Tenaya Therapeutics, Inc. (TNYA) Earnings Call Transcript & Summary

Yes. So TN-401 is going after the leading genetic cause of arrhythmogenic right ventricular cardiomyopathy. And this affects about 40% of those patients, and we estimate that to translate to roughly 70,000 patients in the U.S. alone. So like TN-201, this is an orphan, but it's a large indication. So again, I think investor and strategic interest is high here because we're not talking about ultra-orphans. And so this is defined. The hallmark of the disease is electrical instability and different forms of arrhythmia with the potential of sudden cardiac arrest and death, being a pretty significant source of morbidity in this condition. And there's no approved pharmacological agents here. People are using generic medicines to try to manage the arrhythmia here. Nothing yet approved to address the underlying genetic cause. Of course, we're not alone in advancing a gene therapy. I know we'll talk about that. But that's TN-401 in a nutshell, it's an AAV9 gene therapy, giving a full-length copy of the human gene into the hearts and with the intention of improving the electrical instability in these patients. And so far, so good. The data release we just did really proved that we are achieving what we set out to achieve.

Perfect. Great. Thanks for that intro. And I mean I'll throw in some comments here as part of my question that we will discuss the data. And of course, you'll pepper in a little more data commentary, hopefully. But as you engage regulators because this is very similar to 201 in the sense that there's a lot to look at with regard to the path of PKP2-associated ARVC, which endpoints are your favorites? And do you believe what you showed recently, the PVC burden signal of about 64% reduction is robust enough to serve the registrational endpoint?

Yes. So let me -- a couple of comments here. So when we presented at ASGCT, we were pleased to have been accepted as a late-breaker presentation. So it was a live presentation audience, very well-received data. We presented data for the first 6 patients that have been dosed with TN-401 and all 6 had meaningful improvements. That was the headline. And particularly in the hallmarks of electrophysiology or electrical instability, PVCs and NSVTs, we saw meaningful improvements in both for the patients who had elevated data at baseline. Safety, product was well tolerated at both doses. And one thing that's different from TN-201 here, it's -- we don't deal with that. We are dealing with a single population that presents with high electrical instability. So that simplifies the story a little bit in some ways. We're not dealing with a pediatric population or an obstructive. It's all of these patients have high uncontrolled electrical instability despite standard of care medications and despite interventions like ablations. And on that backdrop, we did this, a single dose of TN-201. We saw, on average, a 60% reduction for dose cohort 1, on average, a 67% reduction for dose cohort 2, so the average is 64% that you're referring to. Individually, some patients had a reduction of 30%, some patients had reductions of as high as 80%. This average of being in the 60% to 67% range, yes, physicians would consider this clinically meaningful. In fact, when we released the data, I'd invite anybody who's listening to this, if they have not already done so, look at the data release that the company did after ASGCT, where we included a KOL back and forth the dialogue with one of our KOLs, Dr. Giudicessi from the Mayo Clinic, and Dr. Whit Tingley, our Chief Medical Officer, had questions covered the landscape, the unmet need, the patient, how they present and also talked about objectively how do they look at these data. And he said, yes, I think if you're at a population level, you're getting above 50%, you are in clinically meaningful zone. We know from the literature and we know from modeling that there's a direct correlation of reduction of PVCs and NSVTs, which are frequent and it's happening every day. There's a direct correlation between achieving that and reducing the risk of rare but severe ventricular fibrillation events, including and up to leading to sudden cardiac arrest and death. So this effect that we're achieving here mathematically translates to lower risk of a much worse long-term bad outcome like sudden cardiac arrest. Physicians recognize that. They know that, and so they've appreciated our data. I would also say that people have noticed that our data have been so far to date, there are others in this space, the deepest and most consistent and most consistently deep reductions compared to others. All 6 patients had a reduction in PVCs. And of the 2 patients who had elevated NSVTs, they both came down. To the best of my knowledge with the data that's in the public domain, our other peers do not yet have the same kind of depth and consistency that we're showing in the improvements in electrical instability. So we're feeling good about both our efficacy and our safety data. And the KOLs are too. Last point I'll make, like I said, on 201, somebody did the market research and kind of asked KOLs immediately after data release and very similar, we got very high marks from KOLs on the TN-401 performance to date. People showed high confidence in the data and a high interest in participating in studies and prescribing if a product like that was available. So I think we're getting validation from the outside. It's not just we're drinking our own Kool-Aid, but we're getting validation from the outside.

No, absolutely. Data are everything. So with that said, look, I'm going to ask it this way because this is my job. And of course, it's your comfort level to which you'd like to talk about the competition you were referring to or your peers. And of course, this is Rocket and Lexeo. So I guess, all with relatively small numbers of patients. Do you view, and this could be an entirely separate scientific call, but differences with regard to the capsid, the construct, the dosing regimens, early safety profiles, where do you feel differentiation might exist?

Yes. So look, I mean all 3 companies are -- the one thing that everybody is trying to do is use AAV to deliver a full-length copy of the human gene. That's where they're all similar. After that, there's a lot of differences and how those differences translate to differences in results. I'm not smart enough, but I don't think even the field is smart enough to know. We are using AAV9. Others are using other capsids like AAVrh10 and AAVrh74. We think AAV9 comes with the best validation from both a safety perspective as well as transduction of the heart. So we like this our selection of capsid. All 3 companies are using cardiac-specific promoters, but not all cardiac-specific promoters are created equal. So it is possible that, that introduces some differences. I believe 2 out of 3 of the companies, us and Lexeo are using Sf9 as the manufacturing platform. I believe Rocket is using HEK. How does that translate to any differences in how the product is expressed, translated, whatever, who knows? Doses, Lexeo and us, we're using -- we're both in the 2 to 3 range for the first dose and 6E13 for the high-dose cohort, whereas Rocket started at 8E13 and they're not escalating from there. So the fact that we have good data and the most consistent and deep data at even 3E13 compared to what I think we've seen with other products at 6E13 or even 8E13, we like that. We like where we're sitting there that even at 3E13, we're getting better data than others are getting at higher doses. Which of the particular elements of the product or the manufacturing is contributing to that? We don't know. Is it just a law of small numbers? It's too early to say. So we're not declaring success. But right now, early days, we're pleased with the data that we have on both efficacy and safety. And look, this is the competition is good for patients. And ultimately, there may be room for more than one product, right? And so I think it's too early to call winners or losers or best-in-class or first-in-class, but we like the position that we have with the safety and efficacy data that we've generated to date. Each company has -- is engaging with the FDA, and maybe that will be a good. I didn't answer your question earlier about endpoints, so we can go there next. And so we'll have to see what each company is able to negotiate about a path to pivotal studies, both in terms of timing and endpoints and design. And there may be some opportunities for differentiation there as well that will materialize. So -- but we can talk about endpoints next, but I think that's my overall take on the competitive landscape today.

Yes. No, look, I mean, someone else to do the heavy lifting for the regulatory standpoint is not always a bad thing. And I guess, yes, I think it's an important question with regard to the delivery viruses and the promoters and what have you. And of course, you're bringing me back to my early days as a virologist. So it's having me geek out as well. So maybe if you have comments on commentary and then we can link both assets together with regard to internal operations.

Yes. The commentary on what sorry, specifically, Joe?

The endpoint.

Endpoint, yes, yes. So look, I mean, I think you had asked us earlier what do we think is our preferred endpoint and each company may be doing something slightly differently. But generally, we have generally said that we are supportive of all the things we're measuring, and we're measuring a lot of things, but all the things are supporting. We're measuring, we think that PVCs, plus or minus NSVTs, PVCs are a logical endpoint, and we say that objectively with KOL feedback. If you look at the papers, the papers generally emphasize PVCs as the predictor of when you need to get an ICD or predictor of long-term mortality. There are other factors as well, including NSVTs. There was recently a paper that came out that we were pleased to see that where several KOLs from around the world got together and wrote a paper and basically put their thumb on the scale of PVCs as a preferred endpoint in ARVC. They weren't talking specifically about PKP2, but they were talking about in the field of ARVC for a variety of reasons, PVCs may be the preferred endpoint. And there was actually a former FDA leader on that paper as well. So if you're -- any of your audience have not yet seen that paper, I would point to that as it's one thing for us to say we like our stuff or we like that endpoint. It's another thing when somebody on the outside says it. So I think that's a good objective comparison. Whatever the endpoint we select here, Joe, what I would say is one advantage that we have, and I think in terms of these discussions with the regulators and making the case for a particular study design is that we have the largest natural history study in the world. So we have something called RIDGE. So our interventional study is called RIDGE-1, our non-interventional or natural history study called RIDGE, more than 185 patients at more than 20 sites in 6 countries, right? That's more than 2,500 patient years of data, including some retrospective data of these patients as well as we're prospectively following them. That's 185 patients we're actively following. That gives us an advantage in terms of, I think, patient recruitment, particularly once we get into pivotal studies. But also for these discussions about endpoints, what's a good endpoint for accelerated approval? What might be a good endpoint for full approval? When you're dealing with endpoints like PVCs that are so highly variable, you kind of need to solve that with a large data set to help narrow in on the answer to these questions and to be able to make statistical arguments about why a particular design, whether it's a single arm or external control or placebo-controlled, there's very many different designs that are possible. The natural history gives us an advantage to help put the data and the statistics into perspective. And I think -- so in addition to the positive data and efficacy and the safety we have, we also like our natural history study to support the arguments we're going to make about endpoints with the FDA. And we've committed to give an update on that by the end of the year as well.

No, that's very helpful. So Faraz, it's like what I alluded to earlier is I wanted to link both assets, 401 and 201, with regard to the important decision tree that you're going to have upcoming. And that is what's the gating step for a pivotal start? And how do you look to sequence the 2, especially given their shared manufacturing and capital requirements?

Yes. Well, first thing I'd say, Joe, is I'll complicate the question further. We've talked -- spent most of our time talking about 201 and 401. But as you may recall, one thing we introduced earlier this year is our TN-301 small molecule. And with the time that we have allotted today, we can't do a lot with that today here. But that is a very exciting another asset that we've reintroduced the world, already complete -- already clinical stage, already completed a Phase I, doing some Phase II enabling work. This is our highly specific HDAC6 inhibitor with broad clinical utility in everything from large cardiac indications like HFpEF to cardiac adjacencies like PH, PF or PAH to neuromuscular conditions like with cardiac and skeletal involvement like DMD or other muscular dystrophies. I mean we -- this is an incredible asset. It's a rare pipeline in the pill and industry. And we've indicated that we're going to give an update on our plans for that asset in the second half of this year, which indication, what design, what catalyst, moving it forward on our own or with a partner, I think all that to come. So in a way, your question is we got to take an even bigger step back and say, what's the best way to move Tenaya forward from here, recognizing that we have 3 clinical stage assets, TN-201, 401, which we've covered today, 301, which I just touched on. And I think that's going to be the exciting part about the next couple of months between now and year-end is that we do intend to paint a picture of this is where we've landed on regulatory alignment on the gene therapies. This is our desired plan on 301. What's the best allocation of capital, right, for Tenaya going forward to maximize patient impact and shareholder value, right? And so the answer may be let's go full bore on 1 or let's go full partial bore on 3 or 2 or let's spread out on 3, but then focus within a particular subpopulation so that we can manage the spend and burn. So more to come on that front, Joe, let's just say that we have high conviction in all 3 assets based on what we can see today. And so that's more to come. I mean that would be a good problem to have if you have 3 clinical stage assets and you're picking. You're not forced to back a particular asset because that's the only thing you've got, which unfortunately, some companies are in that position. But if we have 3 solid assets and then the ask is like, okay, we want to raise enough capital to do X and Y or X and Y and Z or X and Y or X and Z, whatever it is, whatever that permutation is that makes the most sense for shareholder value and patient impact. That's what we'll be revealing our thinking by year-end. So stay tuned. Good reasons for your audience if they haven't already done so, do some homework on all 3 clinical programs to meet us certainly after the conference -- during the conference and after the conference and so that we can engage deeply in all 3 programs ahead of catalysts coming up in the second half of the year.

Absolutely. That's very helpful. Faraz, this commentary. We were extremely helpful for the listeners. Like you said, I encourage everyone to really take a look at the data, take a look at the papers, get in contact with the company, me or what have you, so we can help out. And thanks again, and looking forward to the updates in the second half.

Yes. Thanks a lot. And I guess I would be remiss, my CFO would shoot me if I didn't say, look, our cash position, we updated it with the last earnings release. We have cash through Q3 of 2027. So we're still sitting on more than a year of cash on hand. And so that puts us in a position to get to these catalysts and then engage with investors about how we're building the company from here. But actually, that's our cash runway and cash position as of the most recent earnings. So looking forward to seeing some of you at the HCW conference, either at the meeting or afterwards. And thank you, Joe, for the opportunity.

Great. Thank you, Faraz.