On Tuesday, March 4, 2025, Eli Lilly and Company (NYSE: LLY) participated in the TD Cowen 45th Annual Healthcare Conference. The discussion highlighted both the promising advancements in Eli Lilly’s pipeline and the challenges faced in a competitive market. Key topics included developments in diabetes, obesity, and oncology treatments, alongside strategic insights into future growth areas.
Key Takeaways
- Eli Lilly is advancing late-phase pipeline products, notably Orforglipron and Retatrutide, with significant market potential.
- The oncology portfolio is expanding, with Japerka aiming for label expansion in CLL treatment.
- Verzenio maintains its position in the high-risk population despite competition.
- Future focuses include Alzheimer’s prevention and addressing cardiac disease through Lp(a) reduction.
- Clinical trials are being tailored to improve efficacy and manage side effects.
Financial Results
- Orforglipron, an oral GLP-1 agonist, is expected to demonstrate efficacy similar to semaglutide in Phase 3 trials.
- Anticipated weight loss in trials includes 5% to 7% in diabetes and up to 15% in chronic weight management.
- Verzenio remains competitive in high-risk populations, though Kaskali is gaining traction in non-overlapping areas.
Operational Updates
- Clinical trials for Orforglipron are underway, focusing on transitioning patients from injectable to oral therapies.
- Japerka is undergoing five randomized studies, with key results expected in 2025, including a head-to-head study against ibrutinib.
- Verzenio continues as a standard care treatment, with patient regimen length being a crucial factor.
Future Outlook
- Orforglipron is positioned as a maintenance therapy, with efforts to ensure broad access to weight management solutions.
- Lilly is generating data to support Japerka’s use across various lines of CLL therapy.
- Alzheimer’s disease prevention is a priority, with a blood test for early detection in development.
- Lilly is pursuing strategies to address Lp(a) for cardiac disease, pending outcome studies.
Q&A Highlights
- GI side effects of Orforglipron are deemed manageable, with modified titration schedules to reduce issues.
- Japerka is not immediately threatened by BTK degraders, which may serve as post-treatment options.
- Verzenio and ribociclib present different tolerability profiles, influencing physician treatment choices.
In conclusion, Eli Lilly’s strategic efforts at the conference underscore its commitment to innovation and growth across multiple therapeutic areas. Readers are invited to refer to the full transcript for a comprehensive understanding.
Full transcript - TD Cowen 45th Annual Healthcare Conference:
Steve, Host, T. E. Cowan: Well, good afternoon, and welcome once again to T. E. Cowan’s forty fifth Annual Healthcare Conference. We’re delighted to have with us again this year Eli Lilly. Joining us from the company is Jake VanArden, who is President of Lilly Oncology.
So thank you so much, Jake, for being with us.
Jake VanArden, President, Lilly Oncology: Steve, thanks for having me.
Steve, Host, T. E. Cowan: Me. So, while we’re gonna spend 95% of the time in this session on oncology, I’ll start out with a more broad question. And that is, Jake, what what are the key upcoming pipeline catalysts for Lilly overall as an entity?
Jake VanArden, President, Lilly Oncology: Yeah. So I think, you know, in the late phase portfolio on the r and 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 Orford Lipron program. This is the small molecule oral small molecule, GLP-one non peptide 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 two diabetes. The second study will be in obesity. I think those are and there’s more coming after that. Those will be really important readouts, I think, for this medicine and for this class, especially, you know, for an oral small molecule that we can manufacture at scale. We’ve I’ll come back to maybe that that medicine in a second as I maybe run through some of the other catalysts and we can then talk about before I go from a little bit more.
Just sticking with the chronic weight management portfolio will also get the first readout from the Retrotide program. This is the triple acting injectable incretin. The first study there is in patients who are overweight and have osteoarthritis of the knee. So, you know, 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, you know, this calendar year.
So, you know, that’s a medicine that we think can offer like a a real step change actually in weight loss and outcomes for, you know, likelihood higher BMI patients who can’t get to goal on, medicines like tirzepatide. You know, this is a medicine that, you know, we hope will allow them to get to goal, with a higher frequency. So, you know, there’s a big phase three 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 j perka protobrutinib program. This is the PTK inhibitor of ours that’s on the market today in a fairly narrow indication.
And, you know, 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 in newly diagnosed CLL patients. The other is a head to head study against ibrutinib in CLL. Both pretty important studies for evidence generation and hopefully label expansion of that medicine over time.
So, it’s, gonna be exciting year on the late phase side. And, of course, on the early phase portfolio, we’ve a lot going on across our therapeutic areas. And the 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, you know, 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. And if do you wanna talk a little bit more about orforglipron just given the focus on that medicine?
Steve, Host, T. E. Cowan: Sure. There’s tremendous focus among investors on that medicine. And so we kind of look at it in two buckets, efficacy and safety, and there seems to be less concerned about efficacy that that’s pretty much not going to be an issue, but safety is a bit more of a concern. So why should we not be concerned about the safety profile that comes out of these trials?
Unidentified speaker: Yes. So I think maybe just
Jake VanArden, President, Lilly Oncology: take a step back and we can talk about like what do we think this medicine is based on its the data we’ve generated in phase two. I think we’ve been pretty consistent over time that, you know, this is a single acting oral incretin, and the profile that we observed in the phase two looks very semaglutide like. That that’s what we expect out of these studies. And so I think as you think about what to expect, at least in these first two readouts on the efficacy side, both for A1C as well as weight reduction, like, you gotta look at the sort of right comparable studies from the semaglutide program. The first diabetes study to read out is a forty week endpoint.
Of course, the time in which you look matters a lot in these studies. And so in that and and we know that patients with underlying diabetes experience less weight loss than those without diabetes when they take incretin medicine. So, you know, that’s a study where the prior semaglutide studies we suggest call it a 5% to 7% body weight loss at that forty week time point. And then in the chronic weight management study that’ll read out a few months after that, that’s a seventy two week endpoint. And again, in patients without diabetes, you can look at the comparable semaglutide studies there.
You can also even look at five milligrams of tirzepatide and SIRMOUNT one there. Those are settings where the comparable studies would suggest roughly a 15% weight loss at that moment in time. Of course, these studies remain blinded. I don’t I don’t have information you don’t have. But based on what we learned in phase two and the precedent studies for Sema and tirzepatide, that’s what we expect.
On the safety side, you know, I think the the the sort of common side effects that patients experience on incretins, notably the GI side effects, I think those, I think, are we are unlikely to be surprised by when we unwind these data. What I think is is the risk I think that’s yet to be discharged on safety is just uncommon idiosyncratic things that happen when novel small molecules are put into large populations. And I don’t say that because, again, I know anything. Like, we remain blinded to these data and to the extent that there are uncommon things that occur even on a blinded basis, we wouldn’t actually know about that. So it’s sort of an unknowable component of any new small molecule administered to large populations that until we discharge the risk, we haven’t discharged it.
And, you know, we’ll all be paying close attention to that, you know, when the diabetes study first reads out. Okay.
Steve, Host, T. E. Cowan: Questions from the audience on Orphic Lebron or any of the three key events this year? Len?
Len, Audience Member: I was wondering, as I see the GLP ones over the next five years, my concern isn’t about the arguments that some have whether the weight loss was 18 or 25%. You know, the upper end may only be for a small percent of patients, But I’m looking at the borrowers, especially yours, perhaps being used some patients as maintenance therapy once they’ve lost the weight that they want to lose on the injectable. Do you see that as being a potential significant component? Because you don’t need to lose more weight. You just wanna maintain it for the oral drug people who either wanna take an oral, they don’t wanna take injections or for economic considerations that might be less expensive?
Steve, Host, T. E. Cowan: Do you mind paraphrasing the question?
Jake VanArden, President, Lilly Oncology: Sure. The question from the gentleman in front was about the sort of use case of oforglioprot as a maintenance incretin after achieving a certain amount of desired weight loss on one of the injectable drugs. Yeah. That’s absolutely something that we foresee as a possibility. In fact, we’re running actually a clinical trial transitioning patients who’ve chosen to transition off of the injectables on to overbought on.
So we’re studying this exact phenomenon, and I I think I don’t know that that would be something that everyone wants, but there will probably be some percentage of the population who wants that. You know, the addressable population for chronic weight management in The United States is alone is about a hundred million people. So the notion that, like, assuming that we surmount the access barriers that currently exist, the notion that, like, a hundred million people are all gonna choose the same thing, I think, is not realistic. The patients are gonna choose different medicines and regimens depending on their comorbidities and depending on their lifestyle. So, you know, our job is to generate as much data as we can for all of these different patient segments and enable access broadly, and that’s what we’re trying to do.
Steve, Host, T. E. Cowan: Let me just follow-up on something you said earlier. So when we were talking about safety, you said the GI side effects are unlikely to be of a surprising nature, and it’s very understandable. But I think investors might be worried more about the rate of those GI 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
Jake VanArden, President, Lilly Oncology: AEs? That’s a good I don’t know if I would guide to, like, a specific number because this is a that’s even sort of more imprecise, so to speak, than talking about weight loss percentages. But I do think that, you know, 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 like the GI side effects that are most talked about. And remember, you know, the titration schedule that we ultimately deployed in the phase three is different than what we used in phase two.
We learned from that to try and ameliorate some of the side effects that we saw in phase two. And 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 three, 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 gonna wanna 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, you know, we’ve we’ve done a very similar thing with the o four program, and we’ll see how that plays out. But I I feel reasonably optimistic about it.
Steve, Host, T. E. Cowan: Okay. Other questions? Yes.
Jake VanArden, President, Lilly Oncology: You’re saying a GIP only medicine? Sort of a different idea entirely. I don’t I mean, we’re not exploring sort of that specific concept.
Steve, Host, T. E. Cowan: Other questions? Okay. Let’s dig into oncology and let’s start out with the drug that you mentioned, Jake, and it’s, Japerka. So you mentioned that there are several readouts coming in 02/2025. Which which of them is the most important relative to ultimately building and establishing this brand even further?
Jake VanArden, 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, you know, 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, you know, we can deliver a lot of value for patients and for the business by, 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, you know, the guidelines are a little bit ahead of the label as of right now. That’s not that uncommon in oncology. So I I mentioned that to say that, like, we’re all on a sort of stepwise 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 gonna 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 I’m I’m just wanna 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 physician’s 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 do you wanna treat with monotherapy JPRC in the first line? Do you want to treat with a combination of, two years time limited J Perka plus Venetoclax and Rituxan in the second line? Are you interested in J Perka plus venetopax for a year in the first line? That’s a study we’re running in common in with the German CLL cooperative group.
So we’re just trying to cover all of our bases of regimen and line of therapy.
Steve, Host, T. E. Cowan: Okay. Ultimately, do you see the need to in the first line, do you see the need to run against the current incumbents head to head?
Jake VanArden, President, Lilly Oncology: We’re running a study against ibrutinib. That study is going to read out this year. I think that will generate important evidence that can be compared to ibrutinib, but also people, I’m sure, will cross draw compare to other studies that have compared their drugs to ibrutinib. That’s natural despite the caveats that you have to apply. Now if you’re asking, do I think we need to run a head to head study against the other two, interestingly, in in mantle cell lymphoma, we actually are running a head to head study against dealer’s choice of covalent BTK inhibitor.
So admittedly a different disease, but we actually are going to have a decent data set of Purdo versus Akyla and Purdo even versus XANU in the context of the mantle cell phase three that we’re running. I I think in all likelihood, peep people will do some read read through from that to CLL. I think that’s sort of natural despite them being different diseases.
Steve, Host, T. E. Cowan: Okay. And do you see the BTK degraders as meaningful competitive threats to JPR?
Jake VanArden, President, Lilly Oncology: Not yet. I I, I think those medicines look pretty good based on their phase one datasets. They actually remind me a lot of the phase one dataset that we had for perturbutinib about five years ago. And so I they have an efficacy quotient in patients who’ve relapsed on perturbrutinib. That that’s good if it’s an important option for those patients after PIRTL.
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 talk to physicians about that class, I think at least today, they see them as post JAY PIRCA medicines.
Steve, Host, T. E. Cowan: Okay. Let’s dig into Verzenio, very important oncology asset for sure. I have to admit, it really does look like ribociclib has a lot of momentum. So how does, how does Lilly maintain its franchise here and not lose too much share to to the competitor?
Jake VanArden, President, Lilly Oncology: Yeah. I’m not particularly surprised at the velocity of Kaskali’s uptake since the approval on EBC. Remember, the same dynamic happened when Verzenio was first approved in EBC. I think that’s somewhat natural for a class that’s this mature. These medicines have been on the market for a long time.
Most prescribing physicians have used all three of them plenty. And of course, in the adjuvant setting, we’re only talking about two of the three, but the point still holds. And and even even so, in the case of us with Monarchy, in the case of, Kaskali with Natalie, these adjuvant datasets were in the public domain and sort of broadly discussed and debated for a long time even before the EBC approvals from FDA. So I don’t think it should come as a surprise that you see, like, a brisk uptake really immediately post approval. We saw that with Resideo.
They’re experiencing that with, Kaskali. When you when I walk when we look at the sort of new patient start data, it looks to us that, currently they’re getting about fifteen percent of the, call it, jump balls for the patients that overlap between us. That’s a number that’s not that surprising to me. I think these medicines are different. They have pretty different side effect profiles.
Neither one is squeaky clean, but as a result, have different patient populations for whom they address. Of course, Kaskali is three years long. Verzenio is two years long. So patients on Verzenio can move on with their life sooner. I think that’s compelling to a lot of men and women in this treatment setting.
So there’s different choices people will make. What we hear pretty consistently is that, you know, for the Verzenio high risk population, Verzenio remains standard of care for a variety of reasons, and that Kaskali is broadly being used in the population that’s non overlapping. I think the ex the the sort of new patient start data actually fall right in line with that. And, of course, it’s still early days, so we’ll see how that evolves over time.
Steve, Host, T. E. Cowan: Okay. What are the, the pros and cons of initiating an early breast cancer trial in the, n zero and the n one patients?
Jake VanArden, President, Lilly Oncology: The you’re talking the population that Natalie studied that’s
Steve, Host, T. E. Cowan: not in monoclonal antibodies? Yes.
Jake VanArden, President, Lilly Oncology: Like for Verzenio right now?
Steve, Host, T. E. Cowan: Yes.
Jake VanArden, President, Lilly Oncology: It’s pretty late life cycle to start a new adjuvant trial for Verzenio studying that population. I don’t think that’s high likelihood. I mean, for Xenia was likely to be an IRA negotiated product in the next couple years and the, you know, US patent expires in 02/1931. So the timeline of running adjuvant studies like that is probably in the rearview mirror for Xenia alone. That having been said, and now I’m switching gears a little bit, but you know for Imblinestrin, our oral SERD, EMBER four is the adjuvant study we’re running for that medicine.
And that is a study that actually has inclusion criteria from a patient population perspective that are much more similar to Natalie. So, you know, we learned from the Natalie experience in the way we designed them before.
Steve, Host, T. E. Cowan: Okay. I do want to get to, emilynestrant, 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 CDK4. And in the past, when I’ve asked you that, you’ve responded, well, Verzenio is the most selective of the foursix inhibitors, fourfour already. So the advantage of a pure four is not not that great. Is there any change in your view in that regard?
Jake VanArden, President, Lilly Oncology: Not particularly. Again, I think, actually, like, the CDK four phase one datasets that I’ve seen are compelling. They’re they’re they they look pretty good. The problem is that, like, it’s not sort of 2014 again. Now the CDK four six class exists.
Some of these drugs have prolonged overall survival. 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 so I 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.
Steve, Host, T. E. Cowan: Okay. Questions about, Verzenio before we move on to the cert class? Yes.
Unidentified speaker: So last night at dinner, you were pretty adamant that you don’t think the overlapping population with East Valley will change much for this 15% that you cited so far. We had the parties here earlier. They’re pretty adamant that they’re going to go after that and see significant growth there. So why do you think they’re wrong? How are you gonna hold them off?
Because they only pointed towards cardiac risk factors as a reason for choosing for Zendio. Is there anything else we’re missing there?
Jake VanArden, 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 lumbers. And we’ll see whether that changes or not, but I I think the treatment regimen length is a is a big thing for patients and providers, and especially if they view the efficacy as broadly similar. There there 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 the similar very similar.
But, you know, 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 Kaskali 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, like, force patients off the drug and, like, cause real problems. I think for the physicians who have that, like, once they sort of don’t wanna do it again.
And you saw that even in the context of the Natalie study itself. So again, I don’t I don’t wanna make too forward looking predictions about how that fifteen percent will evolve. I don’t know. But what physicians tell me today is that these are sort of two different populations that they’re thinking about.
Steve, Host, T. E. Cowan: So let’s move to the SIRDS. In what ways is Imlena Strand, different than other SIRDS in development?
Jake VanArden, President, Lilly Oncology: So I think that, you know, there’s the medicines themselves, and then there’s how the medicines are developed. On the medicines themselves, you know, there are, I think differences in particular on the safety side that we’ve seen over time. There there are certain surge in development that have, either ophthalmic toxicities, cardiac toxicities, changes in lipid levels. You know, these types of things, which, by the way, the field doesn’t even understand why would any of these things even occur. But, you know, Imbunesrin 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. You know, patients in the adjuvant adjuvant setting take endocrine therapy for five to ten years. It’s a pretty long time. And if the medicine is intolerable, then they’re not gonna be able to stay on it.
If they’re not gonna be able to stay on it, they can’t get the efficacy. So, you know, 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 three EMBER three study that read out last year was just seeing the tolerability profile of the agent in a sort of rigorous phase three study. We had phase one data many years ago, but, you know, you always look to a phase three 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, you know, we’ve developed our medicine in the metastatic setting in combination with CDK four six for Zenio. I think that led to, I think, a pretty differentiated set of outcomes that have excited clinicians now admittedly in this in second line breast cancer. And then, you know, our adjuvant program is differentiated on 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 foursix period. We are patients that enter the study get randomized to, switch from their aromatase inhibitor backbone to immunestrin or stay on the aromatase inhibitor. And so in a way, it’s sort of a pure SIRD versus AI comparison. And we think we know from historical studies that, in a SIRD versus AI comparison without CDK four six in the backbone, the SIRD wins. And so that’s the basis of that that experiment that we’re running with the IMBR4 study.
Pretty big swing if that study hits. That’ll be a very, very important new medicine, for us. And, you know, in the meantime, we hope to be launching it in metastatic disease later this year.
Steve, Host, T. E. Cowan: Speaking about, EMDR4, do the results of EMDR3 and the fact that it didn’t reach significance in the overall population concern you at all about the probability of success of EMDR4?
Jake VanArden, 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 MR3, remember the comparator in that study, and this is really important, the comparator was fulvestrant, another SIRP. The comparator in EMBER four are aromatase inhibitors, not a SIRT.
And so in the context of EMBER three, what we saw is that in the ESR one wild type population, the comparison of imlanesterin versus fulvestrant has a progression free survival hazard ratio of about one. They look very, very similar. 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 imlonextrin looks similar to fulvestrant, then imlonextrin ought to beat an aromatase inhibitor too. So if anything, like, the randomized data we got from number three furthered my conviction in the likelihood of number four working. Okay. Sure.
Len, Audience Member: Reference to the Falcon data. Is there anything else that shows that the CFS server versus
Jake VanArden, President, Lilly Oncology: That is the main body of evidence in fairness. I mean, you only have a handful of these experiments that have been run. Right? You have Falcon without CDK four zero six and you have Parcelpal with CDK 4 0 6. I think many of us in the field have made our judgments rightly or wrongly on the basis of those two seminal experiments.
Parcel was hugely impactful into how we were thinking about the development program. You’ll note that I think we’re the only company with a novel cert that chose not to run a first line study, because there you have to run concurrent CDK four six and Parcival would suggest that those that that that’s a study that won’t work. Obviously, like, we’ll see later this year, I think, whether we were right or wrong because some of the competitor 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, m before isn’t running concurrent with CDK four six. It’s actually running after the CDK four six period.
We did that very deliberately in part because of Parsifal.
Steve, Host, T. E. Cowan: 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 is already pretty much a game changer, right, but but but could put the company on a even greater trajectory. And and you noted three things, and what jogged my memory is one of them was number four, which we’ve already discussed. The other two were LPA and Alzheimer’s disease prevention.
Len, Audience Member: Yeah.
Steve, Host, T. E. Cowan: So maybe you could just spend in our last few seconds just to spend a moment as to why you view those or Lily views those as game changing events.
Unidentified speaker: Yeah. So, you know, as it
Jake VanArden, President, Lilly Oncology: relates to Alzheimer’s disease prevention, I think we know who that 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, you know, yes, we have, you know, the the launch of this of Kisumma as an example in the in symptomatic disease, has gone, you know, somewhat moderately. I think as we transition the medicine to preventing the occurrence of symptoms of this disease with a blood test as the sort of entryway to getting the medicine, I think we’ll be having a very very different conversation with patients. I think that that looks very different than, like, slowing the course of the disease that is otherwise progressing.
Steve, Host, T. E. Cowan: And by
Jake VanArden, President, Lilly Oncology: the way, all of the evidence we have from both the denanumab studies as well as even the laconumab studies, which suggests 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 three, is an even earlier version of that same biological idea. So that gives us a lot of conviction that the study will have a big effect size. And, of course, you know, 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 borne out.
So we we actually we need the study to read out to prove that to us. Patients with, with preclinical is what the term is preclinical 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 and these, amyloid related safety events with the amyloid lowering agents. And so we’re hopeful that patients with lower amyloid burdens in the in the brain will experience, meaningfully less safety issues with the medicine. But if, you know, if we can 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, you know, Lilly as a result as a follow through to that.
And then, you know, l p little 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 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 a lot of unknowns here. We don’t know, like, how low do you need to go?
How long do you need to go to to keep it low? What will the effect size be upon the intervention? So, you know, today, the evidence around l p little 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 correlative 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, you know, excited about the work we’re doing in both primary and secondary prevention there.
Steve, Host, T. E. Cowan: We do have a cardiology panel ending today, and LPA will be a topic. Well, thank you so much, Jake. This has been a wonderful conversation and lots to look forward to.
Jake VanArden, President, Lilly Oncology: Thanks for having us, Steve.
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