Regeneron Pharmaceuticals, Inc.

Welcome to the Regeneron Pharmaceuticals first quarter 2026 earnings conference call. My name is Kevin and I'll be your operator for today's call. At this time, all participants are on a listen-only mode. Later, we will conduct a question and answer session. Please note this conference is being recorded. I will now turn the call over to Ryan Crow, Senior Vice President, Investor Relations. You may begin.

Thank you, Kevin. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron and welcome to our first quarter 2026 earnings conference call. An archive and transcript of this call will be available on the Regeneron Investor Relations website shortly after our call concludes. Joining me on today's call are Dr. Leonard Schleifer, Board Co-Chair, Co-Founder, President, and Chief Executive Officer, Dr. George Yancopoulos, Board Co-Chair, Co-Founder, President, and Chief Scientific Officer, Marion McCourt, Executive Vice President of Commercial, and Chris Fenimore, Executive Vice President and Chief Financial Officer. After our prepared remarks, the remaining time will be available for Q&A. I would like to remind you that remarks made on today's call may include forward-looking statements about Regeneron. Such statements may include but are not limited to those related to Regeneron and its products and business, financial forecasting guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement, changes to drug pricing regulations and requirements, and our drug pricing strategy. intellectual property, pending litigation, and other proceedings, and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarter ended March 31, 2026, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise. In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available on our quarterly results press release and corporate presentation, both of which can be found on the Regeneron Investor Relations website. Once our call concludes, the IR team will be available to answer any further questions. With that, let me turn the call over to our President and Chief Executive Officer, Dr. Leonard Schleifer. Len.

Thanks, Ryan. Thanks to everyone for joining today's call. We were pleased with Regeneron's performance to start 2026, highlighted by strong commercial execution across our key growth products. continued pipeline progress, a disciplined approach to capital allocation, and our agreement with the U.S. government to lower drug prices for American patients while preserving innovation. Starting with the financials, we delivered double-digit growth across both revenues and earnings. Total revenues increased 19% compared to the first quarter of 2025, and non-GAAP earnings per share increased 15%. demonstrating our ability to deliver strong operating performance while continuing to invest in our science and long-term growth opportunities. Global Dupixent net sales increased 31% on a constant currency basis to $4.9 billion in the quarter. Growth was broad-based and driven by continued strong demand across multiple approved indications and geographies, reinforcing Dupixent's position as the foundation of our immunology franchise. We also continue to advance our efforts with next generation therapeutic approaches to strengthen our leadership position in inflammation and immunology. ILEA-HD US net product sales increased 52% year over year to 468 million. We continue to see encouraging physician adoption of ILEA-HD, reflecting confidence in its clinical profile and dosing flexibility. We resubmitted an application seeking FDA approval for filling of the ILEA-HD pre-filled syringe at Catalin, Indiana, where the FDA has recently conducted a site reinspection. In addition, the FDA did not act by the April 2026 PDUFA date for the company's regulatory application for a second contract manufacturer for the PFS. Therefore, this application remains pending. Regeneron and both third-party filling manufacturers are working closely with the FDA to resolve all outstanding issues, and we anticipate a regulatory decision on one or both applications during this quarter. In oncology, global entire net product sales grew 54% to $438 million, driven by continued uptake in advanced cutaneous squamous cell carcinoma and advanced non-small cell lung cancer, as well as early contributions from the adjuvant CSCC indication, which received FDA approval in the fourth quarter of 2025. Turning briefly to our pipeline before George provides more details in his remarks, we've continued to make meaningful progress across multiple therapeutic areas, so far in 2026. Last week, we received FDA approval of Otarmine for genetic hearing loss, marking an important milestone for patients with this ultra-rare condition, and we have committed to offering this product for free. While this may seem like an unconventional decision, we believe it's the right one for Regeneron, and it reflects the ethos that we live by, pushing the boundaries of science to benefit humanity. Moving to other advances in our pipeline, we presented positive Phase III data for semdisoran, our investigational siRNA that targets C5 in generalized myasthenia gravis, which demonstrated a differentiated efficacy, safety, and convenience profile relative to approved myasthenia gravis therapies. We submitted a new application utilizing a priority review voucher and anticipate an FDA decision in the fourth quarter. In metabolic disease, we and HANSO announced positive phase three data in China for olotorapatide, our in-licensed GLP-GIP receptor agonist, with full data expected to be presented by HANSO later this year. To PICSIN, achieve multiple regulatory milestones, expanding the eligible patient population to younger age groups and to new diseases. In addition, the FDA accepted our biologics license application for Garitosumab and granted priority review with a decision in August, representing another important step forward for our rare disease portfolio. Briefly, on capital allocation. We continue to take an approach that balances internal investment, which we believe offers the greatest long-term return for shareholders, with direct return of capital through share repurchases and dividends, as well as business development. In support of that approach, Our board authorized a new $3 billion share repurchase program, reflecting confidence in our business and financial position. We also recently entered into strategic collaborations with Thelix and Trinetics. Finally, last week, we entered into a most favorite nation pricing agreement with the United States government, achieving our shared goals of ensuring timely and affordable access to groundbreaking medical advancements for medical patients, maintaining the United States leadership in biotechnology, innovation, and manufacturing, and addressing the imbalance in the distribution of costs for medical innovation, which we have long argued has placed a disproportionate burden on American patients. In closing, the progress we've made so far in 2026 reflects the strength of our science and execution and sets a solid foundation for an exciting remainder of the year. With that, I'll turn the call over to George to discuss our R&D progress in more detail.

Thanks, Len. I'll start with our differentiated approach to treating complement-mediated diseases, which was highlighted last week at our latest Regeneron Roundtable Investor Event. Our core strategy is to deploy customized approaches using an siRNA, an antibody, or a combination approach. depending on the level and durability of complement inhibition required for each disease. For example, it appears that in generalized myasthenia gravis, or GMG, that partial blockade with the C5 sRNA alone delivers optimal efficacy, safety, and convenience, while in PNH, complete blockade requiring combination of the sRNA with our C5 antibody is required to optimize efficacy. For myasthenia gravis, we presented results from the Phase III NIMBL trial at the American Academy of Neurology Conference, which were also simultaneously published in the Lancet. Symdisarine, our investigational C5 SRNA as monotherapy, as monotherapy met the primary and all key secondary endpoints with subcutaneous delivery every 12 weeks, delivering a 2.3-point placebo-adjusted improvement in the MGADL endpoint at week 24. In registrational clinical trials for the leading approved C5 inhibitors, which are administered as large volume intravenous infusions, dose every two weeks or every eight weeks, placebo-adjusted improvements in the same MGADL endpoints have ranged from 1.6 to 1.9 points at similar time points. For some disarray, clinically meaningful efficacy was demonstrated by week two. Moreover, these improvements deepened over time and were sustained through week 24 with no indication of waning efficacy between doses. The totality of the data, including mostly mild to moderate adverse events, support a compelling profile for some different as a standalone quarterly therapy for this disease. These data have been submitted to the FDA and we expect a regulatory decision in the fourth quarter of this year. In PNH, our phase three lead-in results reinforce the requirement for the combination of syndicerine plus pozolomab, our C5 antibody, to deliver complete and sustained disease control. Leading results suggest that our combination will provide best-in-class control based on LDH measures, and that patients who are uncontrolled on revolizumab can largely be controlled when switched to our combination. Enrollment in the registrational enabling cohort of the Phase III study is now complete, and results are expected late in the fourth quarter of this year. Additionally, in P&H, and as part of our ongoing complement strategy, we recently initiated a first-in-human study evaluating SRNA that targets complement factor B. This approach is initially intended for the 20% to 30% of patients who, despite optimal C5 therapy, remain anemic due to extravascular hemolysis, but also has the potential to expand to a broader P&H population. If successful, siRNA targeting of CFB could overcome the limitations associated with current CFB inhibitors, which require daily dosing and carry the risk of catastrophic hemolysis if doses are missed. In ophthalmology, our C5 approach in geographic atrophy is on track to deliver interim data from the exploratory cohort of our Phase III study in the fourth quarter of this year, which will help inform our pivotal strategy. As a reminder, we are evaluating some discerning, with or without pozellumab, administered systemically with the goal of slowing the growth rate of GA lesions while avoiding ocular safety issues that have been observed with certain approved intravitreal therapies. However, to ensure that we have optionality depending on what we learn clinically, we have also recently begun clinical development of an intravitreal formulation of pozolomab, and we'll also follow up with a co-formulation of pozolomab with Aflibicept, since some of the patients also develop wet AMD while being treated for their GA. Now, turning to immunology and inflammation, and starting with dupixin. In the United States, dupixin was recently approved as the first and only medicine for allergic fungal rhinosinusitis, or AFRS, in adults and children six years and older. AFRS is a specific type of chronic rhinosinusitis with nasal polyps that more often requires surgery and is associated with higher rates of postoperative recurrence. Depixin was also approved in the United States and Europe as the first targeted medicine for children 2 to 11 years of age with chronic spontaneous urticaria, expanding the eligible patient population beyond adolescents and adults. This approval reinforces the expanding role of Depixin across diseases driven in large part by type 2 inflammation and across a broad range of ages. Regarding our efforts to develop next-generation approaches to the Depixin pathway, We have previously disclosed that we have developed innovative, the last immune-derived, fully human, long-acting antibodies and bispecifics that target the IL-4 receptor itself, as does DUPI, as well as the IL-13 and IL-4 cytokines that act through this receptor. We are on track to initiate a first in human trial for our IL-13 antibody by the middle of this year, both in healthy volunteers and in patients with atopic dermatitis, with plans to execute an expedited path to regulatory approvals. Beyond Dupixent lifecycle opportunities, we continue to advance our next wave of immunology and inflammation programs. Our goal is to keep exploring genetically validated targets that have the potential to become future pipeline and product opportunities. We're initiating a first-in-human study of an antibody to a target identified by the Regeneron Genetic Center as being genetically linked to several diseases, such as lupus, Sjogren's, and primary biliary cholangitis. We're also continuing to evaluate the best path forward across respiratory and sinonasal diseases for itapicoman, or interleukin-33 antibody. In chronic rhinosinusitis with nasal polyp, our Phase III studies are ongoing, with results expected in 2027. Regarding COPD, We, Sanofi, and global regulators continue to discuss a potential third phase three study. The no decision has been made on whether to move forward. Turning to oncology. On Fianelmab, our lag-free antibody in combination with Liptile, our phase three study in metastatic melanoma remains on track, with results expected later in the second quarter of this year. The primary analysis of progression-free survival will now consider all patients enrolled in the study with a minimum follow-up of six months. In adjuvant melanoma, the study continues following the first interim analysis, with the second interim analysis, and if necessary, a final analysis, both expected in the second half of this year. We also continue to advance pivotal studies for linazific in multiple myeloma and pre-malignant conditions, and expect to have results by early 2027, from our study in multiple myeloma patients that have received at least one prior line of therapy, as well as MRD negativity results in 2028 from our study in first-line myeloma patients who are ineligible for stem cell transplant. Our first-line study for Otranexamab in first-line follicular lymphoma is fully enrolled. This is the only study exploring a bispecific as monotherapy versus the current standard of care, which is RCHOP, across this bispecific arena. Moving to anticoagulation, we initiated additional Factor XI registrational studies in stroke prevention in patients with atrial fibrillation who are not candidates for direct oral anticoagulants, as well as cancer-associated venous thromboembolism. Additional studies in peripheral arterial disease, peripherally inserted central catheter-associated thrombosis, secondary stroke prevention, as well as SPAF and DOAC-eligible patients, are all expected to commence this year. Initial registration studies from studies in venous thromboembolism prevention following knee replacement surgery are expected in the first quarter of 2027. Turning to obesity. In March, Hanzo reported positive phase two results for olotorapatide, our in-licensed GLP-GIP agonist in Chinese patients with obesity, which compared fairly cross-trial to a previous Chinese study of terzepatide for obesity. In this randomized, double-blind, placebo-controlled trial of 604 adults across 33 sites, oliverapatide met its co-primary endpoints and delivered up to 19% mean body weight loss at week 48. We were also encouraged by the safety results, in particular, the gastrointestinal tolerability profile. Hanzo is planning on presenting these promising results at a medical meeting later this year. Building on this momentum, our olatorepetide phase 2 study in obesity is enrolling rapidly, and later this year we expect to initiate two global phase 3 programs, one in patients with obesity and another patient with obesity and type 2 diabetes. In parallel, our work on the olatorepetide-praline combination continues. with our first clinical study of weakly prevalent initiating shortly. In rare diseases, Len already mentioned the FDA approval of Otarmine, formerly known as Dibiota. This was an incredibly meaningful moment for the company, as it is not only our first gene therapy approval, but one of the most striking successes with gene therapy in history, restoring for this first time a sensory function in humans. As published in the New England Journal of Medicine, Nearly half the children who were born profoundly deaf were able to regain hearing at normal levels within one year of treatment. The mother of one of these children recently told the President of the United States a heartwarming story of how her son was now able to hear her say that she loved him. We decided to make Otamany free in the United States because we believed it was the right thing to do for these families. We hope this highlights and reminds the world that it is the biopharma industry, which is frequently viewed so negatively, that is often responsible for delivering such medical miracles to humanity. Regeneron is a different type of company that attracts the best and the brightest to join our fight against disease because we have a heart and a soul as well as a mission and a willingness to play the long game. Another rare disease that we have been studying for many years is fibrodysplasia ossificans progressiva, or FLP, a devastating condition in which muscle and soft tissues are progressively invaded and replaced by abnormal bone formation. The FDA has accepted for priority review the BLA for garitosumab, or active innate blocking antibody, with a PDUFA date in August of 2026. If approved, garitosumab would become the first and only available treatment shown to prevent abnormal bone formation in FLP patients. In genetic medicines, our first in human trials testing siRNAs targeting superoxide dismutase, or SOD1, in amyotrophic lateral sclerosis, alpha-synuclein for Parkinson's disease, and MAP-TAO for Alzheimer's disease on rolling patients, and our initial MASH siRNA program readings targeting PsiB, PNPLA3, and HSD17B13 are expected by the end of this year. Concluding with recent early-stage research updates, the Regeneron Genetic Center recently announced a collaboration with Trinetics to access de-identified electronic health record data from a global network representing 300 million patients, creating an opportunity to connect large-scale genomic and proteomic cohorts to real-world clinical data in ways that can accelerate drug discovery, translation, development, as well as providing new ways of addressing digital health Regeneron also announced a strategic collaboration with Telex to co-develop and commercialize next-generation radiopharmaceutical therapies, combining Regeneron's antibody discovery and oncology capabilities with Telex's radiopharmaceutical development and manufacturing expertise. In summary, we remain focused on advancing our late-stage, mid-stage, and early-stage programs, as well as innovative research. which we firmly believe has the potential to continue to change the practice of medicine. With that, let me turn it over to Mary.

Thanks, George. Our first quarter results represent a strong start to 2026. Our market-leading brands, Idea HD, Dipixen, and Liptio, delivered ongoing growth based on their clinical profile and our ability to execute effectively in competitive markets. begin 2026 well-positioned to advance our portfolio and are excited by upcoming opportunities to change the lives of even more patients. Starting with ILEA HD and ILEA, which delivered combined U.S. net sales of $942 million in the first quarter, ILEA HD net sales were $468 million, representing 52% year-over-year growth. During the quarter, physician demand for ILEA HD increased sequentially by 10%. Despite typical first-quarter seasonality, Additionally, in the first quarter, wholesaler inventory levels were reduced to the normal range. ILEA-HD now has the broadest label and greatest dosing flexibility of any anti-VEGF medicine, following recent label enhancements to include retinal vein occlusion and additional dosing options that range from every four weeks through every 20 weeks. We are encouraged by physician adoption following these label enhancements. Importantly, we also look forward to the upcoming FDA decision for the ILEA-HD pre-filled syringe, which, if approved, would bring what we believe is a best-in-class device to retina specialists and help drive continued uptake for ILEA-HD. In the first quarter, ILEA's U.S. net sales were $473 million, representing a 36% year-over-year decline. This reflects ongoing conversion to ILEA-HD, competitive pressures, and patient affordability issues. Additionally, during the first quarter, there was only a modest reduction in ILEA inventory and continued inventory absorption is expected to negatively impact net product sales in the second quarter by approximately 20 million. Looking ahead to the second quarter, we expect to achieve sequential unit demand growth for ILEA HD that is consistent with the 10% sequential demand growth in the first quarter. Conversely, for ILEA, we anticipate that demand will decline in the mid to high teens in the second quarter ahead of the potential launch of additional biosimilars in the second half of the year coupled with the factors that I highlighted earlier. Together, ILEA-HD and ILEA lead the innovative branded anti-VEGF category with more than 100 million injections of ILEA-HD and ILEA administered worldwide since launch. Additionally, in the U.S., ILEA-HD now contributes half of net sales for a retina franchise. Turning to Dupixent, which continues to transform the lives of more than 1.4 million patients worldwide with type 2 inflammatory diseases that are currently on treatment. In the first quarter, Dupixent net sales were $4.9 billion, representing 31% year-over-year growth on a constant currency basis. U.S. net sales grew 35% year-over-year to $5.6 billion. We continue to see growth across all nine indications, including recent launches, making Dupixent the number one biologic medicine prescribed by dermatologists, pulmonologists, allergists, and ENTs. Across the blockbuster indications of atopic dermatitis, asthma, nasal polyps, and eosinophilic esophagitis, Dupixent continues to drive strong growth based on its differentiated clinical efficacy, safety profile, and physician's strong preference for this brand. Uptake is also strong across more recent launches, including chronic obstructive pulmonary disease, chronic spontaneous urticaria, bolus pemphigoid, and allergic fungal rhinosinusitis. These launches across a growing range of age groups provide a runway for even more patients to benefit from Dupixent. With annualized global net sales of nearly 20 billion and significant room for further market penetration across syndications, Dupixen is well-positioned for sustained growth over the near and long term. Turning to Libtio, which delivered 438 million in global net sales in the first quarter. In the U.S., net sales were 286 million, as Libtio continues its strong trajectory as the leading immunotherapy for advanced non-melanoma skin cancers. The recent launch of Libtio in adjuvant CSCC is also an emerging growth driver, with encouraging uptake and positive feedback on this paradigm-changing treatment. Liptio is the only NCCN category one preferred immunotherapy option for eligible adjuvant CSC patients. In non-small cell lung cancer, Liptio is established as the second most prescribed first line immunotherapy treatment in the U.S. and we expect continued growth through 2026 as we gain incremental share in lung cancer and drive uptake in adjuvant CSCC. Onto Linazific, which is in its second full quarter on the market. Early launch momentum has been driven by positive physician experience, a differentiated clinical profile, lower hospitalization requirements, and convenient dosing schedule. We expect continued gradual uptake as we work to advance our clinical program in earlier lines of therapy. I also wanted to spend a moment highlighting our expanding rare disease portfolio. Avkiza is now in its fifth year on market in the U.S., and delivered net sales of 46 million for the quarter, representing 48% growth year-over-year. Eftiza is well-established as a leading treatment for homozygous familial hypercholesterolemia, with more than half of all diagnosed U.S. patients currently on Eftiza or in the process of starting Eftiza. As highlighted by Len, we are also launching Otarmony, which is the first and only gene therapy for children born with genetic hearing loss, In addition, we look forward to the anticipated FDA decision on Garitosumab in August. Garitosumab is our potential treatment for FOP and has been shown to prevent 99% of abnormal bone formation. In closing, our strong first quarter results demonstrate growth potential across our portfolio. We continue to advance our inline brands while also preparing for multiple potential indication in new product launches. including for some discernt for generalized myasthenia gravis, where there is significant commercial opportunity in this large and growing market. We remain well positioned to deliver meaningful benefits to patients worldwide across a growing number of diseases. And with that, I'll turn the call over to Chris.

Thank you, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis unless otherwise noted. Regeneron performed well in the first quarter, highlighted by double-digit growth on both the top and bottom line. First quarter 2026 total revenues grew 19% from the prior year to 3.6 billion, driven by higher Sanofi collaboration revenue, as well as strong growth in net sales of ILEA HD in the US and Libtyo globally. First quarter diluted net income per share grew 15% to $9.47 on net income of 1 billion. Beginning with the Sanofi collaboration, first quarter total Sanofi collaboration revenues were $1.6 billion, of which $1.5 billion related to our share of collaboration profits. Regeneron's share of profits grew 42% versus the prior year, driven by Dupixent sales growth and improving collaboration margins. We now expect the Sanofi development balance to be fully repaid by the end of the second quarter. As a result, we expect Sanofi collaboration revenue to step up to reflect our full share of collaboration profits starting in the third quarter. Moving to buyer. First quarter net sales of ILEA and ILEA 8MIG outside the U.S. were $729 million, inclusive of $333 million of ILEA 8MIG sales. Total buyer collaboration revenue was $287 million, of which $240 million related to our share of net profits outside the U.S. Other revenue grew 109% in the first quarter to $171 million. This included $101 million related to our share of profits from Arculus and royalty income from Alaris. Now to our operating expenses. R&D expense was $1.4 billion in the first quarter, reflecting continued investments to support Regeneron's innovative pipeline, including pivotal programs across late-stage opportunities in hematology, oncology, complement-mediated diseases, and anticoagulation. First quarter SG&A was $560 million, reflecting investments to support the launch of Liptio and Adjuvant CSCC and to drive continued growth of ILEA-HD. First quarter matching contribution to Good Days, an independent nonprofit patient assistance foundation, were de minimis. We remain committed to matching up to $200 million in 2026 to support patient access and affordability. Non-GAAP gross margin on net product sales was 86% in the first quarter. Our GAAP gross margin was 76%, which was negatively impacted by costs incurred due to a temporary interruption in bulk manufacturing at our Limerick, Ireland site. We have now resumed initial production in the facility and expect to resume full production by the end of the second quarter. As a result, we anticipate our GAAP gross margin will continue to be negatively impacted in the second quarter as production returns to normal levels. This interruption has not impacted and is not expected to impact the availability of any products. Regeneron generated $848 million of free cash flow in the first quarter of 2026 and ended the quarter with cash and marketable securities less debt of $15.8 billion. We repurchased $800 million of our shares in the first quarter and announced this morning that the Board of Directors has authorized a new $3 billion share repurchase program. With this new authorization, we have approximately $3.4 billion available for share repurchases as of today, and we remain opportunistic buyers of our shares. We have made some minor changes to our 2026 financial guidance. including updating our GAAP gross margin guidance to be in the range of 77% to 78%. This reflects actual and expected costs incurred as a result of the aforementioned temporary manufacturing interruption. A full summary of our guidance can be found in our earnings press release published earlier this morning. In conclusion, Regeneron is off to a strong start in 2026 with financial results that position us well to continue investing in our pipeline delivering breakthroughs for patients, and driving long-term value for shareholders. With that, I'll pass the call back to Ryan.

Thank you, Chris. This concludes our prepared remarks. We will now open the call for Q&A. To ensure we are able to address as many questions as possible, we will answer one question from each caller before moving to the next. Kevin, can we go to the first question, please?

Thank you. Ladies and gentlemen, if you have a question or a comment at this time, please press star one, one on your telephone. If your question has been answered or you were to move yourself from the queue, please press star one, one again. One moment for our first question. Our first question comes from Tyler Van Buren with TD Cowan. Your line is open.

Hey guys, good morning. Thanks for the question. So Dupixent continues to be a monster delivering strong performances quarter after quarter after quarter. And it now looks like it will well exceed 30 billion of global sales. So given that we get a lot of questions from investors, not just on lifecycle expansion, but the Santa Fe collaboration. So can you discuss your willingness to work on lifecycle expansion efforts within the Santa Fe collaboration or come to an agreement on commercializing these assets? together in order to take advantage of the Dupixent rebate wall and the status of that as opposed to moving lifecycle expansion candidates forward yourself and potentially further building out the commercial infrastructure.

Tyler, it's Len. Thanks for that very poignant question. Maybe it'll give me an opportunity to publicly thank Paul Hudson for all the work he did on Dupixent since 2019. Thank you, Paul. We wish you good luck in your next chapter. Also, as of today, Sanofi's new CEO, Belen Garijo, is officially, I think, the CEO today. So we want to welcome Belen and wish her luck, and we look forward to working with her and the rest of her team. Tali, you're right. Dupixen is a remarkable product, as Marion detailed and George outlined. It's helping so many different people with so many millions of people with different diseases. and is a financial juggernaut for the company. We are always open-minded to transactions, certainly leveraging what we've built in terms of both development capabilities as well as commercial capabilities has merit to it. We can do these things ourselves. We've had interest from many different places to sort of take on some of the the next opportunities with us, but we're open-minded, and I look forward to talking with Belen and her team in the coming weeks and months, et cetera.

Thanks, Glenn. Let's move to the next question, please, Kevin. One moment for our next question.

Our next question comes from Terrence Flynn with Morgan Stanley. Your line is open.

Great. Thanks. This is Chris on for Terrence. We have a question about Phenlymeb in metastatic melanoma. Is the PFS differentiation enough to capture majority share, or do you think you need OS as well? Thank you.

Well, it obviously depends on the results. It depends on exactly what the PFS results are, but the study is also designed so that If we have a substantial OS benefit, we will see that as well. And so the hope, of course, is that the study will show both a PFS and an OS benefit. But, you know, the results remain to be seen.

Thanks, George. Let's move to the next question, please. One moment.

Our next question comes from Chris Raymond with Raymond James. Your line is open.

Hey, this is Sam Lee-Chon for Chris Raymond. Just one on the ILEA pre-filled syringe. So any commentary on why FDA missed the April PDUFA? Was that a request for more information or a backlog issue? And then you noted there was a re-inspection at Catalan, Indiana, and you've resubmitted. Can we read in between the lines and assume that means the site inspection was positive? And what's kind of your overall guidance on timing for either of these applications? Thank you.

Yeah, so thanks for the question. I think we've told you what we know. We don't, if the inspection turns out to be positive, then I think they will approve the drug. So we await, and both applications are pending. And the only thing I can say is that based on our conversations and how hard everybody's working at this and the FDA, I think desire to, you know, get these sites up to the standards they want, as well as get the products out there that are waiting that we anticipate action on one or both of these during this course.

Thanks, Len. Let's move to the next question, please.

One moment. Our next question comes from Corey Kasimoff with Evercore ISI. Your line is open.

Hey, good morning, guys. Thanks for taking the question. Wanted to ask about linazific and kind of the outlook in the multiple myeloma spaces. we talk with docs there's obviously excitement about the potential of bcma by specifics the main pushback on widespread adoption is the infection risk they carry especially in earlier stage patients so curious what you make of the debate and how you're trying to mitigate this in your trials going forward thank you so the debate of their use compared to what it's exactly existing standards of care like that i see et cetera so

Obviously, all of these approaches carry significant infectious risks. As we've shown in our study, the disease itself carries substantial infectious risk. And if you actually look at our detailed data and publications on the matter, it actually turns out that the longer you treat these patients, the more you control their disease, the more functional their bone marrow becomes. Actually, infectious risk goes down over time. which is actually quite stunning. So I think that the profile, if you really look at it, of the bispecifics in general, and our bispecific in particular, are very, very promising, not only in terms of their impressive efficacy, but in terms of their overall side effect and tolerability profile, including, of course, the infectious risks. So we think that this is going to become the dominant class for the treatment of this disease as well as its precursors. And we believe that if you look at the data that our agent is certainly competitive, if not indeed best in class across all parameters here.

Thanks, George. Let's move to the next question, please, Kevin. One moment.

Our next question comes from with Bank of America. Your line is open.

Hi, good morning. Thanks for taking my question. As you think about NextGen, Ducey, how are you thinking about the importance of having a late-stage program, you know, clearly defined before the US IP for Dupixent goes away, whenever that might be, just given the increasing number of potential long-acting injectables and other oral agents that might come online? Thanks.

Yeah. Look, the... We don't know how long the patent life will be for DUPI because we have lots and lots of intellectual property out there, lots of different types of patents, use patents, formulation patents, in addition, obviously, to the composition patent. In terms of how we think about this, to us, we want to leverage our knowledge in immunology. We don't necessarily think about having to exactly replace or work on. We have nearly 50 things in the pipeline, and we're looking forward to bringing as many important ones forward as we can. But we do have a number of these that George, I think, talked about. The extended interval Dupixent, going after long-acting IL-13, IL-4, other diseases that we haven't even covered with DUPI, such as allergic diseases, in general, food allergies and so forth. So I think there's a lot of opportunity, and one shouldn't just focus on a simple replacement or what have you, and one shouldn't assume when the patent for DUPI will actually expire.

Okay. Thanks, Glenn. Let's move to the next question, please.

One moment. Our next question comes from Carter Gould. But, Cantor, your line is open.

All right, great. Good morning. Thanks for taking the questions. Maybe to change it up a bit, for George, as you spoke about the co-injection of C5 with the Flibercept, should we think about that as more of a convenience play sort of with the co-administration or potentially more of, I guess, a label expansion as you think about potentially preventing wet AMD, I guess, forming, for lack of a better term?

I think those are both interesting possibilities. It could be used to actually prevent the development of the way MD and or to treat the patients who develop it. And very importantly, as you probably know, there's a lot of evidence and suggestions about the causes of the occlusive retinal vasculitis that is seen with the other agents that are, for example, totally different kinds of molecules and pegylated and so forth. And these, some of the characteristics of those molecules are associated with this occlusive retinal vasculitis. We hope and we believe, based on our experience with biologics, with ilea, and with this particular antibody, that we may not only have these convenience benefits, but perhaps most importantly, we may also avoid the very tragic, very horrific side effects that are seen with the existing agents, which would allow them to be much more broadly used. Moreover, we would think, once again, as our experience indicates in the history with ILEA, that we could have much longer acting versions. And moreover, depending on how the data looks with the systemic as well as the local versions, one could imagine even combining to allow for very long-acting injections in the eye. So there's a lot of possibilities that could address better safety profile, as well as convenience, as well as potentially even efficacy.

Thanks, George. Next question, please, Kevin.

One moment.

Our next question comes from Evan Siegerman with BMO Capital Markets. Your line is open.

Hi there. Thank you for taking my question. I'd love for you to walk me through the commercial considerations for developing your combo GLP-1, GIP, plus Proluent, and how can you accelerate the development to remain competitive in this rapidly evolving market?

Well, the way we look at it, and I think Len came up with this terminology, imagine if you invented a GLP that was as good as the currently best-in-class agent, let's say Terzepatide, and acted very much the same, but also lowered your bad cholesterol by more than 50% and was shown to decrease your risk of cardiovascular outcomes like heart attacks and death. That GLP would become the preferred GLP on the planet, especially if you priced it at a very similar price. Why would anybody take any other GLP? We are very... buoyed by the data that we see coming from our collaborators in China, where the cross-trial comparisons show that as we predicted based on our due diligence of the molecule, that it behaves, if anything, as well as trisepatide. And of course, our folks in the lab have been busy working developing co-formulated forms of this GLP together with our Prowl unit, which we believe we can be delivering by a very similar, convenient auto-injector approach using the same approach as the GLPs are delivered as well. And we believe that we can price it very competitively to the GLPs. And we would think that, honestly, any physician prescribing it or any patient thinking about it would say that why would they ever take a GLP especially since we know of the profound co-morbidities associated with cardiovascular risk and the hyperlipidemia in the same population. Why would they ever take a GLP if they had the option of taking a GLP that also lowered their lipids and also decreased their risk of bad cardiovascular outcomes? So to us, honestly, it sort of seems like a no-brainer. Obviously, there will be competition. But we believe we have potentially a best-in-class GLP and a best-in-class PCSK9. And the convenience for many people of these autoinjectors is now becoming so pervasive that we think a large segment of the population will offer them. Now, this is, of course, not even presuming that the side effect profile that we see in China more broadly pertains in our upcoming global studies. So, we think this is a very, very exciting and a very, very large opportunity.

George, could you just correct the misunderstanding about weight loss not lowering lipids?

Yeah. So, thank you, Len. It's a great point. As many people obviously know, weight loss and the GLPs can provide cardiovascular outcome benefits, but they do this by creating benefits across a wide variety of different risk factors, and they only lower your bad cholesterol by a few points, in contrast to the 50% to 60% lowering that we see with the PCSK9 blockers. So this will be a real add-on in terms of the cardiovascular benefit and the lipid benefit compared to just GLP alone, which by themselves, though, they benefit outcomes. They do very little in terms of your lipid profile, so many patients are obviously left with still high risk based on their lipid profile if they're either obese or especially obese with type 2 diabetes where dyslipidemia there is a very serious and common comorbidity concern.

Finally, the use of cholesterol lowering drugs is now finally catching up, I think, to the science where the recommendations are to start earlier and longer. So I think that your indicated population to lower cholesterol and lose weight is going to be even broader. So as George said, this is a really significant opportunity.

Well, and very importantly, from the public health perspective, though recommendations are all about how focus on your lipids, much earlier widespread use of lipid-lowering medications, they are dramatically underutilized in the world. Unfortunately, this causes incredible morbidity and death. Heart disease is still the leading cause of death in the United States, in part because of the underutilization of these incredible weapons we have. We think in a Trojan horse sort of way, this will provide incredible public health benefit by having all the people who are really so worried about their weight loss also get the lipid benefit, which will have this dramatic benefit, which is unfortunately underutilized and underappreciated.

Okay, thank you, Len and George. Let's move to the next question, please.

One moment. Our next question comes from Alexandria Hammond with Wolf. Your line is open.

Thanks for taking the question. Can you share a little bit more on your clinical strategy to expedite development of your next-gen INI assets, particularly Soupy Doopy? How do you expect to be able to kind of leverage the changes within FDA to further speed this development up, and has there been an ongoing dialogue with the regulators?

Thank you. We've obviously, we're world leaders in this field. We created the field. We did the first studies in atopic dermatitis in the field. And we are well positioned, we believe, to expedite and accelerate the programs as rapidly as possible. And we feel very good about our position and our plans here.

Okay. Thanks, George. Let's move to the next question, please.

One moment. Our next question comes from Salveen Richter with Goldman Sachs. Your line is open.

Thanks for taking my questions. Just regards to the lifecycle strategy for Dupixent, which is broad and multi-pronged, where do you feel you have the most line of sight, and how are you optimizing the IL-4 agent or SUBI-DUBI? Thank you.

Yeah, I think what George said is that we have a lot of experience here We don't need to give out all of our details to help any competition that might be out there, but the team knows what they're doing. Suppy Doopy is one that Sanofi and Regeneron, by mutual agreement, can add to the collaboration. We have the knowledge, the capabilities, and the desire to do this as efficiently as possible.

Okay, next question, please, Kevin.

One moment. Our next question comes from Christopher Schott with JP Morgan. Your line is open.

Hi, this is Taylor Hanley on for Chris Schott. Thank you so much for taking our question. We were just wondering, on LIBTIO, can you provide any color on the drivers of performance this quarter? Was there anything one time in there? How much of this was driven by the new indication, CSCC? And is this a good baseline to think about growing off of going forward? Thank you.

So, sure, very happy to take the question, and I think the Leptio performance certainly is strong. I would characterize the strength based on certainly the advances that we've seen in our skin indications. Now with adjuvant CSCC, very exciting to help this group of patients with Leptio. There's been a lot of enthusiasm, and certainly the clinical profile of Leptio in this indication was highly distinguishing. We also see performance in our lung cancer indication U.S. and international performance are strong. I would characterize the quarter, though, by comparison to a year-over-year comparison in a quarter that had some movement in inventory. We can certainly go back and share more of the details with you on that, but it's a very strong quarter, but there is some comparison that favored this quarter.

Thanks, Mary. And next question, please. One moment.

Our next question comes from David Risinger with Lering Partners. Your line is open.

Yes.

Excuse me. Thanks very much. So, hi, Len and George. My question is for you. So, Regeneron spends aggressively on R&D, but the investment community lacks confidence that the company's candidates will move the needle commercially. in particular versus established competitors. So could you please highlight the pipeline candidates in late stage development that will have cards turning over in the near term or relative near term, i.e. in the next, I don't know, 18 months or so that you have the greatest confidence in that can generate multi-billion dollar peak sales that investors will be able to see more clearly in the next 18 months or so. Thank you very much.

That's perhaps the most penetrating in the 160-odd conference calls I've done, penetrating and detailed question. But unfortunately, David, it'll probably take several hours to answer. We have a robust pipeline. We do have, obviously, highlighting the C5 franchise, where we'll have more data and an approval action. We will have 11, I think, phase 3 trials ongoing in our anticoagulation program, which is a massive opportunity. We have our linazific and our ogenextamab, our bispecifics in myeloma and lymphoma ongoing. I think George just talked about our OLA plus an OLA plus ALI as a near term. And obviously, even in this quarter, we have Fianlumab plus Liptio and metastatic melanoma. So, maybe I'll leave that for openers. And we have more and more things. We've got some exciting data coming out that we haven't even talked about. And I didn't just mention, so lots going on when you have 48 exciting things in development.

Can I just say, I mean, I want to comment that past performance should be the strongest indicator of future performance. There's only one company in recent history that out of its own labs produced two 10 billion plus blockbusters. And let me remind you that I think you and probably a lot of other investors never saw those coming or ignored what we were saying about them. So I think that investor confidence, I think, should in large part be reflecting historical performance and the recognition that where blockbusters come from, sometimes for the investor community, can't be directly anticipated. And the best way of producing very important big drugs is by having very exciting molecules across all stages of development that have enormous opportunity. And if you just look at oncology programs, whether it's phenylenolactile, whether you look at linozific, whether you also look at ojonextamab and follicular lymphoma, these are all potential blockbusters. The C5 Franchise is a pipeline in a franchise, multiple blockbuster opportunities there. Our Factor 11 customized approaches are looking more and more exciting, especially based on competitor data using, we think, inferior and less convenient approaches. And we just covered the obesity opportunity, which arguably could become the preferred obesity approach that not only addresses obesity but more aggressively addresses cardiovascular morbidity. So I know it's hard to think of a more exciting pipeline in the entire industry.

Thanks, Glenn and George. We have time for two more questions, Kevin.

One moment.

Our next question comes from Jeff Meacham with Citi. Your line is open.

Hey, guys. Good morning. Thanks for the question. On Fianlumab and lung, I just wanted to see if you guys can give us a bit more context for not moving to phase three, maybe what was observed in the data, and from a tolerability perspective, is there any read-through to melanoma or broader solid tumor in terms of strategy? Thank you.

Yeah, I think that we've been talking about this for a long time. I mean, we never indicated that we were excited about this opportunity. Our data from earlier stage studies was always pointing us to the melanoma opportunity. Once we see that data, it'll certainly guide our thinking forward and in terms of going into additional cancer settings as well. But as we've been saying for a while, we never had any reason to really believe that this was going to be a game changer in the lung cancer space.

And Jeff, there's no negative read-through from any new side effects, anything unanticipated. Great. Thanks, Len and George.

Last question, please, Kevin. One moment. Our last question comes from Brian Abrams with RBC Capital Markets.

Your line is open. Hey, good morning. Thanks for taking my question. We were intrigued by the inclusion of milder patients in your long-acting IL-13 study versus contemporary AD trials. So I was wondering if you could talk about the potential untapped opportunity for systemic biologics here and the degree to which you can broaden the market even beyond where Doopie is used now. Thanks.

Certainly in patients with mild disease, there's a lot of unmet needs. This is a potential area for greater understanding and advance for treatment. I think we'll have to wait and take a look at clinical profile and opportunities and determine from there. But it is a large population. And when the patient or the parent of the child with mild disease, it really isn't mild. It's aggravating. It's difficult. And certainly there's a lot of unmet need and potential.

Yeah, and I have to say, there was certainly in the early days a bias by investigators and the agency against using, quote unquote, a powerful biologic. It could be immunosuppressive. Remember, we didn't find it to be immunosuppressive. In fact, in the moderate to severe cases of atopic dermatitis, we actually saw less infections in patients who had skin lesions healing. It is not immunosuppressive on the on the side of the immune access, which deals with the kind of infections that people are used to with biologics or might be with some of the orals that suppress both arms of the immune system. As George has talked many times, the type 2 immunity is not something we rely on to keep us healthy from infections. It might play some role in parasitic infections. But you've got so many people having been treated now And now thinking about going earlier makes some sense.

All right. That's all the time we have for today. Thanks to everyone who dialed in for your interest in Regeneron. We apologize to those folks remaining in the Q&A queue who did not have a chance to hear from today. As always, the investor relations team at Regeneron is available to answer any remaining questions you may have. Thank you once again and have a great day.

Thank you, ladies and gentlemen. This concludes today's presentation. We thank you for your participation. You may now disconnect and have a wonderful day.