All right. Hi. Good afternoon, everyone. Welcome to day two, I guess the end of day two, of our Cantor conference. My name's Olivia Brayer. I'm one of the biotech analysts here at Cantor, and really excited about this afternoon's discussion. Hot off a very successful IPO, we have Travis Murdoch, who is CEO of Braveheart Bio. Travis, thanks for being here. Thanks for having me. I want to go back to the beginning for a minute, which admittedly wasn't all that long ago for this company. You've built the company around a single asset in a mechanism that has already been pretty well established. Maybe just can you talk about what you saw in this asset that made you want to build a company around? Sure. Yeah. No. It's a little over a year ago that I joined as the first employee at Braveheart. For me, I, at the time, was at Biogen and just had recently sold my previous business, HI-Bio, to Biogen, joined Biogen, and was enjoying myself actually launching some phase III studies and working with Chris Viehbacher, who now ends up being our chairman. There was emerging data from this program, which ultimately was presented last year at ESC. For me, the initial dataset that I found quite compelling was really around the rapidity and depth of gradient reduction in patients with obstructive hypertrophic cardiomyopathy in that initial phase I-B data. That was really the data for me that got me to get excited in the asset, join, and really start the company build with a great team. Yeah, and fast-forward a year and change, you now have two phase II datasets that you've been able to take a look at for this asset. What have been some learnings along the way? I know it's been a very short time horizon, but obviously a lot's been going on. Yeah. I think it's a really unique time for hypertrophic cardiomyopathy patients. We're seeing data emerge that really supports not only in the obstructive form of the disease, where now there's two approved agents, but also emerging data in the non-obstructive form of the disease where there have been no approvals. Over the last year, we've seen both external catalysts across the industry, and we've also had some really promising data emerge for our lead program, BHB-1893, in both obstructive and non-obstructive HCM. I think it's a great moment in the industry, and we're really focused on executing now on global phase III studies. Yeah. A question that I get a lot is just how to think about the opportunity set between the two, right? You have obstructive and non-obstructive, as you alluded to. From a patient population perspective, maybe obstructive is the bigger today. Is that the right way to think about it? Is obstructive maybe the bigger opportunity for you all, or could non-obstructive maybe be the area that you differentiate the most? To your point, there isn't a drug approved today in non-obstructive, so maybe a bit more of an unmet need. How do you think about the pros and cons of both as you weigh the opportunity set that you have with the two indications? Sure. I would just see the opportunities slightly differently. I think they're both large opportunities. From an epidemiologic perspective, in previous years, it was thought that the obstructive form of the disease is actually larger than the non-obstructive form. I think what we're starting to see now as therapies make their way through development, is that in fact, there are probably more patients with a non-obstructive form of the disease than was originally perceived. We're seeing some new epidemiologic data emerge that the end market there is large, and probably as large as the obstructive form. From the perspective of how we think about BHB-1893 sitting in those markets in a future state, I think there are different aspects of differentiation and potential differentiation that would drive, at least in our market research, adoption of a next-generation agent in obstructive, really around potential for differentiation on efficacy, safety, and/or ease of use. In the non-obstructive form of the disease, obviously there's a lot of white space. But we think that an agent that has a potential to be disease modifying from the perspective of structural improvements as well as showing improvements in feel and function would be a really optimal TPP. Yeah. Maybe we'll start with the non-obstructive opportunity, just given as you characterize it, there is a bit more of a white space there. You do have phase II data. You are looking up to ramp up a phase III and finalize a trial design. Maybe just at a high level, talk about the phase II data that you have produced today. What efficacy metrics do you put the most weight on, and where do you feel like you've maybe found the most differentiation in your clinical profile at this stage? Sure. We have a 12-week placebo-controlled study that was run by our partner, Hengrui, in the non-obstructive form of the disease, 28 patients per arm. I think the data were very encouraging and highly directional across metrics. I would include a number of key metrics. We saw rapid deep reduction in biomarkers, including NT-proBNP and troponin. We saw improvements in measures of diastolic function that were quite significant. So there's metrics on echo of cardiac relaxation, including e' prime, septal and lateral e' prime, that actually moved from abnormal values to normal values, paired with decreases in measures of really the back pressure of left atrial volume index, as an example. So those echocardiographic parameters and then also measures really of the disease, where we saw decreases in wall thickness, as an example. When we take those metrics and look at them, they really suggest that there is a potential for reverse remodeling, and we think that's very exciting. We saw highly directional data as well in terms of KCCQ and peak VO2 and dose effects there that we think are highly directional and suggest a potential for real efficacy in this disease. Interestingly, when we did our market research, we did pretty extensive market research with ClearView. One of the things that came out of that was that these improvements in cardiac structure really are quite important to physicians as they think about treatment options. If you could have an agent that replicates that in a global phase III program, that would be an important part of how physicians think about treatment decisions. Because, as you know, we want our patients to feel and function better, but ultimately, this is a disease of cardiac structure. So being able to show improvements in structure is an important part, I think, of the narrative. Yeah. On that point of reverse remodeling, as you think about your phase III and potentially having patients on therapy longer, with longer exposure, do you think you could see maybe even a more pronounced effect over time in phase III than what you're seeing in your phase II profile so far? I think we're very encouraged to see that profile at 12 weeks, to your point. I think we're continuing to digest data more broadly from others. What we've seen, at least in the obstructive form of the disease with longer-term follow-up, is our changes that consolidate over time. I think it's, again, encouraging. We'd hope to see if we can continue that trend with a longer time point in the phase III study. One of the questions that I get asked about pretty often, and I am sure you do as well, is just the translatability of a Chinese data set, and an effect size in a Chinese patient population to Western populations. What do you say to that? Yeah. I think as we have spent time on the data very extensively, I think context is really critical here. The way that we see the data set is, I would say, and the generalizability is through four different lenses. The first is that the disease biology here doesn't know a boundary, and so we believe the disease biology to be highly congruent across geographies. The second is that practice patterns are actually very similar between China and other global populations, in part because there have not been great treatment options. Beta blockers often get used, calcium channel blockers and CMIs and, in the case of the obstructive form of the disease, surgical options. The third is that we have the benefit now of seeing in precedent CMI studies, cardiac myosin inhibitor studies, for both approved agents, data cross-geographically, and we think that demonstrates that similar response across geographies. The final piece, I would say, is the pharmacokinetic properties and how they may differ. We have an ethno-bridging study in Australia in healthy volunteers, and so have a good confidence that the pharmacokinetic properties of the molecule will translate. Okay. For non-obstructive, we now have two phase III readouts recently, right? We obviously have ODYSSEY, which didn't hit statistics, and we have ACACIA-HCM, which we just saw more detailed data a couple of weeks ago. What do you make of the fact that some people may say that CMIs are one for two in non-obstructive as a potential read-through to your program? I recognize and I am a believer that you guys actually may have a differentiated molecule on your hands. But as you think about the trial designs, as you think about the data that we have seen so far from an effect size perspective, what is kind of your takeaway from the ODYSSEY and ACACIA-HCM data sets? I think we were hopeful to see the ODYSSEY be a positive study. We are encouraged to see the work on ACACIA-HCM and that could be a valuable treatment option for patients. I think one of the things that as we look at BHB-1893, we are now really starting to understand the mechanism both in terms of preclinical data that we are generating on a post hoc basis, but also the emerging structural data that is in this placebo-controlled study. I think what we are learning is that not all of these agents are the same. That is probably not surprising. These are all allosteric inhibitors. As an example, we understand that mavacamten and a number of cardiac myosin inhibitors actually can bind in the same pocket. Really that suggests that these pockets can have quite pleiotropic effects. We should not necessarily expect that what we see from a trial in one agent is going to be true for another. Mm-hmm. Was there anything from the full data sets from both of those studies that has maybe changed or informed your view for how you will ultimately decide your own phase III, the NobleHeart study? Yeah. We are still digesting the data. It was only a week and a half ago. I do think it is valuable to be students of the past. We hope to really learn from that with our investigators and continue to build a development program that takes advantage of these learnings. Any thoughts on effect size of the class based on what we've seen so far? I recognize maybe the treatment deltas looked somewhat similar between the two arms or between the two studies, but the arms looked a little bit different. What do you make of that and how to think about when you think about ultimately a placebo control arm, how would you expect those patients to perform as you think about again, tying that back to your own study? Right. Yeah. I would say we've seen differing placebo effects to your point. In both studies they were larger than have been seen with in the obstructive form of the disease. In fact, in our phase II study we saw similar placebo effects to ODYSSEY, but I think what was encouraging with our data was that there was a 5.5 point KCCQ change in the high-dose arm with the dose effect. So encouraging data, especially given that over 50% of patients in that high-dose arm had a 20 plus point change in KCCQ. So I think suggestive in fairly early time point that there could be a meaningful clinical effect and I think one of the learnings from the recent data is that those clinical effects can consolidate further over a longer period of time. Mm-hmm. Is there a clinical bar? I recognize it's not all about KCCQ, right? Especially given the data that you guys have on hand. Is there a clinically meaningful threshold when you do your market research and you talk to doctors and physicians that they're hoping to see from future assets in the non-obstructive space? I think right now there's just huge unmet need, so any agent that's able to move the needle Yeah is going to be valuable for patients. At ESC there's a lot of discussion around this topic and I think that there's always going to be that risk-benefit discussion, right, for emerging agents. I think for us we found the data to be very encouraging from ACACIA-HCM, but we also think that there's room for improvement for patients and really hope to optimize the development path here for BHB-1893. What are you able to share with us today about your phase III design and when can we expect to get more definitive updates there? We'll be able to share more into the fall. We're planning currently for this to be a study with a 36-week endpoint. We are planning to use dual primary endpoints of KCCQ and peak VO2. But we'll be able to share more specific detail into the fall. Is the goal to be second to market? That's the goal. Okay. Well why don't we turn to obstructive. Also some really interesting phase II data there. You have now come out with your phase III trial design. So maybe we'll start there. Competitive class, there are multiple CMIs on the market. I know you guys are looking to do something different. So maybe you can tell us about where that differentiation comes from and how you're actually implementing that in your phase III design. Sure. So in the phase II data set, this was an open label dose ranging study across three different dosing regimens followed by an open label extension which is ongoing. I think we were particularly encouraged on the efficacy side by the rapidity and depth of reduction in gradient, which is a key. It is the treatment target for the class and for surgical intervention. The fact that we saw over 86% of patients have what is considered a complete Valsalva gradient response, we thought was very encouraging, especially these were patients that had high gradients at baseline. We would hope to seek to replicate that in a phase III program. The second piece that was encouraging was the relationship between gradient response and LVEF reduction and the latter being quite shallow and also the pharmacokinetic being tight. This is by virtue, we think of the fact that this is an agent that is cleared both renally and hepatically, so it has got mixed clearance. The third is that, at one week, we already see very deep responses, which has not been the case for other agents. Even though these patients were titrated weekly, what we found is the majority of patients who started on 40 mg actually were served by the starting dose. One of the things we have learnt in our market research is that one of the key barriers to uptake for these agents, and particularly in the community, is it is not the fact that we use echocardiography to monitor treatment targets, it is the frequency and number of echoes that are required to get patients onto effective therapy. Really, as we move into phase III, those three aspects of potential differentiation we are really seeking to shore up in a phase III program. LIONHEART-HCM, which is our phase III, which we just announced this week, is now screening patients. We are planning a highly simplified titration regimen. But one that we think has an opportunity to still capture the efficacy that was seen in the phase II program. You are, to your point, you are doing that one-step titration approach in phase III. Is the goal essentially to eliminate the maintenance phase of echoes altogether? I think that when you think about patients with this disease, they regularly get echoes to monitor the course of their disease, often on, say, a yearly basis if they are on a CMI. In our market research, the greatest burden has been more in the initiation phase rather than the maintenance phase. I think we are having a number of discussions with FDA around ways to further relieve the need for echoes in both the maintenance and initiation phase. I think as a base case, notionally, the idea that we could have a fixed dose for most patients and not require titration really would help alleviate the number of echoes required. Is the hope here that maybe you could even expand the market in terms of number of patients that are on CMIs? I recognize it is of course a market share, that gaining market share is of course important, but could you also expand maybe potentially the number of patients that are actually receiving CMIs with a more or maybe less burdensome monitoring scheme? Yeah, I think it speaks a bit to the design that we have. We have two phase III programs. One is being run by our partner, Hengrui, which is on top of standard of care. Then we are planning a study with the other design, which would be a head-to-head versus beta blockers. What we've heard in the community, in particular, where penetration of this class is quite low, is the echo burden particular and the number of echo Valsalva maneuvers with echoes is an impediment to community physicians picking up these medications. We think that the combination of having data that could be supportive of use in an earlier setting, as well as having this highly simplified dosing regimen could be really impactful in terms of expanding the use beyond centers of excellence. Okay. Yeah, and you bring up an important point. Your partners do have phase III data coming next year. Can you maybe just talk about the importance of that data set that's coming next year? I recognize it's not necessarily on top of beta blockers, so there is a nuance. But as you think about the de-risking of your own program, and as you think about next steps from a regulatory perspective, what will you learn in the first half of next year from that phase III data set, and how do you actually apply that to your own company and program? Yeah. It will be an important readout for us. We are expecting that data from our partner, Hengrui, in the first half of next year. I can say that they've been a fantastic partner to us and are in many ways just a highly competent organization in terms of their ability to stand up and run high-quality studies. We certainly think that that's going to be an important further validation of all the attributes that we talked about. I think what's unique about this situation is that we've also had some very productive regulatory discussions around using that as part of our filing package, which could be an accelerant for us. I think we all recognize that we live in an interesting geopolitical climate. But at least to date, we've had strong interactions about using that and an interim analysis of our ongoing phase III study as an initial filing package. I recognize there are external factors that are out of your control. It's the FDA, I'll leave it at that. But let's fast-forward six months or so. Let's say Hengrui has positive phase III data next year. You have your interim analysis, I think, in the back half of next year. Where would that leave you in terms of your discussions with the FDA? Are you operating under the assumption that there is a very realistic chance for an accelerated path? Yeah, I think we believe that because of all the things that we talked about, that the relevance of this data as a foreign data package is quite high. We've laid out that argument to the agency and of course they'll reserve matters for review. It's part of a filing package, but there was support for that as an initial approach. Of course, we'll continue to have interactions with FDA into next year. Mm-hmm. As you think about your own interim analysis, maybe just talk about the decision to include that as a pre-specified interim analysis. What will we learn from your interim analysis? Again, I recognize that that may be a big part of your filing strategy, so how robust of an interim analysis will it end up being? Sure. We are planning this interim analysis, 60 patients of data. We have chosen to 2-to-1 randomize our study from a patient centricity point of view. We would have 40 patients on drug and 20 on placebo. The current plan is for that to be at 12 weeks, really focusing on gradient safety and pharmacokinetic properties. As part of our discussions with the agency, they have asked us to include Asian patients in that analysis, and so we plan to do so to help support further the relevance of pharmacokinetic properties across these two geographies. I think it is going to be a robust data package. We hope to validate in a global population some of these differentiating properties that we saw and have it form an important part of our regulatory package. There are some other data sets that are coming potentially next year or maybe even later this year. As you think about the OLE data sets that are ongoing, both for obstructive and non-obstructive patients, what should we expect to learn? Sure. I think the nearest term, later this year, we expect with our partner, Hengrui, to announce further data from the open label extension. All patients who are in the obstructive phase II program, that was a 12-week study. Patients were washed out. They actually did a repeat CPET measurement after washout, so they re-baselined those patients. Then they were placed into the open label extension for a year. Again, had CPET measurement at one year. I think what will be great is to see how we know some of the data from that study. We know that we are seeing similar complete gradient responses. At 28 weeks, we saw 86% of patients have a complete Valsalva response. I think what will be particularly interesting is to see how patients, whether they are able to further improve their exercise capacity at a year, and so we are looking forward to sharing that data. Okay, great. Travis, in the last minute or so, your valuation comes up in a lot of my conversations with investors. Obviously, you all have had a very successful IPO. When you think about, again, the opportunity set, going back to obstructive and non-obstructive, I do not know if you are ready to put numbers around it per se, but when you think about what your drug could be from a revenue perspective, any thoughts on how big these markets could really be and how big of a growth opportunity set you have? I will leave the exact numbers to you, Olivia. No, I think our view is that these are some of the largest orphan opportunities that exist, and that not only are they large end markets, but they are also less crowded, honestly, than a number of other orphan markets, some of which our CFO, Paul, and I both were in the IgAN space previously. We look at the number of entrants that are likely supported there, and we think there is a large opportunity here. Okay, great. You know what, maybe I will sneak in one last question. The other question I get a lot is, would you all look to further partner or would you look to potentially have a strategic collaborating partner at some point? We also come from a number of companies that have transacted in the past. I would say what I love about this particular indication set and now with the tank full post IPO, we really have the capital to take ourselves well into 2029, and so we feel like there is a very hearty standalone path here. Yeah. Well said. Well, congrats, Travis, and thanks for being here. Thanks so much.