Whitney Ijem. I am one of the biotech analysts here at Canaccord, and it is my pleasure to be joined by Tenaya. I think I said good afternoon. Tenaya, this afternoon, pleased to be joined by Eric Hyllengren, CFO. Thank you for making the trip. Thank you for coming. We have a lot to cover, so diving right in. For anybody who is not familiar with the story, can you provide just a high-level overview of what attracted you to the company, because you are relatively new, and what is the team trying to build over the next five-10 years? Yeah, great one. Thanks for having me, Whitney. I have been in the chair almost a month, so still new guy. When I thought about Tenaya and joining the company, really it is about the mission. We are looking for precision medicines for heart disease. We are modality agnostic, so we have gene therapy, we have small molecule, but really we are 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. The team. The team that I met with during the interview process, very excited and energized to succeed in this space. We have a big year here, Q4, and we will get into this, but regulatory updates coming, our plans for advancing our small molecule TN-301. Also we will talk about those in Q4, so a lot of near-term events for the company as well. Okay. Excellent. Maybe starting with TN-201, gene therapy. Can you just briefly review what that is? What is MYBPC3-associated HCM, and the kind of key unmet need in this patient population? Right. As you said, with MYBPC3 in HCM, we are talking about about 120,000 patients in the U.S. here. That is about 20% of all HCM. Really what we see with these patients is a thickening of the left ventricle, so the heart is not able to pump blood where it needs to go in the body effectively. There is really a lack of effective treatments out there, especially with folks with more severe disease. We feel like targeting this area really our gene therapy can improve outcomes and results for these folks. Okay. Which endpoints are most important to you guys as you guys are monitoring the data and as you are talking to the physicians as well? Sure. As I mentioned, these left ventricles thicken, or 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 are having discussions with regulators on appropriate endpoints, but the data we have shown to date has been very strong in that area, so we would think that would be appropriate. Okay. Got it. 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, yeah, if there has been any changes there as the study has evolved over time? Yeah. So in this cohort 2, it is 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. I think also what is important is from a feel and function kind of symptoms, those improved as well for most patients. So it is not just LVMI, but it is how these folks are feeling. Okay, perfect. You just touched on it as well with safety, all important in general, but particularly against the bad things that have been happening in the broader cardiac gene therapy space. Can you talk about what you have seen there— Yeah. ...with what you have had? Right. Very well tolerated thus far. Favorable safety profile at both doses. We really have not seen, I think maybe what you are hinting at is some other folks in the space have seen some issues. We really have not seen that, so we are very confident that what we are moving forward is safe. Mm-hmm. Okay. The data so far in the ongoing expansion cohort in adults. Correct. You are also running a natural history study in pediatric patients. Right. What was the rationale for that study, and what are you learning so far? Yeah. When we started, there really was not a whole lot of data out there in pediatrics, and so we thought that there was a need there to look at that population. Really, the younger the age of the symptom onset, the higher the complications later on. So it is really can you catch these patients early? So thought that that was a good thing to look into, and we are. Yes, we think that there could be a possibility that ultimately we study this in pediatric down the road. Mm-hmm. Okay. You are 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 as adult-focused? Yeah, I think both are on the table, and those conversations are iterative. We are undergoing those right now as we speak, so we are going to have an update in Q4, but I think the expectation is we will have some pieces of the puzzle put together. Will it be this all-encompassing one-shot? Maybe, maybe not. These are ongoing conversations that we are having with regulators. Okay. Which regulators? Is that mostly a U.S. discussion, or are you looking? Both the U.S. and Europe. I guess probably you might say TBD, but I will ask it anyway. How might the pivotal path in pediatric patients look different than adults? We will start there. Yes. So answer is TBD for sure. But again, we think the unmet need is high in the pediatric space. We think that we could go maybe faster there. That is part of the discussion we are having with regulators, just given that there really are no effective treatment options for pediatrics in this space. So, yeah, we would like to look at that for sure. Okay. Would the endpoint be different there, or is that kind of what the natural history study's informing? Right. That also is part of these discussions. We'll have to see how that plays out. Okay, perfect. As I recall, the plan has always been to move forward in peds, hence this natural history study. 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 pediatric patients as yet? Well, I think it's just from a safety perspective; you want to make sure it's good in adults before you're going to move into pediatrics. I really just think that's it. We feel like what we've shown so far has been favorable, and so would think that would make sense to move into peds as a next step. Mm-hmm. Okay, got it. Maybe talk about the competitive landscape. You mentioned nothing for the pediatric patients. What does it look like in adults? How should people, investors, be thinking about TN-201 competing in that landscape? Yeah, we think there's space. If you think of the opportunity of approximately 120,000 patients in the U.S., as I mentioned, there's space there. 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 ultra-rare disease at 120,000 patients in the U.S. Okay, got it. All right. I think we'll switch over. I could ask more, but I'll switch over to TN-401, which is the second gene therapy program targeting PKP2-associated ARVC. Same line of questioning here. Can you briefly talk about the disease, the patient population, and the key unmet need? Sure. Start out with patient population, about 70,000, 75,000 patients in the U.S., so slightly smaller. This is really just around the electrical signaling of the heart, right? 90% of these patients have over 500 of these PVCs, these premature ventricular contractions, per day. If you've ever had a couple, you're like, what's going on with my heart? So these are a serious complication. 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. That's really been our target so far. Okay, got it. Can you briefly review the clinical data there as well? What have you seen? What are the key endpoints that we all should be focused on from an efficacy perspective? Sure. First, starting out safety clean. Still clean safety profile there. Really, we are looking to see what is the impact on electrical instability and so measuring PVC reductions. What we've seen in all patients is about a 60%-67% reduction in PVCs, and with that's out to 52 weeks in some patients. Again, seeing those reductions and also comparing to what some others have done, we feel that our data's very favorable. It's small number of patients, but very impressive so far. Mm-hmm. Perfect. On that PVC count reduction, I think it's an average of 64% reduction, for six patients that you've talked about. What are you hearing from patients? Is that clinically meaningful, or how should we all be putting that into context? Yeah. So what we hear and what KOLs have said is about a 50% reduction is meaningful. By doing that, you are also cutting your odds of having a future VA event in half as well. We like how our data stacks up against that and think that hopefully future data can repeat, but it is a good start. Mm-hmm. Okay, got it. You mentioned the competitive landscape. There are two other [GRB competitors out there doing similar things, I guess. How do you think the data compare so far against what you have seen from others, and how might TN-401 differentiate? Yeah. I think we have seen greater reductions in PVCs versus others, and again, clean safety profile. It will all kind of play out here in terms of who the winner is. I do not necessarily think there is 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 will have a little bit more durability data that we will bring across for TN-401, as well as a regulatory update there. We feel like we are in a good spot. Mm-hmm. Okay. Is there a similar pediatric angle here that could be faster or shorter as TN-201? Could be, although I think we would probably focus more on adults, but it's still in play, and those discussions are still ongoing. Okay. Perfect. Excellent. All right. I think I am going to switch over to TN-301. Honestly, it has been a while since we have thought about this program. We have talked about it. Can you remind us of the mechanism? This is the small molecule, as you mentioned earlier. Why are we hearing about it again? Why is now interesting? Yeah. Right. This is the HDAC6 inhibitor that we have. We have run phase I; we have 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 has been some activity in the broader space around not only HDAC6 or HDACs, but just heart failure and these indications that we are looking at as well. We are reintroducing it, I guess you could say. We really are encouraged by the preclinical and the phase I data that we have seen thus far and are looking forward to thinking about indications and what types of studies we might want to run with this. Again, that is another Q4 event for us. Okay. Got it. I guess, what did you learn from the preclinical and the phase I study? I think phase I was in 72 patients. Key learnings from that? Yeah. I think three things. One, safe, well-tolerated. Two, we're hitting the target. Then three, the PK/PD is implying probably a daily dosing. I think those three things were very important for us and would make us feel really good about moving into phase II. Mm-hmm. Okay. You mentioned this, but there was a time when that data came out, and you said, okay, great. We'll be focusing on partnerships. We're going to focus on gene therapy internally. I guess you talked a little bit about what has changed. Can you get more specific there? Is it data that's come out of the space? Is it progress with other similar molecules or just maybe more internal data that's generated, help people get confident in the choice to bring it back? Yeah. I think it's internal data conviction. Also, there's been some external validation with givinostat and DMD. I think just in general, more excitement even from the investment community around, okay, for a very minimal investment or moderate investment, there could be a very large opportunity here in heart failure, for example. I think just more of a general swell of enthusiasm behind it. Mm-hmm. Okay. Got it. What work is ongoing now internally that will help set the stage? Yeah. So we're doing phase II-enabling work, including tox, and including phase II design. So, again, figuring out indications, studies, size, cost, and the good thing is that's more in our control, versus waiting for a regulatory alignment with the FDA, for example. So our plan is to come out in Q4 and unveil those plans and then start phase II in the second half of next year. Okay. Got it. On the indication selection point, you've talked about HFpEF and DMD. Yeah. As potential indications. Two very different indications. So why did you throw out those two, and are those the two that we should be thinking about? Could both move forward? Were those just examples, and it could be something else? How are we? Yeah. Those two definitely are the ones that internally we have studied the most. And pursued the most and have the most knowledge about and conviction. But there could be others, as you mentioned. The HDAC6 inhibition, I think, can apply to others. So we'll take a look at that, and we're listening to the community of where maybe it might make sense to go. But definitely, HFpEF and DMD are at least the first two that are on our minds right now. Mm-hmm. Okay. Could you move, would you start two-phase II studies, or is it really going to be choosing? That's my it depends answer. As CFO, I would love to have and give my head of R&D all the money he wants to do what he wants with these exciting molecules. We're looking at that. What I would say is we're looking at potentially multiple indications, maybe multiple different types of studies, quick, maybe your more traditional development path. All that to say, we'll have some ideas in Q4 about what we could run. Okay. I'll wait for Q4. It's going to be a big quarter. Definitely. Just last quick one. There was an HDAC6 deal done by Novartis, maybe a couple of years ago. I don't know. Have there been any updates, or is there any evolution of that program that's informing you or reinvigorating? We are interested to see how that goes. Is what I would say. Very smart people over there. We are watching closely, and based on their card flip, sure, it could inform which direction we go. Okay. Got it. Excellent. All right. On the all-important topic of cash then, which will inform a lot of this, you ended the second quarter with about $78 million, about a year, I believe. So how should investors be thinking about the prioritization, particularly now as TN-301 is kind of coming back into the mix? Right. So that is right, $78 million cash through Q3 of next year. But these pivotal studies, phase II studies I am talking about, are not contemplated in that runway. So we are looking to get this regulatory clarity, number one, to determine, all right, what do the pivotal studies look like for TN-401? What are the phase II plans for TN-301? Then based on that capital need, we will likely come back to investors and ask them to help us finance that. We are looking at non-dilutive capital options as well. I am taking a close look, obviously, internally at our spend. But really it is going to play out here, again, in Q4 to get that clarity on shape and size of pivotal studies and how much does that cost. Mm-hmm. Okay. Is there a scenario where thinking specifically, I guess, of any of the programs, thinking specifically about TN-301, but you do the phase II enabling work, you figure out the path forward, and then the question is, are you still evaluating partnerships in there? Is that still a potential option there, or are you now very focused on doing phase II internally? Yeah, I think we'd like to execute phase II internally on TN-301, but then I think given the potential large indications that it could go into, partnerships probably make sense, both from a financial and then just a capability perspective of running phase IIIs with thousands of patients in them. We would be open to that. Okay. Got it. So it's more about generating phase II to maybe get to a different and next level kind of valuation inflection point, but still be interested in a partnership. Yes, I'd agree with that. Okay. Got it. Okay, and then I guess, assuming both positive data we've seen from both gene therapy programs, assuming those both move forward as well, if you were to be in a position to have to prioritize one or the other, how would you do that? What would you be thinking about? Yeah. So now you're going to make me pick my favorite child, right? Yeah. No, I think— We all have one. We all have one, and they know who it is, right? But I really do think I hate the depends answer, but we're going to look at, from a capital deployment perspective, what makes the most sense. What are the, I hate to say, highest probability bets, but this is a tough business we're in, but we need to look at that. And then also, when are the next milestones coming for these programs? Quite honestly, it's hard to ask investors to wait three years before you turn a card over on a phase II, for example, right? So we would look at both timing of data, quantum of spend, and then where we think we have the biggest bang for the buck. We'd love to fund it all, right? And maybe we can. But it's also going to depend on what those pivotal study designs do ultimately look like. Yeah. Okay, perfect. Speaking of non-dilutive capital, you fairly recently announced a collaboration with Alnylam— Yeah. ...that brought in a $10 million upfront payment. Can you discuss how did that partnership come together? Honestly, it caught, I think, myself and some other people off guard a little. So yeah, how did it come together? What was the strategic rationale? And I guess, what are you guys doing? What are they doing? Yeah. This is all about identifying novel genetic targets for cardiology indications. It's been going great, in terms of a collaboration perspective. They are reimbursing us for our research capabilities. As you mentioned, we have the $10 million upfront, over $1 billion of potential milestones down the road. And really, they get access to our cardio expertise, and then they get a license to develop and commercialize these down the road. But it's really been a great enabler, I think, for us and our research organization. And yeah, my head of research is thrilled with the partnership thus far. Mm-hmm. Totally. It's great validation of the platform and name, that everybody's heard of Alnylam in the cardio space, no less, looking at you guys. So can you talk a little bit more about the internal capabilities, or what is the secret sauce that you all have that Alnylam was interested in? Yeah. I think it's our identification of the targets and the deep knowledge and expertise in this space that our research folks have. And so I think they identified that as something that was attractive to them. And obviously, the idea is together we move faster down the road. Mm-hmm. Okay. And I guess, should we be thinking about potential for additional collaborations kind of with that same thought in mind, or was that kind of the one that you were pursuing? How should we think about that? Yeah. This one certainly made sense. I think we're always looking at things for whatever could make sense. Non-dilutive capital, sure, it's good, but you're giving up something in value at some point, and so I don't go in blindly there. But we have a very strong BD organization and team, and we're always looking at things. Okay. Got it. All right. We covered a lot of ground. Anything else that I didn't ask you, or that investors aren't asking you that you wish they were? I think, and we've talked about this a little bit today, but I think there are really two categories where one is this regulatory clarity on TN-201 and TN-401 that we'll be making progress on here in Q4. We'll give an update. I think that hopefully will take a lot of uncertainty out of the ultimate pivotal path for the programs. And then number two, we owe the clarity on the phase II and our plans there for TN-301, and we're already kind of sensing renewed excitement around that program. As I mentioned, that's in our control, and we'll come out in Q4 with that as well. So kind of two sides of the coin there. But the good news is we don't have to wait that long, and we'll have some hopefully good and exciting news to bring across. Good. Okay. Awesome. Yeah, I should ask, do you think early Q4? [inaudible] Q4. Q4. All right. Stick with that. Excellent. Well, thank you so much for taking the time today. This has been super helpful. Thank you, Whitney. And thanks, everyone, for listening. Thank you