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

Good afternoon. So Tenaya this afternoon. Thanks, everyone, for joining. My name is Whitney Ijem. I'm one of the biotech analysts here at Canaccord. And it's my pleasure to be joined by Tenaya. I think I said this out. Good afternoon. So Tenaya this afternoon. Pleased to be joined by Eric Hyllengren, CFO. So thank you for making the trip. And thank you for coming. We have a lot to cover, so diving right in.

And for anybody who's not familiar with the story, can you provide just a high-level overview, what attracted you to the company because you're relatively new? And what is the team trying to build over the next 5, 10 years?

Yes. Great one. Thanks for having me, Whitney. I've been in the chair almost a month. So still new guy. And yes, I mean, when I thought about Tenaya and joining the company, really, it's about the mission, right? So we are looking for precision medicines for heart disease. We're modality agnostic. So we have gene therapy, we have small molecule. But really, we're trying to address the underlying cause of the disease. And so the mission of the company really resonated with me. Also the science, when I looked at the data presented to date, strong data, very encouraging. And the team, the team that I met with during the interview process, very excited and energized to succeed in this space. And then, we have a big year here, Q4, there'll be -- and we'll get into this, but regulatory updates coming. Our plans for advancing our small molecule 301. Also, we'll talk about those in Q4. So a lot of near-term events for the company as well.

Okay. Excellent. So maybe starting with TN-201, the lead gene therapy, I think. And so can you just briefly review what that is? What is MYBPC3, it's a mouthful, associated HCM, and the kind of key unmet need in this patient population?

Right. So as you said, with MYBPC3 in HCM, we're talking about 120,000 patients in the U.S. here. So that's about 20% of all HCM. And really, what we see with these patients is a thickening of the left ventricle. And so the heart is not able to pump blood where it needs to go in the body effectively. And there's really a lack of treatment -- effective treatments out there. And so especially with folks with more severe disease. And so we feel like targeting this area, really our gene therapy can improve outcomes and results for these folks.

Okay. And which endpoints are most important to this as you guys are monitoring the data and as you're talking to the physicians as well?

Sure. So, as I mentioned, these left ventricles thicken, they get large. So reducing the thickness of the left ventricle, LVMI, Is very important to us. We feel like that then would contribute to better outcomes. We're having discussions with regulators on appropriate endpoints, but the data we've shown to date has been very strong in that area. And so we would think that would be appropriate.

Okay. Got it. And the expansion cohort in the study is ongoing. Can you remind us which dose is being used? What the target enrollment is? And I guess, yes, if there's been any changes there as the study has evolved over time?

Yes. So in this Cohort 2, it's the higher dose, so 6E13. Cohort 1 was half of that and really well tolerated from a safety perspective. And again, the LVMI reductions we saw were very meaningful in the majority of patients. And I think also what's important is from a feel and function kind of symptoms, those have improved as well for most patients. So it's not just LVMI, but it's how these folks are feeling.

Okay. Okay. And you just touched on it as well, but safety, all important in general, but particularly against the backdrop of things that have been happening in the broader cardiac gene therapy space. So can you talk about what you've seen there and what you haven't?

Yes. So -- right, very well tolerated thus far, favorable safety profile at both doses. And we really haven't seen -- I think maybe what you're hinting at is some other folks in the space have seen some issues. We really haven't seen that. So we're very confident that what we're moving forward is safe.

Okay. And the study -- the data so far in the ongoing expansion cohort in adults. You're also running a natural history study in pediatric patients. So I guess what was the rationale for that study? And what are you learning so far?

Yes. So when we started, there really wasn't a whole lot of data out there in pediatrics. And so we thought that there was a need there to look at that population. And really, the younger the age of the symptom onset, the higher the complications later on. So it's really can you catch these patients early. So I thought that, that was a good thing to look into, and we are. And yes, we think that there could be a possibility that ultimately, we study this in pediatric down the road.

Okay. And you're planning to engage with regulators to figure out the path forward. Is it both in adults and peds? Or should we be thinking about the ongoing conversations that is adult focused?

Yes, I think both are on the table, and those conversations are iterative. So -- and we're -- those are under -- we're undergoing those right now as we speak. And so we're going to have an update in Q4, but I think the expectation is we'll have some pieces of the puzzle put together. Will it be this all-encompassing one shot? Maybe, maybe not, but these are ongoing conversations that we're having with regulators.

Okay. And which regulators, is that mostly a U.S. discussion or are you looking at...

Both the U.S. and Europe.

Okay. Perfect. And I guess, probably you might say TBD, but I'll ask it anyway. How might the pivotal path for pediatric patients look different than in adults as well for most of the therapy?

Yes. Yes. So answer is TBD for sure. But again, we think the unmet need is high in the pediatric space. And so we think that we could go maybe faster there. That's part of the discussion we're having with regulators, just given that there really are no effective treatment options for pediatrics in this space. And so yes, we'd like to look at that for sure.

Okay. And would the endpoints be different there? Is that kind of what the natural history studies inform you?

Right, right. And that also is part of these discussions. So we'll have to see. Yes, we'll have to see how that plays out.

Okay. Perfect. And as I recall, the plan has always been to move forward in peds, hence, this natural history study. So first of all, correct me if I'm wrong. But second of all, what did regulators want to see or why haven't you been dosing in pediatric patients as yet?

Well, I think it's just -- from a safety perspective, right, you want to make sure it's good in adults before you're going to move into pediatrics. So I really just think that's it. And we feel like what we've shown so far has been favorable. And so we think that would make sense to move into peds as a next step.

Got it. And maybe talk about the competitive landscape. You mentioned nothing for the pediatric patients. What does it look like in adults? And how should people, investors, be thinking about 201 competing in that landscape?

Yes, we think there's space. I mean, if you think of the opportunity of approximately 120,000 patients in the U.S., as I mentioned, there's space there. And so we feel like there's some unmet need, and we can play with existing therapies out there and especially in the pediatric area where there really is nothing. So it's small, but it's not an ultra-rare disease at 120,000 patients in the U.S.

Okay. Got it. Okay. Got it. All right. I think we'll switch over. I can ask more, but I'll switch over to TN-401, which is the second gene therapy program targeting PKP2-associated ARVC. Same line of question here. So can you briefly talk about the disease, the patient population and the key unmet need?

Sure, sure. So start out with patient population, about 70,000, 75,000 patients in the U.S., so slightly smaller. And this is really just around the electrical signaling of the heart, right? So 90% of these patients have over 500 of these PVCs, these premature ventricular contractions per day. And if you've ever had a couple, you're like, "What's going on with my heart?" so these are serious, serious complication. And so we feel like if we can regulate and reduce those PVCs, it's going to then lead to better outcomes and prevent events down the road that you don't want, including sudden cardiac death. So that's really been our target so far.

Okay. Got it. And can you briefly review the clinical data there as well, kind of what have you seen? What are the key endpoints that we all should be focused on from an efficacy perspective?

Sure, sure. So first, starting out safety, clean, still clean safety profile there. And really, we are looking to see what is the impact on electrical instability and so measuring PVC reductions. And what we've seen in all patients is about a 60% to 67% reduction in PVCs and with that out to 52 weeks in some patients. So again, seeing those reductions and also comparing to what some others have done, we feel that, that our data is very favorable. It's a small number of patients, but very impressive so far.

Perfect. And on that PVC count reduction, I think it's an average 64% reduction, the first 6 patients that you've talked about. So is that -- what are you hearing from -- is that clinically meaningful? Or how should we all be putting that into context?

Yes. So what we hear and what KOLs have said is about a 50% reduction is meaningful. And by doing that, you're also cutting your odds of having a future VA event in half as well. So we like how our data stacks up against that and think that hopefully, future data can repeat, but it's a good start.

Okay. Got it. And you mentioned the competitive landscape. There are 2 other gene therapy competitors out there doing similar things, I guess. So how do you think the data compare so far between what you -- against what you've seen from others? And how might 401 differentiate?

Yes. So I think we've seen greater reductions in PVCs versus others, and again, clean safety profile. So it will all kind of play out here in terms of who the winner is. I don't necessarily think there's only going to be one winner or space for one winner. But you look at our data even out to 52 weeks, and in Q4, we'll have a little bit more durability data that we'll bring across for 401 as well as a regulatory update there. We feel like we're in a good spot.

Okay. And is there a similar like pediatric angle here that could be faster or shorter as 201?

Could be, although I think we would probably focus on -- more on adults, but it's still in play, and those discussions are still ongoing.

Okay. Perfect. Excellent. All right. I think I'm going to switch over to TN-301. And honestly, it's been a while since we've thought about this program. We've talked about it. So can you remind us of the mechanism? This is a small molecule, as you mentioned earlier. Why are we hearing about it again? Why is it now interesting to you?

Yes. Right. So this is the HDAC6 inhibitor that we have. And we've run Phase I. We've had exciting preclinical data. I think there was a prioritization choice early on to focus on the gene therapy, just given resources that we had at the time. There's been some activity kind of in the broader space around not only HDAC6 or HDACs, but just heart failure and kind of these indications that we're looking at as well. And so we're kind of reintroducing it, I guess, you could say, and we really are encouraged by the preclinical and the Phase I data that we've seen thus far and are looking forward to thinking about indications and what types of studies we might want to run with this. And again, that's another Q4 event for us.