Good morning. Welcome once again to TD Cowen's 46th Annual Healthcare Conference. I'm Phil Nadeau, one of the biotech analysts here at Cowen. It's my pleasure to moderate a fireside chat with Enliven. We have with us Rick Fair, CFO, and Ben Hohl, sorry. Rick Fair, CEO, Ben Hohl, CFO. Guys, I'll kick it to you to begin, just a state of the company, question. What is the current state of Enliven? Biggest challenges, biggest strengths, and what will Enliven do to create shareholder value? Awesome. Thanks for having us. I appreciate it, Phil. Thanks to Cowen for including us here. State of the company is strong. I think that's the way you're supposed to kick off a State of the Union address, right? State of the company is strong. I joined Enliven in December, so it's been almost 3 months since I joined as CEO and company's in great shape. We're making great progress. You know, I think for this year, our focus is really about getting ELVN-001 launched into its first phase 3 study. We have really, really strong phase I data, which I'll talk about here today. Expect to meet with health authorities midyear to align on dose selection for our phase three study to align on a phase three study design and expect to get that study started before the end of the year. We're off to the races for our first approval, hopefully in second-line plus CML. I think you'll see a data update from our phase I study midyear as well. We submitted an abstract to EHA. Expect to present updated phase I results this June. Beyond that, it's really about building out our lifecycle plans for the asset. We have an interest in the front line. We think we have a very competitive molecule with a great efficacy, safety, tolerability, convenience profile. Think it could be competitive in the frontline setting. This year we'll spend time getting health authority input on what will be required to initiate a phase 3 study in front-line CML and begin to start generating some phase 1 data in front-line patient population to get a little bit of a snapshot of our safety and efficacy in those patients. Those are our kind of priorities, and our path to value is really about maximizing the value of Enliven-001 in CML broadly. Rick, you mentioned you just started as CEO. What attracted you to become the CEO of Enliven? I guess more broadly, what was the rationale for the change in the C-suite that recently happened? Yeah. I'll start with maybe the rationale for the change. For those of you who knew Sam Kintz, my predecessor, he was the founder of the company, a medicinal chemist by training, started the ELVN- 001 program and some other programs as well, really looking to differentiate on known biology with novel and differentiated chemistry and targeting markets of big opportunity. That's really panned out well in 001. As Sam was staring down his first phase 3 trial of his career, thought maybe this isn't really where I'm best suited, and also he has a really great passion for discovering new molecules and a passion for entrepreneurship. Really felt like it was the right time to hand off the company to somebody with more experience in late-stage development and commercialization. He engaged the board in a discussion on that midyear last year to say, "Hey, let's find a successor that has the right experiences for this and pass off the company to him or her." I was looking for opportunities after spending some time in solid tumor CAR- T cell land at Bellicum. We wrapped up that company in 2024, took some time off and was looking for a company with less scientific risk after banging my head against a solid tumor CAR T wall for a while. I was really looking to get back to my roots. I'm a commercial person by training, spent 20 years at J&J and Genentech, leading commercial organizations and developing late-stage molecules, specifically in cancer in the case of Genentech. Having launched a number of cancer medications globally, loving late-stage development and that process of bringing, maximizing the value of asset with the way you develop your drug and bringing it to patients, all the way through reimbursement and launch. I was looking for a company like Enliven, so we found each other. It worked out well and joined in December and so far so good. Enliven recently pre-presented updated data from 001. Can you remind us of the highlights of that data and maybe put them into context among the other CML agents? Yeah, sure. We put out a release in January ahead of the JP Morgan conference, sharing some updated results from our phase Ib. We had a phase 1 presentation at last year's EHA, and we had some new data from our phase Ib that we wanted to share. The key takeaways from that, we have a very heavily pretreated patient population in our phase 1 study. The rationale for this is our study started as a first-in-human study that required failure of all approved therapies, at a very low subtherapeutic dose. The patients that enrolled in our phase 1A in particular were very late line, patients, heavily pretreated. We know from all of the TKI experience that those patients are less likely to respond. Our phase Ib data set included more than half the patients in that study were 5th line and later patients, so very, very late line patients. We know that's a predictor of non-response. They are also patients more likely to have failed their last TKI due to lack of efficacy instead of tolerability, which is also a predictor of non-response. Lastly, about 1/3 of the patients in that study had prior ponatinib exposure. Ponatinib, given its safety liabilities, is generally reserved for patients who've failed other TKIs and are having a hard time getting their disease under control. All of those are markers of a very treatment-refractory population. You know, based on those markers and quantitating them, we have the most difficult phase I trial population ever in CML, including other agents that are being developed in parallel. Despite all that, we have really good efficacy results, and we wanted to share those in January. What we saw, we presented our data in two cohorts. An 80 milligram cohort that was fully mature data set and a less mature randomized cohort between 60 milligrams and 120 milligrams. What we saw was great efficacy. MMR achieve rates in the two groups between 38% and 53%. Cumulative MMR rates, I think between 47% and 69%. These are really excellent results given that heavily pretreated patient population. We didn't say anything about safety at that time because we really had no new safety findings from our EHA presentation last year. This drug's extremely well-tolerated. The safety, it's a very specific ATP- competitive TKI, so the safety events that you see are on target. We don't see any meaningful off-target toxicities. You know, things like arthralgia, thrombocytopenia, these are classic markers of BCR-ABL1 TKIs. You know, the safety results we reported last year are basically we haven't seen any differences in our patient population. We will present at EHA again this year. We'll give a fulsome update on the safety and efficacy profile, but it's very well-tolerated. We saw treat discontinuations due to AE reported at EHA last year of 4.4%. Very, very well-tolerated drug and those are the results that we have. We have a very competitive agent. We're highly confident that we are better tolerated than second-generation TKIs, as well-tolerated as asciminib, and in cross-trial comparisons in a treatment-refractory patient population, probably more effective than both. The 60/120 group was particularly striking in the MMR rates. A big improvement of what we saw before and even. Yeah. -different than the 80 milligram group. Yeah. Any theory as to why that data looks so much better? Absolutely. We presented that data for a very specific reason. For those of you who saw that release, you may have wondered why we grouped the dose cohorts the way we did. We weren't trying to make a point about dose, we were trying to make a point about data maturity. What we've seen, looking at patient-level data is we have no dose response, meaningful dose response in safety or efficacy between 60 and 121, 120 milligrams, and we didn't expect that. We basically have at 60 milligrams essentially, full target coverage, we didn't expect to see greater efficacy results as we dosed higher. The reason why we see a difference in those two cohorts is about data maturity. The way that achieved MMR by 24 weeks is calculated in a phase I study, basically means less mature data looks better. MMR or major molecular response is calculated in an ongoing phase I study by including anyone who's passed the landmark of 24 weeks and anyone who responded before the landmark of 24 weeks. If I've been on study 12 weeks and I have a response, I'm counted in the numerator and the denominator of that major molecular response rate calculation. If I haven't responded and I'm not out 24 weeks, I'm censored from the efficacy analysis entirely. Just by math, when you take an immature data cut with a lot of patients who are not yet efficacy evaluable, you see very high MMR rates. As those patients cross 24 weeks, you see MMR rates come down to its ultimate plateau. In the dataset we presented, 80 milligrams was fully mature, so all of those patients had crossed 24 weeks, had an MMR achievement rate of 38%. That's not going to change. Our 60 and 120 milligram cohort was had more recently enrolled, and of the 41 patients in that group, only 26 were efficacy evaluable. You know that the other patients aren't on study for 24 weeks and have not yet responded. We'd expect the 53% we saw there to trend down over time as those patients cross the 24-week marker. The reason we presented that was that our competitor Terns had presented data at ASH that was less mature than either of those two cohorts and had very, very high MMR achieve rates. Our point was simply to say you need to really understand how mature the data are before you interpret the number. It's not really about the number. The number only matters after everybody's crossed 24 weeks and you know what it really was. That's the regulatory endpoint and that landmark analysis only happens after all the patients are mature. You referenced in your opening comments about how heavily pretreated the patients were in this study. Can you go into a bit more detail about how heavily pretreated these patients were, perhaps against what we saw in the asciminib studies and what that could do to the MMR rates? Yeah. It's, it's really, really important. You know, the as I've taken to saying the two things that you need to know in interpreting an MMR in a phase I are who's in the study and how mature are the data. Those are really both important. In the phase Ib cohort, as I mentioned, more than half the patients were 5th line plus. Two-thirds of those patients had seen asciminib previously. A third had seen ponatinib. More than half had failed their prior TKI due to lack of efficacy versus tolerability. Those are all predictors of lower response rates. Those numbers are all higher proportions than were previously seen in the asciminib trials or that have been seen in other contemporary phase I studies in this neo. How would you position 001 in the competitive landscape against asciminib or the Terns' molecule? Where do you think it's gonna fit in? I think initially our study will be a second-line-plus study. We expect, by the time we come to market, asciminib will be well taken up in front and second-line, so that'll be the majority of their use. We would expect a lot of the patients in our study and ultimately in our commercial uptake to be patients who've been on asciminib and either couldn't tolerate it or lost efficacy to it potentially due to an allosteric- resistant mutation. I think we will do very well in the post-asciminib population in second and third line after they've been used in front and second line. I think what we hear from clinicians is it would be unlikely for them to use an allosteric after an allosteric's failed. We think we have an advantage in patients who've previously seen asciminib and are moving on to another drug. An ATP competitive agent there is not going to be susceptible to the same allosteric resistance mutations that an allosteric would. We think we would have an advantage there in our first launch in being taken up in patients who've previously seen asciminib. In the long run, or I guess maybe the medium run, maybe not long run, the competition in frontline will be about the best profile overall and, you know, treatment selection in this indication is not all about efficacy. It doesn't operate like a classic hematology oncology kind of indication. It's the totality of the profile, efficacy, tolerability, safety, convenience. You know, these patients are gonna be on these drugs for potentially decades, so do they have drug-drug interactions, food effects, things that will affect safety or convenience of the treatment? We think we have a very clean profile there. Asciminib has some liabilities in some of those areas. The Terns molecule looks, you know, competitive as well. I think it'll be profile dependent about how the first line shakes up, but we like our chances. We have a molecule that looks as well-tolerated and more effective than asciminib in a late line population. If that translates to the front line, we can do really well there. How would you counsel investors to analyze the data that we're gonna see at EHA from you as well as the competitors? What are the important efficacy measures that we should be paying attention to? Which ones do maybe investors emphasize too much that they shouldn't pay attention to, and what's important on the safety side? Well, I think, you know, major molecular response is an important endpoint because it's the regulatory approvable endpoint. You need to pay attention to that. Hopefully, what I've tried to communicate here today and you've taken away from this is don't just look at the number, but look at the patient population and the data maturity to really understand what that number says in trying to make any cross-trial comparisons or interpretation about the molecule. MMR is really important. Other endpoints of interest, deep molecular response is an increasingly interesting endpoint. you know, there are patients who can get into a prolonged deep molecular response who can then come off drug and do well and achieve treatment-free remission. That's really attractive. As the drugs get better, there are more and more patients that might be eligible for that, so that's interesting. You know, we hear from our clinicians in our study about patients in our study that they feel really well. That's a little hard to measure, but we certainly will explore that in our phase 3 study with some PRO instruments to try and get at what does the feeling really well mean. It's probably just a really well-tolerated drug that controls your disease well, but we'll try and quantitate that. That can be interesting, but I think the primary things to focus on are the, you know, efficacy as measured by MMR and safety and tolerability. Those are the key drivers of treatment selection in today's market. You mentioned alignment with the FDA this year on a second-line plus pivotal study. Can you talk a bit more about Enliven's expectations for the design of that trial and what else needs to be decided upon today or agreed to with the FDA? Our hope is to conduct a second-line plus study head-to-head versus physician's choice of first and second generation TKIs. Our logic again is that for with the adoption of asciminib into earlier lines of treatment, the choice the physician will have to make most is where do I go next? Their current choices are first and second generation TKIs, and we think we're the best ATP competitive agent. We're gonna show that in a head-to-head trial against the best available agent as determined by the physician. We do need to achieve health authority buy-in to that, and the questions are, is second line plus a patient population that's acceptable to them? asciminib, obviously their first trial was in 3rd-line plus. We think our drug is very well-tolerated and very effective and should be acceptable as a 2nd-line agent. The control arm, you know, we need to get agreement on that. I can't imagine a better trial than, you know, choosing against all available agents. That's a real-world study that answers the question that clinicians have. I think we're confident that that design will be acceptable to regulators. We have to go get that agreement. What are Enliven's thoughts about moving into the first line and doing a first line trial? Is that something that you're contemplating and could happen as a step after starting the second line plus study? For sure. We have an awesome looking molecule. It's very safe, very effective, well-tolerated. Again, very clean profile for long-term use, and we think patients in the front line should have access to it. For 2026, I think our goal is to really set the table for that study. I think one question is what do we need to show health authorities to be allowed to start a phase 3 trial in front-line CML? You know, these are patients that have essentially normal long-term survival and do no harm is really important to regulators, and we still have an experimental agent. They may ask us to generate a larger safety database, and they may want us to generate some phase 1 data in front-line patients to demonstrate safety and meaningful activity before we go there. This year will be about getting health authority input. We are initiating a phase 1 study in front line patients to get a little data there, and that will inform decisions there. Hopefully by the end of the year, we'll have clarity on what health authorities expect and can guide to a better, you know, plan and timeline around front line. Novartis Q4 call had some notable updates on Scemblix, including approximately $1.6 billion annual run rate at the Q4 rate-. Mm-hmm. As well as increasing share in the first line. What learnings does Enliven take from Scemblix's launch, how does that inform your commercialization strategy as well as the need in CML? You wanna take that? Yeah. I mean, I think it shows 2 things, that doctors really do want new drugs, and the CML market is huge. You know, I think. There are generics available, there are multiple drugs available, but I think, you know, what we continue to learn is that there are a lot of issues with the 1st and 2nd-gen drugs and, you know, new and better agents will get used throughout different lines of therapy in the market. I think it really does bode well for us, especially as we think about our mechanism, which is an ATP competitive drug, and so it's very complementary to a Scemblix. As we look to run that second-line plus pivotal trial and to fill in the gaps post Scemblix when a lot of docs don't exactly know how to treat patients coming off Scemblix right now. I'd add one thing to what Ben said, which is this issue of how products are taken up in CML. It's not like an oncology indication, it's more like a chronic disease indication. You know, I developed a lot of cancer drugs. You go head-to-head against best available standard of care and beat it on a survival endpoint, and you get used. asciminib is getting taken up in the frontline, not having demonstrated superior efficacy to second-generation TKIs in the frontline. It's getting taken up because it's effective in frontline patients, it's well-tolerated, it's better tolerated than second-generation agents, and it's capturing a massive business in frontline based on that. You know, I think one question we get that you may have wanted to ask, Phil, is, you know, are you thinking about doing a head-to-head study against asciminib? That's a long, expensive trial. We don't think we need to show it. We think we have a great profile of a drug. We think we'll show great efficacy and safety better than second-generation and first-generation TKIs, and we'll get taken up based on the totality of our profile. As we've talked to KOLs, they suggest that in the first line, there is somewhat of a movement towards curative therapies that give patients an option to stop if they seem to have eradicated the disease. How does that figure into your treatment or your development program? I think it's a great thing to aspire to and we're seeing it in real-world use. It's a little hard to show in a study because that's an incredibly long study. You know, the standards here are achieve a long-term 2- 3 year deep molecular response, withdraw treatment, and then, you know, 5 years later, you've shown treatment-free remission. That's an 8-year study by my math after you've enrolled it, that's a lot. I think it's looking at deep molecular response in the frontline is really useful to see what proportion of patients have a shot to achieve treatment-free remission, that's important. The other thing we're thinking about is combining an allosteric with an active site TKI. This is something sorry, Novartis tried to do with asciminib and combining with first and second-generation TKIs. They were really never able to achieve the promise of that because of the safety profiles of those TKIs and, you know, a very clean, highly specific active site or ATP competitive agent like ours combined with an allosteric like theirs could lead to more and more patients getting into DMR and potentially getting off treatment down the road. We'd love to explore that in an early data set and are thinking about the best way to and the right timing for that. That would be another way to get there and potentially get more patients there. How does Enliven size the market opportunity for 001 and what's assumed in that in terms of its place in the treatment paradigm? Yes, I think by the U.S. CML market opportunity, I think we generally view it as roughly a $9 billion opportunity. Because patients with CML no longer generally die from their CML, the market patient population continues to grow over time. The incidence rate is roughly 10,000 in the U.S., so that patient population is actually growing pretty quickly. As I think about the different lines of therapy and our opportunity, roughly 50% of the patients are in the frontline and 50% are in the second-line plus. You know, after our first pivotal trial, we'd likely have access to, you know, the second-line plus 50% of the market. You know, as I think about, again, thinking about the Scemblix launch, you know, they initially launched in the third line plus, and most people believe that with that indication alone, they'd already be doing $1 billion in sales right now. You know, as you think about all those opportunities, it really just shows you that the opportunity is very large here. Burke, maybe, in the last few minutes, a couple other questions on other parts of the organization. 002, you announced you're gonna seek strategic alternatives for that. What was the rationale behind that decision, and any update on the potential partners? Yeah. As we think about that program, you know, it's all in the context of ELVN-001. I think it's really the most important thing is we truly believe that we have a huge opportunity and ELVN-001 is a winner. As we thought about, you know, de-developing ELVN-002, the drug is doing what we expected it to do. As we kind of look at the larger market opportunities in the HER2 positive space, those are combination therapies, and as the treatment paradigm continues to change within HER2 moving up, it really became difficult to generate proof of concept data early. So we were gonna have to commit to running some later trials that would, you know, roughly cost $200 million-$300 million. As we think about that in the context of 001, that became hard to stomach as a small biotech company. We decided to look for potential partners for that program. You've disclosed that Enliven is working on other preclinical programs, although none have been specifically defined. Any update on the preclinical efforts? Yeah. Sam, after finding me and stepping down as CEO has assumed the role of head of pipeline for us. We have a very focused pipeline effort currently. Our primary focus is on a Graves' disease program. We haven't disclosed a target, but it's a potentially transformative opportunity for us if we can get there. It's been a tough area to drug and Sam and Joe Lyssikatos, our CSO are working on it. We aren't saying much about it until we really feel confident we can get a development candidate, we can get into the clinic. Should we do that, we'll talk about it a lot 'cause it's potentially, again, transformative for Enliven, but if we get there... That's our primary focus in the pipeline today. We'll talk more about pipeline potentially in the future, you know, as we, get our phase 3 trial up and launched and turn our attention to the future. In terms of strategy for ELVN-001, are you committed to taking that to commercialization worldwide yourself? Do you think that there's an opportunity to partner it for, particularly development and commercialization overseas? Yeah. I think one of the goals in finding a CEO with my profile is to be able to do this ourselves. I can't join the company. My mindset is I'm here to build a great company for the long run. Part of that is developing this drug and launching this drug. I know the organization is committed to that. We're looking at it as a long-term effort. You know, I'm also a realist. I recognize that this is a very large drug candidate opportunity. Pharmaceutical companies may be interested in it. If they are interested in it, you know, we would, for the right transaction, right proposal, right partner, be open to that. You know, big pharma resources put against an opportunity like this can be useful, but that. You know, I didn't come in the company to turn around and sell it. I'll build the company until somebody tells me it's time to stop. For 2026, you mentioned a couple milestones in terms of EHA and the FDA alignment. Can you lay out the catalyst calendar for us? When could we see additional data from 001, and when do you expect to have regulatory clarity? Yeah. We've submitted an abstract for EHA, that just happened last week, we expect to present data in June on an update on our phase 1B, and we'll be in parallel with that data presentation, having interactions with health authorities that we probably can comment on in the third quarter, and expect to launch the study by year-end. Perfect. In terms of finances, can you remind us of your cash balance and what runway that affords? Yeah. We have runway into the first half of 2029, roughly $460 million of cash. That should take us well past top-line pivotal data for that second ELVN-001 trial that we're talking about. Great. Those are all the questions I have, or I had. Anything else I should have asked you that would be important for investors to know? When you're looking at MMR rates in phase 1 trials, look at the patient population enrolled and the maturity of the data before you decide how effective a drug is. I think we're done. Thank you for an interesting session. Appreciate it, Phil. Thank you. Thank you.