Eli Lilly and Co at TD Cowen Healthcare Conference Transcript

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

Question: Steve Scala - TD Cowen - Analyst : 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. 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. 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 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? 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 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. 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 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. 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 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. 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

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. They've all prolonged progression-free

Question: Steve Scala - TD Cowen - Analyst : Okay. Questions about Verzenio before we move on to the SERD class? Yes. Unidentified Participant So last time, I think you were pretty adamant that you don't think the overlapping population with Kisqali will change much for this 15% that you've cited so far. We had the (inaudible) here earlier, they're pretty adamant that they're going to go after that significant growth there. So why do you think they're wrong? How are you going to hold them off? Because they only pointed towards cardiac risk factors as a reason for choosing Verzenio. Is there anything else we're missing there? Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology All I can do is reflect what physicians tell me and us when we interact with them, and it seems as though, at least in this treatment setting, they're interested in being more splitters than lumpers, and we'll see whether that changes or not. But I think the treatment regimen length is a big thing for patients and providers and especially if they view the efficacy as broadly similar. They're actually -- there is some false equivalence there even being applied, but okay, like we do have a more mature data package than they do and we always will because of when it read out. There are some physicians who see that for what it is, and there's others who look at the two efficacy quotients and say, they're sort of very similar. But I think Verzenio has known GI tolerability issues. We've tried to manage those with dose reductions, and some physicians use different kinds of dose titration schedules to manage that. Okay, I think Kisqali has cardiac monitoring and I think there's a lot of physicians in the real world who've had rare but real liver enzyme issues that force patients off the drug and cause real problems. I think for the physicians who have that once, they sort of don't want to do it again. And you saw that even in the context of the NATALEE study itself. So again I don't want to make too forward-looking predictions about how that 15% will evolve because I don't know, but what physicians tell me today is that these are sort of two different populations that they're thinking about. 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

Question: Steve Scala - TD Cowen - Analyst : Speaking about EMBER 4, do the results of EMBER 3 and the fact that it didn't reach significance in the overall population concern you at all about the probability success of EMBER 4? Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology Not really actually. In fact, sort of the opposite, and this goes back to what I was just saying a second ago. Like, if you look at EMBER 3, remember the comparator in that study, and this is really important, the comparator was Fulvestrant, another SERD. The comparator in EMBER 4 are aromatase inhibitors, not SERD. And so in the context of EMBER 3, what we saw is that in the ESR1 wild-type population, the comparison of Imlunestrant versus Fulvestrant has a progression-free survival hazard ratio of about 1. They look very very similar. 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 You might say like, well, Jake, isn't that a problem? Well, in the context of the adjuvant design, no, because there we're comparing to an aromatase inhibitor. And if historical studies are right and Fulvestrant beats an aromatase inhibitor and Imlunestrant looks similar to Fulvestrant, then Imlunestrant ought to be an aromatase inhibitor too. So if anything, the randomized data we got from EMBER 3 furthered my conviction in the likelihood of EMBER 4 working.

Question: Steve Scala - TD Cowen - Analyst : We're down to only a minute left. I thought one of the most interesting points at dinner yesterday evening was your identification of things that could be game changers to Lilly. And Lilly's already pretty much a game changer, right? But could put the company on an even greater trajectory, and you noted three things, and what jogged my memory is one of them was EMBER-4, which we've already discussed, the other two were LP(a) and Alzheimer's disease prevention. So maybe you could just spend, in our last few seconds, just to spend a moment as to why you view those -- or Lilly views those as game changing events. Jacob Van Naarden - Eli Lilly and Co - Executive Vice President, Chief Executive Officer - Loxo Oncology at Lilly, President - Lilly Oncology Yeah. So as it relates to Alzheimer's disease prevention, I think we know Alzheimer's disease remains a public health epidemic, a leading cause of death in this country, a huge cause of morbidity to families that have a loved one with this disease. And yes, the launch of this, of Kisunla as an example, in symptomatic disease has gone somewhat moderately. 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 as we transition the medicine to preventing the occurrence of symptoms of this disease, with a blood test as the sort of entry way to getting the medicine, I think we'll be having a very different conversation with patients. I think that looks very different than slowing the course of the disease that is otherwise progressing. And by the way, all of the evidence we have from both the Donanemab studies as well as even the Lecanemab studies would suggest that the earlier you go, admittedly in patients with symptoms, the larger the effect size you observe. Of course, patients who have amyloid pathology in the brain but no observable symptoms, which is the population in TRAILBLAZER 3, is an even earlier version of that same biological idea. So that gives us a lot of conviction that this study will have a big effect size. And of course, in the context of preventing a disease, we also need to observe a safety profile that's amenable to a positive risk benefit quotient. That has yet to be born out, so we actually -- we need the study to read out to prove that to us. Patients with pre-clinical, is what the term is, pre-clinical Alzheimer's disease, pre-symptomatic, tend to have lower amyloid burden in the brain. We know amyloid burden does correlate with the onset of ARIA-E and these amyloid-related safety events with the amyloid lowering agents. And so we're hopeful that patients with lower amyloid burdens in the brain will experience meaningfully less safety issues with the medicine. But if we can deliver a medicine that can prevent the occurrence of this disease, I think that'll be a big game changer for public health and Lilly as a result -- as a follow through to that. And then LP(a) is, in many ways, I think it's like the highest profile unaddressed for underlying cause of excess morbidity in cardiac disease and there's a lot of genetic evidence to suggest that lowering this will have an impact on patients' cardiac outcomes. And of course cardiac disease remains one of the biggest killers globally, including in the United States. Still a lot of unknowns here, we don't know. Like, how low do you need to go, how long do you need to keep it low? What will the effect size be upon the intervention? So today, the evidence around LP(a) is a little bit more correlation than causation because none of the actual drug intervention studies have read out yet, but I think that the genetic risk combined with the corelative studies we've seen, I think, are about as tight as one of these ideas gets, and now it's just a matter of seeing whether or not that translates into a big effect size in the context of these outcome studies. And excited about the work we're doing in both primary and secondary prevention there.