Enliven Therapeutics, Inc. (ELVN) Earnings Call Transcript & Summary

And how should investors think about the probability, the treatment duration and persistence ultimately become more important commercial lives than early MMR.

I mean I think in the class, that's been the case, right? These are very long duration therapy. So these patients are diagnosed typically in their mid-50s and are on treatment for life. And a decent version, say, 50% to 60% stay on the first drug they ever take. So I think the treatment duration is the commercial driver here more than share. Obviously, you have to get share to get treatment duration. But yes, I think we expect that's a major driver and it is a feature of this drug class that you tend to see -- if you respond, you tend to see durable responses.

And that's why we talked 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.

Yes.many 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. So I just don't feel good on this medication. So that's why it is a -- it's a both, not either question.

Sure, sure. I guess with the rise of it, just a general question, the rise of China originated innovation, sort of just your line of sight on what becoming 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.

Yes, sure. So I'd say, to answer your question on the CML front, the only assets that we've seen -- are aware of that are coming out of China are additional allosteric TKIs like semi -- and we -- so far, we've seen relatively limited differentiation there. And so 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 it doesn't mean somebody won't take a stab at a me-too very highly specific ATP competitive agent like ours. But to date, not good, we haven't seen that. As far as thinking about China broadly, -- we are -- our pipeline today consists of ENLIVEN 001, our CML assets program in engraves disease that we hope will advance to the clinic sometime in 2027 and beyond that, we've really worked up our discovery effort. So the building of a pipeline and Enliven beyond those 2 programs will likely be about business development. And obviously, China represents the hottest area for that and would be likely the source of a few pipeline for us important to us.

So my next question, I think you've just answered it, but I'll ask it anyway. So I guess, can the precision design capabilities that produce 1 systematically repeated or those successes largely program specific. But I think the answer to the question is that BD rather than.

Yes. I mean, I think the team that started in live and 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. And they worked on a number of programs, 2 of them have made it to the clinic to date. -- in 001 in CML 002 is a HER2 program that we're no longer pursuing further in the clinic. And I've mentioned our grades disease program behind it. There were other programs that we developed that we always have the option to taking forward, but we think these are the best and the most deserving clinical development. We're not doing new discovery work in enliven to expand that pipeline further.

And how would you balance and pursue highly validated targets. We're pursuing novel biology that may offer greater upside but substantially high risk.

Yes. The premise of the company has been to really focus on known biology. I would say the programs that if the clinic to date, obviously, are not just known biology, but targets that are well validated with approved therapies. Our greatest 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 a new biology. That's not in our DNA.

And when you think, I guess, sort of looking forward to live 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 with former.

Yes. I mean I think our current pipeline is a little interesting in that it's got 1 program in hem/onc and 1 in an autoimmune thyroid condition. So I think that 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 1 roof. So we always have the option to monetize 1 or both of the assets in different ways. And then depending on the choices we make there, building 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 1, maybe for the audience, just sort of size out what you think the market opportunity here is in the U.S. and then maybe extend beyond potential ex U.S. U.S. plants.

Sure. So 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 suitable it's about half of a frontline opportunity and half of a second line plus opportunity. And then 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 incidents and extending survival.

Sure. I guess on capital allocation and the balance sheet, with a strong cash position, in what specific milestones would justify increasing investment rather than preserving capital?

I mean as we think we have $895 million of cash that gets us into 2030. I think the main thing, as we thought about the rates that we did post the EHA this year, as we really want to get through the top line pivotal data for the second-line positive trial. So I think we want to maintain that flexibility because that has a huge catalyst for our company. and 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 2 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. And maybe for investors, just map out the catalyst path that you see for the next 6, 12 and 24 months.

Sure. So Phase III study start this year additional Phase II data from our enable trial -- we'll be initiating a Phase I trial in combination with an allosteric inhibitor to demonstrate potential ability to drive deeper responses for more patients. We'll initiate that trial in '27. So we'd expect data to start to read out from that -- we'll also be initiating a Phase II front-line study in CML, single-arm study with a cooperative group that we anticipated starting in 2027 and should start to read out data and then, of course, potential IND clearance and Phase I data generation from our Graves' disease program, which I can't give a specific guidance to on time line, but I think it's reasonable to assume we could get that into the clinic in the first half of next year, if successful. And if we do that, then data readouts probably follow within the 6- to 12-month time frame from that.

Sure. We've got a couple of general questions, if you can indulge me here. First 1 is on Aon. So are you implementing AI across your business? And can you point to any specific examples where it's changed the cost or decision or even a POS?

Yes. Yes. I think we're implementing AI in every way that we can figure out how to implement it. It's embedded in all aspects of our business. I think the primary advantages are, I think, accelerating our clinical and regulatory work, getting study start-up, getting regulatory documents generated and those sorts of things are low-hanging fruit that we've 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 and the way that we are generating and looking at our clinical data and so forth. So specific wins, it's mostly about time lines and efficiently currently, but I can't think of an example where I think it's enhanced our probability of success yet, but again, given what I said about discovery, we're not doing a lot of AI applied travel science because we're really focused on developing the programs that we've already established.

And last of the general questions, but we've been asking all our companies this just sort of a snap survey. But on the -- I guess, sort of on the regulatory front, sort of where you're most focused. I mean it sounds like FDA but we've got questions like MF and tariffs, et cetera, but it sounds.

Yes, FDA and other global health authorities. -- getting our Phase III study start 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 sexing 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.

Sure. And I don't know if it's too early to ask, but I'll ask but just your assumptions around pricing. too early to ask Yes. I won't be doing much of if I didn't Look, I think we're 5 minutes early, but I've come to the end of my questions, but what didn't I ask that I should have or what message would you like to leave investors with I mean 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 derisked 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. And those are hard things to find. So that's interesting for investors, GIC and others. And we have a potential transformative agent in our pipeline. Grave's disease is in 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. And 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 changed the profile of enliven considerably to a multi-asset and multi-therapeutic area.

Wonderful. Well, we might park the conversation there. But thank you, Rick. Thank you, Ben.

Thank you -- appreciate it, John. Thank you.