Eli Lilly and Company - Q2 2023

Transcript

Operator (participant)

Ladies and gentlemen, thank you for standing by, and welcome to the Lilly Q2 2023 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, Joe Fletcher, Senior Vice President of Investor Relations. Please go ahead.

Joe Fletcher (SVP of Investor Relations)

Good morning. Thank you for joining us for Eli Lilly and Company's Q2 2023 earnings call. I'm Joe Fletcher, Senior Vice President of Investor Relations, joining me on today's call are Dave Ricks, Lilly's Chair and CEO, Anat Ashkenazi, Chief Financial Officer, Dr. Dan Skovronsky, Chief Scientific and Medical Officer, Anne White, President of Lilly Neuroscience, Ilya Yuffa, President of Lilly International, Jake Van Naarden, President of Loxo at Lilly, Mike Mason, President of Lilly Diabetes, and Patrik Jonsson, President of Lilly Immunology and Lilly USA. We're also joined by Michaela Irons, Mike Sprengnether, and Lauren Zerkle of the Investor Relations team. During this conference 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 3.

Additional information concerning factors that could cause actual results to differ materially is contained in our latest Form 10-K and Subsequent Forms 10-Q and 8-K filed with the Securities and Exchange Commission. The information we provide about our products and pipeline is for the benefit of the investment community. It's 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 non-GAAP financial measures. I'll turn over the call to Dave.

David Ricks (CEO)

Thanks, Joe. In the second quarter, Lilly's momentum continued. We advanced our R&D pipeline, progressed our ambitious manufacturing agenda, and delivered strong financial results. Our business saw an acceleration of revenue growth, driven by Mounjaro, Verzenio, and Jardiance.

As base period headwinds from COVID-19 antibody revenue and Olumiant loss of exclusivity recede, we do expect strong growth to continue in the quarters ahead. Lilly has made substantial progress in advancing our pipeline of innovative medicines in recent years, the past few months have been particularly noteworthy. In early May, we shared the top-line results of the phase 3 TRAILBLAZER-ALZ 2 trial, which showed donanemab treatment slowed clinical decline in Alzheimer's by 35%. While differences in enrollment criteria and study design make cross-trial comparisons difficult, this represents the greatest percentage cognitive slowing in a primary endpoint of any disease-modifying Alzheimer's disease treatment reported to date, and the only phase 2 to phase 3 replication to date.

Three weeks ago, at the Alzheimer's Association International Conference in Amsterdam, simultaneously published in JAMA, we shared the detailed results, including new analysis, which demonstrate the potential of even greater cognitive slowing in patients in the earlier stages of Alzheimer's disease. At the ADA Scientific Sessions in June, we shared positive phase II data on two next-generation diabetes and obesity product candidates, orforglipron and retatrutide. Less than two weeks ago, we shared top-line results from the SURMOUNT-3 and SURMOUNT-4 phase III trials, which showed participants on tirzepatide following intensive lifestyle intervention or with continued tirzepatide treatment, achieved up to 26.6% mean weight loss. Dan will share more perspectives in his R&D update on these and other exciting areas of pipeline progress. Moving to our results, you can see on Slide 4 the continued progress made on our strategic deliverables so far this year.

Excluding revenue from Baqsimi and from the sales of COVID-19 antibodies in 2022, Q2 revenue grew 22% on 23% volume growth. Volume growth in Q2 is driven by Mounjaro, which leads our new products category. That category also includes Jaypirca and now Omvoh, which saw its first sales in Japan in Q2 and launched in Germany in July. In the second quarter of this year, new products and growth products categories combined contributed approximately 26 percentage points of volume growth. These products, coupled with potential upcoming launches, solidify Lilly's strong growth profile through this decade. We've had several important pipeline updates since our Q1 earnings call. For mirikizumab, approval in the EU and resubmission of our U.S. application, with regulatory action expected by the end of this year.

Regulatory submissions in the U.S. for tirzepatide for chronic weight management, regulatory submission of donanemab for traditional approval to the FDA and EMA, following the positive phase III results from the TRAILBLAZER-ALZ 2 trial, positive phase III top-line readouts for SURMOUNT-3 and SURMOUNT-4 in the third and fourth global studies evaluating tirzepatide in chronic weight management. The second quarter also was productive for business development. We've commented in the past on our active exploration and pursuit of external innovation and are pleased to have announced agreements to acquire two clinical stage companies in the second quarter, DICE Therapeutics and Versanis Bio. These companies operate in different therapeutic areas, each is a fit with Lilly's strategy. We also closed the sale of global rights to Baqsimi, the financial impact of this transaction is reflected in our Q2 results.

After quarter end, we closed the sale of rights to our olanzapine portfolio, which will be reflected in our Q3 financial results. Both these transactions are now incorporated into our updated 2023 financial guidance. We continued to progress the most ambitious manufacturing expansion agenda in the 147 history of our company. We're happy to share that commercial production to support our incretin portfolio has begun at our Research Triangle Park site in North Carolina. Beyond the capacity expansion that will come as we ramp production at this site, we're also pursuing other near-term paths to expand access to our incretin to patients around the world. Anat will provide more detail on these efforts. Finally, we distributed over $1 billion in dividends this quarter.

On slide five, you'll see a list of key events since our Q1 earnings call, including several important regulatory, clinical, and other updates we're sharing today. Without further ado, I'll turn this over to Anat to share our Q2 results.

Anat Ashkenazi (CFO)

Thanks, Dave. Slide 6 summarizes financial performance in the second quarter of 2023. I'll focus my comments today on non-GAAP performance. In Q2, revenue increased 28% versus Q2 of 2022. Excluding revenue from Baqsimi and from COVID-19 antibodies in the base period, revenue increased 22% or 23% on a constant currency basis. This acceleration of revenue growth was achieved despite lingering headwinds from a limited loss of exclusivity in the U.S., which occurred in the first half of last year, and the effects of which should normalize going forward. Gross margin as a percent of revenue was flat in Q2 at 79.8%. Gross margin in the quarter benefited from product mix, including one-time revenue from the sales of rights to Baqsimi, which was offset by increases in manufacturing expenses related to labor costs and our investments in capacity expansion.

Total operating expenses increased 14% this quarter. Marketing, selling, and administrative expenses increased 18%, driven by higher marketing and selling expenses associated with recent and upcoming new product launches and additional indications. R&D expenses increased 32%, driven by higher development expenses for late-stage assets and additional investments in early-stage research. This quarter, we recognized acquired IPR&D charges of $97 million or $0.09 of EPS. In Q2 2022, acquired IPR&D charges totaled $440 million or $0.46 of EPS. Operating income increased 69% in Q2, driven by higher revenue, including revenue associated with the sales of rights for Baqsimi and lower IPR&D charges, partially offset by higher R&D and SG&A expenses.

Operating income as a percent of revenue was 27% for the quarter and reflected a negative impact of approximately 115 basis points attributable to acquired IP R&D charges. Our Q2 effective tax rate was 16.1%. This represents an increase of 190 basis points compared to the same period in 2022, driven by the impact of the new Puerto Rico tax regime and the sales of rights for Baqsimi. At the bottom line, we delivered earnings per share of $2.11 in Q2, a 69% increase versus Q2 of 2022, inclusive of $0.43 of EPS associated with the sales of rights for Baqsimi. On slide 8, we quantify the effect of price, rate, and volume on revenue growth. This quarter, U.S. revenue increased 41%.

When excluding revenue from COVID-19 antibodies and Baqsimi, U.S. revenue grew 30%, driven by robust growth from Mounjaro, Verzenio, and Jardiance. Net price in the U.S. increased 2% for the quarter, driven by Mounjaro access and savings cards dynamics. Excluding Mounjaro, net price in the U.S. decreased by low single digits, consistent with prior trends. As I mentioned on our Q1 earnings call, we expect Mounjaro access and savings cards dynamics to have an even greater effect on reported U.S. price changes in the second half of this year. Europe continued its growth trajectory, with revenue in Q2 up 6% in constant currency, driven primarily by volume growth for Verzenio, Jardiance, and Taltz. Volume in Europe increased 12% in the second quarter.

For Japan, Q2 revenue increased 7% in constant currency as we continued to see robust growth in our newer medicine, led by Verzenio, and to a lesser extent, Jardiance, Olumiant, and Mounjaro, the last of which launched in Japan in April. Moving to China, revenue increased 20% in constant currency, with volume growth only minimally offset by price declines. Volume growth in Q2 was driven by Tyvyt and Verzenio. We are pleased to see our China business return to growth. Revenue in the rest of the world increased 19% in constant currency, as volume growth of 20% was driven by Mounjaro, Verzenio, and Jardiance. Slide nine shows the contribution to worldwide volume growth by product category. As you may recall, on our Q1 earnings call, we simplified the categorization of our products with a focus on two categories: new products and growth products.

As you can see, the new and growth categories combined contributed 26 percentage points of volume growth for the quarter. The volume growth for all others category was driven by the sale of rights to Baqsimi. The lack of revenue from COVID-19 antibodies compared to the base period was a milder headwind to growth in Q2 compared to Q1, and will continue to be a modest impact to prior year comparisons. Slide 10 provides additional perspective across our product categories. I'll speak more about Mounjaro shortly, but first, let me highlight the continued outstanding performance of Verzenio, which saw worldwide sales growth of 57% in Q2, as OUS volume grew 82%, while U.S. volume grew 47%. Jardiance also continued its strong performance, with worldwide sales growth of 45% for the quarter. There have been two notable regulatory approvals for Jardiance in the last two months.

In June, the FDA approved Jardiance for the treatment of type 2 diabetes in children 10 years and older, making Jardiance the first and only SGLT2 inhibitor approved for this patient population. In late July, Jardiance was approved in the EU for the treatment of adults with chronic kidney disease. After almost a decade on the market, Jardiance continues to demonstrate its importance to patients across a number of cardiorenal metabolic conditions. Trulicity performance has held up well in a growing and dynamic incretin market. In Q2, we saw worldwide Trulicity revenue decline by 5%, as modest volume growth was more than offset by price erosion. In international markets, Trulicity volume continues to be affected by measures we have taken to minimize potential disruption to existing patients, including communications to healthcare professionals, not to initiate patients on Trulicity.

We remain confident that Trulicity will continue to be an important option for HCPs and patients in years to come. Moving to slide 11, I will share some perspective on Mounjaro's performance. We continue to be pleased with the strong momentum of Mounjaro as more type two diabetes patients benefit from the medicine. Mounjaro's revenue in the U.S. grew to $960 million for the quarter. In Q2, we continued to make progress in expanding access to Mounjaro, and access reached 73% on July first for patients with type two diabetes across commercial and Part D. We estimate that the percentage of paid scripts from Mounjaro in Q2 was approximately 67%, up from approximately 55% in Q1. As a reminder, we define paid scripts as those prescriptions outside of the $25 non-covered copay card, but inclusive of the $25 covered copay card.

Since the $25 non-covered copay card program will expire on June 30th, we would expect the proportion of paid scripts next quarter to be 100% under this definition. Looking forward to the rest of the year, we expect continued growth in new-to-brand prescription, as well as ongoing improvement in access. Lastly, regarding the demand and supply outlook for our incretin, we're pleased that commercial production has started at our RTP site in North Carolina. Even as we ramp up capacity at RTP, we believe supply will likely remain tight in the coming months and quarters due to significant demand. Given the expected global demand for tirzepatide, as we mentioned on previous earnings call, we are moving forward with different presentations to bring tirzepatide to more patients faster. To this end, we initiated a bioequivalent study in early April for a multi-dose KwikPen device.

In many OUS markets, we expect to launch tirzepatide first in vial form later this year and transition to a multi-dose KwikPen as approved and available in these markets starting in 2024. The launch of the vial and KwikPen presentations for tirzepatide will leverage existing manufacturing assets and capacity. We're excited about the opportunity to expand the number of people we can help in the short term and long term with these additional options. On slide 12, we provide an update on capital allocation. In the first six months of 2023, we invested $5.7 billion in our future growth through a combination of R&D expenditures, capital investments, and business development outlays. In addition, we returned nearly $2.8 billion to shareholders in dividends and share repurchases. Slide three presents our updated 2023 financial guidance.

Given the strong performance in our underlying business, as well as revenue from the sales of rights for Baqsimi and olanzapine, we are increasing our 2023 revenue guidance by $2.2 billion to a range of $33.4 billion-$33.9 billion. Approximately $1.5 billion of this increase is driven by business development activities, including the sales of rights for the olanzapine portfolio and Baqsimi, while the remainder reflects strong underlying business performance. Our updated FX assumptions based on recent spot rates are listed and represent a de minimis impact to the updated guidance. Our guidance for gross margin as a percent of revenue has increased to approximately 80%, driven by the sales of rights for Baqsimi and our olanzapine portfolio. We're also increasing the range of operating expense guidance for the year.

Marketing, selling and administrative costs are now expected to be in the range of $7.2 billion-$7.4 billion, with the increase driven by additional investment in recent launches and preparation for launches of new medicine and line extensions expected later this year. The range for research and development expenses has been increased to $8.9 billion-$9.1 billion, reflecting positive dynamics across our portfolio, including success and events in our early-stage assets, positive enrollment trends in our late-stage studies, broadening of the clinical program for a next-generation incretin, and expected incremental expenses from business development activities. We have incorporated IPR&D charges that have been incurred through Q2 2023, which totaled $202 million. Other income and expense and tax rate guidance have also been updated.

OID is now expected to be between $0 and $100 million in income, up from prior guidance of $100 million-$200 million in expense. We've also increased our estimated effective tax rate to be in the range of 14%-15%, up from approximately 13%, reflecting the impact of the sales of rights for our olanzapine portfolio and Baqsimi. Based on these changes, we have raised our full-year reported EPS guidance to now be in the range of $9.20-$9.40 per share, and raised our non-GAAP EPS guidance to be in the range of $9.70-$9.90. I will turn the call over to Dan to highlight it, our progress in R&D.

Dan Skovronsky (Chief Scientific and Medical Officer)

Thanks, Anat. It's been a productive and busy few months for Lilly R&D. Since our last earnings call, we've had a few major readouts across our therapeutic areas, and we've announced several business development transactions. Let me start with the data that we shared in June at the American Diabetes Association. We presented over 40 abstracts across our portfolio and shared data during 2 ADA-sponsored symposia. The first was for the phase III results from the SURMOUNT-2 study of tirzepatide in adults with obesity or overweight and type 2 diabetes, which was simultaneously published in the New England Journal of Medicine. The second symposium was for the results from 2 phase II trials of retatrutide, our GIP, GLP glucagon triagonist in adults with obesity and overweight, as well as in people with type 2 diabetes.

The retatrutide results in obesity and type two diabetes were simultaneously, simultaneously published in New England Journal of Medicine and Lancet, respectively. We also shared an oral presentation on our phase II trial results for orforglipron, our once daily nonpeptide oral GLP-1 in adults with obesity or overweight. These results were simultaneously published in New England Journal. We also presented results from a phase II trial of orforglipron in patients with type two diabetes, and these were published in The Lancet. Clearly, we're proud of all of this data in diabetes and obesity portfolio. Since we discussed the top-line data for SURMOUNT-2 tirzepatide trial during our last earnings call, I'll focus my updates today on the phase II data shared for orforglipron and retatrutide, starting with orforglipron on slide 14.

The orforglipron presentation highlighted safety and efficacy data across six dose arms in our phase II study in obesity, with an overall mean body weight at baseline of 109 kilograms, orforglipron demonstrated an average of up to 14.7% body weight reduction at 36 weeks. At the second-highest dose tested in the study, 75% of participants reached a weight reduction goal of 10% or more. We also shared data showing a dose-dependent decrease in systolic blood pressure and an overall improvement in lipid levels. The most common adverse events were GI-related and generally occurred earlier in the trial during the titration phase and were mostly mild to moderate. While we've not yet shared the dosing details for our phase III studies, these phase II results have informed our approach on dose escalation.

We also presented data at ADA from a similar phase 2 study of orforglipron in people with type 2 diabetes, the results of which are highlighted on slide 15. Orforglipron demonstrated a mean reduction in hemoglobin A1C at 26 weeks of up to 2.1%. Over 90% of participants on the highest 3 doses achieved A1C levels less than 7%. We initiated phase 3 trials for orforglipron in both obesity and type 2 diabetes in the second quarter. We look forward to those results in 2025. For retatrutide, the full results of 2 phase 2 trials were presented during an ADA-sponsored symposium, which discussed efficacy and safety in adults with obesity or overweight, with at least one weight-related comorbidity, as well as in people with type 2 diabetes.

There was also a segment of the symposium focused on liver fat and NASH-related biomarker data in patients with non-alcoholic fatty liver disease, which showed relative liver fat reduction of over 80% at 24 weeks for the two highest doses. Slide 16 highlights key results from the obesity phase 2 trial, in which retatrutide met the primary endpoint at 24 weeks, demonstrating mean weight reduction up to 17.5%. The safety profile of retatrutide was similar to other incretin-based therapies. In a secondary endpoint of weight reduction at 48 weeks, participants treated with the highest dose of retatrutide demonstrated a mean weight reduction up to 24.2% or almost 58 pounds on average. If confirmed in registrational trials, we believe that magnitude of mean weight reduction would represent a new high watermark for weight loss from a pharmacologic agent at this time point.

It's also worth noting that the phase II retatrutide trial in obesity was well-balanced between genders, with females representing just under half of all participants in the trial. This was intentional and is atypical for incretin clinical trials in obesity, which often have a higher proportion of female participants, a subgroup that typically experiences greater weight loss than males. Indeed, in the retatrutide phase II obesity trial, the mean change in body weight for female participants at the highest dose was 28.5%. Given these encouraging results, we moved rapidly to initiate the TRIUMPH phase 3 program, which will evaluate the safety and efficacy of retatrutide for chronic weight management, obstructive sleep apnea, and knee osteoarthritis in people with overweight and obesity. These 4 phase 3 trials will each run between 68 and 80 weeks.

The trajectory of weight loss seen in the phase 2 study reinforces our belief that retatrutide can potentially represent a further improvement and additional option for patients seeking pharmacological treatment for obesity and its complications. While retatrutide's phase 2 results in obesity garnered much attention at ADA, the phase 2 results in patients with type 2 diabetes are also very encouraging, with participants receiving retatrutide achieving a hemoglobin A1c reduction of up to 2% on average, in addition to meaningful levels of weight loss. I'm pleased to share that we plan to advance retatrutide into phase 3 for type 2 diabetes. Moving to tirzepatide on slide 17. We were delighted to announce in late July that SURMOUNT-3 and SURMOUNT-4 trials of tirzepatide in obesity met all primary and key secondary objectives.

In key secondary objectives for both these studies, participants achieved similar mean weight reduction, 26.6% in SURMOUNT-3 and 26.0% in SURMOUNT-4. While these two trials were not required for our chronic weight management submission to the FDA, they provide important additional information regarding the role tirzepatide plays in maintaining or adding to the weight loss achieved with either intensive lifestyle intervention or pharmacotherapy in adults living with obesity or overweight. SURMOUNT-3 evaluated tirzepatide following an intensive lifestyle modification program and demonstrated that even in people who have a weight loss response to lifestyle intervention, tirzepatide provides significant additional weight loss. SURMOUNT-4 was a randomized withdrawal study in which all participants received tirzepatide for a 36-week lead-in period, at which point half the participants were switched to placebo and the other half continued treatment with tirzepatide.

This study demonstrated that those participants who continued on tirzepatide experienced continued weight loss, while those who switched to placebo started to regain weight. These data reinforce our understanding that obesity is a complex, chronic disease for which multiple treatment approaches, including lifestyle modification and effective medications, are needed. We believe tirzepatide is well positioned to be one such treatment option. Accordingly, we submitted an application for tirzepatide for chronic weight management to the FDA during Q2. The FDA granted this application priority review designation, and we anticipate FDA action by year-end. Slide 18 shows select pipeline opportunities as of August fourth, and slide 19 shows potential key events for the year. I've covered the major updates in diabetes, including the advancement of orforglipron and retatrutide into phase 3 since our last earnings call. Turning to our neuroscience portfolio.

Three weeks ago, at the AAIC meeting in Amsterdam and simultaneously published in JAMA, we were excited to share the detailed results from the TRAILBLAZER-ALZ 2 study, highlighting donanemab's robust efficacy profile across a number of new analyses that reinforce our belief in the medicine's ability to meaningfully slow the progression of Alzheimer's disease, especially in patients earlier in disease progression. We covered the results in some detail during our AAIC investor call, I won't cover that again, except to note that we've submitted donanemab to the FDA and to the EMA for approval. We look forward to FDA action before the end of this year. Shifting to oncology. Launch progress continues with Jaypirca and mantle cell lymphoma. We were pleased to have the detailed chronic lymphocytic leukemia results from the BRUIN phase 1/2 trial published in New England Journal in early July.

Following discussion with the FDA, we've now submitted an application for accelerated approval for Jaypirca in CLL patients previously treated with both a covalent BTK inhibitor and venetoclax, based on the results from the BRUIN Phase 1/2 study. We expect FDA action by year-end. During the quarter, we completed the regulatory submission in Japan for pirtobrutinib for patients with MCL. We continue to study pirtobrutinib in multiple Phase 3 trials and look forward to the results from the BRUIN CLL-321 trial in CLL, which we now expect to see before the end of this year, and it has been added to our key events slide. In other oncology developments, at ASCO in June, we presented new data from the Verzenio monarchE trial in high-risk early breast cancer.

For the first time, we showed data demonstrating that efficacy of the medicine in this setting is not compromised when patients undergo dose reductions. We believe that the ability to manage Verzenio's side effects while preserving efficacy could be very important to ensuring that patients complete their two years of therapy. This is an emerging part of Verzenio's differentiation in this class. We're also very excited about last week's announcement regarding the randomized trial of Retevmo in treatment-naive RET fusion-positive lung cancer. As we communicated in the press release, this randomized trial was declared successful on its primary endpoint of progression-free survival, the first time any targeted therapy in lung cancer has ever shown superiority to a PD-1 plus chemotherapy regimen.

While we remain disappointed by the low levels of genomic profiling done at the time of lung cancer diagnosis, we're hopeful that these data will continue to advance the practice of genomic-driven medicine. We look forward to sharing the full results of the study at an upcoming medical meeting. In our earlier stage oncology portfolio, the combination experiment of our KRAS G12C inhibitor with pembrolizumab continues to mature nicely. We're now working to initiate phase 3 trials in first-line G12C-mutated lung cancer in the next six to nine months. More broadly, we're excited to see the overall progress of our oncology portfolio. In addition to last week's Retevmo announcement, we expect another seven randomized trial readouts and four to six new first-in-human trials across small molecules and biologics in oncology over the next 12 months.

With the acquisition of Loxo Oncology 4 years ago, we catalyzed a change in the strategy and direction of oncology at Lilly, and we're seeing the fruits of the, these efforts. Finally, in immunology, we have several updates related to mirikizumab. At Digestive Disease Week in May, we presented new analyses from the phase 3 LUCENT-1 and LUCENT-2 studies, demonstrating that remission of key symptoms of ulcerative colitis, including bowel urgency, was associated with significant improvement in a quality-of-life assessment in adults with UC. In Q2, we launched mirikizumab, marketed as Omvoh in Japan, as a treatment for adults with moderately to severe active UC. In late May, we received approval for Omvoh in the EU and have subsequently launched Omvoh in Germany and plan additional launches in the EU later this year. In the U.S., we've resubmitted our application to the FDA.

We now expect regulatory action by the end of this year. For lebrikizumab, our IL-13 monoclonal antibody under regulatory review for atopic dermatitis, we presented a new secondary analysis at the Revolutionizing Atopic Dermatitis Conference in May. This post hoc analysis demonstrated improvement or clearance of face or hand dermatitis in adult and adolescent patients treated with lebrikizumab. These are parts of the body that are highly visible and for which dermatitis can be particularly burdensome and stigmatizing. We expect regulatory action for lebrikizumab in both the U.S. and EU later this year. Together with Almirall, our development and commercialization partner in Europe, we look forward to potentially bringing this important medicine to patients who suffer from this chronic disease.

Looking earlier in our immunology pipeline, we were pleased in May to have the detailed results from our phase 2A study of parasolimab in rheumatoid arthritis, published in the New England Journal. These data were first presented as a late-breaking abstract at the American College of Rheumatology annual meeting in late 2022, and represent the first clinical evidence that stimulating the endogenous PD1 inhibitory pathway could be an effective approach to treat rheumatologic disease. As you can see, Q2 was another productive quarter for Lilly R&D, with important progress in each of our therapeutic areas. Now I'll turn the call back to Dave for closing remarks.

David Ricks (CEO)

Thank you, Dan. Before we go to Q&A, let me briefly sum up our progress in the second quarter. This quarter saw an acceleration of revenue growth as our recently launched product portfolio gathers momentum. Excluding COVID-19 antibodies and baqsimi revenue, we grew 22%, driven by Mounjaro, Verzenio and Jardiance. The quarter also saw a continuation of investment in our future growth, in our manufacturing expansion, in late-stage medicines, in early-phase capabilities, and in business development. Notwithstanding these long-term investments, we continue to expect our revenue will grow more rapidly than our expense base in the coming years and see significant opportunity for margin expansion. We also achieved meaningful advances in our near-term pipeline, with positive phase...

positive top-line results, detailed data disclosures, and submission of donanemab for traditional approval to the FDA and EMA, and completion of the tirzepatide submission in chronic weight management, alongside positive top-line results from two more phase 3 trials for the SURMOUNT program. We also shared data from 4 mid-stage clinical trials for orforglipron and retatrutide, and initiated phase 3 trials for both assets. Lastly, we announced several targeted business development moves intended to bolster our early and mid-stage portfolio and our R&D capabilities. We returned over $1 billion to shareholders via the dividend. Now I'll turn the call over to Joe to moderate the Q&A session.

Thanks, Dave. We'd like to take questions from as many callers as possible and conclude our call in a timely manner. We will respond to 1 question per caller, so ask that you limit to 1 question per caller, as we'll end the call at 10:15 A.M. If you have more than a 1 question, you can reenter the queue and we'll get to your question if time allows. Paul, please provide the instructions for the Q&A session, and then we're ready for the first caller.

Operator (participant)

Thank you. At this time, we will be conducting a question-and-answer session. If you have any questions, please press star one 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 one 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 pull for questions. The first question today is coming from Louise Chen from Cantor. Louise, your line is live.

Louise Chen (Managing Director and Senior Research Analyst)

Hi, thank you for taking my question. Just wanted to ask you about the Novo SELECT study that came out this morning. What kind of read-throughs do you see for the industry, and do you think it will help improve reimbursement for obesity overweight drugs? Thank you.

Joe Fletcher (SVP of Investor Relations)

Thanks, Louise. We'll go to Mike for that question on the recent SELECT news.

Dan Skovronsky (Chief Scientific and Medical Officer)

Thanks, Louise. I assume we probably would get a question on the Select trial. Thanks for starting out the call with that. You know, the Select trial read out as we expected. I think the results are great for the anti-obesity medication class.

Mike Mason (President, Lilly Diabetes)

It should really support access for any payers who are on the fence of whether they should add anti-obesity medications or not. It, I think importantly, it should turn the conversation on the benefits of weight loss away from aesthetics and more toward the health benefits of people living with obesity. When you look overall, there are 236 obesity-related health complications. To name a few, obesity increases the risk of type 2 diabetes by 243%, coronary heart disease by 69%, hypertension by 113%, dyslipidemia by 74%. You know, the overall cost of obesity-related complications and comorbidities are massive, accounting for $370 billion in direct medical costs, over $1 trillion in indirect annual costs in the U.S.

People living with obesity or overweight drive 2.7 greater healthcare costs than normal weight individuals. You know, the global health stakeholders really needs to be moved beyond the debate and really move to action on the AOM class. With tirzepatide's potential to provide over 20% weight loss, it should provide great value for payers. We have a comprehensive real-world evidence plan and clinical plan to demonstrate tirzepatide's value, including our MMO outcomes trial. Based on the SELECT trial results, we can't wait to see the results of tirzepatide's MMO study. We do believe that additional weight loss will matter. This is a fantastic day for people living with obesity. Now, do I think most payers will adopt AOMs overnight because of SELECT trial? I don't think so. I think, as I said earlier, those who are on the fence, this will push them over.

I think it is an important milestone in a long-term goal to get broad access for anti-obesity medications.

Louise Chen (Managing Director and Senior Research Analyst)

Thank you, Mike. Paul, next question.

Operator (participant)

Thank you. The next question is coming from Geoff Meacham from Bank of America. Geoff, your line is live.

Geoff Meacham (Managing Director, Senior Pharmaceuticals Analyst)

Hey, guys, thanks for the question. I know that we're a year into the Mounjaro launch, but I wanted to get a view of persistent rates. The question is, are you seeing drug holidays after weight loss troughs? I wasn't sure if there were differences between diabetes and obesity indications at this point, just with regard to duration of use. Thank you.

Speaker 25

Thanks, Geoff. We'll go back to Mike for that question on persistence rates of Mounjaro.

Mike Mason (President, Lilly Diabetes)

Okay, Geoff, thanks for your question. Right now, we only market Mounjaro for type 2 diabetes, the only in-market real-world persistency rates that we have are for Mounjaro in the type 2 diabetes patients. What we do know is that people living with type 2 diabetes have had good experiences with Mounjaro. In the 1st launch, like at the 1st phase of launch, before we've made savings hard and experienced supply spot outages, type 2 diabetes patients using Mounjaro did have better persistency than Trulicity, which is important because Trulicity historically has had the best compliance in the diabetes market.

We're confident in the experiences that people who use Mounjaro for type two diabetes have, and we're excited to see what that will be for people living with chronic weight management when and if we get approved by the FDA.

Geoff Meacham (Managing Director, Senior Pharmaceuticals Analyst)

Thanks, Mike. Paul, next question.

Operator (participant)

Thank you. The next question is coming from Tim Anderson from Wolfe Research. Tim, your line is live.

Tim Anderson (Managing Director, Senior Equity Research Analyst)

Thank you. Just going back to SELECT, a commonly held view is that, you know, positive results benefits every company in the category, and that's our view as well. Of course, Novo will be able to make the claim for quite some time that they're the only drug to have a proven cardiovascular benefit. Could that actually give them a big commercial advantage in the marketplace on things like pair coverage, that would actually be to Lilly's detriment? Thank you.

Speaker 25

Thanks, Tim. I'll go back to Mike for that question, a follow-up on SELECT.

Mike Mason (President, Lilly Diabetes)

No, it's a good question. I don't think that'll be the case. What we've seen is payers opt in to the class, not a particular drug, so I don't think that'll give them a differential impact within payer access. I think commercially, typically, healthcare professionals, when they see results like this, it really helps the class more than any one individual product.

Tim Anderson (Managing Director, Senior Equity Research Analyst)

Thanks, Mike. Paul, next question.

Operator (participant)

Thank you. The next question is coming from Kerry Holford from Berenberg. Kerry, your line is live.

Kerry Holford (Head of Global Pharmaceutical Equity Research)

Oh, hi there. Thank you for taking my question. On the guidance, please, and OpEx. Clearly, operating costs are higher than at least the market anticipated in Q2, and you are now guiding to spend more on SG&A R&D through this year. I'm just interested to learn more about what has changed through this quarter to prompt you to raise that OpEx outlook versus your previous outlook. Can you elaborate on the key drivers of that, please? Thank you.

David Ricks (CEO)

Thanks, Kerry, for the question. Yes, we'll go to Anat for that commentary and the OpEx guide and additional context.

Anat Ashkenazi (CFO)

Thanks, Kerry, for the question. We have raised, you're right, both SG&A guidance as well as R&D. The SG&A increases are primarily as a result of continued investment in the upcoming launches we have yet this year. As we're seeing the opportunities, we're excited to, to invest efficiently behind these opportunities and make them, a reality for patients and for Lilly.... On the R&D side, Dan provided a robust outline of the progress we've seen in our pipeline, and there are really, I would say, 3 to 4 key drivers of that increase. One is additional new studies that we've announced, primarily in phase III, and you've seen the broadening of the investments we're making in our increasing portfolio, initiating multiple phase III studies for both, orforglipron and retatrutide, and announcing new studies.

Coupled with continued advancement, we're seeing great success in our early stage pipeline, and we're investing behind that. We're also seeing continued success in our enrollment rates for, for currently, for our phase III program, so that's continued to enroll well. Then the three business development transactions, the inbound that we've announced, are now gonna be incorporated in our second half R&D run rate. All these combined are the drivers of the increase this year. They represent really a tremendous opportunity for continued investments in a very successful pipeline.

Kerry Holford (Head of Global Pharmaceutical Equity Research)

Thank you, Anat. Paul, next question.

Operator (participant)

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

Chris Schott (Senior Analyst, Major and Specialty Pharmaceuticals)

Great. Thanks so much for the question. Can you walk through expectations for Mounjaro volumes and ASP as you move through 3Q and 4Q, given the change in the patient assistance program on June 30th, as well as the North Carolina facility coming online? Specifically, I was wondering, do the IQVIA scripts we're now seeing largely reflect the change to the patient assistance program? Should we expect volumes from North Carolina to be a meaningful contributor to capacity this year, or is that more 2024? Thank you.

Dan Skovronsky (Chief Scientific and Medical Officer)

That's close to multiple questions there, Chris, but let me hand over to Mike to provide expectations on Mounjaro volume and gross to net dynamics as we move in the second half, given the RTP news and then also given the changes to the co-pay program at the end of June. Mike?

Mike Mason (President, Lilly Diabetes)

Hey, Chris, thanks for those questions. We, we did make the change, the $25 savings program did expire at the end of June 30th. Anything that you see in IQVIA is post that change, and you'll see that volume of those individuals who were using an uncovered plan, no longer in our trends. We were very happy with what we saw with Mounjaro paid TRXs in the quarter, as they grew nearly 60% in the quarter. As we go forward, we'll our manufacturing team is working on bringing on new capacity at North Carolina and then a few more areas. As that production comes on and ramps up, we will see, you know, some benefit from, you know, that supply.

We ultimately, that will help build inventories up and help eliminate any spot outage that we see. In the short term, because we're seeing really unprecedented demand, we do still expect to see tight supply and some spot outages on Mounjaro through the end of the year. I think ultimately, as that manufacturing capacity ramps up, we will be out of the spot outage that we see. In the next couple of months and quarters, I think we'll still see tight inventory.

David Risinger (Senior Managing Director, Senior Research Analyst)

Thanks, Mike. Paul, next question.

Operator (participant)

Thank you. The next question is coming from Terence Flynn from Morgan Stanley. Terence, your line is live.

Terence Flynn (Equity Research Analyst)

Great. Thanks so much for taking the question. Was just wondering if you could provide any perspective on how you're thinking about the potential for a single brand for Mounjaro or a split brand, ahead of the potential FDA action on the obesity indication? Thank you.

Dan Skovronsky (Chief Scientific and Medical Officer)

Thanks, Terence. Mike, I'll hand that over to you for commentary on single brand versus multiple brands for tirzepatide.

Mike Mason (President, Lilly Diabetes)

Yeah, thanks for the question. We're evaluating all alternatives, and we'll announce our decision at approval.

Dan Skovronsky (Chief Scientific and Medical Officer)

Thanks, Mike. Next question, Paul.

Operator (participant)

The next question is coming from Colin Bristow from UBS. Colin, your line is live.

Colin Bristow (Analyst)

Hey, good morning. Congrats on the quarter. I heard the sort of positive commentary regarding the commercial supply coming online at RTP. Just as we think about 2024, how likely is it, and what do you foresee in terms of supply potentially capping the sales potential in 2024? Is the decision to move forward with the vial and multi-dose pen in any way related to delays at the RTP site? Thank you.

Dan Skovronsky (Chief Scientific and Medical Officer)

Thanks, Colin. I'm gonna hand to Anat to talk a little bit about the, the RTP commercial supply and supply dynamics in the near term.

Anat Ashkenazi (CFO)

Colin, let me first start with the end of your question on, just to clarify, RTP. RTP is now live and producing for commercial purposes, and it's online, in line with our expectations, so there are no delays. It's progressing as we had expected. I'm incredibly proud of the work that the manufacturing team have done to, to get us to this point. As Mike alluded, there will be a gradual increase in available capacity coming out of that site. We've mentioned in the past, it's a large site with multiple lines. They'll come online, gradually and provide more products into the marketplace. As we think about 2024, I suggest we step back and look comprehensively at our manufacturing agenda and capacity plan. RTP is one site.

It's obviously of high interest just because of the proximal nature, and it's the first one that's launched out of the number of sites we have under construction. In parallel, we have been working and continue to work to expand capacity in existing sites. We're working with partners and CMOs to supplement capacity. You know, our strategy is first and foremost to have an internal build, but then we supplement externally as needed. We're also progressing rapidly with our site in North, the second site in North Carolina, in Concord, which you recall we've announced last year. That could potentially go live in terms of production in the second half of 2024.

Gradually, we will see some relief of supply at the end of the, or towards the end of next year, and then continue to grow from there. As you know, these are not the only 2 nodes of capacity. We're also adding outside of incretin and for incretin API capacity in Ireland, as well as 2 large sites in Indiana. We're expanding capacity broadly to support both the incretin portfolio, but then the broader Lilly portfolio, and managing a broad set of networks outside of Lilly. A complex manufacturing set of nodes that we're working towards. We'll comment specifically on 2024 when we provide guidance in terms of what you should expect in revenue.

This is how you should think about the gradual increase in supply with both RTP, internal capacity elsewhere, as well as CMOs. The additional presentation is meant to provide options for patients, and as we've said, we'll start launching outside the U.S. with these presentations. Which should provide additional capacity as well. As I stated earlier, manufacturing facilities in line already exist within Lilly, for example, the vial production. We have those facilities. We don't need to construct new ones. That provides us with the option to start with these as early as the end of this year and then going into next year.

Dan Skovronsky (Chief Scientific and Medical Officer)

Thank you, Anat. Paul, next question.

Operator (participant)

Thank you. The next question is coming from Steve Scala from Cowen. Steve, your line is live.

Steve Scala (Managing Director, Senior Pharmaceutical Analyst)

Oh, thanks so much. How should we think about the MACE reduction powering in SURMOUNT MMO now that we have the SELECT results? SURMOUNT MMO likely won't be as robust, given the population studied, but would Lilly consider a win something half of SELECT's 20% MACE reduction, or would that be viewed as disappointing? Thank you.

David Ricks (CEO)

Thanks, Steve. I'll hand over to Dan for that.

Dan Skovronsky (Chief Scientific and Medical Officer)

Yeah. Thanks, Steve, for your provocative question here. Actually, of course, we, we expect tirzepatide to show a very important benefit. I, I think on the MMO study, there, there's several important differences, as, as you're alluding to. I think for the most part, though, they run in the opposite direction as, as you're suggesting, which would indicate a potential for an even larger effect size for SURMOUNT MMO. The most important difference is the drug itself. Remember that tirzepatide is a GLP-GIP co-agonist, and GIP has some very significant benefits on weight loss and metabolic health overall. We've seen that in a number of different trials and confirmed that with some interesting experiments on a GIP monotherapy as well.

Given the properties of this drug, given the level of weight loss we've seen in previous trials, given the important effects on blood pressure, on lipid profiles, and on other biomarkers that indicate lower cardiovascular risk, we should be very confident in a large effect size coming out of the MMO study. There are some differences in the population. Our study includes both a primary and secondary cardiovascular risk population. We also have a different primary endpoint, although, of course, we have the 3-point MACE as a secondary endpoint. Our primary includes 2 other events related to cardiovascular risk. Other than that, I would say that many of the patient characteristics are gonna be quite similar.

Our study is obviously much earlier, and as an event-driven study, it's, it's gonna take some time to read out. I think you were also asking about what would be considered a, a, a victory here, and I think we'll just sort of wait and, and see the data and understand it a-as it comes, but no reason to expect anything less than what was seen today.

David Ricks (CEO)

Thanks, Dan, and thanks, Steve, for the question. Paul, next one.

Operator (participant)

Next question is coming from Umar Rafat from Evercore. Umar, your line is live.

Umer Raffat (Equity Research Analyst)

Hi, guys. Thanks for taking my question. I wanted to zoom in on orforglipron, and specifically on the case of liver enzymes above 5x and a case above 10x, as well as the treatment-emergent hepatobiliary disorders. I know the slides mentioned safety was similar to other incretins, and my question is: Is your opinion on liver safety driven by the fact that these liver enzymes self-resolved, or is it some preclinical data like the GSH adduct formation, et cetera?

David Ricks (CEO)

Thanks, Umar, for the question. I'll hand over to Dan for that question on orforglipron liver dynamics.

Dan Skovronsky (Chief Scientific and Medical Officer)

Yeah, thanks for the question. Of course, there's been more attention on liver safety for orforglipron following the competitor announcement from Pfizer on one of their two oral GLP-1s. We don't see any read-through from that. Of course, we, we've looked very carefully at liver safety. Maybe just starting at a high level, if you look at the supplementary data from the, in the journal publication, or you can see in, in the obese population that in terms of group averages, there's actually an improvement on liver enzymes with treatment of orforglipron. That's not surprising.

We know that this disease, obesity, is, is characterized in, in many patients by excess liver fat, which can cause inflammation and liver abnormalities, and when you reverse that, you see an improvement in, in liver function. Of course, when people come off the drug, the, the, they could get fat in their liver again, and, and liver enzymes could go up. What we saw in, in this trial, were a couple of patients scattered across arms, including placebo, with excursions in liver enzymes, as you point out. I think there was one patient with a, a bit of a higher excursion in, in liver enzymes on orforglipron, that returned to, to normal levels, while maintaining on therapy. That's generally not a pattern that we see in drugs that cause liver injury.

Surely, in phase 3, we'll keep an eye open for all possible safety consequences. I think I've frequently cautioned investors on all of our molecules that phase 3 is really the place where you can get surprised by any new safety findings. We'll be watching liver safety closely, but not with any particularly heightened concern versus other adverse events that we'll also be watching carefully. This is a new molecule. This is the first time that we're exposing large, large numbers of patients to it for many years, or many, many months, I should say, and we'll be monitoring safety carefully.

David Ricks (CEO)

Thanks, Dan. Paul, next question.

Operator (participant)

Thank you. The next question is coming from David Risinger from Leerink Partners. David, your line is live.

David Risinger (Senior Managing Director, Senior Research Analyst)

Yes, thanks very much. My question is for Dan, please. How are you thinking about whether future orthogonal mechanism weight loss drugs can deliver the cardiovascular outcomes of incretins, even if they match weight loss on a pound-for-pound basis? Thank you.

Speaker 25

Dan?

Dan Skovronsky (Chief Scientific and Medical Officer)

Yeah. Thanks, David. It's, it's a very good question, of course, particularly today. You know, we, we think we understand how the biomarkers from incretin therapy, translate into cardiovascular benefits. Some of those biomarkers, should be translatable to other mechanisms, but depending on how orthogonal those other mechanisms are, there could still be some uncertainty. One, I think, you know, important understanding, though, is that obesity itself, including, I think particularly where the fat is deposited in the body, so for example, visceral fat particularly, is, contributes to, to adverse health outcomes, including adverse cardiovascular outcomes, and therefore, reversing that, should provide, a cardiovascular benefits across mechanisms. Obviously, when we get to very orthogonal mechanisms, each, each one will need its own data to demonstrate that.

Recently, our focus has been on mechanisms that could stack on top of incretin therapy to give additional benefits, in which case there could be a good read-through from the incretin trials. Thanks, David.

Speaker 25

Thanks, Dan. Next question, Paul.

Operator (participant)

Thank you. The next question is coming from Chris Shibutani from Goldman Sachs. Chris, your line is live.

Chris Shibutani (Managing Director, Senior Analyst, Biotechnology Equity Research)

Great. Thank you very much. Trulicity and Mounjaro, can you talk a little bit about the dynamics there? In particular, are you seeing switching? Just trying to get a sense for how you're seeing the supply and then the revenue dynamic.

Speaker 25

Thanks, Chris. I'll hand over to Mike to talk about Trulicity and Mounjaro and any switching dynamics or observations we have. Mike?

Mike Mason (President, Lilly Diabetes)

Yeah, no, good, good question. Obviously, something we've taken a look at since the launch. Really haven't seen any trend breaks in what we've seen and how much of, of Trulicity is being converted over to Mounjaro. We see about 13%-14% of patients coming on to Mounjaro, come on from Trulicity. Really no changes from what we've seen at launch. Overall, you know, our goal is to, to grow the entire Lilly incretin franchise, and we did that well in Q2 by growing revenue by over 58%. We're pleased where we're at with the with our Lilly incretin pipeline, our portfolio, and are excited to, to grow it further in quarters to come.

Speaker 25

Thanks, Mike. Paul, next question.

Operator (participant)

The next question is coming from Mohit Bansal from Wells Fargo. Mohit, your line is live.

Mohit Bansal (Managing Director, Senior Analyst, Biopharma Equity Research)

Great. Thank you for taking my question. Congrats. I have a comment and a question. Comment from my associate that Lilly needs to have two calls, one for Mounjaro and one for everything else. My question is, the question is basically, how should we think about the long-term supply now that the success of CV trial would likely spur more demand here? I know in the past, you talked about double of Trulicity eventually. How should we think about the eventual supply of Mounjaro and Trulicity combined?

Speaker 25

Thanks, Mohit. We'll take your comment under advisement. It's a fair point. To your question on long-term supply, I'll maybe hand back to Anat to talk a little bit more about manufacturing dynamics and plans.

Anat Ashkenazi (CFO)

Yes. Mohit, I would echo a few of the things I said earlier. I outlined the expansion we are gonna be seeing in our manufacturing footprint across our portfolio, so it's not just to support the incretin portfolio, but certainly with the RTP site in North Carolina and Concord, they're both for, to support our incretin portfolio. They're both large sites. We did not provide the specific quantities, but we said that once RTP comes online, by the end of the year, we expect to double capacity from where we were last year. Just use that kind of as a reference point. Trulicity and Mounjaro, as you know, are both utilize the same auto injector, so they run on the same platform, and these lines are interchangeable, which allows us to manage production plans across our sites.

Andrew Baum (Head of Global Healthcare, Managing Director Equity Research)

... based on where we want or need to produce a product or market demand, et cetera. We're going to be expanding our internal footprint to support the incretin portfolio, as well as continue to leverage external partners to supplement that capacity.

Speaker 25

Thanks, Anat. Paul, next question.

Operator (participant)

Thank you. The next question is coming from Evan Segerman from BMO. Evan, your line is-

Evan Segerman (Analyst)

Hi, guys. Hi, guys. Thank you so much for taking the question. I'm going to ask one on donanemab, shake it up a little bit. In submitting for donanemab full approval, are there any nuances that you needed to discuss with the agency following the CRL earlier this year? Does FDA have everything that they need, based on the data that we saw last month? Thank you so much.

Anne White (President, Lilly Neuroscience)

Thank you so much for the question on donanemab. Just to refresh everyone's memory, we had submitted accelerated approval submission, which was designated as a priority review. We did receive a CRL, CRL, just based really on wanting more exposure. It was a pretty simple request. Our resubmission was TRAILBLAZER-ALZ 2, the phase 3 study, which certainly fulfilled any expectations on the CRL. As well as good news, I think going through the accelerated approval, the FDA had the chance to review all the aspects of the submission, preclinical manufacturing, and others. I would say we feel pretty confident at this point about the quality of our submission, and they've accepted that. They're reviewing it for traditional approval. As we've said, we expect action by the end of the year.

Speaker 25

Thank you, Anne. Paul, next question.

Operator (participant)

The next question is coming from Robyn Karnauskas from Truist Securities. Robyn, your line is live.

Robyn Karnauskas (Managing Director, Senior Biotech Analyst)

Hi, thank you. I guess I have a big-picture question. When you're in payer discussions right now ahead of approval for weight loss from Mounjaro, for those payers that are not willing to cover, not on the fence, what do they need to see? Do you expect the cadence of supply versus access to shift in five years? Can you give us a sense of what that looks like and what they really need to see? Thanks.

Speaker 25

Thanks, Robyn. I'll hand over to Mike, because it sounds like the question is more around kind of payer discussions longer term, and for those that are more, maybe reticent, what, what, what might eventually, move some of these payers. Mike, do you want to comment?

Mike Mason (President, Lilly Diabetes)

Yeah, I think there's a couple of dynamics that will play out. I mean, first of all, we need to build a long-term clinical and real-world evidence to support payers' decisions. We're doing that. We're spending literally billions of dollars in clinical evidence to show what tirzepatide and our pipeline can offer patients who have obesity and payers with regards to medical cost savings. We're confident in our modeling that payers will see medical cost offsets with tirzepatide. So I think that'll be an important piece of it. I think the other dynamic is, you know, a lot of times we focus on the clinical story, but there is things beyond the economic analysis that I think will play a role.

If you, if you go and, and really discuss, with people who live with obesity, you know, improving their health is a top personal goal. Sadly, when we look at the data, 82% of people living with obesity experience physical functioning, reductions, while 77% experience reduced mental and emotional well-being. Patients using tirzepatide showed significant improvements in physical, mental, and emotional well-being in the SURMOUNT-1 trial. It's clear from the patient testimonies that we had in our SURMOUNT clinical trials, that tirzepatide can meaningfully improve the lives of people with obesity. The massive interest that we see in obesity medications is really driven by the fundamental desire for people living with obesity to improve their health.

People living with obesity should have a loud and powerful voice in this debate, and I think that's going to be a big component of payer decision, whether that be an employer or be a state or, or federal government. I think what you're going to see is over time, you're going to see data like, like the SELECT data, data like MMO or other clinical trials, continuing to build the case on economic side for these, while you're going to see the voice of people living with obesity who really want a better life, more hope for the future, who will be demanding access for these agents. I think both over time, will continue to build access across the U.S. as well as globally.

Speaker 25

Thank you, Mike. Paul, next question.

Operator (participant)

The next question is coming from Andrew Baum from Citi. Andrew, your line is live.

Andrew Baum (Head of Global Healthcare, Managing Director Equity Research)

Thank you. A non-Mounjaro, non-donanemab question coming up. We estimate there's about $2 billion of Dupixent in the US from adults with atopic dermatitis. When you are thinking about the launch of lebrikizumab, given the relatively little clinical differentiation and therefore the need to replace this Dupixent, could you just comment on how you're thinking about the launch? I'm assuming similar to Wegovy or Dupixent, something similar to Mounjaro or Dupixent, the obvious thing would be to launch a very, very large bridge program in order to secure former access, tapping into that high-deductible patient population. Just interested in your thoughts here, please.

Speaker 25

Thanks, Andrew, for diversifying the question set. I'll hand over to Patrick, President of Lilly Immunology, to weigh in on lebrikizumab and how we're thinking about positioning. Patrick?

Patrik Jonsson (President, Lilly Immunology and Lilly USA)

Well, thank you very much for the question on lebrikizumab. You're not based upon the data we have seen, we realize it's not a head-to-head, we're extremely encouraged by the maintenance data, having more than 80% of patients achieving skin clearance at week 16 and maintaining it at week 52. We really believe that we are positioned to launch a first-line biologic that actually has less frequent dosing than, than Dupixent. That's a big differentiator, targeting the most relevant cytokine for atopic dermatitis being IL-13, with a slow off rate and high potency. From an access perspective, we see the atopic dermatitis market growing significantly, we know that patients are looking forward to options here. We are believing that PBMs are willing to enter into discussions to enable a rapid access of lebrikizumab.

Of course, here we can capitalize on the strong footprint we have in dermatology and the portfolio we currently have in immunology. Our strategy will entirely focus on value and differentiation with our medicine and what it brings to the marketplace for atopic dermatitis.

Speaker 25

Thank you, Patrik. Next question, Paul.

Operator (participant)

Thank you. The next question is coming from Carter Gould from Barclays. Carter, your line is live.

Carter Gould (Senior Analyst, U.S. Biopharma Equity Research)

Great. Good morning. Thanks for taking the question. Appreciate all the color on the manufacturing side. At the same time, not a lot of those sites you talked about, those were sort of in your plans to start the year. I guess my, my question is, as we think about sort of the de-risking of orforglipron, the move to phase 3, has that in any way changed your sort of expected build-out for your longer-term manufacturing needs and, and really on the, on the, on the peptide side of the incretin side? Thank you.

Speaker 25

Thanks, Carter. Great question. I think, Dave wants to maybe jump in on this one.

David Ricks (CEO)

Sure. I'll jump in. I mean, just as we think about this over the long term, first of all, versus where we started the year, there is one change we're talking about today, which are these new presentations that we'll be launching beginning even this year into the next year. It's important for people to know that the constraint we experience now is in the parenteral auto-injector space. The degree we move outside of that, using our multi-dose pen that's currently developed for insulin and we're redeveloping for tirzepatide, or certainly the vial, which is quite accessible and high volume systems available, we'll be able to make more than we had planned previously, just to be clear. That's on top of sort of an on-schedule expansion at RTP in the other North Carolina site, as well as other internal nodes of capacity.

I think that's good news for Mounjaro. That all said, for the prior questions here, will that be enough to meet demand? I'm not so sure. While the volume is moving up into the right, we, we need more, and, you know, news like today's news will only expand the opportunity. You're right to point out that other molecules, and orforglipron in particular, could play a big role in meeting global demand for obesity treatment and all the related complications, because it's a completely different technology in that it's using oral solid, and there's quite a bit of capacity around the globe for, for that. Now, orforglipron is a complicated molecule to make. It's got many steps, but it puts us in a using a different set of assets and processes than the current ones we're using.

That's an important program, particularly for global access and availability over the long term. Just to remember as well, you know, two years ago, we were probably treating 10 million people globally with incretins. The WHO is estimating there'll be 1 billion people with obesity and related conditions by 2050, I believe. A long way away from getting all the way to that. We need things like orforglipron to work for us to, to meet the needs of all the patients in the world.

Speaker 25

Thanks, Dave. Paul, next question.

Operator (participant)

The next question is coming from Trung Huynh from Credit Suisse. Trung, your line is live.

Trung Huynh (Equity Research Analyst)

Thanks for squeezing me in, guys. Just one on IRA. One of the components that's been implemented in the part is the Part D redesign that starts impacting in 2024, and then there's going to be some more meaningful changes in 2025. On our calculations, we think it should benefit products under $25,000 a year, like your GLP-1 portfolio, but a negative for drugs priced above $25,000 a year. Given the mix of products you have in your portfolio at various different price points, directionally, how do you see that impacting earnings in the next few years?

Speaker 25

Thanks, Trung. I'm gonna hand to Anat for that comment, for that response on the IRA and potential impacts.

Anat Ashkenazi (CFO)

Yeah. If we, I think you were referring to the Part D redesign associated with removing the coverage gap, I'll also mention the negotiation. I wouldn't necessarily look at what the, the dollar amount is, but rather, you're right, there are gonna be varying degrees of impact on products based on how quickly they move through the catastrophic phase. Just to give an example from Lilly, if you're thinking about an oncology product where patients get to the catastrophic phase very quickly, there is probably an additional cost associated with that, with that for us, moving from the previous 70% coverage gap to the 10% participation in the initial phase and then 20% in the catastrophic phase. For other indications, it might be the opposite. There is a mix there.

Important to think about the fact that given that patients are now gonna have a limit of out-of-pocket when they get to the pharmacy counter, hopefully, that should improve adherence and compliance to medication, which should drive, obviously, better health outcomes for these patients, but also as we're thinking about medication kind of adherence. There's gonna be some pushes and pulls of that part of the IRA. The more significant one that I, that I would refer to is the so-called negotiation that we have as part of that, that's gonna come later in 2026 and 2028, with the first cohort of products to be announced this year.

I think that could have quite a meaningful impact on the drugs that are gonna be negotiated in terms of the price discounts that the government is gonna arrive at as part of that process.

Speaker 25

Thanks, Anat. I think we're through the main queue, but I know a few people have reentered and wanna be true to our word. We've only got about a minute left, so maybe just one last question, Paul, that's in the queue, and then we'll wrap up.

Operator (participant)

Certainly. The last question is a follow-up from Kerry Holford from Berenberg. Kerry, your line is live.

Kerry Holford (Head of Global Pharmaceutical Equity Research)

Well, lovely. Thank you. Just a quick one on Verzenio. Just interested to see whether you can tell us what proportion of those drug sales now are represented by use in the early breast cancer setting. Given we've now seen the Kisqali NATALEE data at ASCO, just interested to hear how you're thinking about competition coming into that space.

Speaker 25

Thanks, Kerry. All right, I'm gonna hand over to Jake for that last question on Verzenio and the proportion of sales and early breast versus metastatic, and maybe some commentary on NATALEE. Jake?

David Ricks (CEO)

Yep, thanks for the question. You know, I answer, the proportion of sales really on new patients starts NBRx. You know, TRX is sort of a lagging indicator, of course, that takes into account different durations of therapy. What we're seeing on the, on the NBRx side is about, call it, between 30% and 45% of prescriptions are in early breast cancer versus metastatic, and obviously, that number bounces around sort of week to week, month to month. That's more or less in line with what we expected. That's what's happening there. On the, on the competitive dynamics in the adjuvant setting, you know, now that we've seen the NATALEE data from Kisqali at ASCO, which, by the way, were not really surprising to us.

I think, you know, when you take a step back, and this is sort of both our opinion as well as what we've heard from thought leaders, we just really don't see what the Kisqali 3-year regimen is giving to patients to justify the additional year of therapy relative to the 2-year regimen that we've offered patients with Verzenio. You know, obviously, cross-trial comparisons notwithstanding, if anything, you see a marginally larger effect size with the 2-year Verzenio regimen in high-risk patients. Obviously, the NATALEE study studied a larger population. You know, the node-negative patients are at lower risk and frankly not part of our indication. We didn't study those patients. I think to the extent that folks wanna use Kisqali there, that's not really our business. Maybe it could be beneficial for those patients, I can't really say.

I think the other thing, and Dan mentioned this in the prepared remarks, is that there's been a lot of talk in the past, of course, about the differences in the tolerability of these two agents. I think one of the things that perhaps was somewhat surprising in the data we saw at ASCO was the high rate of discontinuations for toxicity of Kisqali, especially with many patients still on therapy, so that number, of course, will go up with more follow-up. I think these two drugs, while they have different tolerability profiles in terms of what the side effects are, they actually have somewhat similar overall tolerance profiles. Importantly, the Verzenio tolerability can actually be managed with dose reductions without sacrificing efficacy. It's not clear that the same is true for Kisqali, given the nature of those adverse events.

We continue to feel really good about what Verzenio can offer to patients and its competitive profile in the marketplace, and that's been validated by, in talks with prescribing physicians. We continue to feel good, and we just gotta make sure that all the patients who can benefit from the medicine, know that it's out there for them. Thanks for the question.

Speaker 25

Thanks, Jake. Dave?

Anat Ashkenazi (CFO)

Great. Well, we appreciate your participation in today's earnings call and your interest in the company. It's been a very productive first half of the year for Lilly, and we look forward to continuing our momentum into the second half. Thanks again for dialing in, and as always, please follow up with the IR team if you have questions we have not addressed on today's call. Have a great day.

Operator (participant)

Thank you, 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 August 21st at midnight. You may access the replay system at any time by dialing 800-332-6854 and entering the access code 213952. International dialers can call 973-528-0005. Again, those numbers are 800-332-6854 and 973-528-0005, with the access code 213952. Thank you for your participation. You may now disconnect your lines.