's-
Well, we're very excited about that program. I mean, you know, you can see what the transferrin receptor work has done for Denali. And just a shout-out that we recently hired a fabulously talented scientist from Denali, who's gonna be running our non-viral delivery program. And, I think he came to Voyager because he was pretty excited about what he saw initially. So, stay tuned. We hope to have some very exciting news on that front in the future.
Yeah, it sounds like some of your large collaborators even are talking about the Inflation Reduction Act and the impact it could have on small molecule development for the CNS. I feel like this would be a great lifecycle management tool for a large pharma looking to extend runway. Is that fair to consider as it relates to partnership deals there?
I think it could be. I mean, obviously, when you have some breakthrough platform technology, it's gonna open up oligos getting into the brain in ways that we, they couldn't before. And so I think it's very exciting what it could do to oligos, antibodies, and other modalities. And I think that, you know, obviously, a lot of these large pharma companies are interested in this type of technology.
Yeah. Great, well, we'll have to stay tuned. Thank you all so much for taking the time to walk us through the Voyager story. A lot of interesting science going on.
Thank you.
Thank you.
Thank you.
Yeah. All right.