Eli Lilly and Co at TD Cowen Healthcare Conference Summary

The following is excerpted from the question-and-answer section of the transcript.

Question: Steve Scala - TD Cowen - Analyst : <_ALACRA_META_ABSTRACT>So while we're going to spend 95% of the time in the session on oncology, I'll start out with a more broad question, and that is, Jake, what are the key upcoming pipeline catalysts for Lilly overall as an entity? Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology Yeah, so I think, in the late phase portfolio on the R&D side, there's probably a handful of things I would highlight for the remainder of this calendar year. I'm sure most people are waiting on the readouts of the Orforglipron program. This is the oral small molecule GLP-1 nonpeptide agonist that we initiated a pretty broad program around. And we can talk about the studies that are reading out this year. The first study will be in Type 2 diabetes. The second study will be in obesity. I think there's more coming after that. Those will be really important readouts, I think, for this medicine and for this class, especially for an oral small molecule that we can manufacture at scale. I'll come back to maybe that medicine in a second as I maybe run through some of the other catalysts and we can then talk about Orforglipron a little bit more. Just sticking with the chronic weight management portfolio, we'll also get the first readout from the Retatrutide program. This is the triple-acting injectable incretin. The first study there is in patients who are overweight and have osteoarthritis of the knees. So in that study, we'll be looking, of course at changes in weight, but also pain scores associated with the osteoarthritis. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 04, 2025 / 6:50PM, LLY.N - Eli Lilly and Co at TD Cowen Healthcare Conference I think at the most recent earnings call was the first time we talked about that study actually reading out this calendar year. So that's a medicine that we think can offer like a real step change actually in weight loss and outcomes for, in all likelihood, higher BMI patients who can't get to goal on medicines like Tirzepatide. This is a medicine that we hope will allow them to get to goal with a higher frequency. So there's a big Phase III portfolio there too and that's the first study to read out. And then on the oncology side, I'll just highlight, this is a big year for the Jaypirca pirtobrutinib program. This is the BTK inhibitor of ours that's on the market today and a fairly narrow indication and there are five randomized studies that we started for this medicine, but only one of them has yet read out. At least two others will read out this year. One is against chemo immunotherapy and newly diagnosed CLL patients. The other is a head-to-head study against a Pirtobrutinib in CLL. Both pretty important studies for evidence generation and hopefully label expansion of that medicine over time. It's going to be an exciting year on the late phase side. And of course on the early phase portfolio we've got a lot going on across our therapeutic areas and the hope is, by the end of the year, we know a lot more about what those medicines are and can accelerate their development, particularly in oncology where we put a lot of medicines into the clinic over the course of the past year and expect to do so this year too. So maybe I'll pause there. Do you want to talk a little bit more about Orforglipron, just given the focus on that medicine?

Question: Steve Scala - TD Cowen - Analyst : Okay. Questions from the audience on Orforglipron or any of the three key events this year? Len? Unidentified Participant I was wondering, as I can see the GLP-1s over the next five years, my concern isn't about the arguments that some have whether the weight loss was 18% or 25%. The upper end may only be for a small percent of patients, but I'm looking at the orals, especially yours, perhaps being used for some patients as maintenance therapy once they've lost the weight that they want to lose on the injectable. You see that as being a potential significant component because you don't need to lose more weight, you just want to maintain it. Or an oral drug people who either want to take an oral, they don't want to take injections, or for economic considerations it might be less expensive.

Question: Steve Scala - TD Cowen - Analyst : Let me just follow up on something you said earlier. So when we were talking about safety, you said the GI's side effects are unlikely to be of a surprising nature, and that's very understandable, but I think investors might be worried more about the rate of those GI's side effects as opposed to the side effects themselves. So based on related studies, what would you say would be a reasonable or a likely nausea rate or other GI safety issue rate of AEs? Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology That's a good one. I don't know if I would guide to like a specific number because that's even sort of more imprecise, so to speak, than talking about weight loss percentages, but I do think that we have commercially successful injectable incretins like semaglutide and Tirzepatide that have different rates of adverse events. And yet these are, in general, pretty well tolerated medicines that patients really like. So I think that if the medicine ultimately delivers on a semaglutide-like profile, I think we've said that in the context of both safety and efficacy, at least as it relates to the GI side effects that are most talked about. And remember, the titration schedule that we ultimately deployed in the Phase III is different than what we used in Phase II. We learned from that to try and ameliorate some of the side effects that we saw in phase II. We've had a lot of experience, of course, over time with various titration schedules. I think, if you rewind the clock on like the Tirzepatide experience, I think when we modified that titration schedule going into Phase III, there was a lot of talk of like, wow, you guys are exploring so many different doses and it's such a long titration. Are you sure patients are going to want to do this? Like, isn't there a simpler way? I think that turned out to be the right course and ultimately patients and physicians are fine with it, and I do think we've mitigated some of the GI side effects that we might have otherwise seen. So we've done a very similar thing with the orfor program and we'll see how that plays out, but I feel reasonably optimistic about it.

Question: Steve Scala - TD Cowen - Analyst : Other questions? Okay, let's dig into oncology and let's start out with the drug that you mentioned, Jake, and that's, Jaypirca. So you mentioned that there are several readouts coming in 2025. Which of them is the most important relative to ultimately building and establishing this brand even further? Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology I think that this is an interesting medicine in the sense that it's entering into a relatively mature space. There are three covalent BTK inhibitors, largely competing for new patient starts and newly diagnosed CLL. Our medicine works when those medicines stop working, and it works for a pretty prolonged period of time and it's because the binding mechanism of the drug is completely different. And so our initial focus with this medicine for as long as we've been developing it was really in that sort of second line and beyond treatment setting. I think we can deliver a lot of value for patients and for the business by utilization of the drug there. And we're not yet there even today. Even today, we have a label that's much more confined to patients who've not just been on a covalent BTK inhibitor, but also venetoclax. That's a pretty niche indication. Today the NCCN guidelines actually recommend the drug for a broader population, and so the guidelines are a little bit ahead of the label as of right now. That's not that uncommon in oncology. So I mentioned that to say that we're all on a sort of step-wise journey here. And there are some physicians that want to use the drug in newly diagnosed patients, and there's some physicians who want to use the drug in second line, there's some that want to wait and use it in third line. Our job is to generate all the data to get all of these indications on the label so that physicians can use it however they want to, and I think if we fast forward in five years, my guess is that you're going to see like a lot of different treatment patterns as to where this medicine is used, but that -- like most, if not all, patients with CLL at some point see this drug in the course of their journey. And so to answer your question more pointedly, it's sort of the sum of them all rather than any given one of them that like I'm most focused on because I just want to get to the point where we have all the labeled indications and the entire pivotal program has read out, and then we can walk into the physicians' offices or I can meet with physicians at medical meetings and sort of say, okay, like which of these regimens is most interesting for your patient population? Do you want to treat with monotherapy Jaypirca in the first line? Do you want to treat with a combination of two years' time limited Jaypirca plus venetoclax and Rituxan in the second line? Are you interested in Jaypirca plus venetoclax for a year in the first line? That's a study we're running with the German CLL cooperative group. So we're just trying to cover all of our bases of regimen and line of therapy.

Question: Steve Scala - TD Cowen - Analyst : Okay. And do you see the BTK degraders as meaningful competitive threats to Jaypirca? Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology Not yet. I think those medicines look pretty good based on their Phase I data sets. They actually remind me a lot of the Phase I data set that we had for pirtobrutinib about five years ago. And they have an efficacy quotient in patients who've relapsed on pirtobrutinib. That's good if it's an important option for those patients after pirto. We don't have one of those medicines, and I think the companies that do have to figure out sort of how to make them more broadly relevant, if at all. When I talked to physicians about that class, I think at least today, they see them as post-Jaypirca medicines.

Question: Steve Scala - TD Cowen - Analyst : Okay. What are the pros and cons of initiating an early breast cancer trial in the N0 and the N1 patients? Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology You're talking the population that NATALEE studied that's not in monarchE, like for Verzenio right now?

Question: Steve Scala - TD Cowen - Analyst : Okay, I do want to get to Imlunestrant, but let me ask one more on Verzenio, and that is that -- and I've asked you this question in the past about these novel CDKs like the Pfizer CDK-4. And in the past when I've asked you that, you've responded, well, Verzenio is the most selective of the 4/6 inhibitors, 4/4 already. So the advantage of a pure 4 is not that great. Is there any change in your view in that regard? Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology Not particularly. Again, I think actually like the CDK4 Phase I data sets that I've seen are compelling. They look pretty good. The problem is that like, it's not sort of 2014 again. Now the CDK4/6 class exists. Some of these drugs have prolonged overall survival. REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 04, 2025 / 6:50PM, LLY.N - Eli Lilly and Co at TD Cowen Healthcare Conference They've all prolonged progression-free survival. In an oncology, you have to run a head-to-head study and win on efficacy with a compelling hazard ratio. And that's hard when the sort of only modification you've made is minor. And so I think like to me, that's why we haven't entered this space because I think winning a study like that is pretty difficult.

Question: Steve Scala - TD Cowen - Analyst : So let's move to the SERDs. In what ways is Imlunestrant different than other SERDs in development? Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology So I think that there's the medicines themselves and then there's how the medicines are developed. On the medicines themselves, there are I think differences in particular on the safety side that we've seen over time. There are certain SERDs in development that REFINITIV STREETEVENTS | www.refinitiv.com | Contact Us consent of Refinitiv. 'Refinitiv' and the Refinitiv logo are registered trademarks of Refinitiv and its affiliated companies. MARCH 04, 2025 / 6:50PM, LLY.N - Eli Lilly and Co at TD Cowen Healthcare Conference have either ophthalmic toxicities, cardiac toxicities, changes in lipid levels, these types of things which by the way, the field doesn't even understand why any of these things even occur. But Imlunestrant doesn't seem to have any of these issues. And I know we don't tend to talk about sort of tolerability as sort of a main driver of oncology programs, but in this context, when -- like the main reason this entire class was invented is to change outcomes for patients in the adjuvant setting. Patients in the adjuvant setting take endocrine therapy for 5 to 10 years. It's a pretty long time. And if the medicine isn't tolerable, then they're not going to be able to stay on it. If they're not going to be able to stay on it, they can't get the efficacy. So we've always been very focused on the tolerability profile of our medicine. And it was one of the bigger learnings actually from the Phase III EMBER 3 study that read out last year was just seeing the tolerability profile of the agent in a sort of rigorous Phase III study. We had Phase I data many years ago, but you always look to a Phase III for sort of a more rigorous determination. That was a big sigh of relief. In many ways, it sort of surprised us on the upside as to how well tolerated the agent was in that setting. And then on the development side, we've developed our medicine in the metastatic setting in combination with CDK 4/6 Verzenio. I think that led to a pretty differentiated set of outcomes that have excited clinicians now admittedly in this in second line breast cancer. And then, our adjuvant program is differentiated on the basis of both design and timeline. We're running an extended endocrine switch study, so this is in the adjuvant setting after the CDK-4/6 period. We are -- patients that enter the study get randomized to switch from their aromatase inhibitor backbone to Imlunestrant or stay on the aromatase inhibitor. And so in a way it's sort of a pure SERD versus AI comparison. And we think we know from historical studies that in a SERD versus AI comparison without CDK-4/6 in the backbone, the SERD wins, and so that's the basis of that experiment that we're running with the EMBER 4 study. Pretty big swing if that study hits, that'll be a very, very important new medicine for us. And in the meantime, we hope to be launching it in metastatic disease later this year.

Question: Steve Scala - TD Cowen - Analyst : Okay. Unidentified Participant (inaudible) you referencing the outcome data, is there anything else that shows efficacy of (inaudible) Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology That is the main body of evidence in fairness, and we only have a handful of these experiments that have been run, right? You have FALCON without CDK4/6, you have PARSIFAL with CDK4/6. I think many of us in the field have made our judgments, rightly or wrongly, on the basis of those two seminal experiments. Unidentified Participant So I guess how does PARSIFAL study (technical difficulty) Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology PARSIFAL was hugely impactful into how we were thinking about the development program. You you'll note that, where I think we're the only company with a novel SERD that chose not to run a first-line study because there you have to run concurrent CDK4/6 and PARSIFAL would suggest that that's a study that won't work. Obviously, we'll see later this year, I think, whether we were right or wrong because some of the competitors studies will read out and we'll find out whether or not that was the right conclusion to draw. It also impacted our development thinking for the adjuvant setting because, as I mentioned earlier, EMBER-4 isn't running concurrent with CDK4/6. It's actually running after the CDK4/6 period. We did that very deliberately in part because of PARSIFAL.