Good afternoon, and welcome once again to TD Cowen's Seventh Annual Oncology Innovation Summit. I'm Phil Nadeau, one of the biotech analysts here at Cowen, and it's my pleasure to moderate a fireside chat with Enliven Therapeutics. We have with us today Rick Fair, CEO, and Ben Hohl, the CFO and Head of Corporate Development. Gentlemen, I'll kick it over to you to provide a brief state of the company overview. What are the most important events for the company over the next year, and what does Enliven need to do to create shareholder value? Hi. Thanks, Phil. I appreciate you having us here and thanks to the Cowen team. State of the company, as we find it here in May of 2026, is strong. We're very focused on execution as we prepare for our first phase III trial in second-line plus CML. We're busy building the organization capable of executing multiple pivotal trials, potentially multiple clinical programs over time and preparing for a commercial launch in CML just a few years away. Busy time, an exciting one for us. Say over the next year or so, value drivers for us, it's very much focused on ELVN-001 and CML. I think in the near term, we have to align with health authorities on the second-line plus pivotal trial that we want to conduct. We have to initiate it and drive accrual so that we get a readout as soon as we can and get to our first approval. At the same time, we really have to prepare for a frontline study. We have an excellent profile, which I'm sure we'll talk more about today. I think it'll be very competitive in newly diagnosed CML. Our plans for this year are really about engaging with health authorities to find out the requirements they have to allow us to start a pivotal trial in frontline CML and to initiate a phase II IST, which will allow us to start generating a little bit of data in frontline CML, both to support health authority interactions, but also to start to illuminate the profile, which we think will be outstanding. Those are our priorities for now. Great. Starting with the upcoming EHA meeting. In conjunction with the EHA abstract, you shared data from the phase I-B trial of 001 and CML. Can you walk us through the highlights of that data? Sure. I will caveat by saying that the data cut we used to submit the abstract was the December of 2025 data cut, which was the same data cut we used to issue our press release in January. You may have noticed the efficacy data were the same. The data that we show there, outstanding safety and tolerability profile, would emphasize a very low discontinuation rate due to AEs of about 6%. Very low dose reductions due to AEs, less than 10%. We'll obviously cover more of the safety data in detail on our total phase I study population at the meeting. What we see is a really well-tolerated drug, which is what we expected, given that we have this highly specific mechanism that's very targeted at ABL1. I think on the efficacy side, the efficacy data headline numbers you saw previously in January, achieved MMR rates of 38% in the mature 80 mg group, 53% in the less mature 60 and 120 randomized cohort. Everyone who entered the trial in MMR maintained their MMR status. Our cumulative MMR rates ended up at about 47% and 69%, respectively, in those two dose groups. As we've talked about previously, the difference between those dose groups has nothing to do with dose. It has everything to do with data maturity. We know from our data, from precedent studies in CML and from competitors that are currently developing in phase I studies, achieved MMR rates are distorted if you look at them early in the trial prior to everyone crossing the landmark of 24 weeks. These are achieved MMR by 24 weeks. They count anyone who's past 24 weeks, any patient who has responded early prior to 24 weeks, and anybody who's discontinued early prior to 24 weeks, but it excludes in the calculation anybody who's on study but hasn't yet responded and hasn't crossed 24 weeks. We know that the immature data inflates a bit the achieved MMR rates. We think truth is probably closer to that high 30 number, in this very heavily pretreated and resistant patient population, which we think is a great figure. If you compare that to precedent studies of asciminib in their phase I study in a slightly less heavily pretreated patient population, you saw achieved MMR rates in the mid-20s. We're high-stepping in terms of an efficacy profile there. The new efficacy data point in our abstract was really about efficacy explicitly in patients who'd been previously treated with asciminib. This is a question we get a lot. I think people are very excited about the notion of having a selective ATP-competitive inhibitor like ELVN-001 to sequence with allosterics like asciminib to address different mechanisms of resistance. We show data that deliver what we expected, that because the mechanisms of resistance are different, we don't expect different efficacy outcomes in patients who've previously been on asciminib. We saw excellent achieved MMR rate of 38% in those patients, cumulative MMR rate of 47% in those patients, very consistent with the overall population. I'll remind that these patients who had received asciminib were some of the worst of the worst patients in our study. Over 90% of them, 92%, had at least three prior treatments, so fourth line and later, and a full 37%, more than a third, had received five or more treatments, so six line plus. Really heavily pretreated patient population that had seen asciminib, and despite that, we saw great efficacy outcomes. I think those are the highlights. We're pretty excited about the data set, and at the EHA meeting, we will present the full complement of safety and efficacy data on an updated data cut we took in March. You'll get a few more months of follow-up, about 20 additional patients enrolled and a comparable number of additional efficacy evaluable patients to look at at the meeting. As we start to think about the EHA presentation, it sounds like you're suggesting the 80 mg cohort that we've already seen is probably indicative of what a mature data set would look like. Is that fair? Yeah, I think that's right in this patient population. The two things to think about when you're thinking about looking at phase I studies in CML is what patients are enrolled and how mature is the data. Those are the two big drivers. This is a very heavily pre-treated, highly treatment-resistant patient population. In that group, yes, I think the high 30s number that we've reported is more real, or if you want to think of it that way, than the mid-50s number we presented in the less mature cohort. That said, it's really important to note that we've continued to accrue patients. What's happened in the three months between the data cuts is our 60 mg and 120 mg group matured and our 80 mg group unmatured as we restarted enrollment at 80 mg QD, which was the dose we think is appropriate for future development. You could expect all things being equal, that if you looked at those numbers at EHA, that the achieved MMR rate will be down a little bit in the 60 and 120 group and up a bit in the 80 mg group based on data maturity alone. Got it. Said simply, we don't see a dose response in this range at this size of a sample. We have very good target coverage at 60 mg. Between 60 mg and 120 mg QD, we don't see any material differences in efficacy or safety. Got it. Okay. In terms of the measures we should pay attention to, it sounds like you're focusing on the MMR-achieved rates. Is that fair? If so, what other efficacy measures will help flesh out the profile? Yeah, sure. MMR achieved is the regulatory approvable endpoint, and it's in actually MMR achieved at 24 weeks. It is a landmark analysis, which is a bit different than the MMR by 24 weeks that I described, which is sort of a running count in a phase I study. That's why we focus on it. It's also important to patients. It's been correlated with long-term overall survival. It's an important measure. That said, in real life, what we find in CML is, especially in earlier lines of treatment selection is driven a lot by tolerability. All of these drugs control disease reasonably well to varying degrees, and sequencing these drugs together doesn't seem to affect overall survival. The order in which you choose them doesn't really matter. I think physicians and patients are really striving early in therapy to find a well-tolerated, effective agent that they can stay on for the long term. We think this is a lot of what's driving the asciminib uptake into earlier lines of treatment. The safety and tolerability profile we think is really, really important, and so we encourage people to look at the overall safety events, the tolerability profile, and discontinuations and dose reductions due to adverse events, which is a good sort of overall global score of how well-tolerated the drug is. As far as other efficacy measures beyond MMR, secondary endpoints that are of interest, deep molecular response, especially earlier lines of therapy. There are patients who want to get to a deeper level of response and potentially to a treatment-free remission, so that's an important metric, less so later lines of therapy, where that's generally less achievable. In those later-line patients, MR2 can even be a decent lower bar efficacy hurdle. They may not be able to get into MMR with any treatment if they're multi-TKI resistant, but if they're able to stay in MR2, they can live a normal life and thrive. I think those are secondary endpoints of interest, but I'd focus people on safety tolerability and MMR achieved to predict regulatory success. On the safety toler- One thing I'd just add there, I think is also just, Rick mentioned roughly 20 more patients would be added. We'll be looking at a patient cohort now, in the phase I of roughly 160 patients at this point in time, and with a median duration that continues to get longer and longer. We have multiple patients, a large patient population over a year, handful over two years. This really is a fulsome data set at this point. I think really trying to drive home that safety and tolerability profile is important. On the safety and tolerability profile, are there adverse events that are particularly harmful to the patients? Anything that CML patients are particularly sensitive to or attuned to less first and then second? How important are dose reductions and discontinuations in the overall AE profile? How should we weigh those versus the incidence of actual adverse events? Yeah. I think if you look broadly at CML with the approved therapies, the adverse events that are of most concern are generally off target. Cardiovascular adverse events, and pancreatic toxicity, pancreatitis. These are potentially serious safety issues in addition to potentially affecting how much dose intensity you can achieve. The safety profile of the -001, because of its specificity, is really about on-target effects. You care about cytopenias like thrombocytopenia. You care about sort of musculoskeletal nuisance side effects, aches, arthralgia, and the like. We do see some lipase increases. We haven't observed clinical pancreatitis, but it's certainly a lab value to watch and to note. The reason why I sort of cite it as discontinuation and dose reduction due to AEs as a good global score is it sort of takes all that into account. Says, "Can patients take the full dose of this drug?" We think a lot of the differences in efficacy you see in these drugs has to do with dose intensity. Can you get to an optimal dose that will achieve full target coverage and achieve the efficacy outcomes you want and stay on it for the long term? Particularly with second-generation TKIs, that's a real challenge. We think that's a good way of looking at a global assessment of tolerability. That's really helpful. A key area of investor controversy has been the relative potency and competitive position of ELVN-001 versus TERN-701. Sure. How would you compare and contrast the two molecules based on the data that's been generated so far? Yeah. We work differently. TERN-701 is an allosteric that looks very similar chemically to asciminib or SCEMBLIX, the market leader in the current CML landscape. ELVN-001 is the only selective TKI. Again, in some ways, it binds to the same binding site as first and second-generation TKIs, but it does it in a different way that reduces its affinity for off-target kinases. It's really, really selective to ABL1 and therefore, again, the adverse events that we observe are not similar to the second-generation TKIs, which are mostly off-target. Comparing to TERN-701, these are both really well-tolerated agents based on early data. They're both highly effective agents. They're both very selective as asciminib is. I think they're competitive in development. The way we think about ELVN-001's positioning here is as the only selective ATP-competitive agent, we believe we work really well in sequence with the allosterics. Now, asciminib's there first, so they will be widely taken up in front and second-line when we enter the market and when TERN-701 enters the market. The primary clinical question that we think people will have at that point is, what do I do after asciminib? There are some patients who don't tolerate it. There are some patients who don't achieve efficacy or develop resistance mutations to it. What do I do next? What we hear consistently is a highly selective ATP-competitive agent would be the drug of choice there. It works differently. It will have different mechanisms of resistance. It will potentially address clones that are resistant to an allosteric, whereas we don't believe TERN-701 will do that because it's, again, largely the same molecule. I think in that sense, we feel very well-positioned in our first launch to enter a market that is dominated by SCEMBLIX and to capture second and third-line share for patients who don't do well on it. In the long run, these drugs will all compete in front line CML. They're all good drugs. They're well-tolerated. They're effective. We're all going to do front-line studies. I think there, the competition will really be profile dependent. It's a little hard to predict based on the very small data set we've seen from Terns, the bigger data set we have, but albeit in a very heavily pretreated and late-line patient population. I'll say what I know, which is if you look at our phase I study versus asciminib, we have a more heavily treated and resistant patient population enrolled, we have a higher MMR achieved rate and very similar rates of discontinuations due to AE, with some differences in safety and tolerability profile, which we think will be advantages. On top of that, we have a lower propensity for drug-drug interactions. We're not a CYP3A4 substrate or inducer, we feel like that's an advantage for a drug you'd have to take for the rest of your life. We have no food effects, you can take it at any time of day with or without food. We know that SCEMBLIX has a food effect that affects when and how you can take the medication. I think if you stack all those things together, we feel like we have a very competitive profile in frontline CML. I think TERN-701, the jury's out. We've seen a very small data set. I think Terns and Merck have disclosed that their data set has eroded since we last saw it at ASH. That makes sense based on it maturing and based on them starting to treat more challenging patients than they did earlier in their study. I think the long-term profile of that drug is in some doubt. I'd say chemically what it looks like is asciminib, and so what TERN-701 appears to be is high-dose asciminib. We know from the asciminib experience that high-dose asciminib was slightly more effective, slightly higher single-digit, 4% or 5% improvements in MMR rates, but also came with increased safety and tolerability liability, which makes sense. I think for those reasons, there are reasons to believe that's not going to be a game changer relative to SCEMBLIX in frontline CML, but it's really too hard to say based on the data they've presented. Great. Turning to the pivotal study, you've guided to the initiation of a second-line-plus pivotal trial later this year. Can you discuss the likely design of that study, and in particular, which population is the right one for the first pivotal? Our proposal to health authorities will be a second-line-plus randomized study against a physician's choice of TKIs. Our rationale for that is, as I described, the market that we will enter in second-line-plus CML in the future will be heavily SCEMBLIX dominated. The question to ask there is what is the ATP-competitive agent of choice to go to next? We're doing the randomized study that I think will prove that definitively. That's the proposal we'll take to health authorities, and we should have answers to that and a clear guidance on the study that's endorsed by health authorities in the third quarter. Great. I think you said you're taking the 80 mg, or you're likely to take the 80 mg forward. Is that correct? Correct. Our proposal is to take 80 mg forward. Our rationale is in relatively small numbers in each individual dose, but we've done a relatively large phase I, and we did the randomized cohort for Project Optimus purposes, and 60, 80, and 120 mg look essentially identical from a safety and efficacy perspective in CML patients. The rationale for 80 is really about our modeling. If we look at target coverage modeling, PK/PD modeling. There's a small percentage of patients who might be slightly underdosed at 60 mg, particularly those who are taking PPIs. At 80 mg, we can expect that even if a patient's taking our drug with PPIs, that they'd have full target coverage and optimal efficacy. That's the rationale for 80. There's no toxicity liability of 80 over 60, so we don't see a reason why health authorities would object to that. That's the rationale, and we'll get that confirmation in our upcoming interactions and guide to that in the third quarter as well. Great. In terms of endpoint, sounds like the regulatory precedent is for MMR achieved at week 24. Is that fair? Can you remind us, is it likely to be a superiority comparison or a non-inferiority? Yeah. It's a superiority comparison on MMR at 24 weeks. I will add a small caveat that 24 weeks is the precedent in third- line -plus CML that's struck by asciminib. There really isn't a precedent in second-line-plus CML. That is a discussion for health authorities. As you know, the precedent in frontline CML is 48-week endpoint. It's between those two bookends. Yeah. Got it. Okay. What else do you hope to learn from the regulatory interactions? I think in our near-term interactions, aligning on dose and aligning on the phase III protocol for our first study are the highest priorities. I think at some point this year, if not in those interactions, a subsequent Type C meeting, we also want to get some input on frontline plan. Our question there really has to do with what is the safety database required for us to start in frontline CML. These are patients that have lots of approved therapies. They have relatively normal overall survival. Taking an experimental medication to frontline CML requires some amount of safety and efficacy data. We have a large data set that's been described in our phase I. We want to hear from health authorities how many patients, for how long do they need to be followed before we'd be allowed to start a frontline trial. We'll get that guidance this year. We'll also initiate a phase II IST in frontline CML this year to start generating some data. I think with that, we'll be able to guide to a more firm timeline on frontline CML. We will go as fast as we can. We think we have a competitive profile there, so it's really about getting health authority alignment before we can get started. Got it. Okay. In terms of a frontline design, would the ASC4FIRST trial be a reasonable proxy? Yes. Perfect. Novartis' Q1 call included some notable updates on SCEMBLIX, including Q1 sales of $433 million and increasing share of first-line patients. Just what are the key learnings that Enliven is deriving from the SCEMBLIX launch, both in the relapsed/refractory space as well as the earlier lines of therapy? Yeah. Ben, do you want to take that one? Yeah, sure. I think, like you mentioned, the SCEMBLIX launch is going incredibly well. Now annualizing at $1.7 billion of revenue only with five full quarters of the broad label of launch is pretty incredible. I think that's exceeding most people's expectation. They also, last year, updated the peak sales guidance to greater than $4 billion as well. I think both of those things are pointing to this is going really well. This is a large market. What does it show us? It shows that doctors and patients, they really do want new drugs, and they're willing to prescribe new drugs. Just the CML market, it really is huge and can support multiple blockbuster drugs. Where do you see TKI ultimately fitting into the treatment paradigm? Maybe the most prominent pushback we get on Enliven is aren't there a lot of BCR-ABL TKIs already on the market and in development? Do we need another? Yeah, we do. I think as I've tried to point out, I think the key is our selectivity as an agent. If you think about the choices in the market today, you have a selective allosteric that's being taken up in first and second line because it's just better tolerated and more effective than first and second generation TKIs, which are kind of dirty drugs. They have lots of off-target effects. The notion of having a complement to that you can sequence with an allosteric to address resistance mutations and keep patients on therapy controlling their disease in the long run is really, really attractive. When you look at our rates of discontinuation due to AEs, they're comparable to the 6% that we see with asciminib in its later line pivotal trial. Our rates of dose reduction due to AE are lower than what you observed in asciminib in its late line trial, and there's no comparison to the second-generation TKIs that are the current choices today. As SCEMBLIX has sort of swept the market because it's more effective and better tolerated, we expect that Enliven will do the same and really combine with the allosterics to offer better treatments than are currently available today with the first and second generation options. I think a lot of those skeptics probably would've said the same thing before the SCEMBLIX launch as well, and look how that's doing. Perfect. In terms of the pipeline, we discussed TERN-701. Any other notable candidates out there? One that is sometimes brought to our attention is the Ascentage compound. What's your thought of the- Yeah. Olve is a potent drug. It is a me-too, me-better ponatinib. ponatinib is reserved for patients who are multi-TKI resistant or have certain resistance mutations. We don't expect them to be a competitor to ELVN-001. If the profile pans out, they'll probably replace ponatinib in fourth line plus CML. We will be competing for the first three lines of therapy with the allosterics. Couple of corporate questions to finish up. I guess first, additional programs, you've disclosed that there's a pipeline or a pre-clinical pipeline, but not really given much detail around it. Any programs there that you'd like to discuss or any guidance you'd like to give on when we could learn more about the pre-clinical pipeline? Yeah. Strong message to everyone. We're very, very focused on ELVN-001 and CML and getting that to market as quickly as we can. We do have a program in Graves' disease. It's been a challenging area to find a development candidate we believe who can achieve our target product profile, which is why we haven't talked much about it. I think when we have a candidate we feel confident is going to make it to the clinic, we will definitely talk more about it. We're excited about the opportunity. As one investor called it, a comically massive opportunity if we have a drug that works in Graves' disease, and we'll be humble about it till we're ready to move something into the clinic. Keep you posted. Lastly, can you remind us of your cash balance and how long that is expected to support operations? Yeah. Ben? We have roughly $450 million of cash, that's we guide to into the first half of 2029. That should get us through top line pivotal data of the second-line-plus pivotal trial. Great. With that, we are out of time. Thanks so much for hopping on with us today, and best of luck at EHA. We're looking forward to the update. Yeah, appreciate it. Thanks, Phil. Thank you.