Q2 2025 Earnings Call Transcript

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q2 2025 Earnings Conference Call. [Operator Instructions] I would now like to turn the conference over to your host, Mike Czapar, Senior Vice President of Investor Relations. Please go ahead.

Good morning. Thank you for joining us for Eli Lilly and Company's Q2 2025 earnings call. I'm Mike Czapar, Senior Vice President of Investor Relations. Joining me on today's call are Dave Ricks, Lilly's Chair and CEO; Lucas Montarce, Chief Financial Officer; Dr.

Dan Skovronsky, Chief Scientific Officer and President of Lilly Immunology; Anne White, President of Lilly Neuroscience; Ilya Yuffa, President of Lilly USA and Global Customer Capabilities; Jake Van Naarden, President of Lilly Oncology; Patrik Jonsson, President of Lilly International; and Ken Custer, newly appointed President of Lilly Cardiometabolic Health. We're also joined by Marc Kemen, Susan Hedglin and Wai Wong of the Investor Relations team. During this call, we anticipate making projections and forward-looking statements based on our current expectations. Our actual results may differ materially due to several factors, including those listed on Slide 4. 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 and it's not intended to be promotional and is not sufficient for prescribing decisions. As we transition to our prepared remarks, please note, our commentary will focus on our non-GAAP financial measures. Now I'll turn the call over to Dave.

Thanks, Mike. Q2 was a strong quarter. We delivered robust revenue growth, shared top line clinical data from multiple Phase III programs and invested in several initiatives that will support our future growth. Today we shared positive top line data from the ATTAIN-1 orforglipron trial in people with obesity.

In ATTAIN-1, patients taking the highest dose of orforglipron lost more than 27 pounds or 12.4% of their body weight. In addition, the safety and tolerability in ATTAIN-1 was consistent with the injectable GLP-1 class. Orforglipron also met all secondary endpoints in the study, improving key markers of metabolic health such as blood pressure, cholesterol and inflammation. This is the second positive Phase III trial for orforglipron we reported this year, and we're encouraged by these results.

Our goal from the beginning was to create a medicine that has a clinical profile consistent with approved GLP-1 while offering the convenience of a once-daily pill and the production flexibility of small molecule chemistry to meet global demand. We believe this medicine has the potential to make a significant impact on human health, and we will now work with urgency to submit orforglipron around the world to meet the global challenge of obesity. On Slide 6, we list key Q2 financial metrics and highlight progress related to our strategic deliverables. Revenue grew 38% compared to Q2 2024, driven by our key products.

These include Ebglyss, Jaypirca, Kisunla, Mounjaro, Omvoh, Verzenio and Zepbound. In the U.S., we continue the robust uptake of Zepbound and Mounjaro, and Lilly gained market share in the incretin analog class for the fourth quarter in a row. Mounjaro also recently became the market leader in the U.S. in total prescriptions within the type 2 diabetes incretin market. Outside the U.S., we continue to launch Mounjaro in new countries.

These include Mexico and Brazil, most recently. We have now launched Mounjaro in most major markets. Q2 was also a quarter of continued investment for Lilly. In addition to increasing commercial activities to support our newest medicines we started multiple new clinical programs.

While the company is experiencing rapid revenue growth, we're also increasing our R&D investment as early phase program data continues to impress us, and to support our future growth of the company. Our financial performance in the first half of 2025 was strong. And as a result, we raised our revenue and earnings per share guidance. Lucas will cover this in more detail during the financial update.

In addition to the results from ATTAIN-1, we achieved several key milestones since our last earnings call. These include the U.S. FDA approval of a new dosing schedule for Kisunla, the positive European CHMP opinion for Kisunla. Announced positive results in the SURPASS-CVOT Phase III trial for tirzepatide in people with type 2 diabetes and heart disease.

We announced positive results in the BRUIN CLL-314 Phase III trial of pirtobrutinib in CLL and SLL. And we launched the 2 highest doses of Zepbound in vials in the United States. We announced and closed the acquisition of SiteOne Therapeutics, which expands Lilly's pain portfolio and adds a clinical-stage non-opioid pain program to our mix. And Verve Therapeutics, which adds new genetic medicines for cardiovascular disease with potential to only be administered once in a person's lifetime.

We made progress in Q2 and throughout the first half of 2025 to bring new manufacturing capacity online. We produced more than 1.6x the amount of salable incretin doses during the first half of 2025 when compared to the first half of 2024. This includes a significant step-up in capacity from our recently constructed facility in Research Triangle Park, North Carolina. We will continue to bring more capacity online in the second half of 2025 and expect our production capabilities to increase further. We also plan to announce the location of 2 of our new U.S. manufacturing facilities later this quarter.

During the quarter, we distributed $1.3 billion in dividends and executed approximately $700 million in share repurchases. Before I turn the call over to Lucas, I'd like to offer some perspective on the drug pricing reform discussion that's going on. While we support the administration's position that medical research costs need to be shared more equitably across developed countries. It's also true that the U.S. pharmaceutical market has significant defects, which shift cost to consumers and increase red tape.

These problems also require urgent reform and make apples-to-apples comparisons of ex-factory pricing inaccurate and misleading. At Lilly, we've already implemented several initiatives, which directly lower patient costs for our most commonly used medicines. We operate a direct-to-consumer model at scale through LillyDirect, which provides more affordable access to Lilly medicines. This includes our leading weight loss medications Zepbound at a discount of more than 50% off the list price.

We also led in resolving insulin pricing issues in our country by reducing list prices by 70% and ensuring broad access to $35 monthly patient costs, including for Medicare. Negotiated prices in Europe come with broad access, low patient co-pays and without administrative hurdles like prior authorizations. There are also no intermediaries that distort prices, and hospitals do not seek profit by selling medicines and marking them up. If we import foreign price controls and insert them into a U.S. system that isn't built to function for patients, we risk embracing the worst of 2 worlds, the low productivity and output of Europe's biopharma sector with the high out-of-pocket and distorted prices of the U.S. insurance market.

Both today's patients and the future of new cures and treatments will suffer along with the United States competitiveness. Of course, we will engage and are committed to working constructively with the administration to find solutions that both benefit patients while preserving the hope for tomorrow's cures and the scientific base that has made America the envy of all in global pharmaceutical innovation. Now I'll turn the call over to Lucas to review our Q2 results.

Thanks, Dave. As shown on Slide 7, Q2 was another strong quarter of financial performance. Revenue grew 38% compared to Q2 2024, driven by our key products. Gross margin as a percentage of revenue was 85% in Q2, an increase of 3 percentage points versus the same quarter last year.

The increase in gross margin was primarily driven by improved cost of production and favorable product mix, which were partially offset by lower realized prices. Marketing, selling and administrative expenses increased by 30% as we continue to increase investment to support our newest launches across therapeutic areas and geographies. R&D expenses increased 23%, driven by higher expenses for late-stage assets and additional investment in early-stage research. Our non-GAAP performance margin, which we defined as gross margin less R&D, marketing, selling and administrative expenses, as a percentage of revenue was 45.9%.

Performance margin increased by more than 6 percentage points from Q2 2024 driven by revenue growth. Our Q2 effective tax rate was 16.5%, consistent with Q2 2024. At the bottom line, earnings per share increased 61% to $6.31, including of a negative impact of $0.14 from acquired IPR&D charges. This compares to $3.92 in Q2 2024, which also includes $0.14 of acquired IPR&D charges. On Slide 8, we quantify the effect of price, rate and volume on revenue growth.

U.S. revenue increased 38% in Q2 driven by strong volume growth of Zepbound and Mounjaro, partially offset by an 8% decline in price. In Europe, revenue grew 77% in constant currency, reflecting the strong uptake of Mounjaro. Japan revenue grew 7% in constant currency, driven by Mounjaro and Ebglyss. In China, revenue increased 19% in constant currency, driven by volume growth of Mounjaro.

Revenue in the rest of the world decreased by 1% in constant currency, driven primarily by stocking in the base period related to Mounjaro launches in new markets. This impact was largely offset by volume growth of Mounjaro and Verzenio this year. Slide 9 provides an update of the performance of our key products. Beginning with immunology, Ebglyss continues to perform well in atopic dermatitis.

New patient starts and revenue trends are strong and total prescriptions have nearly doubled since Q1. We also made progress securing access and Ebglyss is now covered by all 3 of the largest pharmacy benefit managers that represent 90% of people with commercial insurance. For Omvoh, we are 1 full quarter into the launch in Crohn's disease and are making progress in a competitive market. The new citrate-free formulation is available in most major markets and we are seeing positive trends in new patient starts in the U.S., Germany, Japan and other international markets. Moving to oncology.

Physician feedback on Jaypirca continue to be very positive. While still only approving later lines of CLL and MCL, we have seen a strong uptake within the label population and encouraging trends regarding time on therapy. We continue to generate additional data in Phase III trials that we believe will support an expanded label and use in early settings. We recently announced positive results of BRUIN 314 in CLL and SLL, is another positive step forward those goals.

Verzenio global sales grew 12% in Q2 driven by volume growth. Verzenio continued to be the NBRx and TRx market leader in the U.S. and a standard of care in high-risk early breast cancer. U.S. prescriptions grew by 4% in Q2 compared to Q2 2024 and international volume grew by 18%. Within neuroscience, Kisunla is continuing a steady launch trajectory, and we are making significant progress in driving health care system readiness and adoption.

In the U.S., we are seeing a strong diagnostic growth driven by PET and the acceleration of blood biomarker test. This momentum is leading to more people being diagnosed and accessing treatment. Over 1,500 physicians and 150 of the top health care organizations have started patients on Kisunla. Outside the U.S., efforts are progressing as well with approval in 13 countries.

In Europe, we anticipate approval and launch later this year following the recent CHMP positive opinion. Finally, moving to cardiometabolic drugs. Mounjaro and Zepbound both delivered impressive performance. Mounjaro posted $5.2 billion of global sales and exited the quarter with more than 50% of new type 2 diabetes incretin prescriptions in the U.S.

Mounjaro also became the U.S. market leader in total type 2 diabetes incretin prescriptions in July and has gained 8 percentage points in total prescription share of market during the first 7 months of 2025. With the recently announced positive results from SURPASS-CVOT, we look forward to submitting this data to global regulators to support a label cardiovascular indication. Outside the U.S., tirzepatide is now launched in most major markets. As a reminder, Mounjaro is marketed as a single brand for both chronic weight management and type 2 diabetes in all international markets except Canada and Japan.

While the initial reception of recent launches in Mexico, Brazil, China and India has been excellent, the commercial activities have been measured to ensure demand doesn't exceed supply and that patients and physicians have a good experience. Zepbound performance was strong in Q2, contributing $3.4 billion of sales. Zepbound continues to be the U.S. market leader in the branded anti-obesity market with 2/3 of total patients taking Zepbound. We recently launched the 12.5- and 15-milligram single-use vials in LillyDirect.

All doses of Zepbound are not available in the vial presentation. While we want to secure broader reinvestment of anti-obesity medicines, we are encouraged by the uptick of Zepbound in vials. The cash pay vials were approximately 20% of total U.S. Zepbound prescriptions and over 35% of new prescriptions in Q2. As a reminder, effective July 1, the CVS pharmacy benefit manager began excluding Zepbound as an offering for patients on its template formulary insurance plans.

This has caused significant disruption to patients, and we strongly disagree with the decision to restrict access to medicines for patients. As demonstrated in randomized clinical trials, incretin medicines for chronic weight management are not all the same. While it's still early, we have seen this decision negatively impact Zepbound prescriptions during July and expect it to be a headwind to the rate of volume growth in Q3. We remain confident in the long-term growth outlook for Zepbound as the most widely used incretin therapy in the branded anti-obesity market. On Slide 10, we provide a view on the U.S. incretin analog market, which include prescription for both type 2 diabetes and chronic weight management.

Q2 was another quarter of steady market growth as total prescriptions grew by 41% compared to Q2 2024. Lilly performance was again strong with share of market reaching above 57%, an increase of 3.8 percentage points compared to Q1 2025. While market growth continue to be robust, overall penetration into the addressable population is still low and we believe significantly more patients can benefit from incretin therapy. On Slide 11, we provide an update on capital allocation. Moving to Slide 12, this is our updated expectation for our 2025 financial performance. We are encouraged by the underlying performance we saw across the business in the first half of the year.

We are increasing the bottom and the top end of the revenue range as well as our expectation for performance margins and earnings per share. We now anticipate our revenue will be between $60 billion and $62 billion. This range reflects the strong performance and a tailwind from foreign exchange rates. We will continue to invest to support our newest launches and to develop new medicines.

Given our updated expectations for revenue growth, we now expect non-GAAP performance margin to be between 43% and 45.5% as a percentage of revenue. The potential effect of tariffs remains dynamic, and we will continue to update our estimate as the situation changes. We expect the 2025 impact of currently announced tariffs to be modest, and this has been factored into our 2025 guidance range. At the bottom line, we have increased our outlook for non-GAAP earnings per share and expect EPS of $21.75 to $23. As Dave mentioned earlier, we exceeded our incretin salable doses production in the first half of the year and expect to bring more capacity online during the second half of 2025. We expect to produce at least 1.8x the number of salable incretin doses in the second half of 2025 compared to the second half of 2024. Now I will turn the call over to Dan to highlight our progress on R&D.

Thanks, Lucas. We've made quite a bit of progress since our last earnings call. During just the past 2 weeks, we shared 3 Phase III readouts from some of our most important molecules. I'll start with these.

Last week, we announced results from the tirzepatide SURPASS-CVOT trial, where tirzepatide demonstrated cardiovascular protection in a landmark head-to-head trial which was the first ever cardiovascular outcomes trial comparing 2 incretin therapies in people with type 2 diabetes and cardiovascular disease. It included over 13,000 participants across 30 countries and it is the largest and longest study of tirzepatide to date. As shown on Slide 13, tirzepatide achieved the primary objective of the study, demonstrating non-inferiority compared to Trulicity with an 8% lower rate of MACE-3 events. Tirzepatide showed consistent results across all 3 components of the MACE-3 composite endpoint.

We were particularly impressed to see the rate of all-cause mortality was 16% lower on tirzepatide versus dulaglutide. Because this trial did not include a placebo arm, we conducted a prespecified indirect comparison analysis of matched patient level data from the REWIND and SURPASS-CVOT studies. This analysis showed that tirzepatide reduced the risk of MACE-3 by 28% and reduced all-cause mortality by 39% compared to putative placebo. We're very pleased with these results, which show that in addition to the well-established best-in-class weight loss and A1C control, tirzepatide now also provides a cardioprotective benefits and may provide more wide-reaching health improvements, including greater kidney protection and a reduced overall risk of death.

We look forward to detailed results being presented at the EASD Meeting in September and published in a peer-reviewed journal. We plan to submit these data to global regulators by the end of this year. The SURPASS-CVOT results reinforce our enthusiasm for SURMOUNT-MMO, which enrolled over 15,000 participants with obesity, and will assess the impact of tirzepatide on reducing morbidity and mortality. This is an event-based study and the rate of accrual will dictate the timing of the readout.

While SURPASS-CVOT and SURMOUNT-MMO are likely the largest randomized trials we'll conduct with tirzepatide, we'll still explore additional indications for this molecule. And we're excited to have started a new Phase III trial in people with type 1 diabetes. Moving on to orforglipron. As Dave mentioned, today we're excited to announce top line results from our second orforglipron Phase III trial, ATTAIN-1. This trial included people with obesity, but without type 2 diabetes.

As shown on Slide 14, patients in ATTAIN-1 lost on average between 7.8% and 12.4% of their body weight after 72 weeks depending on the dose. At the highest dose, the average participant on orforglipron lost more than 27 pounds, and approximately 40% of people on this dose lost more than 15% of their body weight. We also saw notable improvements on important drivers of cardiovascular risk, including non-HDL cholesterol, triglycerides and blood pressure. Moving to Slide 15. We are very pleased with the safety profile of orforglipron in ATTAIN-1. The most commonly reported adverse events were gastrointestinal, which is consistent with the GLP-1 class.

Discontinuations due to adverse events were low, with 5% to 10% of patients discontinuing orforglipron across doses. There were no hepatic safety signals. We look forward to sharing detailed results from ATTAIN-1 also at the EASD Meeting in September and in a peer-reviewed publications. With today's readout, we've now seen results from 2 large Phase III clinical trials involving over 3,600 participants.

And we're highly encouraged with what we've seen thus far. The data from these first 2 pivotal studies provide evidence that a once-daily oral GLP-1 can achieve efficacy and safety in line with injectable GLP-1s. Orforglipron has the potential to be a more convenient alternative to injectable treatments and to be utilized to support early disease intervention in the primary care setting. With these data in hand, we're now working to move quickly towards our first regulatory submissions yet this year.

We expect results from 4 additional orforglipron Phase III trials over the next 5 months, 3 trials in people with diabetes from our ACHIEVE program. and 1 additional trial from the ATTAIN program in people with diabetes and obesity. ATTAIN-1 and ATTAIN-2 will support global submissions for chronic weight management, which we expect in Q4. In addition to the ongoing Phase III trials for orforglipron in diabetes, obesity, weight maintenance and obstructive sleep apnea, we initiated a new program for orforglipron this quarter, ATTAIN-Hypertension, focused on reducing systolic blood pressure at 36 weeks as the primary endpoint.

This is the first study of orforglipron that includes patients with a baseline BMI as low as 25. We also announced plans to initiate a new Phase III trial in people with knee osteoarthritis pain in overweight or obesity starting later this year. Moving to pirtobrutinib. We announced positive results from the BRUIN CLL-314 Phase III trial of pirtobrutinib compared to ibrutinib in people with CLL/SLL. This trial included treatment-naive patients as well as patients previously treated but not with the BTK inhibitor.

Pirtobrutinib met the primary endpoint of response rate non-inferiority compared to ibrutinib and had a nominal p-value for superiority that was less than 0.05. While progression-free survival data were immature, there was a positive trend in favor of pirtobrutinib. Additional testing for progression-free survival is planned as part of a future analysis. Of note, the subpopulation of treatment-naive patients had a particularly pronounced progression-free survival trend in favor of pirtobrutinib. This subpopulation had the longest follow-up which is encouraging for what we might see more broadly across the total study population over time.

This is a second positive Phase III trial to read out for pirtobrutinib as we continue to build evidence supporting the potential role for this medicine in earlier settings. We look forward to the readout of BRUIN CLL-313, which assesses pirtobrutinib versus chemoimmunotherapy in treatment-naive CLL/SLL later this year. We expect these data in combination with BRUIN CLL-314 to form the basis of regulatory submissions globally. In addition to our recent Phase III readouts, we also have updates on several other important molecules, donanemab, retatrutide and olomorasib.

For donanemab, we had 3 important milestones since our last earnings call. First, we were pleased to receive a positive opinion from the CHMP in the EU. We look forward to approval and launch there later this year. Second, the modified dosing schedule was approved in the U.S., further strengthening the safety profile for donanemab, and we expect the modified dosing regimen to be part of the EU labeling at launch as well.

Finally, we shared long-term extension data from TRAILBLAZER-ALZ 2, which demonstrated that, over 3 years, donanemab-treated participants showed increasing clinical benefit despite most participants having completed treatment within the first 18 months of the trial. In a separate part of the extension study, patients initiating donanemab after 18 months of placebo, also demonstrated disease slowing once they started donanemab. These data reinforce the value of early intervention and support the limited duration dosing approach with sustained and increasing long-term benefits for treatment. For retatrutide, we started a new Phase III trial in chronic low back pain in overweight or obesity, called TRIUMPH-7. This is our second pain study for retatrutide in addition to the ongoing study in osteoarthritis pain of the knee, TRIUMPH-4 from which we expect results later this year.

We are excited to announce plans to initiate a Phase III study in high-risk metabolic dysfunction-associated steatotic liver disease or MASLD later this year. This trial includes both retatrutide and tirzepatide, and it will utilize non-invasive tests to enroll patients who are at high risk of major adverse liver outcomes, with a primary objective of reducing the occurrence of such outcomes. This novel trial design more closely mirrors how physicians diagnose this disease in clinical practice and will enable simultaneous development of both medicines each compared to placebo. In a prior Phase II trial in MASLD, retatrutide reduced liver fat by over 80%.

And in a Phase II trial in MASH, tirzepatide led to over half of patients meeting criteria for resolution of MASH without worsening of fibrosis. We believe each of these medicines has the potential to make a profound impact on this disease, and we look forward to initiating the study later this year. Moving to olomorasib. We started a Phase III trial in unresected adjuvant lung cancer.

This marks the fourth indication we are simultaneously pursuing for olomorasib in KRAS G12C-mutant lung cancer as part of the SUNRAY-01 and SUNRAY-02 programs. We believe olomorasib in combination with immuno-oncology agents in an early setting could improve the standard of care for patients with KRAS G12C-mutant lung cancer. I'm also excited that through business development, we've added new molecules to our portfolio and new colleagues to our team, and it's a pleasure to welcome new team members from SiteOne and Verve to Lilly this quarter. With SiteOne, we added a new pain asset into our neuroscience portfolio, STC-004 is a Nav1.8 inhibitor that's shown encouraging early data to treat pain.

We believe this molecule could be an important non-opioid therapy for pain in the future. Through the acquisition of Verve Therapeutics, we added several genetic medicines for cardiovascular disease that may only need to be given once in a lifetime. The most advanced programs are VERVE-102, which targets PCSK9, and VERVE-201, which targets ANGPTL3. And in our early phase portfolio, we advanced nisotirostide, our PYY analog agonist into a Phase II trial in people with diabetes. And we initiated Phase I clinical trials for glucose-sensing insulin, a PTK7 antibody drug conjugate in oncology and a next-generation triple agonist in cardiometabolic health.

We also discontinued 2 Phase II programs, Kv1.3 antagonist for psoriasis and mazisotine for pain, and 2 Phase I programs itaconate mimetic in immunology and SCAP siRNA in MASH. It was a productive period since our last earnings call, and we still have an ambitious R&D agenda for the last 5 months of 2025. I'll now turn the call back to Dave for some closing remarks.

Thanks, Dan. We're really pleased with all the progress in Q2 across our strategic agenda. We've had another quarter of strong financial results. We continued the build-out of our manufacturing footprint and advanced our pipeline, as Dan just highlighted, with external and internal R&D projects.

We have good momentum as we enter the second half of 2025, and we're focused on execution with our currently marketed products, and we're investing in the next wave of medicines that we expect will drive growth in the near and more distant future. So now let me turn the call over to Mike to moderate a Q&A session.

Thanks, Dave. We would like to take questions from as many callers as possible. So consistent with prior quarters, we will respond to one question per caller, and we'll end the call promptly at 9:30 a.m. Please provide the instructions for the Q&A session, and then we are ready for the first caller.

[Operator Instructions] The first question today is coming from Chris Schott from JPMorgan.

Just wanted to kick off with orforglipron. There's obviously a bit of a debate out there this morning on the weight loss profile you're showing for the product, which clearly looks efficacious but maybe a touch below Wegovy. Can you just help put the data into context and just, in general, your thinking of where orfo fits into the treatment landscape versus Zepbound and Wegovy now that you have these results in hand?

Great. Thanks, Chris. We'll go to Ken to answer the question about the orforglipron profile.

Yes. Thanks, Chris, for the question about orforglipron. We're really pleased with the data we've disclosed this morning, really the idea that you can get 27 pounds of weight loss from a single pill and also get really encouraging effects on other important biomarkers, things like blood pressure, lipids, inflammatory biomarkers and fasting glucose. Those are a lot of the things that HCPs are really managing when they think about preventative care.

Now you're getting that all from a single oral pill, but we can manufacture at scale. We also know that simplicity matters in this space and the instructions for use here are going to be pretty simple. Take it once a day without regard to food and water. Of course, the data we're sharing today are in patients with overweight and obesity, but we are evaluating orforglipron in a lot of other settings that includes other disease areas like diabetes and obstructive sleep apnea and OA knee pain.

We're also evaluating in other context for the treatment of obesity. Right now, we have the ATTAIN-MAINTAIN study ongoing, which is also testing orforglipron as a potential maintenance therapy for patients who have lost drugs -- who lost weight on drugs like Zepbound, to see whether they can keep that weight off. So we really see a wide-ranging opportunity for orforglipron. I couldn't be more pleased with the totality of the profile we disclosed this morning.

The next question will be from Seamus Fernandez from Guggenheim.

Mine is actually on pricing and the pricing environment going forward. I was just hoping, Dave, you could discuss a little bit more your views on the path for price with orforglipron and the growing number of assets coming to market. I think that's been probably the #1 overhang, especially as it relates to the continued availability of compounding. So just trying to get a better understanding of where you see price going and maybe if you can provide some thoughts on compounding in that context and how you maintain tirzepatide compounding off-market when it's being ignored with semaglutide.

Thanks, Seamus. Dave, we'll go to you to talk about the broader pricing environment and potentially weaving in some compounding commentary.

Okay. Yes. Thanks, Seamus. As relates to compounding, let me just deal with that first.

We've always been concerned about this because of the patient safety risk that exists. And every day, we get calls from patients concerned that they are getting ill on a medicine they think is ours, and it's not. This, of course, was allowed during drug shortage. There's no drug shortage.

And we really think that regulators and law enforcement officers in the U.S. need to step up their game to really eliminate this. That's why we have an FDA and a structured regulatory process in the U.S. And so we want to see that, and mostly because people are being harmed. We see robust growth in the marketplace in the U.S., 42% total incretin growth over last year, good sequential growth.

And of course, Lilly's growth is more than double that. So we're -- the business is fine, but people shouldn't be harmed. That said, I think on pricing, we've always had a philosophy across all medicines, including with incretins, to price to value. And given the profile we present to consider offsetting other health care costs, including medicines, the value to the patient, the value in the economy as well, and here with GLP-1 and incretin mechanisms, we're seeing profound value, frankly.

So we're noticing a difference in when we offer consumer level pricing outside of insurance. But inside of the health care system, which is most of the business, we think that we'll expect single-digit erosion like we do other chronic medications in net pricing, while maintaining a value point on list that makes good sense. That's not considering any new policy environment, but that's our philosophy going forward. So as we have a suite of products with somewhat perhaps more value in patients with more complicated obesity, or those that may be have less complicated obesity, but medicines like orforglipron that could reach the masses, of course, we'll consider those factors in price setting at the list level and then the net will find its level in negotiations.

And you can continue to expect Lilly to offer consumer level pricing as long as we have such a large hole in coverage in our country for important chronic disease like obesity that should be covered. Those are our views on pricing.

The next question will be from Geoff Meacham from Citibank.

Dan, on orforglipron, looking at the discontinuation rate, it looks competitive for ATTAIN and ACHIEVE. But can you talk about how the GI adverse event rates changed over the course of the studies? And were there common futures among those with the highest adverse event rates? Obviously, thinking how this could play out from a commercial context.

Thanks, Geoff. Dan, we'll go to you to talk about some of the orfo, GI profile over time.

Yes. Thanks, Geoff. No surprises in there. The GI profile was as expected for a GLP-1 agonist, which is to say that most of the side effects occur early in the disease -- early in the treatment course or with dose escalations, and then they go down over time.

In terms of any specific patient characteristics that predicted, I don't believe we saw that in the study nor have we seen that in prior studies with GLP-1. So really no differences here that we thought were noteworthy versus monotherapy GLP-1 injectables.

Next question will be from Tim Anderson from Bank of America.

I wanted to ask -- it's kind of a compounding question in a way, I guess. Canadian generics for Novo's semaglutide, they're likely to launch in early '26. I think everyone can agree that tirzepatide is a better product, but won't this still cause a lot of trouble in the market where there's a big cash pay channel and where we already know that patients have proven themselves to be price-sensitive and willing to use a lesser product like a knockoff semaglutide? Seems to me Canadian generics are just a replacement for that compounding channel, and they'll keep that headwind alive even if compounders get shut down.

And we're talking about a product here that will have gone through a regulatory review cycle, not by FDA, but by another regulator. So with that launch 6 months away, is that a headwind that we should expect may continue?

Okay. Thanks, Tim, for the question on the Canadian generics impact. We'll go to Ilya to answer that one.

Yes. Thanks for the question. Maybe I'll touch on what we're currently seeing in the U.S. market and if you assume looking at the self-pay market that what we're seeing in vial performance and overall market is continuing to grow at rapid pace. We're seeing that our offering with the vial with Zepbound and the profile that we have with Zepbound is meeting a need for patients even in the context of noise, whether you have compounded or sema in the market.

If you take a look at just the growth that we've seen in Q2, we've generated over 1 million TRx in vial in Q2. And we recently launched last week, the highest doses of vial available for Zepbound. And we're continuing to see health in that market. Roughly 20% of our overall TRx is coming from the cash pay market and we continue to see strength overall, both in self-pay and in covered. We're seeing around 65% share market in new therapy starts for Zepbound overall.

So we see health in the market and where Zepbound provides a greater value.

The next question will be from David Risinger from Leerink Partners.

So I was hoping to better understand the evolution of U.S. employer coverage for anti-obesity medicines and the prospects. So my understanding is that coverage has been pretty flat on a net basis over the last 18 months, let's say, since January of '24, meaning the net covered lives has been flattish. If you can confirm that that's correct. And then can you talk about the outlook for the net change in U.S. employer coverage for anti-obesity medicines over the next 6 months or so for January of '26?

Great. Thanks, Dave, for the question. We'll go to Ilya to talk about the progress in the Zepbound employer coverage opt-in.

Sure. Thanks for the question, Dave. As we take a look at employer coverage, it's important for us to grow coverage over time. What we've seen in different offerings across the different plans, and some are more complex than others, and we've seen an increase overall, but it has been steady around 50% to 55% employer opt-in coverage.

At the same time, we are seeing new benefit designs, like, for instance, Evernorth, a cap on out-of-pocket for employees that make the prior authorization simplified, and that may grow employer opt-ins over time. That's something that we're working through. Our outlook is that as evidence grows and we find new ways and also different plan designs are available to different employers that, that will continue.

The next question will be from Terence Flynn from Morgan Stanley.

Congrats on all the progress. Just wondering on orforglipron in light of the ATTAIN-1 data, if you can just frame expectations for us down for the upcoming ATTAIN-2 Phase III data. And then any early insights into the potential CMMI obesity, Medicare/Medicaid pilot that I think we saw some press reports about?

For that we'll go to Ken to answer the question on expectations for ATTAIN-2.

Thanks, Terence, for the question on ATTAIN-2. We're very pleased with what we disclosed this morning in ATTAIN-1, which is our first Phase III study in obesity without diabetes. And of course, we had a great result with ACHIEVE-1 in patients with diabetes. So as we look ahead to ATTAIN-2, we expect similarly encouraging results. The exciting thing about ATTAIN-2 is that will be our third Phase III study, and it sets us up to submit to in obesity by the end of this year.

So really no change in expectations here. The team is full speed ahead preparing for submission by year-end and a potential approval next year.

The next question will be from Courtney Breen from Bernstein.

Just coming back to another question on orfo. As we looked at kind of comparing the data between ATTAIN-1 and ACHIEVE-1, we do see that kind of nausea, vomiting, constipation all appear a bit higher in this ACHIEVE-1 study. Can you talk a little bit about the differences in those data points that we're seeing between those 2 studies and what that might mean for adherence in the real world?

Courtney, thanks for the question on comparing ACHIEVE versus ATTAIN. I think, Dan, maybe a couple of quick comments.

Yes, sure. Thanks, Courtney. I think the side effect profile in both of these trials was consistent with past experience for GLP-1 monotherapy in these populations, which are different, as you're pointing out, that side effect profiles can be different in people with type 2 diabetes versus people without type 2 diabetes and with obesity. So I think we feel quite confident overall about the profile here.

Of course, I think I'd just emphasize once again this is a GLP-1 monotherapy. We know that dual agonism with GLP-1 and GIP1 can offer superior results. We have that as an injectable as tirzepatide. But I think, actually, this is as good as it gets for GLP-1 monotherapy here in a once-a-day small molecule oral.

So we're pretty excited with the profile.

The next question will be from Mohit Bansal from Wells Fargo.

Dan, if you could comment on the gender split in the orforglipron study, if there was any difference versus any other trials for GLP-1 that you would want to highlight here?

Thanks, Mohit, for the detailed question. We'll go to Ken to talk about the gender split, if there's anything to flag?

Thanks, Mohit. Gender split for baseline population in ATTAIN-1 was about 64% across the board, well balanced across -- or 64% female across all arms, balanced. Nothing really to remark on here.

The next question will be from Asad Haider from Goldman Sachs.

Congrats on the quarter. Just going back to channel dynamics. On the LillyDirect channel, clearly, Zepbound growth has been getting a lot of momentum with the new-to-brand prescriptions. Where do you think this could stabilize?

And how is that segment changing the landscape on pricing? And then related, I think, Lucas, you previously framed this DTC offering for Zepbound as a hedge or a bridge solution as you continue to grow access in the reimbursed channel. So any evolution in your thinking on that front given DTC offerings are now getting framed as one way to satisfy the administration's demands on drug pricing?

Okay. Thanks for the question, Asad. Lucas, you want to give some commentary on the LillyDirect sort of evolution and outlook from here?

Yes, sure. Thanks, Asad, for your question. First of all, I just wanted to highlight the great products that we see in LillyDirect. I think Ilya alluded about the total TRx prescription that we see in the second quarter, 1.1 million TRx, fantastic growth.

And now we are adding the 12.5 and 15 milligrams launch as well. So great progress that we are seeing, and you see that data as well that you have access, Asad, in terms of the number of total TRx as a percentage of the total Zepbound business. So progressing very nicely, very pleased with that. You mentioned about, again, the hedge.

Yes, I shared that with you a time ago. That's the way that we think about it, going back to the previous questions about employer. As we see that progressing, we always thought that it would be a gradual progression on the employer access. We see the LillyDirect as an option to bridge that, right, as a hedge strategy to bridge that.

So we still see it the same way, but is progressing very nicely and it's growing very -- is actually contributing to our performance this quarter and for the rest of the year as well. So that's more of the commentary and the color that we can provide today on that.

The next question will be from Umer Raffat from Evercore.

I'm just still trying to get my head around the orforglipron data. On the one side, I see your efficacy estimand at 11.5%, placebo adjusted, being very consistent with what Novo showed with their oral sema data in OASIS 4. But on the more important ITT-like treatment estimand, orfo is tracking at 9% placebo adjusted. Oral sema is almost 14% placebo adjusted. And I'm just trying to understand what explains that delta.

And does it prompt the need for a 45-milligram cohort considering how the safety is tracking?

Thanks, Umer. We'll go to Dan to provide maybe some final commentary on pain.

Yes. Thanks, Umer. I'm not sure I tracked exactly with your numbers. But look, I think overall, the profile here landed pretty much where you could expect a GLP-1 monotherapy to land.

It's tough to compare different trials done at different time periods in different populations. But I think overall, given the patients we enrolled and the trial we ran, this is what GLP-1 agonism can give you. I don't see this as any issue at all in the real world or in -- for patients or doctors. I know Wall Street is kind of focused on the exact numbers here in making cross-trial comparisons, but I don't think that carries over to the real world at all.

Next question will be from Steve Scala from TD Cowen.

With what is widely viewed as disappointing orforglipron data, it seems injectables are where it's at for the foreseeable future. On the Q1 call, Lilly said the likely impact of the Novo deal with CVS would be modest. But today, you are saying there could be an impact in Q3. And for Lilly to call it out in the prepared remarks, it must be pretty meaningful. So can you tell us what changed in the marketplace for the injectables?

Great, Steve. Thanks for the question. Maybe to give some commentary on CVS, we'll go to Ilya.

Sure. Thanks, Steve, for the question. As we take a look at our Q2 performance and the health of both the market and where Zepbound has gained share, and we added around 1.7 million TRx in Q2, the overall impact, I think what we've discussed prior is a couple of hundred thousand TRx volume that may vary. It's still early in the transition to CVS and, obviously, that creates frustration for employers, for providers, for patients, and we don't agree and disappointed with CVS decision.

At the same time, in terms of impact, you'll have some medical exceptions, and overall, in the context of growing 1.7 million TRx, we view -- and you look at July TRx as a proxy where on average, it's back to around May average TRx, we see continued growth and very good performance across all segments for Zepbound, both in covered as well as our cash pay market. And so we expect continued growth. I think the commentary is more about the rate of growth. So obviously, some new patient starts related to CVS template only may have some impact on growth.

But overall, the growth is healthy across all other segments.

The next question will be from Alex Hammond from Wolfe Research.

Another one on orforglipron. So I noticed you included the total discontinuation rates in the PR when you normally don't. Does that suggest that you think there was an underlying driver of these unusually elevated dropout rates across all arms? And could they have impacted efficacy?

Thanks, Alex. We'll go to Ken to talk about the inclusion of the overall discontinuation rates and how that may have been in some other press releases as well.

Yes. Thanks, Alex, for the question on discontinuation rates. What we disclosed, of course, with the rate of discontinuation in ATTAIN-1 for placebo of 29.9%, and then for orforglipron, ranging from 22% to 24%. We don't think there's anything remarkable there.

And we've disclosed these information on previously Lilly programs. I think on SURMOUNT-1, we did. Maybe to put this in a little bit of context, if you look at analogous studies in obesity, really placebo rates are in the 20s. If you take maybe step one, 22% placebo rate for discontinuation and about 5 points lower for active comparator.

That's exactly what we see here on the delta. So really nothing remarkable here. The more important thing to look at, of course, patients can discontinue study for a whole host of reasons. They can just withdraw their consent because it doesn't fit with their life, maybe they're not getting the efficacy they need, and that's why we typically see lower rates in the active drugs, which is what we see here, or an adverse event.

Now the rates for adverse events, as Dan noted, a range between 5% and 10% for orforglipron. That's exactly where we'd expect to be for an oral GLP-1 single agonist. So really nothing remarkable here.

The next question will be from Akash Tewari from Jefferies.

What's Lilly's appetite to committing to launching new products at net parity pricing between the U.S. and Europe, given a significant amount of your newly launched products in Europe are actually not getting reimbursed anyway? And more broadly, it sounds like we're in an impasse between the administration and the industry. What's your confidence we'd be able to get kind of a bespoke solution with the administration absent new legislation?

Great. Thank you, Akash. We'll go to Dave to talk on the engagement with the administration and kind of new product launch strategy.

Sure. Yes. I mean just on the discrete question you're asking, I think we believe long term, we should rebalance pricing between U.S. and Europe in terms of who's bearing the cost for really the amortized R&D and the risk we took. That's a rational thing.

And it's, in my career, gotten more and more out of whack. So I think here, the President's right to call that out. The question is really how. And as you know, the European governments don't exactly -- they're not signing up to pay more for drugs.

So we need trade tools to rebalance that equation. We've been very clear on that advocacy with both European and U.S. governments. And in the U.S., we need to deflate the gross-to-net bubble because there's this huge artificial thing that needs to get deflated. The problem of doing that suddenly is all those cash flows into hospitals and premium support for seniors and Part D, et cetera, you can't collapse it all once, it would be very difficult, I think.

So the idea of new products gives it sort of a ramp, but we need these other structural changes on the U.S. side and the gross-to-net environment in Europe in terms of the total reimbursement set up to get there. But we'd be excited to enter that world. And actually, I'll point out in a few cases, we are narrowing the gap substantially on new products. And some of that's for the reason you point out that some countries, reimbursement is just a tough equation.

So what's the point of lowering that? So watch that space. I think this is an area there could be progress under the President's agenda. And I think you'd see most pharma companies interested in moving in that direction.

The question is how do you step into it.

Great. Thank you, Dave. We've got time for probably 2 more questions.

Next question will be from Kerry Holford from Berenberg.

A questions from me, please, on the cash channel. So yesterday, Novo stated it would make Ozempic available via its cash pay channel later this year. Are you planning to do the same for Mounjaro? And if not, why not? And I'm not sure if you mentioned this earlier, but can you confirm whether you intend to use the cash channel for orforglipron on that aftermarket?

Great. Thanks, Kerry, for the question. We'll go to Ilya to comment on our thoughts on the cash channel.

Sure. Well, first, I think we're learning a lot in the cash channel, LillyDirect. And a lot of that has to do with the consumer journey, and it's varied across different segments where you have significant coverage versus not. And with Mounjaro, we have significant coverage, so over 90% coverage in both commercial as well as Part D.

And so I'm not sure if that necessarily provides an additional avenue. With Zepbound we see significant growth because we do have coverage gaps in commercial. And obviously, we also have coverage gaps without having the ability to cover anti-obesity medications in Part D. So we see this as an opportunity for us to meet that need.

Of course, we'll evaluate other brands that we put through LillyDirect, we have a number of avenues to come to LillyDirect on different brands to make sure that people can access the health care system in a better way. And so that's something that will evolve over time.

And the final question will be from Evan Seigerman from BMO Capital Markets.

A follow-up on the MFN conversation. I appreciate you're not going to share the details of your interaction with the administration. But can you provide some practical examples of what you and the industry can do to help achieve the goals of getting price parity globally?

Thanks, Evan. We'll go to Dave to answer the question and then to provide closing remarks.

Yes, sure. I don't have a lot to add to what I said to the prior question. I think long term it makes sense to rebalance this. And having an on-ramp makes sense to me because a sudden change in either environment would be difficult to sustain or justify.

So the idea of new products is a reasonable proposition provided that the reimbursement rates in Europe can rise really based on cost for quality analysis and other things, and the U.S. gross-to-net situation can change, and easing into it seems to be rational thing to do. The other piece, which the DTC channel being suggested by the administration, and per the prior question, in addition to offering an outlet for people who don't have coverage, it does provide a kind of real price transparency to consumers, employers and others. And that's a good thing. So we support that as well.

We'll have to see how this plays out. As I said, we're constructively engaging. Hopefully, some progress can be made. And I think it's in the industry's long-term interest to kind of pull these things closer together, and we'll work hard to try to do that.

Thanks for being with us today, everyone, and for as many questions as we got to. I know there's always some we did not. So as in prior quarters, if you have unresolved questions, please contact our IR team. And we appreciate your interest in the company, as always, and look forward to future interactions.

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 1:00 p.m. today running through September 11 at midnight. You may access the replay system at any time by dialing (800) 332-6854 and entering the access code 639732. International callers can call (973) 528-0005. Again, those numbers are (800) 332-6854 and (973) 528-0005, with the access code 639732. Thank you for your participation.

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