Good morning, everyone. I'm Sean Laaman, Head of U.S. Mid-Cap Biotech Equity Research at Morgan Stanley, and welcome to Morgan Stanley's Global Healthcare Conference. Before we commence, to make you aware of some important disclosures, please see those disclosures at the Morgan Stanley Research Disclosure website at www.morganstanley.com/researchdisclosures. If you have any questions, please reach out to your Morgan Stanley sales representative. For this session, we have Enliven Therapeutics with CEO Rick Fair and CFO Ben Hohl. Welcome both of you. Thanks, Sean. Appreciate it. Yeah. Thanks for having us. Awesome. Might as well jump straight in. Starting, I've got a few questions here on, of course, ELVN-001, clinical differentiation and the CML strategy. What is the single most important reason you believe ELVN-001 can ultimately outperform SCEMBLIX commercially rather than simply coexist alongside it? Yeah, thanks, Sean. Again, thanks for having us. We appreciate it. I think candidly, we are very well-positioned in our first launch to be sequenced after SCEMBLIX. SCEMBLIX is going to be well-established as the market leader in first and second line CML when we launch with our second line plus label. In the long run, competing with them in the front line will be about the totality of the profile. We know that treatment selection in the front line is driven by different factors for different patients. For a young fit patient who may be looking for a cure, the most potent therapies are most attractive. Getting patients into a deep molecular response, ultimately a treatment-free remission, is an attractive treatment goal, and there it will be an efficacy choice. I think in looking at our data so far in third and later line patients, we look more effective in terms of driving major molecular response relative to SCEMBLIX. So I think in that patient subset in the front line, it will be an efficacy story. For many other patients, elderly patients, more frail, more comorbidities, it is really about controlling their disease with a well-tolerated agent. Again, their specificity to ABL1 seems to show some differentiation from SCEMBLIX. We are essentially equally well-tolerated in terms of nuisance adverse events and those that lead to treatment discontinuation for those reasons. But we do seem to have some emerging advantages in terms of cytopenias, hem tox, as well as cardiovascular toxicity and hypertension, which may be very meaningful for that patient segment. So can't really answer a single factor. It depends on the patient population. But I think in both of those patient subsets that we see in frontline CML, we have reason to believe we would be better than SCEMBLIX in a first choice. I would also just add, we have some of the convenience factors as well, so we have a better DDI profile and no food effect. So those are things that hurt SCEMBLIX as well. I think that is potential differentiation too. Awesome. Thank you, Ben. If ENABLE-2 is highly successful, what percentage of ELVN-001's long-term value do you believe resides in later line CML versus eventual first line use? Yeah, I think if you look at the markets in the U.S. today, or the market in the U.S. today, about half the opportunity is in newly diagnosed patients, and the other half is in patients who've previously been treated and are on their second or later line of therapy. I think we have reason to believe we'll be comparably successful in both settings. I would say that the base case would be about half and half between frontline and second line plus. Wonderful. What efficacy benchmark would cause physicians to actively switch from other TKIs onto ELVN-001 rather than simply using it in newly relapsed patients? Yeah, it's a good question. It's a little hard to say. Again, I think the treatment decision here is a little unlike other hematology-oncology or oncology indications where efficacy dominates. Here, I think it is more of a totality-of-the-profile kind of question. What I would say is better drugs always cause patients to have conversations with their doctors, and what we saw with SCEMBLIX uptake can't be explained by natural levels of switching. When they entered the market in third and later line therapy with their first approval, they achieved peak shares beyond 50% relatively rapidly in a market that doesn't have a very high rate of switching. That had to be patients saying, "Hey, there's a better treatment available. I'm going to discuss it with my doctor," and then sort of prompted switch. It's a little hard to point to a specific efficacy outcome that will lead to that. But we think the overall profile of our drug will cause many patients to go to their doctor and say, "I hear about this new agent, I want to try it. Wonderful. And I guess of the opportunity set, which is the most important, do you think, superior efficacy versus superior tolerability and/or quality-of-life benefits? It's probably all, but how would you weight that out? Yeah. I think in this class, efficacy and safety and tolerability are hard to separate. I think what we're all doing is we're all hitting the same target, BCR-ABL1, and our ability to hit that target hard enough to achieve better levels of efficacy is, for some drugs, toxicity limited. The primary limitation of the first and second generation TKIs has been that you can't get to a high enough dose to achieve the level of efficacy you want because of the off-target effects. With our very specific agent, we believe we can do that. It's almost not like a trade-off between efficacy and safety here. It is because we have a better tolerated agent, we will be able to dose to higher levels of efficacy, and so we should be able to come out and say, "You should switch to our drug because we have the best of both." And I think that's been the SCEMBLIX experience relative to the agents that were available when they launched, and I think you'll see something similar for ELVN-001. Sure. Thank you. Thinking about CML-treating physicians, according to your market research, what is the biggest unmet need that ELVN-001 could fulfill? I think at first launch, the clinical question that is not answered today is what is the best treatment after a SCEMBLIX failure? SCEMBLIX is being rapidly taken up in earlier lines of therapy. We are seeing increasing numbers of resistance mutations to the allosteric mechanism. The choices that physicians have currently after SCEMBLIX are the first and second and third generation TKIs that have all sorts of safety and tolerability liabilities. I think we will definitively answer the question what the best next choice is, but that is the areas of highest unmet need currently. In the long run, I think I described there is that patient population that would like to get to cure rather than just be on chronic treatment for the rest of their life. The ability to drive patients into a deep molecular response and a durable deep molecular response that leads ultimately to treatment freedom is the primary efficacy unmet need, and we think we have a chance to help contribute to that. Sure. Thank you. I guess sort of as data unfolds, what are the most important clinical endpoints beyond MMR that physicians tell you would determine prescribing behavior? Yeah. I think the regulatory approvable endpoint, as you pointed out, is achievement of MMR, major molecular response, or a 99.9% reduction transcript level. I've already described deep molecular response, which is a log below MMR, so down to a 0.01% transcript level. The importance of deep molecular response is that a patient who achieves a durable deep molecular response has a chance to go off therapy and remain off therapy for life. So that's an endpoint of interest. I think discontinuations due to adverse events is an important endpoint here. I talked about tolerability, and each drug has its own. All of the drugs share their on-target adverse events. Those that have off-target effects have different rates of each of those, but I think a good global assessment for clinicians is could you tolerate the therapy and stay on it? So that discontinuation due to AE rate is, I think, an important decision-making endpoint as well. Thank you. When you model the commercial opportunity internally, which patient population contributes the largest share to projected peak sales? What do you mean by which patient population? Like therapy? Yeah. Post 2G TKI failures, post SCEMBLIX patients, intolerance driven switches, or Oh, where are we capturing share from the most is your question. Yeah, correct. Yeah. Yeah. Candidly, we haven't really modeled that. We're looking at it mostly from a prevalence perspective, not an incidence. Right. and switching model. That said, I think we will capture portions of all, but I think the biggest improvement we will make is the improvement we make over the ATP-competitive agents, so first, second, and third generation TKIs. Okay. On the registrational program, I guess what aspect of ENABLE-2 keeps you awake at night? Sorry, can you repeat that? What aspect of ENABLE-2 keeps you awake at night? Is it enrollment, execution, comparative performance? Got it. Changing treatment paradigm or regulatory interpretation? I'm not laying awake at night worrying about ENABLE-2. The good news about CML is we're not blazing new trails in terms of clinical development here. There's a well-established path to approval. The clinical trial we're running is novel in the sense that it's a second line plus trial, where asciminib did a third line plus trial, but the endpoint is well understood. The comparator performance, these are drugs that have been around for a while, have generated a lot of data, is pretty well understood. At our end of phase I meeting this summer, we were able to clarify the major design parameters of the phase III study, so we have good health authority alignment. This quarter, we're having an end of phase II interaction that will allow us to confirm the other details of the protocol. I guess if I were to lay awake at night, it would be mostly about execution because I think our plan is really, really clear. But I'm really pleased with the way our team has executed so far, and we've maintained or improved our timelines as we've headed towards first patient in. Sure. Thank you. What have you learned from interactions with the regulators that investors may be underappreciating regarding the path to approval, if anything? Yeah, I don't think of anything. You? No, I think at EHA, we also announced the results at the end of phase I meeting, everything has been relatively predictable here in the CML market. There haven't been too many surprises. I think the upside is the FDA is you hear a lot of comments about the FDA. I think our experience so far has been that they're moving ahead. We're getting timely responses. Everything is kind of moving according to plan. Thank you, Ben. How should investors think about the probability that treatment duration and persistence ultimately become more important commercial drivers than early MMR? I think in the class that's been the case, right? These are very long duration therapies. So these patients are diagnosed typically in their mid-50s and are on treatment for life. A decent proportion, say 50%-60%, stay on the first drug they ever take. So I think treatment duration is the commercial driver here more than share. Obviously, you have to get share to get treatment duration, but I think we expect that's a major driver, and it is a feature of this drug class that if you respond, you tend to see durable responses. Sure. That's why we talk about the overall package of the drug being really important. It's not just efficacy, but it's the safety tolerability and the convenience factors that hopefully then drive all of that long duration. Yeah. For the patients who do switch therapies, as many of them switch for tolerability reasons as efficacy reasons, so it's not all about treatment failure. It's, "I just don't feel good on this medication." So that's why it's a both, not either question. Sure. Sure. I guess with the rise of, just a general question, the rise of China originated innovation, sort of just your line of sight on what might be coming on the competitive landscape, and if you can provide any commentary there and whether the rise in China originated innovation changes the way that you think about the world, either in R&D and BD. Yeah, sure. I'd say to answer your question on the CML front, the only assets that we are aware of that are coming out of China are additional allosteric TKIs like SCEMBLIX. So far, we've seen relatively limited differentiation there. I think as far as our position in the market, we feel very secure about it. Obviously, we need to continue to monitor the landscape, and that doesn't mean somebody won't take a stab at a me-too, very highly specific, ATP-competitive agent like ours. But to date, knock wood, we haven't seen that. As far as thinking about China broadly, our pipeline today consists of ELVN-001, our CML asset program in Graves' disease that we hope will advance to the clinic sometime in 2027. Beyond that, we've really wrapped up our discovery efforts. The building of a pipeline at Enliven beyond those two programs will likely be about business development. Obviously, China represents the hottest area for that and would be likely the source of a future pipeline for us. Right. Important to us. Right. My next question, I think you've just answered it, but I'll ask it anyway. I guess can the precision design capabilities that produce 001 be systematically repeated, or are those successes largely program specific? But I think the answer to the question is that BD rather than- Yeah, I think the team that started Enliven generated a lot of novel science. The company was really founded about novel chemistry to develop highly specific, best-in-class molecules against known biology. They worked on a number of programs. Two of them have made it to the clinic to date, 001 in CML, ELVN-002 is a HER2 program that we're no longer pursuing further in the clinic. I've mentioned our Graves' disease program behind it. There were other programs that we developed that we always have the option of taking forward, but we think these are the best and the most deserving of clinical development. We're not doing new discovery work at Enliven to expand that pipeline further. Sure. How would you balance pursuing highly validated targets with pursuing novel biology that may offer greater upside but substantially higher risk? Yeah. The premise of the company has been to really focus on known biology. I would say the programs that have entered the clinic to date obviously are not just known biology, but targets that are well-validated with approved therapies. Our Graves' disease program is against very well-understood biology, but would be a first-in-class molecule, so that's novel for us and an exciting opportunity. But the company is not actively pursuing new biology. That's not- Sure in our DNA. Right. When you think, I guess, sort of looking forward to Enliven in 2030, do you envisage a focused oncology company with a small number of highly differentiated products or a broader multi-asset oncology platform? Sounds like the former. Yeah. I think our current pipeline is a little interesting in that it's got one program in hematology-oncology and one in an autoimmune thyroid condition. I think that's different. I think the long-term view of the company is at some point it may not make sense to have both of those programs under one roof, so we always have the option to monetize one or both of the assets in different ways. Depending on the choices we make there, the pipeline we build behind that would make sense. But I don't think we have a firm commitment to the direction we're headed in that way. Sure. Okay. Back on ELVN-001, maybe for the audience, just sort of size out what you think the market opportunity here is in the U.S., then maybe extend beyond potential ex-U.S. plans. Sure. The market opportunity in CML as we see it today is about a $10 billion total addressable market, if you assume a price commensurate with asciminib or SCEMBLIX. It's about half of a frontline opportunity and half of a second-line-plus opportunity. If you take that globally, because of the lower prices due to the availability of earlier generation generic molecules, you see about another $6 billion opportunity in rest of world. So a $16 billion global market today, growing based on price improvements in the U.S. and also the patient population is growing over time, both incidence and extending survival. Sure. I guess on capital allocation and the balance sheet, with a strong cash position, what specific milestones would justify increasing investment rather than preserving capital? Ben, you want to tackle that? As we think, we have $895 million of cash. That gets us into 2030. I think the main thing as we thought about the raise that we did post-EHA this year was we really want to get through the top-line pivotal data for the second-line pivotal trial. I think we want to maintain that flexibility because that is a huge catalyst for our company. Also getting through into 2030 also would potentially allow us to get through top-line pivotal data for our frontline pivotal trial as well. So those are two pretty important catalysts. Obviously, as we talk about the potential Graves' program as well, that is built into that runway. So I think those are the main things that we're thinking about getting through in terms of the biggest catalyst. Sure. Thank you, Ben. Maybe for investors, just map out the catalyst path that you see for the next six, 12, and 24 months. Sure. Phase III studies start this year. Additional phase I data update from our ENABLE trial in 2027. We will be initiating a phase I trial in combination with an allosteric inhibitor to demonstrate potential ability to drive deeper responses for more patients. We will initiate that trial in 2027, so would expect data to start to read out from that in 2028. We will also be initiating a phase II frontline study in CML, a single-arm study with a cooperative group that we anticipate starting in 2027 and should start to read out data in 2028. Then, of course, potential IND clearance and phase I data generation from our Graves' disease program, which I cannot give a specific guidance to on timeline, but I think it is reasonable to assume we could get that into the clinic in the first half of next year if successful. If we do that, then data readouts probably follow within the six to 12-month time frame from that. Sure. I have got a couple of general questions, if you can indulge me here. First one is on AI. Are you implementing AI across your business, and can you point to any specific examples where it has changed a cost or a decision or even a POS? Yes. I think we are implementing AI in every way that we can figure out how to implement it. It is embedded in all aspects of our business. I think the primary advantages are, I think, accelerating our clinical and regulatory work. Getting studies started, getting regulatory documents generated, and those sorts of things are low-hanging fruit that we have tackled and I think are making good use of the technology there. But I see it being used across our team and certainly in our data management group in the way that we are generating and looking at our clinical data and so forth. So specific wins, it is mostly about timelines and efficiently currently. But I cannot think of an example where I think it has enhanced our probability of success yet. But again, given what I have said about discovery, we are not doing a lot of AI-applied- Sure novel science because we're really focused on developing the programs that we've already established. Sure. Last of the general questions, but we've been asking all our companies this just as sort of a snap survey. On the regulatory front, where are you most focused? It sounds like FDA, but we've got questions like MFN, tariffs, et cetera, but it sounds like FDA. Yeah. FDA and other global health authorities. Getting our phase III study started is the most valuable thing that we're doing, and so that's obviously our primary focus is FDA, EMA, and other global health authorities. But we are turning our attention to MFN and the other things impacting global pricing and launch sequencing decisions. Those are important things to be thinking about well ahead of our first approval. So turning our attention to that here in the coming year. For sure. I don't know if it's too early to ask, but I'll ask, just your assumptions around pricing when- Too early to ask. Yeah. Wouldn't be doing my job if I didn't. Look, I think we're 5 minutes early, but I've come to the end of my questions. What didn't I ask that I should have, or what message would you like to leave investors with? I think the message I'd leave you with, I don't think there are any unanswered questions, but the message that I'd leave you with is we have a large, de-risked phase III asset, high probability of success in a $16 billion global market with a best-in-class profile based on 200 patients treated in the phase I study. Those are hard things to find. So that's interesting for investors, strategics, and others. We have a potential transformative agent in our pipeline. Graves' disease is an increasingly exciting area. There's a lot of unmet need for patients with thyroid disease, and those patients are poorly served by the available treatments today. So it's an area of increasing focus for drug development. We think we have a chance to have a best-in-class asset that is oral once a day and with a really attractive clinical profile. If we get there in 2027, we're really excited that could really change the profile of Enliven considerably to a multi-asset and multi-therapeutic area company. Wonderful. Well, we might park the conversation there, but thank you, Rick. Thank you, Ben. Thank you. Yeah, appreciate it. Thanks, Sean. Thanks. Yeah. Well done.