Regeneron Pharmaceuticals, Inc.

Welcome to the Regeneron Pharmaceuticals Third Quarter 2025 Earnings Conference Call. My name is Shannon, and I will be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. Please note that this conference is being recorded. I will now turn the call over to Ryan Crowe, Senior Vice President of Best Relations. You may begin.

Thank you, Shannon. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron, and welcome to our third quarter 2025 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 McCord, 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 forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement, 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 of different material 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 September 30, 2025, 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 in our quarterly results press release and our corporate presentation, both of which can be found on the 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. For my remarks today, I will summarize our third quarter top line performance, provide an update on ILEA HD regulatory matters, briefly discuss our recent pipeline progress, and close with some comments regarding our discussions with the United States government to lower drug costs for American patients while preserving innovation. I'll then hand the call over to George, who will provide more details on our pipeline progress. From there, Marion will review our commercial performance, and finally, Chris will detail our financial results and guidance. Regeneron delivered a solid third quarter, driven by double-digit net sales growth for three of our leading products. Compared to the third quarter of last year, worldwide net product sales for Dupixent increased by 26% and Libtayo by 24% at constant exchange rates, while ILEA-HD in the United States grew by 10%. Regeneron had Dupixent global net sales for the third quarter were $4.9 billion, as recorded by Sanofi, with strong growth continuing across approved indications in geographic regions. In the United States, Dupixen net product sales grew 28% compared to the third quarter of last year, while maintaining its leadership position in both new-to-brand prescription share and total prescription share across all indications approved prior to this year. Dupixen has now approved the United States to treat eight distinct diseases driven by underlying type 2 inflammation, including diseases of the skin, gut, and respiratory system, spanning age groups from infants to the elderly, and with more than 1.3 million patients globally being actively treated. Dupixent is one of the most widely used biologic medicines. Dupixent's approved indications could potentially address more than 4 million patients in the United States alone, positioning it to remain a strong growth driver over the near, medium, and long term. Global Libtyo net product sales were $365 million, up 24% on a constant currency basis compared to the third quarter of last year. In the U.S., net product sales grew 12%, where Libtyo continues to be the market-leading immunotherapy for advanced non-melanoma skin cancers while building share in lung cancer. Earlier this month, the FDA approved Libtyo in high-risk adjuvant cutaneous squamous cell carcinoma making Liptile the first and only PD-1 antibody indicated for this setting. While it only has been a few weeks since approval, a launch is already off to a great start, and we look forward to treating the up to 10,000 addressable patients in the United States who could benefit from this medicine. Moving to ILEA and ILEA-HD. Affordability issues continue to dampen branded anti-VEGF category growth. As announced in June, we initiated a matching program for up to $200 million in contributions to the Good Days Retinal Vascular and Neovascular Disease Fund. But I am disappointed to report that the match in the third quarter was under $1 million due to lack of donations from other potential contributors. We remain committed to matching future donations to this fund through the end of the year. Despite affordability headwinds, ILEA-HD had a strong performance in the third quarter, with U.S. net product sales reaching $431 million, an all-time high, driven by robust physician unit demand growth, partially offset by a lower net price. We continue to believe that future product enhancements, such as a four-week dosing interval, the inclusion of macular edema-filing retinal vein occlusion, or RVO, and a pre-filled syringe administration are needed to fully unlock ILEA's HD commercial potential. Earlier this month, we were notified by Catalan Indiana LLC, an affiliate of Novo Nordisk, that the FDA classified their facility as official action indicated, or OAI. And to date, the issues identified during the July 2025 inspection have not been completely resolved. On that basis, the FDA issued a complete response letter yesterday for the pre-filled syringe supplemental BLA with the sole approvability issue relating to unresolved inspection findings at Catalan. We continue to execute on our previously announced plan to submit an application to add an alternate pre-filled syringe filler by January 2026, which would trigger a four-month FDA review. We have also been diligently working with an alternate vial filler and have already submitted an application to include them in the ILEA HD BLA with a PDUFA date in late December. This would provide an additional opportunity for the FDA to approve the SBLA for every four-week dosing and RVO, given we believe there are no other outstanding review issues for this application. Moving briefly to our pipeline, which George will soon discuss in more detail, we continue to make significant investments in R&D that have yielded notable progress across several key programs. In just the past three months, we have announced positive phase three or registration enabling data for six distinct programs spanning immunology, neurology, allergy, and rare diseases. Over the next several months, we look forward to rapidly expanding pivotal programs in hematology, oncology, thrombosis, obesity, and other metabolic diseases, as well as allergies, all of which we believe represent an impressive next wave of innovative medicines discovered or developed by Regeneron. Finally, I'd like to take a moment to address our ongoing progress toward reaching an agreement with the US government to help lower the cost of medicines for American patients. We are having constructive discussions with the administration And I'm pleased to share that our priorities are closely aligned. Both Regeneron and the administration are deeply committed to ensuring that American patients have timely and affordable access to groundbreaking medical breakthroughs. We likewise share the goal of preserving the United States position as a global leader in biotech innovation and manufacturing. For more than a decade, George and I have argued that foreign governments have benefited from American innovation without sharing the burden of its cost. We are hopeful the efforts of this administration can level the playing field and convince high GDP nations to contribute their fair share rather than relying on the United States to shoulder the vast majority of this responsibility. By addressing this imbalance, we can ensure a more equitable global system that supports continued advancement in medicine while improving affordability for U.S. patients. Furthermore, we agree that investing in U.S. manufacturing is not only vital for creating jobs and strengthening our economy, but for safeguarding national security. In fact, in testimony before Congress in 2014, Regeneron highlighted the importance of prioritizing biotech manufacturing and innovation in the United States. Regeneron has already made significant commitments in this area including our plans to invest over $7 billion in infrastructure and manufacturing facilities in New York and North Carolina over the coming years. We remain optimistic about finding common ground with the administration that strikes the right balance between achieving our shared priorities while advancing Regeneron's mission of harnessing the power of science to deliver life-changing medicine to patients. In closing, Regeneron's business continues to perform well with impressive commercial execution driving strong financial results in the third quarter. Our pipeline is poised to deliver scientific breakthroughs that can potentially help treat millions of patients and translate into meaningful commercial opportunities. The commercial team remains focused on maximizing growth drivers from our inline brands while successfully launching new products and indications. Finally, we continue to prudently deploy capital with the goal of delivering long-term value to shareholders. With that, I'll now turn the call over to George.

Thank you, Len. Over the last few months, as Len just mentioned, we have delivered multiple important data readouts showcasing the strength of our robust pipeline and the potential to drive future growth. with positive pivotal data for Dupixent, for our C5 program, our cat and birch allergy programs, as well as in our rare disease programs. I will also update progress in oncology, anticoagulation, and other programs. Starting with immunology and inflammation, Dupixent continues to deliver remarkable outcomes in addressing indications driven by type 2 inflammation, potentially adding to its existing approvals for eight diseases in the United States, We are anticipating the FDA's acceptance of our submission for allergic fungal rhinocytositis, or AFRS, in patients aged six years and older, based on positive data that we plan to present shortly. This represents yet another potential opportunity for expanding Dupixent's label. Moving to our IL-33 antibody, itapicumab, which was studied in COPD, for which it met its primary endpoint in one of two replicate phase three trials. We in Sanofi are contemplating another Phase III triphrodite picomab in COPD, pending feedback from regulators. The picomab development is also advancing other respiratory diseases, most notably our ongoing Phase III studies in chronic rhinosinusitis with nasal polyps, where our genetic evidence is compelling. Moving to our innovative and multi-pronged allergy program. As previously announced, our Phase III studies of our antibodies for cat allergy and for birch allergy have yielded statistically significant and clinically meaningful outcomes on primary and key secondary endpoints. These results represent the first proof of principle that targeting allergens with highly specific monoclonal antibody cocktails can achieve improvements in both ocular itch and redness. Importantly, in prior clinical trials, our cat and birch allergy approaches have delivered impressive and durable therapeutic benefits across nasal, respiratory, and skin allergy symptoms. In the coming months, we plan to present these results at an upcoming medical meeting and initiate confirmatory Phase III studies for these programs. In the U.S. alone, these therapies could help approximately 1.6 million people suffering from severe cat allergies and the approximately 1.4 million people suffering from severe birch allergies. Regarding our innovative severe food allergy program, enrollment and dosing are progressing well in our small proof-of-concept trial combining limvoseltamab and dupixent. The first three patients have responded remarkably, with greater than 90% rapid reductions in the allergy-causing imigabalin E levels following a short course of limvoseltamab treatment, which are then maintained and continue to decrease with ongoing dupixent maintenance. Full enrollment of this small initial study is still expected over the next few months. Based on insights gained from the program so far, We are advancing the development of next-generation agents designed to specifically and safely deplete allergy-causing plasma cells, the first of which is expected to enter a clinical trial next year, alongside several other promising novel candidates in immunology and inflammation. Moving on to oncology and starting with Liptia, which was recently FDA-approved as the first and only immunotherapy for adjuvant treatment of high-risk cutaneous squamous cell carcinoma following surgery and radiation. based on the only successful clinical trial in this setting, the C-POST trial data that showed a notable 68% reduction in risk of disease recurrence or death. This approval expands and extends Liptio's leading position in non-melanoma skin cancers. Moving to Fianlumab, our LAG3 antibody study in combination with Liptio. Our pivotal trial in metastatic melanoma is ongoing with enrollment for our progression-free survival cohort completing in last January, and results are now anticipated in the first half of the coming year due to slower rates of event accrual. Linazific, our BCMA by CD3 bispecific, has been approved in the United States and the EU for relapsed refractory multiple myeloma. Linazific has the potential for best-in-class efficacy in this late-line setting compared to the other approved BSMA by CD3 bispecifics, with almost double the rates of complete responses as reported in the respective label. This is the basis for our enthusiasm for studying linazific in earlier lines of myeloma and even in precursor settings as a monotherapy or in limited combinations. Consistent with this, we've recently presented promising Phase II results in high-risk smoldering myeloma patients with linazific monotherapy, demonstrating a 100% objective response rate in 19 evaluable patients with all six patients who had been followed for at least one year achieving a molecular complete response. A Phase III head-to-head study against Darzalex is planned to start in the coming months, with Darzalex having demonstrated a 9% complete response rate in this setting. In addition, we have observed rapid normalization with linazific monotherapy in previously treated light-chain amyloidosis patients, including patients who had previously received and failed a Darzalex-containing combination chemotherapy. Finally, I would like to highlight that Linazific has demonstrated an 83% overall response rate as a monotherapy in newly diagnosed multiple myeloma patients with responses deepening over time. Updated results will be reported at a medical meeting later this year. Altogether, these data give us confidence in terms of pursuing Linazific as a monotherapy or in simplified combination in early lines and precursor settings of myeloma. Though I won't go into detail on uranexamab today, I want to highlight that our phase three study evaluating uranexamab as first-line monotherapy against the standard of care in follicular lymphoma patients is fully enrolled. Similarly to linazific, uranexamab demonstrated potentially best-in-class efficacy in late-line patients, driving our enthusiasm for this approach in the early-line settings. I'd also like to remind you that in the lead-in cohort for this phase three study in first-line follicular lymphoma, Odrinexamab monotherapy demonstrated a 100% complete response rate, further reinforcing the potential of Odrinexamab in this setting. Moving on to our C5 and complement inhibitor programs. Let me remind you that in paroxysmal nocturnal hemoglobinuria, or PNH, where deep blockade of C5 seems critical to prevent breakthrough hemolysis and potentially catastrophic events, the lead-in cohort for our phase three study demonstrated that our once-monthly Subcutaneous regimen combining a C5 antibody with a C5 sRNA may provide the best-in-class disease control with the best-in-class convenience. For PNH patients, we have also just initiated our first in-human study of our sRNA targeting complement factor B, primarily intended for the 20% to 30% of patients who remain anemic despite optimal C5 therapy due to so-called extravascular hemolysis. Moving on to our C5 program and generalized myasthenia gravis. In the third quarter, we announced positive phase three results for our C5 SRNA, simdisarine. This SRNA conveniently dosed subcutaneously every three months shows statistically significant results for the primary endpoint, improvement in the MGADL score compared to placebo, and numerically better results compared to other C5 inhibitor therapies in cross-trial comparisons. The convenience advantage for patients currently being treated with regular intravenous infusions, together with its efficacy and safety profile, positions somedicerine as a potential best-in-class treatment option for this debilitating neuromuscular disorder. We are planning on submitting a U.S. regulatory application for somedicerine monotherapy in the first quarter of 2026, pending FDA discussions, with global submissions to follow. For our C5 program, in terms of our efforts in ophthalmology, we are hoping to complete enrollment in the first quarter of 2026 for the leading cohort of our first Phase III study in geographic atrophy, with initial results expected by the end of 2026. Additionally, in ophthalmology, I'd like to note that we are initiating a clinical trial in active noninfectious uveitis of an intravitrally delivered CD3 monoclonal antibody. which is designed to locally block autoimmune T-cell activity in the eye, marking the first in a new series of novel ophthalmology targets that we will be progressing to the clinic over the next year. Turning to our anticoagulation efforts, and in particular to our Factor XI program involving two different antibodies designed to tailor anticoagulation therapy for each individual patient's needs. Pivotal studies in postoperative venous thromboembolism following total knee replacement surgery are in progress, with data anticipated in 2027. Pivotal studies and other anticoagulation indications are set to launch in the coming months. On November 10th, we will kick off a new investor event series called the Regeneron Roundtable, which will spotlight our various innovative pipeline programs, starting with our Factor 11 story. in which we will provide, for the first time, exciting new clinical data in trials exploring the factor XI antibodies in catheter-associated thrombosis in a provoked subclinical GI bleeding study. Upcoming Regeneron roundtables will spotlight our opportunities in hematologic and solid tumor oncology, obesity, and other areas. Moving to our growing siRNA portfolio, coming out of our research collaboration with El Nino. I'd like to highlight our ongoing clinical studies, including our PNPLA-3 and side B siRNAs in MASH, our SOD and HTT siRNAs in amyotrophic lateral sclerosis and Huntington's disease, and in addition, we plan to begin clinical trials for alpha-synuclein siRNA for Parkinson's disease and our MAP-tau siRNA for Alzheimer's in the coming months. Finally, I'd like to highlight our commitment to developing innovative new approaches in the ultra-rare disease space. In the third quarter, we announced unprecedented clinical benefit using garotosamab in our Phase III Optima trial in fibrodysplasia ossificans progressiva, or FOP. Individuals suffering from this tragic genetic disorder progressively replace their muscle and soft tissue with abnormal bone formations, encasing themselves in a horrific osseous cage. Remarkably, in the Optima trial, we were able to demonstrate a greater than 99% reduction in abnormal bone formation at 56 weeks, offering great hope for this ultra-rare genetic disorder. Regeneron plans a US regulatory submission by the end of 2025. We are also providing new hope for children suffering from another ultra-rare genetic disorder, in which absence of the OTOF gene results in profound genetic hearing loss. As we recently described in the New England Journal of Medicine, our novel gene therapy approach provided meaningful hearing gains in 11 out of 12 treated children, with several achieving normal hearing levels. The FDA recently announced that this program was the first new molecular entity selected for a Commissioner's National Priority Voucher, and we are finalizing preparations for a U.S. regulatory submission this year. This program highlights Regeneron's commitment to advancing the leading edge of biotechnology. In summary, Regeneron has delivered a quarter filled with positive clinical readouts, advancing our pipeline, and reinforcing our leadership in scientific innovation, from groundbreaking advance in addressing some of the most common medical conditions to transformative innovation in the ultra-rare disease space. With that, let me turn it over to Mary.

Thanks, George. Our third quarter performance highlights the strength of Regeneron's commercial portfolio. Today's results demonstrate our ability to drive growth of inline brands and to accelerate launch opportunities, delivering our transformative medicines to even more patients. Beginning with ILEA HD and ILEA, total combined third quarter U.S. net sales were 1.11 billion, comparable on a sequential basis. as a decrease in ILEA net sales was offset by an increase in ILEA HD net sales. ILEA HD net sales grew 10% quarter over quarter to 431 million, again growing faster than any other innovative medicine in the category. ILEA HD unit demand grew 18% quarter over quarter, which was partially offset by ongoing competitive pricing pressures within the category. As ILEA HD grew, ILEA's third quarter U.S. net sales decreased 10% quarter-over-quarter to $681 million, reflecting a commensurate decline in unit demand driven by the ongoing conversion to ILEA HD, patient affordability issues, and competitive dynamics. We expect a similar demand decline in the fourth quarter for ILEA, along with ongoing pricing pressure. Together, ILEA HD and ILEA lead the branded anti-VEGF category based on best-in-class efficacy, safety, and with ILEA-HD durability. And ILEA-HD now represents approximately 40% of Regeneron's U.S. retina franchise. Looking ahead to the fourth quarter for ILEA-HD, we anticipate sequential demand growth to moderate to high single digits as we await label enhancements. Once approved, we believe these enhancements have the potential to generate a significant positive inflection in demand. Now to Depixent. Third quarter worldwide net sales reached $4.9 billion, growing 26% on a constant currency basis compared to the prior year. In the U.S., Depixent's net sales reached $3.6 billion, reflecting 28% year-over-year growth. Depixent leads the market across all established indications, including atopic dermatitis, asthma, nasal polyps, and eosinophilic esophagitis. In addition, Depixin is the main beneficiary of competitor market growth efforts based on its proven efficacy, safety, ease of access, and ability to meet, excuse me, ability to address unmet patient needs. Our recent launches in COPD, chronic spontaneous urticaria, and bullous pemphigoid are progressing very well. Across all launches, Depixin's differentiated clinical profile and growing physician experience are driving strong uptake. In COPD, prescribers see Depixin's benefits across a range of appropriate patient types, and recent market research found pulmonologists expected to substantially increase their prescribing of Depixin over the next 12 months. In lung cancer, excuse me, additionally, there has been rapid uptake among chronic spontaneous urticaria patients, as both dermatologists and allergists embrace Dupixent. In bolus pemphigoid, Dupixent is the first biological medicine addressing a critical unmet need. Physicians are eager to transition elderly patients off steroid therapy, with Dupixent offering them a safer and more effective alternative. In summary, Dupixent continues to transform the lives of patients across indications, geographies, and age groups from as young as six months. There are currently more than 1.3 million patients worldwide benefiting from Dupixent, for multiple type 2 diseases. Turning to oncology and hematology, in the third quarter, Leptio delivered 365 million worldwide net sales, growing 24% on a constant currency basis compared with the prior year. In the U.S., Leptio net sales grew 12% year-over-year to 219 million based on strong demand across all approved indications. In non-melanoma skin cancers, Leptio's strong performance is based on established market leadership and ongoing category growth. We are making encouraging early progress with U.S. launch in adjuvant CSCC where physicians are already embracing Leptio as a new treatment option. We estimate that up to 10,000 eligible patients may benefit from Leptio in this setting. And now in lung cancer, Leptio is now the second most commonly prescribed immunotherapy for newly diagnosed patients. Physicians increasingly recognize Leptio as an important treatment option based on clinical experience, versatility as a monotherapy or accommodation with chemotherapy, and an increasing body of clinical evidence, including recent five-year survival data. Outside the U.S., Leptio sales reached $146 million, growing 47% year-over-year on a constant currency basis, supported by sustained demand and ongoing launches in international markets. Moving to our new hematology therapy, Linazivic, we've made strong early progress in commercializing this important bispecific for fifth-line multiple myeloma patients. Positive launch indicators include physician feedback, formulary listings, pathway inclusions, completion of REMS requirements, and payer coverage. While we expect modest revenue contribution in this heavily pretreated population, linazific is an important therapeutic advance to the hematology community, and we look forward to additional clinical data supporting its potential use in earlier treatment settings. In summary, in the third quarter, Regeneron delivered ongoing growth across ILEA-HD, Dupixent, and Lemtaio, and made important progress in several launches. Our commercial portfolio is well-positioned to capitalize on many near-term growth opportunities, enabling us to deliver more treatments to more patients. With that, I'll turn the call 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. Third quarter 2025 total revenues of $3.8 billion grew 1% compared to the prior year, reflecting higher Sanofi collaboration revenue driven by strong to PIX and sales growth and continued growth in net sales of Liptile Globally and ILEA HD in the U.S., partially offset by lower net sales of ILEA in the US and lower buyer collaboration revenue. Third quarter diluted net income per share was $11.83 on net income of 1.3 billion. Beginning with the Sanofi collaboration, revenues were approximately 1.6 billion of which 1.5 billion related to our share of collaboration profits. Regeneron share of profits grew 34% versus the prior year driven by volume growth for Dupixent and improving collaboration margins. The Sanofi development balance was approximately $900 million at the end of the third quarter, reflecting a reduction of approximately $300 million since the end of the second quarter and approximately $730 million since the start of the year. Dupixent's continued strength has enabled a rapid reimbursement of the development balance in 2025 And we now expect this balance to be fully reimbursed by no later than the end of the third quarter of 2026. Moving to buyer. Third quarter net sales of ILEA and ILEA 8MIG outside the U.S. were 854 million, inclusive of 232 million of ILEA 8MIG sales. Total buyer collaboration revenue was 345 million, of which 312 million related to our share of net profits outside the U.S. Other revenue in the third quarter was $198 million, which included $165 million of profit share and royalties associated with license agreements. The increase from the prior year was driven by higher royalty income from Alaris and growth in our share of profits from ArcaList. Now to our operating expenses. R&D expense was $1.3 billion in the third quarter, reflecting continued investments to support Regeneron's innovative late-stage pipeline, including our pivotal programs for linazific and ortspono and earlier lines of myeloma and lymphoma, our Factor XI program in anticoagulation indications, and our ongoing efforts in other clinical programs. Third quarter SG&A was $541 million, down 12% from the prior year, primarily driven by lower charitable contributions to an independent nonprofit patient assistance foundation. Third quarter 2025 gross margin on net product sales was 86%. The lower gross margin versus the prior year reflects a changing product mix and higher ongoing investments to support our manufacturing operations. Regeneron generated $3.2 billion in free cash flow through the first nine months of 2025. and ended the quarter with cash and marketable securities, less debt of approximately $16 billion. Through the first nine months of 2025, we have repurchased approximately $2.8 billion of our shares, the most ever allocated to open market repurchases in any full fiscal year in our history. We continue to be opportunistic buyers of our shares and anticipate returning approximately $4 billion to shareholders through dividends and repurchases in 2025. Moving to guidance for 2025, we have updated and narrowed the ranges across our financial guidance, which can be found in our press release issued earlier this morning. Finally, as we turn to 2026, we continue to make significant progress across our innovative pipeline and anticipate advancing multiple large registrational programs in myeloma lymphoma anticoagulation obesity and other hematology and solid tumor oncology programs as well as several new assets into the clinic we believe investing in these programs can drive significant long-term value and to support these efforts we currently expect a mid teens percentage increase in r d expense in 2026 relative to 2025. we will provide details on 2026 guidance for other line items early next year. In conclusion, Regeneron's third quarter results demonstrate the ongoing strength of our business and enable us to continue investing in our differentiated pipeline to deliver significant advances for patients and drive 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. Shannon, can we please go to the first question, please?

Thank you. As a reminder to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Our first question comes from the line of Akash Tiwari with Jefferies. Your line is now open.

Hey, thanks so much. It seems like your team has retooled your commercial strategy on ILEA, and it seems related to kind of price. What are you doing on a ground level when it comes to volume-based discounts that's allowing you to take share from Roche and Amgen? And are you seeing more price erosion on ILEA, or are we also seeing that discounting on high dose? And maybe just lastly, should we continue to see volume gains and revenue gains ahead of the label enhancement potentially mid-year? Thanks so much.

Well, I think you may have set the record for the number of questions we're not going to answer. And not because we don't want to. Marion would love to. But I think that there's so many competitive issues ongoing there in terms of our strategy on the ground, our rebates, and so forth. So I'm not sure we're able to really help you out there. Marion, I don't know if you want to add anything.

I think I would just add that when we look at the ILEA HD performance in the quarter, The favorability that we're seeing certainly is related to ILEA-HD, the product and the science, and retina specialists see the clinical efficacy, the safety, and now durability with ILEA-HD, and that is making a big difference.

We do see that until we get these enhancements in place, we can't, I think, see a significant upswing.

I can, Len, if you like, I can highlight what I shared a moment ago. But just to answer the question a bit more completely, for ILEA-HD, I mentioned we anticipate sequential demand growth to moderate the high single digits as we await label enhancements. And we also made a comment on ILEA that we anticipate similar levels of demand reduction in the coming quarter. And as I noted today, we saw a 10 percent reduction in ILEA 2 milligram, and that was in terms of the lower demand quarter over quarter. I hope that's helpful.

Okay, thanks. Thanks, Elaine and Mary. And let's move to the next question, please, Shannon.

Our next question comes from the line of Jeffrey Meacham with Citi. Your line is now open.

Morning, guys. Thanks for the question. I guess for Chris or Lynn, you know, I'm utilizing the balance sheet. You guys haven't historically done larger scale BD, and it seems like that's going to be the case going forward. But in manufacturing, what's the appetite to further expand your plans that you've announced just so you own all elements of the, you know, of manufacturing? Obviously, that would be viewed pretty favorably by the Trump administration as well. Thank you.

Yeah, great question, Jeff. Just on whether or not we would use a balance sheet for large deals, we certainly have no allergy to doing that if we saw the right opportunity. So it's not a question of philosophy there. It's really a question of what would make sense where we think we could create additional value. In terms of investing further in manufacturing, and as I said during our remarks, we've been talking about the need for domestic manufacturing since 2014, I think, in testimony before Congress. We mentioned the over $7 billion investment plan. But I think you do highlight one piece of the whole puzzle that we do not have adequate positioning in is the filling. But I'm pleased to say that we would expect our filling plant to come, which we've invested quite a bit in, Jeff. It's now ready to go, and we expect it to come online during the coming year. So that's a great question, and it should help us sort of control all aspects of the standard biologics manufacturer.

Okay, thanks, Elan. Shannon, next question, please.

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

Thanks for taking the question. Just maybe a question on ILEA-HD. Marion, I think I've heard you talk a lot about the importance labeling enhancements. And, Len, I just heard your comment about share and how important they are. But, you know, I think, you know, we've come to understand maybe the primary need here and the reason for these enhancements and why they're important is for certain clinics to have dosing flexibility so they can center their inventory around one drug. But just maybe, Marion, as you've seen this market evolve, can you talk about how that clinic inventory policies have evolved over time, and especially how private equity in this space may be influencing this? Or is this really more of a, as you're looking for share with clinics that don't necessarily have relatively aggressive inventory policies? Thanks.

So, Chris, my comment would be that the retina community and certainly retina KOLs look for the ability to select the right product for their patients. And I'm not an expert in inventory, but I can share with you that ILEA HD is a newer branded product in the category, two years in the market now. You know, certainly availability, not only inventory-wise, but payer coverage-wise. And then as I mentioned a moment ago, the most important characteristics of the product is this element of profound clinical efficacy, safety that people really can count on, And then, of course, with ILEA-HD, they're getting, for appropriate patients, the ability to have durability that is very, very important for the patients and their caretakers.

Okay. Thanks, Mary. Next question, please.

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

Hi. Thanks for taking the question. George, you mentioned It sounds like likely you and Sanofi are going to do another phase three trial here for IL-33 and COPD. Can you just talk about any new insights you might have learned that drove the differential outcome in the prior two phase three trials, and then what you think you can change or optimize in a third trial here to improve the likelihood of success? Thank you.

Well, due to competitive issues, I'm not going to really comment on most of your questions there. As you said, we're going to have a meeting with the FDA, and that's going to help us decide on our strategy going forward.

Okay. Thanks so much, George. Next question, please.

Our next question comes from the line of Tyler Van Buren with TD Cowan. Your line is now open.

Great. Thanks. Good morning. Congratulations on the quarter. Can you elaborate on the probability of the late December decision on the RVO and every four-week dosing filing with the new filler resulting in an approval? And just a quick follow-up would be, is this the same alternate filler that you used for the recent liptioadjuvant cutaneous squamous cell carcinoma approval?

No, it's a different filler. It's a complicated sort of timeline here because the new filler, has to undergo its review and probably an inspection and review, and it's unclear when that would get done. Ideally, if that could get done before our November timeline for the approval for the PDUFA date for the RBOQ4, that would really be perfect, and we could get it all wrapped up in late November. George Munro, If it turns out that they have to go to December to get the filler approved, hopefully, that would be as far as they have to go. But of course, you know, the FDA looks at all these things pretty carefully. This filler has a very good track record, but it's got to undergo the inspection and so forth. So I suspect that If they got through that in December, then we could rapidly resubmit, or maybe the application would still be on file. We don't know exactly. We're going to have discussions with the FDA. But we believe that there is nothing left to do on that application other than to get the filler in place. So we think we've had very good discussions about label and indications, and all that's fine. But, you know, it's not over until it's over, obviously. But ideally, to summarize, if we could get the filler online before the late November date, it could all be wrapped up then. If not, we would expect and hope that that filler would get approved in December, and then rapidly we would immediately resubmit, and the FDA hopefully could act immediately. That's sort of the to date that we can tell you.

Yes, thanks, Len. Complicated situation. Let's move to the next question, please.

Our next question comes from the line of Evan Seegerman with BMO Capital Markets. Your line is now open.

Hi, guys. Thank you so much for taking my question. Just taking a step back, can you walk me through some of the internal changes you've made with your regulatory manufacturing teams to prevent the CRLs that we've seen of recent years? and ensure that products that should be approved get approved and get to patients as quickly as possible? Thank you.

Now, that's a very pointed question, and I really want to address it head on. The issues that we have had have not been internal regulatory problems. We have a terrific relationship with the FDA. Our regulatory team includes people who used to work at the FDA. or people who've been in the industry doing this for decades. There's no shortage of expertise or relationships on a regulatory front. We've certainly asked that question, the board always asks that question, and there's no issue there. On the manufacturing front, we recognize that it would be more ideal if we could have our own filling. We would have expected to have that by now, but we got delayed dramatically during COVID because of supply chain issues and manufacturing. As I said, we hope that filling will come online next year. In terms of getting backups and what have you, it's a relatively complicated situation. We've been working on backups for quite a long time now. The problem, as you might imagine, is that For good reason, the FDA is very finicky about showing where you're going to make the product, literally what equipment it's going to touch, and then you have to do stability testing and all that over and quality testing, all that for a given filler. And that takes quite a bit of time, quite a bit of resources. So in summary, I don't want to sound defensive at all. We have looked at this. It is not a regulatory problem for us. It is, in some respects, a manufacturing issue in terms of getting online our own filling. Having backup fillers in place is complicated. We're trying to do that. But our biggest problem, frankly, is the FDA has now paid quite a bit of close attention. And I might point out that the biggest companies in the world have had the same issue with fillers, even with the same filler, and they've called us to know how's it going, but they just don't talk about the CRLs that they get, and we know that they're out there. So I'm not sure that we're worse off in that regard, but wherever we are, I'm not happy about it, and we're not happy about it, and we're trying to rectify the situation. I hope that gives you a glimpse into our thinking.

Okay, let's move to the next question, please.

Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is now open.

Hey, good morning. Thanks for taking my question. Just on the pipeline front on the Factor XI antibody program, I don't want you to front run your roundtable, but I know you guys recently started a large Phase II study for the antibodies in AFib. So I'm just curious what you guys are looking for out of that study and maybe out of other Factor XIs in development. to move into registrationals in that and other large indications and really accelerate that program. Thanks.

Well, the Phase II study is a run-in study into what we anticipate to be our Phase III pivotal program there, and we are in pivotal programs in other settings where anticoagulation can be important. And, of course, what are we looking at? We're trying to understand as well as we can the benefit-risk ratio for our two distinct antibodies. We think in this program it's all going to be about benefit-risk. We think that, frankly, in some ways, decreases in bleeding risk are going to be, frankly, more important than, in some cases, the anticoagulation effect. As long as you have anticoagulation effect, but if you have really a safe way of achieving it, we think there's a plethora of settings where these two antibodies can respectively find their place, and particularly in places maybe even much larger than the SPAF indication, where right now use of anticoagulants is very limited because of the bleeding concern. That's what's really limiting the utilization of anticoagulants more widely across many, many, many more settings. And so we think that our approach using two antibodies is going to allow us to really customize and tailorize how individual patients are treated, where we can optimize, we can pick the antibody perhaps with the least bleeding risk for the patients who are most concerned about that, while providing a different antibody with maybe higher anticoagulation capability when that's needed. So we think there's a lot of opportunities here beyond staff. We think that's where the major opportunity is today. We do not think that's where the major opportunity is going to be going forward in the future. We're going to where we think the future is, not necessarily where the current is right now.

And in the future, you'll be having a roundtable to tell them about that.

Correct. November 10th. Thanks, George. Let's move to the next question, please.

Our next question comes from the line of Carter Gould with Cantor. Your line is now open.

Great. Good morning. Thanks for taking the question. Len, you highlighted sort of the meager matching thus far with the foundation, and I guess you framed it remaining committing to that funding until the end of the year, which I guess sort of allude to a potential terminus. At some point, maybe at the start of the year, does it warrant taking a different tack if you don't see any other people match your commitment?

Yeah, I mean, I'd like not to tell people don't bother to make a commitment because we're going to take care of it. That's not our approach. Our approach will be that we will look at it fresh next year and see what the best strategy is to help patients. Good question, though.

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

Our next question comes from the line of Corey Kasimov with Evercore. Your line is now open.

Hey, good morning, guys. Thanks for taking the question. So on the heels of your positive phase three data for Sengisaran, can you outline how you see the commercial opportunity evolving for GMG and what your plans are in Europe with this asset? Thank you.

So before we get to that, maybe, George, could you just remind everybody what's out there and what the limitations of the current therapies are? Because I'm not sure everybody's on the same page on that.

Right. Well, right now, there are two major classes that are being utilized in this space. One, of course, is the C5 class. The other is the FCRN class. In terms of the C5 class, as we know, most of those are administered using these large intravenous infusions, which are very inconvenient for the patients. And in terms of the FCRN class, Those are given via also intravenous perfusions approaches right now, or ultimately they may move to large volume subcutaneous approaches that are also somewhat difficult to self-administer. But in any case, the issues also have to do with safety and efficacy. The thing that's exciting about our program is unlike the FCRNs, which either when you use weekly treatment, you get less benefits, at least cross-studies, from these standard scores, or with the episodic treatment where you have a U-shaped curve, where the patients respond deeply, but then almost revert back to baseline before you give them their next dose. The C5s allow you to have stable, deep control through the entire dosing period. And cross-study comparison, our agent seems to have, in terms of the standard measure, that is being used to evaluate the best cross-trial efficacy that's stable and continuous throughout the dosing period. Now, one important feature of all of these agents, obviously, is they all work by suppressing the immune system to various degrees, either the FCRNs or the C5 via their inhibition of the complement cascade. They both result potentially concerns with efficacy in the case of The C5 is mostly meningococcal infections. As you've probably seen with the FCRN class, with longer usage, they've seen serious infections, for example, resurgence of EBV and even fatal EBV infections. So those are concerns with everything that's available in the class. The thing that's exciting about our program is not only do we seem to have at least potentially best in class and stable efficacy with dosing using the most convenient dosing regimen, which is subcutaneous, once every three months. Nothing like that's ever been seen for this class, delivering this sort of efficacy. But because we only partially inhibit the complement pathway, there is the potential, which we will have to get data to support going forward, that it may offer certain safety benefits for patients. So the exciting thing about the program is we certainly have the most convenient dosing regimen. We seem to have the most consistent efficacy with cross-study comparisons, the deepest control, and the fact that we don't completely inhibit the target in this class. There is the long-term opportunity that we may be able to show that we may have better safety for patients as well here. So it's a very exciting profile, I think, to potentially be able to deliver for these classes, for these class of patients who are really needing better treatments in terms of convenience, in terms of efficacy, but also in terms of safety. Marion?

Sure. So everything we're doing in the launch strategy for commercialization is based on the very encouraging clinical profile that George is describing. So we're very excited about this opportunity. We will be launch ready, and we do feel for this really important category in patients with unmet need. that we potentially have a very highly differentiated product to bring into the marketplace.

Thanks, George and Mary. And let's move to the next question, please, Shannon.

Our next question comes from the line of Simon Baker with Rothschild and Company Redburn. Your line is now open.

Thank you very much for taking my question, my first ever question on the call. I just wanted to go back to your comments, George, on intravitrally delivered CD3. You're trying it initially in uveitis. I just wonder what the scope of your ambition was in that setting, given the role of T cell infiltration in glaucoma, which should be a much bigger indication. Any thoughts on where this could go would be much appreciated. Thank you.

I didn't hear what you said about glaucoma. What is glaucoma?

So there's some evidence that glaucoma is caused in greater or lesser part by T cell infiltration in the eye. So I just wondered if using CD3 antibodies in this setting would potentially encompass that indication as well as uveitis.

Yeah. We're very excited about our C3 antibody program, as you mentioned. We believe that this is the world's first complete blocker of CD3 or T cell function that's ever been evaluated in the clinic. There have been partial blocker, partial agonist to date. We think that going into VI and uveitis, which a lot of data suggests that most, if not all, of these uveitis are related to T cells. If we can block the T cells locally without, because the doses that we're going to be using are very low, they're not going to be having systemic effects, you can have really profound benefit in this high unmet need without subjecting patients to any sort of global or systemic immunosuppression. So we really think this is a very novel, very different approach to active non-infectious uveitis. We think it's the perfect setting to try our CD3 antibody. We have been working a lot on glaucoma. I'm glad that you brought it up. We, I believe, based on our Regeneron Genetic Center, which are world leaders in understanding the genetic basis of disease, we've, I think, uncovered the most important drivers genetically of glaucoma, and we will be rolling out in the very near future our strategy and our programs in a very near clinical program in glaucoma So I'm glad you brought it up. I'm glad you're interested in it. But these are going to be two very different, distinct programs. We're going to have our CD3 program for noninfectious uveitis, and we're going to be rolling out a very special and very exciting program in glaucoma based entirely on our internally discovered genetics capabilities. We think that these programs really have the opportunity to create entirely new franchises in ophthalmology, the way we think about it, one could be the ilea for uveitis, the other could be the ilea for glaucoma. So stay tuned. Thank you, George.

Very exciting. I think we have time for three more questions, Shannon.

Our next question comes from the line of Alexandria Hammond with Wolf Research. Your line is now open.

Thanks for taking the question. On the upcoming Liptile LAG3 readout, it seems like the goal is to outperform Opdilag. but could you share your confidence in demonstrating a stat-safe benefit against Keytruda? And as a follow-up, can you tell us a little bit more about the open label phase three trial you have ongoing against Opduleg? Is it just another show of confidence that your combo can be more potent than the currently approved option?

A lot of questions in there, but first and most importantly, our study is ongoing. As you said, we are trying our combination versus Keytruda. Our hope is that the Keytruda will behave as it has, more or less, historically. And our hope is that, remember, we have two arms in the study, a low dose and a high dose, that the two arms, at least one of them, will behave better than the Keytruda arm. The way we powered the study is that we powered it to not only hit PFS and OS, and with the minimal expectation that if we have a dual leg-like activity, we've powered the study so that we can win in both PFS, but also where a dual leg failed in OS. If, as you mentioned, we have better data than a dual leg, then obviously we will significantly win even more than that. So we've powered the study for a minimal of dual leg-like benefit, but so as to have a large enough OS signal so that we will win with comparable data there. Of course, the data will speak for itself. We'll see whether or not we end up having better efficacy than Keytruda, better efficacy cross-study comparison than Abdullad, and so forth. But we continue to be excited, obviously, about this program. There's obviously a high need here. There was very exciting earlier trial data using our Fianlumab antibody, and so we are anxiously but excited about awaiting the data readout next year.

Yeah, first half of next year is the timing on that. Shannon, next question, please.

Our next question comes from the line of Chris Schott with JPMorgan. Your line is now open.

Great. Thanks so much. Just a quick one on the launch of Linville Seltmab, but just how is that progressing versus expectations? And can you just elaborate a bit on the timelines of when you could actually get this product into some of those earlier lines of therapy, given the profile that this seems to be shaping up here? Is there an ability to pull that forward or accelerate that all in terms of working with FDA, et cetera? Thank you.

So I can take the first portion on the launch, and then I'm sure George will comment on the rest. But certainly, it's early days. But as I mentioned, the progress has been very, very good. We've seen the typical indicators when you have a successful launch ongoing. Physician feedback has been very favorable on formulary listings, pathway inclusion, REMS requirements, payer coverage. So we are pleased with what we're seeing so far, and certainly the enthusiasm of the hematology community for linozific is high, keeping in mind this is the fifth line setting for multiple myeloma patients, so a heavily pretreated population. But to George for earlier lines.

Well, we believe that if one looks at the totality of the data, certainly, you know, if it was me or somebody that I cared about giving the late stage patients any of these treatments, I think linozific would be the choice. based on all the available data out there. And importantly, what this says, if it looks like it has the potential for impressively more benefit in the late-line patients, that of course suggests that it should have also the best benefit for the early-stage patients. Because of that, we've taken on a lot of very aggressive programs in the early stages, not only in first-line myeloma and in second-line myeloma, but in the pre-malignant settings, as I summarized, we now have data in most of these settings, either as monotherapy or in very limited combinations, most of which we've now presented to varying degrees, and the data really is stunning and unprecedented. We're having high rates of seeing molecular complete responses and smoldering, in amyloidosis, which is a pre-malignant condition, but where the protein made by the abnormal cells can cause problems. Once again, unprecedented monotherapy activity in the first-line setting. We've described that. And in later-line settings with new combinations that we're also trying, unprecedented levels of activity. So we think that this program really has the potential to change the face of treatment for patients this disease indications in all of its manifestations, whether it be pre-malignant precursor settings, whether it's early Lyme disease, whether it's second Lyme disease, or whether it's for the late stage patients. So I think this is, you know, an exciting time for the field, and I just want to remind you that in many ways our adrenoxetamab program is quite similar in that particularly in follicular lymphoma where we look like we have the best late Lyme data, going aggressively in early-aligned disease. And once again, we've released the data, leading cohorts of phase threes as monotherapy and so forth. Once again, unprecedented efficacy in these small initial cohorts that we're looking at, which really get us excited that these bispecifics really have the chance to really change the hemologic oncology space in their respective settings.

So let me just add to that before we go to the next question. One is, I think, Inheriting what George is saying there is that all bispecifics are not created equal. The team spends an enormous amount of time with all the technology at hand to select and create bispecifics that we think are different, fundamentally different, and that's why we think we're seeing better data. I just also want to emphasize, we're making a huge commitment here. We expect to conduct as many as 10 registration of trials for Linacific. including, as George outlined, a broad registration program in frontline or even earlier myeloma patients, both for transplant eligible and ineligible. This is a big space. It's a $30 billion market potential. JARS-ALEX alone is annualizing at $15 billion. You saw some cross-study data that suggests that we can outperform. We've had some success where DOSLEX has already failed in the IGA space, and we've had some success in cost study comparisons in the smoldering. So I think this is pretty exciting, as George outlined. It's a huge commitment. You expect us to spend a lot and go as fast as we can. Somebody asked about, can we accelerate with the FDA? We're certainly going to talk with the FDA and advise them that we think we have the best program. How can we work together? You meant amyloidosis, not IgA.

Sorry.

Go ahead.

I meant amyloidosis. Thank you. Thank you, Lynn and George. We also look forward to having a Regeneron roundtable on linazific in December of this year. So let's move to our final question, Shannon.

Our last question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open.

Good morning. Thanks for taking my question. You spoke to novel targets here in INI and ophthalmology. On the GA program in particular, can you speak to what the FDA may be looking for in potential study designs, whether it's slowing GA lesion growth or vision improvements, and whether you need to evaluate against current agents? And just remind us on the INI side when we might hear about these novel targets. Thank you.

Well, in terms of GA, we've already designed and planned our pivotal readout study for geographic atrophy. We are able to go against placebo, and we're primarily looking at slowing down of growth together with, of course, vision control. And as I said, we have data from our, the cohort A from our phase three trial where we expect readout in the second half of 2026, which really will help inform whether this novel systemic approach, which can have a lot of advantages in terms of the issues of having to bilaterally inject two eyes multiple times as opposed to being able to systemically treat, will know whether there's a real opportunity there or not from that data. I think that In terms of our INI programs, I think you'll probably be hearing about one of the first ones, additional ones, additionally to the CD3 program, which is obviously a related INI and ophthalmology program. You'll be hearing it roll out over the next couple months with hopefully a new clinical program initiating next year.

Okay. Appreciate everyone's patience. We went a little over time. and appreciate your interest in Regeneron. Apologize to those who remain in the Q&A queue who do not have a chance to hear from today. As always, the investor relations team here at Regeneron is available to answer any remaining questions you may have. Thank you once again, and have a great day.

This concludes today's conference call. Thank you for your participation. You may now disconnect.