Enliven Therapeutics, Inc. Common Stock Morgan Stanley 24th Annual Global Healthcare Conference

Appreciate it. Yeah. Thanks for having us.

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.

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.

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.

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.