Eli Lilly and Company

Thank you for holding. We look forward to talking with you soon. Please hold the line, and we'll be right back with you.

Ladies and gentlemen, thank you for standing by and welcome to the Lilly Q4 2024 earnings call. At this time, all participants are on a listen-only mode. Later, we will be conducting a question and answer session and instructions will be given at that time. Should you request assistance during the call, please press star, then zero, and an operator will assist you offline. I would now like to turn the conference over to your host, Mike Zappar, Senior Vice President of Investor Relations. Mike, please go ahead.

Good morning. Thank you for joining us for Ilya Lillian Company's Q4 2024 Earnings Call. I'm Mike Savar, Senior Vice President of Investor Relations. Joining me on today's call are Dave Ricks, Lillian's Chair and CEO, Dr. Dan Skowronski, Chief Scientific Officer and President of Lillian Immunology, Lucas Montarse, Chief Financial Officer, Anne White, President of Lillian Neuroscience, Ilya Yufa, President of Lillian International, Jake Van Narden, President of Lillian Oncology, and Patrick Johnson, President of Lilly Cardio Metabolic Health and Lilly USA. We're also joined by Mark Heumann, Wes Tall, and Wai Wong of the Investor Relations Team. During the call, we anticipate making projections and forward-looking statements based on our current expectations. Our actual results could differ materially due to several factors, including those listed on slide four. Additional information concerning factors that could cause actual results to differ materially is contained in our latest Form 10-K and subsequent filings with the SEC. The information we provide about our products and pipeline is for the benefit of the investment community. It is not intended to be promotional and is not sufficient for prescribing decisions. As we transition to our prepared remarks, please note that our commentary will focus on our non-GAAP financial measures. Now, I'll turn the call over to Dave. Okay, thanks, Mike.

2024 was a productive year for Lilly. We grew our top line, advanced our pipeline, and invested in our supply chain to meet the increasing demand for our medicines. Most importantly, we delivered for patients by bringing life-changing medicines to more people around the world. In 2024, our full-year revenue grew 32% compared to 2023, exceeding our first-time guidance by $4 billion. Revenue grew 45% in the most recent quarter as our recently launched products gained momentum. Last year, we announced positive Phase III results for imlumistrin, insulin L-sitora-alpha, and three additional triseptide trials. We also started phase three programs for lepidicerine, remternitug, and olomaracid, based on positive earlier phase data. We continued to complement our pipeline through acquisitions and collaborations. We acquired Morphic Therapeutics and announced a collaboration with OpenAI to invent novel antimicrobials. We opened the Lilly Seaport Innovation Center in Boston as a hub for Lilly's genetic medicines efforts. and announced a new Lilly Gateway Lab in the UK to collaborate with European research. We advanced our manufacturing agenda, announcing investments to expand our footprint in Indiana, in Wisconsin, and in Ireland. Since 2020, our commitments to build, expand, and acquire manufacturing facilities now total more than $23 billion. Importantly, we brought innovative new medicines to patients. In 2024, we received regulatory approvals for Kisunla, Eglis, and a new indication for Zepbound and OSA. This progress strengthens our portfolio of new products and enhances our capacity to drive top-tier growth and margin expansion. As you can see on slide five, we continue to make progress against our strategic deliverables in Q4. Revenue grew 45% in our new products growing by more than $3.1 billion, led by a strong uptake of Monjaro and ZepFound. Q4 also saw solid performance across oncology, immunology, and neuroscience. Our business-excluding incretins grew by 20% in the quarter compared to Q4 2023, excluding the one-time benefits of business development. Since our last earnings call, we achieved several key pipeline milestones. We received approval for a new indication of Zepbound and OMBO. We submitted Imumastrant for metastatic breast cancer and Terzepatide for heart failure. We also announced positive phase 3 results in the Surmount 5 study, where Zepbound demonstrated a 47% greater relative weight loss compared to Wegovy. We strengthened our overall supply position and delivered on our production target to make 1.5 times the saleable doses of Inker to Medicines in the second half of 24 compared to the second half of 23. With more patients using Lilly Direct, the uptake of single-use upbound vials increased. We had no wholesaler back orders as we closed 2024, and wholesalers have been fulfilling orders from pharmacies at very high levels. We continue to augment our internal pipeline with external innovation, announcing plans to acquire Scorpion Therapeutics Mutant Selective PI3K8 a inhibitor program. This transaction will add a clinical stage breast cancer asset to our oncology pipeline. And lastly, we return $3 billion to shareholders via dividends and share repurchases. In addition to that, we announced at the end of the year a $15 billion share repurchase program and the seventh consecutive 15% increase in our quarterly dividend. On slide six, you'll see a full list of key events. It's our Q3 call, including the milestones I mentioned here. and several other updates. Now I'd like to turn the call over to Lucas to review our Q4 and 2024 full-year results and provide details on the 25 guidance.

Thanks, Dave. Slide seven summarizes our financial performance in the fourth quarter and slide eight for the full year. As Dave mentioned, our revenue grew 45% in Q4, primarily driven by Monjaro and SEPA. Performance of our non-increasing portfolio was also strong, as revenue grew 20%, excluding one-time payments related to business development. Gross margin as a percentage of revenue increased to 83.2% in Q4, primarily impacted by favorable product mix. R&D expenses increased 18% from continued investment in our early and late-stage portfolio. In total, we started eight new Phase III programs in 2024 and advanced several new assets into the clinic. Marketing, selling, and administrative expenses increased 26%, mainly driven by promotional efforts to support ongoing and future launches. This includes U.S. direct-to-consumer advertising on Cepan and Moncharo, and U.S. launch activities for Kisanla and Atlas. We also increased our commercial investment outside the U.S. to support international launches of Moncharo. Operating income more than doubled, increasing to $5.6 billion. driven by higher revenue from new products. The effective tax rate was 13.2%. We delivered earnings per share of $5.32, inclusive of $0.19 of acquired IPR&D charges. This compares to $2.49 in Q4 2023, that includes $0.62 of acquired IPR&D. On slide 9, we quantified the effect of price, rate, and volume on revenue growth. U.S. revenue increased 40% in Q4, driven by robust volume growth of 45%. Stefan and Monjarro were again the largest growth contributors, partially offset by declines in trulicity. Realized prices decreased 5% in the U.S. due to favorable changes to estimate for rebates and discounts related to Monjarro in Q4 2023. Europe revenue grew 82% in constant currency, We continue to be pleased with the uptick of Monjaro and how it now launched in all major European markets. In addition to growth from Monjaro, European revenue benefited from one-time payment associated with the amendment of our alliance with Beringer Ingenheim. This was recorded in Jardine's revenue in Q4. Excluding this one-time payment, Europe revenue grew 61%. Japan revenue grew 27% in constant currency. Volume growth was driven by Monjaro, Ombo, Jardines, and Bersenio. In China, revenue increased 13% in constant currency. Taivit and Bersenio drove volume growth. Monjaro was recently made available in China and will proceed with a limited launch as supply becomes available. We expect modest initial Monjaro sales in China due to supply limitations, a more meaningful contribution in the second half of 2025. Revenue in the rest of the world grew 46% in constant currency, driven by volume growth of Monjaro and Versenya. Slide 10 provides an update on our performance of new and growth products. New products more than doubled in Q4 to $5.6 billion, led by global Monjaro sales of $3.5 billion and U.S. setback sales of $1.9 billion. U.S. setback performance is going very well. we began promotional activities this quarter, and we continue to see strong uptake. In Q4, CEPBAN became the market leader in the anti-obesity market as measured by new prescriptions. As shown in 2011, we combined U.S. in-credit and analog market through 45 percent compared to Q4 2023. We increased three percentage points in share of market in Q4 2024. Jaipirka worldwide revenue was $114 million, adding another solid quarter of sequential revenue growth. Worldwide OMBO revenue increased to $57 million. With the recent FDA approval in Crohn's disease, we look to drive broader use in an additional patient population. The Kisangla launch is progressing well, and prescriptions in the US have been steadily increasing. While it is early, we saw positive momentum across key indicators, including volume of diagnostic ordered, access in priority integrated health systems, coverage by Medicare and commercial plans, and number of infusion sites placing orders. We are encouraged by the launch of Eptlys in the U.S. We saw early positive receptivity and high levels of physician engagement. In addition, we expect commercial access with two of the largest pharma benefit managers beginning in March. We now plan an accelerated investment in commercial activities to drive new patients' start. Growth products also performed well, as revenue increased by 13% compared to Q4 2023. Fresenio's growth trajectory continued as U.S. total prescription grew by 15%. In addition to strong execution in the early breast cancer indication, Fresenio revenue benefited from increased U.S. wholesale stocking at year-end. Worldwide, true illicit revenue declined 25 percent, driven by Monjaro switches, and to a lesser extent, lower realized prices. On slide 12, we provide an update on capital allocation. Moving to slide 13 and 14, I will discuss our 2025 financial guidance. As previously shared, we expect 2025 revenue to be between $58 and $61 billion. The midpoint represents approximately 32% growth compared to 2024. We anticipate continued U.S. incretin class growth, consistent with the trajectory of total prescriptions seen in 2024. We expect to launch Monjaro in new markets outside the U.S. and Europe throughout the year. Monjaro international revenue will contribute to overall performance more significantly in the second part of 2025. Given the uptake of newer incretins, we expect trulicity volume to continue declining as fewer new patients are starting on trulicity. We expect oncology, neuroscience, and immunology to also grow revenue in 2025 as Epsiglis, Jaipirka, Ombo, and Kizondla launch uptakes continue. At the portfolio level, we anticipate foreign exchange to be a headwind as the dollar has strengthened relative to other currencies. In addition, we forecast overall net prices to decline by mid to high single digits in percentage terms, including U.S. Part D changes. We continue expanding our manufacturing capacity and estimate to produce 1.6 times the amount of incretin-sellable doses during the first half of 2025, compared to the first half of 2024. Our facility in Concord is anticipated to begin shipping medicines this year, and we plan to make continued progress on expanding our manufacturing network. Our expected ratio of gross margin less OPEX divided by revenue is expected to be between 41.5% and 43.5%. At the midpoint, this reflects approximately 340 basis points of margin expansion compared to 2024. In SG&A, we will continue to invest behind our new launches, including direct-to-consumer efforts in the U.S. to drive new patient activation. In addition, we plan to increase investment outside the U.S. to support the launches of Monjaro in new and existing markets. In R&D, we plan to accelerate our investment in early and late-phase activities. As Dan will share later, We started eight new phase three programs in 2024 and anticipate that investment in those programs will ramp as the studies enroll patients. We also plan to initiate new phase three programs in 2025. While we keep a high bar for what we advance into clinic dial development, we expect to scale our investment in R&D this year. Other expenses is expected to be $600 to $700 million driven by interest expense. We estimate our effective tax rate to be approximately 16%. Earnings per share, or EPS, is expected to be $22.50 and $24 on a non-GAAP basis. This doesn't include a forecast for charges related to IPR&D. Now I will turn the call over to Dan to highlight our progress in R&D and to provide an overview of potential key events we expect in 2025.

Thanks, Lucas. Lily R&D had another productive quarter. I'll cover pipeline progress in Q4, then the 2024 key events, and finally provide potential key events for 2025. Since our last earnings call, two new indications were approved in the U.S. Zepbound for obstructive sleep apnea in adults with obesity and Ombo for moderate to severe Crohn's disease. Both approvals are important milestones and mark an expansion in the number of patients who can benefit from each of these medicines. Moving to regulatory submissions, we completed submissions in the U.S. and EU for Terzepatide for heart failure and global submissions for Imlinestrin for metastatic breast cancer and for J. Perka with the Bruin CLL321 data. I'm also pleased to share that we've submitted an update to the Kusunla U.S. label to include the dosing modification data from Trailblazer L6, and the FDA has granted this submission a priority review. In our Phase III portfolio, we initiated a new program for Orforglipron in obstructive sleep apnea. This program includes two studies under the same master protocol to evaluate if people with obstructive sleep apnea and obesity can benefit from more for glipron. After Zepound was approved in the U.S. as the first and only prescription medicine for obstructive sleep apnea, we're excited to explore if an oral GLP-1 can also deliver a benefit in this disease. Earlier in the pipeline, we advanced a second oral GLP-1 into Phase II in obesity and advanced L-trecobart into Phase II for ulcerative colitis. Three Phase II assets and one Phase I asset have been discontinued based on clinical readouts. In Q4, we also began Phase I studies for four new molecules, one in each of our therapeutic areas. Q4 capped off a productive year of advancing new medicines at Lilly. In total over the year, we started eight new Phase III programs. We disclosed Phase III data from 21 trials, including 17 major publications in top-tier medical journals. We received regulatory approvals for two new medicines, edglis and kasunla, as well as many new indications around the world. And we added 14 new programs to the early phase pipeline. On slide 16, we detail these outcomes for our 2024 milestones. I'm pleased that nearly all of our anticipated milestones came to fruition positively in 2024. Turning our focus to 2025, slide 17 shows key R&D milestones we expect this year. Starting with our late-stage portfolio, we expect to initiate two new Phase III programs this year. First, in oncology, we'll begin an adjuvant non-small-cell lung cancer Phase III program for our KRAS G12C inhibitor, olomaracid, building on its ability to be administered with immunotherapy. Our current metastatic program is progressing well. and we've aligned with the FDA on our Phase III dose through the Project Optimus pathway. We shared a clinical update at the World Conference on Lung Cancer last fall, and we are encouraged by the ability to safely combine olomaracid with other agents. Our new Phase III program will focus on moving to an earlier setting and combining with existing approved agents in both resectable and unresectable KRAS G12C mutant lung cancer to prevent cancer from recurring. The second program is in cardiometabolic health, where we plan to initiate a Phase III trial for orforaglipron in hypertension, adding to the ongoing trials in type 2 diabetes, obesity, and obstructive sleep apnea. I'm excited that this year we're looking forward to reading out multiple orforaglipron trials. We expect to see data from up to five studies in type 2 diabetes and two studies in obesity. Our goal is to generate efficacy, safety, and tolerability profile that is similar to that of an injectable single-acting GLP-1 but through an orally available medicine. The first Orfaglipron Phase III trial to read out will be ACHIEVE-1, which is a 40-week study in patients with type 2 diabetes. These patients have a baseline hemoglobin A1c between 7 and 9.5% and a body mass index of 23 or greater. The trial utilizes six escalating doses in four-week increments to a maximum dose of 36 milligrams. Based on prior studies of Orfaglipron, as well as other GLP-1 therapies, we expect weight loss in people with diabetes to be significantly less than in people living with obesity who do not have diabetes. We anticipate ACHIEVE-1 will read out in Q2 this year, followed by up to four additional type 2 diabetes trials in the second half of 2025 and a potential submission for this indication in 2026. The Orpher-Glipperon phase 3 trials in people with obesity, ATTAIN-1 and ATTAIN-2, are expected to read out in Q3 of this year. These trials will form the basis of our first or for glipron regulatory submissions, which will be for the treatment of obesity, and we expect to occur late in 2025. This year, we also expect data from the Terzapatide Cardiovascular Outcome Study Surpass CBOT. Of course, this is an event-based trial, and the timeline is dependent on the accrual of cardiovascular events. We anticipate data in Q3. While designed to measure both non-inferiority and superiority compared to trulicity, a positive outcome in either would demonstrate that terzapatide reduces the risk of cardiovascular outcomes and would support a labeled indication. Late this year, we expect to see the first data from a triple-acting incretin bred at Trutide, which combines GLP-1, GIP, and glucagon. We believe this potential new medicine can deliver even more weight loss than terzapatide and could potentially provide additional health benefits. The initial study to read out, TRIUMPH-4, is a 68-week study in patients with osteoarthritis of the knee who have a body mass index of 27 or greater. We'll also see multiple additional JPIRCA data sets this year. Physician feedback is very positive on experience with JPIRCA in the currently approved indications, and we hope that generating data in earlier lines of therapy will enable broader use within CLL and MCL. We could see data from additional trials in the first line or BTK-naive settings this year. Moving to neurodegeneration, while we don't have a key event listed in 2025 for Denetimab, we're closely watching the preclinical Alzheimer's disease study, Trailblazer ALS-3. This trial screened patients with a blood-based diagnostic and utilized a fixed duration of treatment with Denetimab. By moving earlier in disease progression, the goal is to reduce the risks of developing any symptoms of Alzheimer's disease. While the current primary completion is projected for 2027, the study will read out when the target number of progression events are accrued. A new focus area for us in 2025 will be to study potential new applications of incretin biology across diseases in neuroscience and immunology. With a pipeline of incretins in clinical development and deep scientific expertise in this space, Lilly is well positioned to match the biologic properties of specific molecules to the desired indications being studied. We plan to start several clinical trials, assessing potential benefits of our incretins in areas that could include brain health, substance use disorder, pain, neuropsychiatry, and inflammation. We'll be prepared to move rapidly into phase three trials based on clinical data and where our conviction is high. Lastly, we expect a number of important regulatory submissions in 2025, including Orpher-Glipron for obesity, as I detailed, Insulin F-cetar alpha for type 2 diabetes, terzapatide for cardiovascular outcomes, and multiple potential data sets for JPERCA. 2025 will be another exciting year for Lilly R&D. Now I'll turn the call back to Dave for some closing remarks.

Yeah, thanks, Dan. So we had a strong financial performance in Q4 and throughout 2024. We finished $4 billion above our first-time revenue guide and $4 per share above our first-time EPS guide. when taking our IPRD charges into account. The incretin market continues to grow rapidly, and Manjaro and Zepound are both gaining share of market. We believe both products are still very early in their launch cycle. In addition, our oncology, immunology, and neuroscience therapeutic areas continue to progress, launching new medicines and delivering strong revenue growth. We have an exciting outlook for growth in 2025 as well. New indications, new manufacturing capacities, new access opportunities, and new markets are all tailwinds to our financial performance. We made significant advances across our pipeline in 2024 and have several exciting readouts, which Dan just highlighted, expected throughout 2025. So now let me turn the call over to Mike to moderate our Q&A session.

Thanks, Dave. We'd like to take questions from as many callers as possible and conclude our call on time. So to that end, consistent with prior quarters, we will respond to one question per caller, and we will end at 11 a.m. If you have more than one question, you may re-enter the queue, and we will get to your question if time allows. Paul, please provide the instructions for the Q&A, and we're ready to take the first caller.

Thank you. At this time, we'll be conducting a question and answer session. If you have any questions, please press star 1 on your phone at this time. We ask that participants limit themselves to one question on today's call. If you do have a follow-up question, please rejoin the queue by pressing star 1 at any time. We also ask that while posing your question, you please pick up your handset if listening on speakerphone to provide optimum sound quality. Please hold while we poll for questions. And the first question today is coming from Tim Anderson from Bank of America. Tim, your line is live.

Thanks so much. Just a question on the guidance, the 2025 guidance. So I think everyone knows the prescription uptake trend didn't show acceleration, hasn't shown it yet. That's been viewed by some as a concern. Does the 2025 guidance require acceleration? or can you get there if scripts just continue on the same trajectory and the slope of that line doesn't change? When I do back-of-the-envelope math, it seems like that's frankly all that needs to occur, and one of your slides suggests that might be the right way to think about it as well, but can you just confirm?

Great. Thanks, Tim, for the question. We'll go to Lucas to talk about the guidance assumptions.

Yeah, we mentioned in my notes that What we expect to see, Tim, is a continuation of basically the total prescription growth that we have seen in 2024. So that's what we built in our 2025 guide for the market.

Great.

Next question, please. The next question is coming from Terrence Flynn from Morgan Stanley. Terrence, your line is live.

Great. Thanks so much. I was just wondering if you could maybe elaborate on your expectations for ZEP-bound payer dynamics and access this year, particularly the impact from the OSA label. I know you've also filed for heart failure and how you expect that to play out over the course of the year, and then anything on next steps on the compounding litigation that we should be focused on. Thank you.

Dangerously close to a two-part question there, Terrence, but we'll go to Patrick to talk about access, and then I'll come back to Dave to make a quick comment about compounding.

Thank you very much. When we look at the commercial access, it remains strong. We have 87% coverage in the commercial space still. And of course, the employer opt-in is a second step of high importance that made progress in 2024. And we expect in terms of employer opt-in that we are north of 50% today. OSA remains an opportunity for us to gain access also in the Medicare segment. And CMS confirmed recently that they will reimburse OSA if Plan D plans decide to list it. And they have 180 days to make that decision from the FDA approval. And we're working with plans right now. And we anticipate to get some Medicare coverage by the second half of this year. And similarly, OSA is also an opportunity for us to get more Medicaid states signed in. We expect FPEF, when and if approved, to have a similar role as OSA, an access opportunity, particularly in Medicare and Medicaid.

Yeah, so regarding compounding, you know, I think our position has been pretty clear. We've been in supply since August, and the FDA took us off the list formally. Later in Q4, of course, the compounding associations are suing to delay that. We oppose that. I'm enjoying that suit. I think the next date coming up is February 18th, where the FDA said that's when you need to stop one form of compounding. Our position has been clear all along. We don't think there's a place for this because we have full supply, and there's no reason to have a non-approved, kind of illegitimate product out there. So, of course, new sheriff in town, new government, and court case pending. So, We don't know the outcome of all that. But that all said, I mean, I think our business is growing nicely in Q4, and we can see that in prescription trends early this year. It's just an unsafe practice that shouldn't exist and long-term probably isn't great for innovators. So we'd like to move on from this and hope that's what the courts and the government decide to do.

Great. Thanks, Dave and Patrick. Next caller, please.

The next question is coming from Courtney Breen from Bernstein. Courtney, your line is live.

Hi, everyone. Thanks for taking the call today. I just wanted to zoom in to Orfaglipron specifically, and I think you took the chance to make the point about diabetes and diabetes population and their weight loss. Can you just talk a little bit more about kind of the potential positioning, particularly in the context of kind of that single injectable GLP-1 kind of anticipated efficacy that you're guiding to?

Great. Thanks, Courtney. We'll go to Dan to talk about the right comparable flip-run.

Yeah, sure. I'll start on the efficacy expectations, and then maybe Patrick can talk about the market positioning here. So, You're right. It's a single GLP-1, and we take pains to mention that because we're not expecting the kinds of efficacy or tolerability, actually, that we see with terzapatide, which is a dual acting agent. Still, as you know, monotherapy with GLP-1 has provided important benefits to many patients, and so we're setting our sights there. This is a first study in type 2 diabetes patients where, as I noted, weight loss is typically quite a bit lower than you see in people without type 2 diabetes. So we sort of index on the efficacy that we've seen in the past with Ozempic, and we'll get that data soon and excited to see it. Patrick?

And from a positioning perspective, you know, we like the idea of having an oral with an injectable GLP-1-like efficacy, and there is a big portion of patients that actually have needle fear. It's estimated in the U.S. to be 20 to 25 percent, and also a group of patients that doesn't necessarily need the amount of weight loss or HbA1c reduction as tirzepatide generates. That might be an opportunity in the maintenance space as well. But lastly, and very importantly, it's an opportunity to scale in markets outside the U.S., taking into account that we don't have a need for refrigeration.

Great. Thanks, Patrick and Dan. Next caller, please.

The next question is coming from Chris Schott from J.P. Morgan. Chris, your line is live.

Great. Thanks so much. Just another Orfaglipron question. You've now launched a pretty wide range of studies, I guess to say hypertension, beyond the initial obesity and type 2 diabetes studies. Can you just elaborate a little bit more on what gives you confidence in running such a wide range of programs without having seen those initial readouts, particularly maybe some of the tall ability profiles with the drugs titration, et cetera? I'm just trying to think how you balance kind of the risk-taking there with the confidence in the asset you have right now. Thank you.

Great. Thanks, Chris. We'll go to Dan for that question.

Yeah. Thanks, Chris. It's a smart question. You know, of course, going into phase three with any drug, particularly a small molecule such as orpaglipron, the biggest risk is safety. And I think as these trials proceed, even though we're not seeing the safety data, we grow more confident in the overall safety profile of the drug because the trials continue uninterrupted. Of course, we won't know for sure until we get that first data readout and then subsequent data readouts. But it's correct that we grow more and more confident in the success of this molecule as each day passes. As for, you know, specifics around tolerability and titration and discontinuations. Those don't really factor into our thinking. We haven't had a look at unblinded data for any of those things, so we can't make assumptions on that yet. Great.

Thanks, Dan. Next question, please.

The next question will be from Jeff Meacham from Citibank. Jeff, your line is live.

Hey, guys. Thanks for taking the question. Just had one on commercial terzapatide in bigger settings like diabetes prevention or, you know, if the surpassed CBOT is successful. You know, would these be a tipping point on broader reimbursement or excess? I mean, it's clear you have a benefit there, but I wasn't sure if commercial payers or Medicare are looking for yet even more data to support, you know, kind of risk-benefit. Thank you.

Great. Thanks, Jeff. We'll go to Patrick to talk about the broader landscape there.

Thank you very much, Jeff. I think the somewhat one extension is definitely defined as game-changing at the provider level, and we are in discussions, of course, with regulatory agencies, but there is no precedent for type 2 prevention as an indication. But the data itself, I think we will utilize to really drive increased employer opt-in, seeing the benefits of outcome studies and treatment of people with pre-liabetes and obesity.

Maybe just a broader point, which we've said before, Jeff, You know, I think a lot of investors are looking for some single event that will, you know, trigger the broad reimbursement or not. And I don't think we've ever really thought of it that way, but rather an accumulation and sort of weight of everything that will grow reimbursement steadily over time. And I think that's actually what we've seen since we launched Upbound last year. U.S. commercial insurance, you know, picking up several points during the year. And even XUS now, we have U.K. reimbursement, etc., But different payers will make different decisions at different times. And I think the data sets you mentioned will be some of the more compelling to create moves. But still then, the way affordability and budget constraints, et cetera. That all said, by the time we get to the end of the decade, it's hard to imagine we are not using obesity medications to prevent what is the precursor condition to so many chronic diseases. And already, the health economics are pretty compelling. And there'll be more data coming beyond that. So long term, we remain really really bullish on this whole category being reimbursed like we expect to reimburse all other medications. Just the schedule for that is going to be more slow and steady, I would say, as you model expectations on a global scale and in the U.S. as well because of the diversity of payers. Great.

Thanks, Dave and Patrick. Next question, please.

The next question will be from Seamus Fernandez from Guggenheim Securities. Seamus, your line is live.

Hi, this is Colleen on for Seamus. Thanks for taking our question. We just wanted to ask on the sustainability of operating margin expansions, looking at some of the longer term for longer term forecasting from Southside consensus. We're seeing estimates nearing 50 percent by the end of the decade. Do you view this as realistic or how are you thinking about the balance between the margins and then also ensuring you're not under investigating on a pipeline under and

Great. Thanks for the question, Colleen. I'll go to Lucas to talk about the long-term operating margin philosophy.

Well, we are very pleased with the results that we've seen in 2024 and Q4, and we provided a guidance for 2025 that is a continuation of that margin expansion. I mentioned 340 basis points expansion in 2025. Thinking more long-term, Our view is how we continue to drive growth in a sustainable manner. And in order to do so, we believe that reinvesting into the business, in particular in R&D, to drive that innovation and growth into the future is a critical success factor for our business. So from that perspective, we mentioned before that we believe that getting into high 40s or 50% is not actually a good way to drive that sustainable growth into the future. So what we are seeing now on that low 40s is, in particular at this time, the right basically balance that we have in terms of investment into the business and also the returns that we generate as well.

Great. Thanks, Lucas. Next question, please.

The next question will be from Evan Siegerman from BMO Capital Markets. Evan, your line is live.

Hi there. This is Conor McKay on for Evan. Thanks for taking our question. Given some of the slower launches we've seen from peers in the Alzheimer's space, can you maybe talk a bit about the lessons you've taken from those and then as well as sort of your experience early days in the Kisuma launch? Thank you.

Great. Thanks, Conor, for the question. We'll go to Anne to talk about Kisuma.

Well, thanks so much for the question about Casimla. And I'll tell you, we are pleased with our momentum so far. What our system, our team is focused on really is system readiness and growth. That's still a significant area of opportunity in the space. So we're partnering with healthcare providers to scale and reach more patients. As far as how it's going so far, Lucas mentioned key indicators that we're watching. To date, we've achieved P&T approvals of over 80% in our key accounts. We have over 800 prescribers. And then an important leading indicator is the diagnostics front, and those results also continue to be encouraging. Ambivis use is more than doubling in the last year, and the use of blood diagnostics grows significantly each month as well. The true challenge here is the healthcare system's readiness, and I think most critically the capacity to detect and diagnose patients. And so we have a number of solutions that we're working on with the healthcare providers to help them increase that capacity, increase the throughput for patients. a lot of educational series as well on how to quickly diagnose and treat these patients. Importantly, I think we're hearing a lot of enthusiasm about the Pro5 Casenla, and that actually helps with these capacity constraints. The once-monthly infusions, the ability to stop dosing once the flask is cleared, all of those physicians have told us are going to help with some of these capacity constraints. So it's been a strong start so far. We didn't learn lessons from the first launch that went out there and applying that learning to what we're doing now, but it's been really positive so far in the terms of the level of support and collaboration that Lilly's been able to bring with her expertise in the field and our long relationships with these customers.

Great. Thanks, Anne. Next question, please.

The next question will be from Umair Rafat from Evercore. Umair, your line is live.

Hi, guys. Thanks for taking my question. It's certainly very encouraging to see the range of new Phase III trials being initiated with Orfaglipron in the past few months. But there's one trial in particular I noticed has not been initiated or may not be in the plans, which is an outcomes trial. I'm just curious, what's the thought process behind that? Thank you.

Great. Thanks, Zuma, for the question. We'll go to Dan to talk about the ORFL development plan.

Yeah. Thanks, Zuma. Of course, it's We're trying to cover a broad landscape of indications here that we think would be important and fit with the advantages an oral medication has, sort of primary care, broad use kinds of applications being prioritized. Outcome studying is an interesting idea. The challenges here in maintaining patients on placebo make it more and more difficult to do those kinds of studies in the U.S., but it's certainly an idea that we're exploring around the world and more thinking to come in the future.

Great. Thank you, Dan. Next question, please.

The next question will be from Steve Scala from TD County. Steve, your line is live.

Thank you so much. I apologize in advance for this question, but over the past six to nine months, there has been a consistent cadence of data points questioning the size of the addressable and accessible obesity market, none of which are news, but include slowing prescription trends, literally meeting demand at least a year early, Bob White- lily instituting DTC and extending copay cards, despite struggling to meet demand lily launching and oh us markets, despite struggling to meet us demand. Bob White- and significant stocking fluctuations and challenges and guiding to take into taken collectively these points are concerning, I think you will say that they all relate to the unprecedented size of the market and and meeting its demand, but can you state. that there has not been any conversations within Lilly questioning whether we are all significantly over our skis on this market and that the manufacturing buildout may simply be too aggressive. Thank you.

Great. Steve, thanks for the apology and the question. I'll go to Dave for that one.

Yeah, Steve, I think you've been calling into our calls for most of my career. I've never had the apology up front, so I appreciate that. I know why you're asking it. And I think the perspective we have is that it's early days on a very, very large opportunity. There's turbulence. I'll own that. We always seek to put projections out that we can hit with confidence, but that are also within the range of possibilities. And in the back half of that year, last year, we fell short of that. But everything we've said is true, and we continue to believe it, that You know, this is a market with hundreds of millions of people globally, that there is a unique thing here in that we can both prevent a large portion of chronic disease with obesity drugs. And last year, we saw proof points on that from Lilly and our competitor. That's not just weight loss. It translates into chronic disease outcomes. You'll hear and see more of that. And people love taking these drugs. We know that because when we run out, which we did last year, They get very angry with us. And so I, you know, being the person who represents to the board the CapEx decisions, I have zero doubt that we have still more building to do and that the capacity we've put in the ground so far is not sufficient to meet global demand. You'll hear more about that from us. Of course, as highlighted on this call, we're getting close to, I think, a relief valve on that, which is the idea that you could have an oral which is scalable in a way that injectable systems just aren't, really test the question legitimately, what is the edge of the demand curve? But we don't think we're close to it right now. We're still gating promotion and gating launches globally. That's a different thing. And we're building facilities as fast as we can to match up those two things, what we can make and what we can sell. And although we're supplying the U.S. market well right now, we'll need to do more. And I'm pretty confident in that. So hopefully that gives you some color on the mindset here and wouldn't overread the turbulence and prediction challenges we have. But long term, we're very bullish and you'll see us act according to that belief.

Thank you, Dave.

Next question, please.

The next question will be from Mohit Bansal from Wells Fargo. Mohit, your line is live. Great. Thank you very much for taking my question.

I have a question regarding sleep apnea. Now that you have sleep apnea on labor, how have the discussions with the prescribers as well as payers have gone so far? The one pushback we hear is that these patients are often treated by sleep specialists and there's a general shortage of those specialists here. So could you talk a little bit about the call points and then how you're thinking about this?

Great. Thanks, Mohit. We'll go to Patrick for the question on sleep apnea, what the discussions are like with some of the prescribers and the initial experience so far.

Thank you very much, Mohit. Yes, you're correct. It's the first pharmacological treatment ever approved for obstructive sleep apnea. There is a lot of lifting on our side, and we will approach that as we are approaching any new disease area, partnering with advocacy organizations, healthcare providers, and massive, massive efforts in terms of medical education. We expect this to go beyond the sleep specialist, but of course we are starting our efforts with the sleep specialist community, and I think that's been very well received so far, and we are meeting with them regularly, conducting speaker trainings, but with the aim to move to primary care, which is a necessity, because this is also a patient population that to a large extent remains undiagnosed, so primary care efforts are going to be required.

Great. Thank you, Patrick. Next caller, please.

The next question will be from Dave Reisinger from Learing Partners. Dave, your line is live.

Thanks very much. So my Inkerton-related questions have been asked. I wanted to just pivot to the long-acting, relaxing candidate, Follin Relaxin. And so the company had advanced it into a CKD trial in the fourth quarter but then recently canceled both the heart failure and CKD programs Dan, I'm hoping you could provide some more color on what drove the action, plus how you now view the long-acting relaxin mechanism, including potential for future development in other cardiopulmonary diseases. Thanks very much.

Great. Thanks, Dave. We'll go to Dan to talk about the Bullen Relaxin Program.

Thank you. I was disappointed with the results from the basic trial for sure. Relaxin is an interesting mechanism, I think, sort of validated by normal human physiology during pregnancy. But unfortunately, the results that we got in this trial didn't support proceeding with this molecule. I read that as speaking to the mechanism, but rather than the molecule. But I know others pursuing this mechanism, and I wish them success where we didn't have it. So we'll have to wait and see.

Thank you, Dan.

Next question, please.

The next question will be from Akash Tiwari from Jefferies. Akash, your line is live.

Thanks so much. So, at JPMorgan, your team mentioned you expect GLP-1 pricing to be relatively stable in 2025. Are you implying that while you'll give additional discounts to the channel to improve access, that will be offset by improved adherence, or is it more Lillie's reached a steady state on discounts, at least until Semic Blue Tide gets put under IRA negotiation in 2026. Thanks.

All right. Thanks, Akash. We'll go to Lucas to talk about GOP1 pricing trends.

Thanks for the question. In terms of the pricing trends that I alluded to in the JP Morgan conference and getting into 2025, first we talk about the Q4. And into 2025, what we mentioned basically is a continuation of the trends. Remember that we had in the base period in 2023 an uncovered copay that basically created quite a lot of noise on the year-on-year comparison. So we talk about basically adjusting by that. There's still single-digit erosion on our pricing trends, and that is the same trends that I alluded that will continue into 2025. In terms of some of the dynamics on the access side, I don't know if you want to comment anything, Patrick, on your side.

I think we have really good access on the Monjaro side, over 90% in commercial and party. And I've already covered the commercial space for a second. We expect access to continue to improve in 2025 as well. In terms of adherence, I think we just need to reflect on the dynamics that we have experienced in this market, partly due to supply constraints. But we are encouraged with what we see on Monjaro. For patients that started in Q2 2023, we actually see a longer adherence with Monjaro than we do with both Trulicity and Endosempic. And as Dave referred to earlier in terms of set-bound, we expect adherence to be long here based upon the first-hand experiences that consumers have.

Great. Thank you, Patrick. Thank you, Lucas. Next caller, please.

The next question will be from Alexandria Hammond from Wolf Research. Alexandria, your line is live.

Thanks for taking the question. With the Roe partnership, how does Lilly envision this relationship evolving? And a follow-up, can you help frame the opportunity associated with step-bound vials, and how is it expected to shift over time?

Great. Thanks, Alex. We'll go to Patrick to talk about step-bound vials and Roe.

Yep. We launched the self-pay system with Lilly Direct back in late August, and we are pleased with the performance so far. In terms of TRX for set-bound, it's still low to mid-single-digit, but in terms of new therapy starts, it's actually in the low teens, so a very good start. The partnership with Roe is not a financial or a marketing partnership at all. It's just the opportunity for eligible patients to have the option of using the Roe platform to purchase FDA-approved authentic medicines. And it's really about connecting that software to really direct self-pay pharmacy. We will lean into additional partnerships along those lines. with partners that really want to ensure that patients get access to authentic and FDA-approved medicines.

Thank you, Patrick. Next caller, please. The next question will be from Chris Shibutani from Goldman Sachs.

Chris, your line is live. Chris, please go ahead with your question. Your line is live.

Apologies, I was on mute. So the Orfaglipron launch, you previously stated that you're doing manufacturing scale-up to be prepared for a full launch at potential approval. What is embedded in that assumption? Can you talk a little bit about the approach for timing of Orfaglipron in terms of diabetes versus obesity? Will it be simultaneous or one before the other? U.S. versus international? We certainly saw the injectable business do a prioritized U.S. launch. And then should we also expect the similar kind of, quote, new product launch cadence with patient assistance programs and the implementation of channel tools like Lilly Direct? Should all those be at the outset?

Thanks. Thanks, Chris, for the very detailed question. We'll go to Dave to talk a bit about the Oracle Launch Prep.

Okay. Waiting for all allowance at some point. Yeah, look, the goal here with Orphor, because it's using different production systems that are available to us, it's a long cycle of processing to get a commercial product, but it's very predictable, and we have access to those platforms inside and outside the company. So we are building for a full launch in the normal pharma sense. And here, pointing out maybe the flip of the earlier question about demand, we have had to gate all these things. to make sure we carefully match supply and demand for the injectables as our competitor. We do not plan for that with Orfor. So we will plan to launch or submit and have approvals and then launch in a full sense, including activities you're used to seeing for primary care products like sampling, copay, full formulary access, and globalization of Orfor glupron as rapidly as possible. And we're building... capacities to do that, and hopefully that will begin in early 26. I think, as Dan mentioned, the first complete package for submission in the U.S. will be obesity. But we expect diabetes to shortly follow, and then these other indications that have been discussed today. Hope that answers the question.

Great.

Thanks, Dave. Next question, please. The next question will be from James Shin from Deutsche Bank. James, your line is live.

Thank you. Good morning. Thanks for the question. Another one for Dan or for Lipron. I appreciate the earlier comments on indexing Orphoglupon's efficacy to SEMA and the Phase III titration schedule. Sorry, excuse me. Can you go over how this titration schedule may impact the Phase II weight loss, A1C, and safety results published in Lancet and New England Journal? Thank you.

Great. Thanks, James, for the question. We'll go to Dan to talk more about Orpho.

Yeah, it's a good question, James, and reminiscent of the theme we had when the terzapatide trials were going. It was a similar transition from a faster titration in phase two to a more gradual titration in phase three. I think that strategy served us well in the case of terzapatide. I'm hopeful for the same kind of outcomes in orpaglifron, which is to say that it mitigated tolerability concerns, so the GI side effects that are just known to this class, seemed to be significantly mitigated by slower titration. And in longer studies, and the first study they read out is not the longest study we have here, in longer studies, we were still able to obtain the sort of plateau kind of efficacy that we expect for the mechanism. So that's what we're hoping for, or for better tolerability and similar efficacy as phase two.

Thank you, Dan. Next question, please.

The next question will be from Truong Huynh from UBS. Truong, your line is live.

Hi, guys. Thanks for taking my question. So for the first ortho study on diabetes, thank you so much for the level set there. I have a similar question on retitutide. We noticed in your slides there was a phase three readout in obesity and overweight patients with osteoarthritis of the knee as a potential event for 25. So one of the primary endpoints is weight loss. Could that be a reasonable comp for the obesity studies in 26, unlike what you flagged with ortho and diabetes?

Thanks for the question, Tron. We'll go to Dan to talk about Retatrutide.

Yeah, I'm glad you asked the question. It's a super smart question. You're probably noticing that the Osteros Thetis trial is shorter than any of the other ones. We've commented before that Retatrutide is going to need longer trials. Most of ours are 80-week-plus trials to reach maximal efficacy. This is a 68-week trial. I think we also know, at least by analogy from the SEMA trials that looked at osteoarthritis and obesity versus a more pure obesity population, that even for similarly-linked studies, there's a diminution of efficacy in terms of weight loss in the OA population for a number of reasons, including different baseline demographics, male, female, BMI, et cetera. So I think we know how to extrapolate out from the OA population to the general population but I don't think you should take the OA population as a point estimate for what will be achieved in a broader obesity population. We should do quite a bit better than that.

Great. Thanks, Dan.

Next question, please. The next question will be from Kripa Devarakonda from Truist Securities. Kripa, your line is live.

Great. Thanks for taking our question. This is Nicole. I'm for Kripa. Can we see some BEMA data this year, and do you still see some benefit with a muscle-preserving drug The recent data from VIRA showed preservation of lean mass, but no incremental weight loss. So, Bhima, do you expect incremental weight loss or weight-neutral but better body composition? Is that what you're looking for?

Thanks for the question. We'll go to Dan to talk a bit about how we're thinking about the BIMA data.

Yeah, thanks for a good question on BIMAgrimab. I think our thesis here has been, in combination with terzapatide, that we could get incremental weight loss or perhaps a similar weight loss, but as you point out, with preservation of what we call lean mass. I think to really show a benefit for combining the two drugs, we're probably going to either need to see the incremental weight loss, or we're going to need to see some real functional benefits to lean mass preservation. I think just lean mass on its own, we don't really know how to understand that. And we've previously noted that we don't see any signs that lean mass changes on terzapatide or, to my knowledge, on any incretin are actually adverse in any way. On the other hand, growing muscle could be a positive in different ways. So we're looking for new positive effects with the MagroMap. The beginning of your question, I realize I didn't come to, which is when do we see the previous Phase II study, which was completed? We haven't been clear on exactly when we'll show that data, but this year is a safe assumption.

Great. Thank you, Dan. I think we have time for one last question.

The final question today will be a follow-up from Dave Reisinger from Lyric Partners. Dave, your line is live.

Yes, thanks very much. I was just hoping you could clarify the comment earlier. I think there was a comment about additional PBM coverage coming in March. I didn't quite catch that. If you could just provide some more color and quantify the potential impact on you know, on the opportunity for script trends following that occurring. Thank you.

Let me cover that, and then I'll just close. I think, Dave, that was referred to MGLIS, which is very new in Cycle, and we do expect two of the three PBMs to cover it, and that gets us excited about activating consumers and raising awareness for that brand. Zepa and Majora have full PBM coverage already. So, great. Let's conclude it there. Thanks for dialing in, everyone, and you're interested in that. today's earnings call, and, of course, in everything about Eli Lilly and Company. If you've got follow-up questions or things we didn't cover in enough detail today in the Q&A, please follow up with the IR team. Mike Sapar leads that now. And everyone, have a great day.

Thank you. And, ladies and gentlemen, this does conclude our conference for today. This conference will be made available for replay beginning at 1pm today, running through March 13th at midnight. You may access the replay system at any time by dialing 800-332-6854 and entering the access code 443-262. International dialers can call 973-528-0005. Again, those numbers are 800-332-6854 and 973-528-0005 with the access code 443262. Thank you for your participation. You may now disconnect your lines.