Q3 2025 Regeneron Pharmaceuticals Inc Earnings Call

Operator: 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, Investor Relations. You may begin.

Speaker #2: Welcome to the Regeneron Pharmaceuticals third Quarter 2020 Earnings Conference call . My name is Shannon , and I will be your operator for today's call .

Speaker #2: At this time , all participants are on a listen only mode . Later , we will conduct a question and answer session . Please note that this conference is being recorded .

Speaker #2: I will now turn the call over to Ryan Crowe Senior Vice President , Investor Relations . You may begin .

Ryan Crowe: Thank you, Shannon. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron Pharmaceuticals, and welcome to our third quarter 2025 earnings conference call. An archive and transcript of this call will be available on the Regeneron Pharmaceuticals 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 Pharmaceuticals.

Speaker #3: Thank you . Shannon . Good morning . Good afternoon and good evening to everyone listening around the world . Thank you for your interest in Regeneron .

Speaker #3: And welcome to our third quarter 2020 earnings conference call in archive and transcript of this call will be available on the Regeneron Investor Relations website .

Speaker #3: Shortly after our call concludes . Joining me on today's call are Doctor Leonard Schleifer board co-chair , co-founder , president and chief Executive Officer .

Speaker #3: Doctor 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 .

Speaker #3: 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 .

Ryan Crowe: Such statements may include, but are not limited to, those related to Regeneron Pharmaceuticals and its products and business, financial forecasting 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 materiality from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron Pharmaceuticals' filings with the U.S. 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 Pharmaceuticals does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise.

Speaker #3: Such statements may include , but are not limited to , those related to , Regeneron and its products and business . Financial forecast and guidance .

Speaker #3: Development programs , and related anticipated milestones , collaborations , finances , regulatory matters , payer coverage and reimbursement , intellectual property , pending litigation , and other proceedings , and competition .

Speaker #3: 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.

Speaker #3: 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 30th , 2025 , which was filed with the SEC this morning .

Speaker #3: Regeneron does not undertake any obligation to update any forward looking statements , whether as a result of new information , future events or otherwise .

Ryan Crowe: 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.

Speaker #3: 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 .

Speaker #3: 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 .

Speaker #3: Doctor Leonard Schleifer . Len . Thanks , Ryan . Thanks to everyone .

George Yancopoulos: 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 EYLEA HD regulatory matters, briefly discuss our recent pipeline progress, and close with some comments regarding our discussions with the U.S. 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 Pharmaceuticals 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 EYLEA HD in the U.S.

Speaker #4: For joining today's call . For my remarks today . I will summarize our third quarter top line performance . Provide an update on Eylea HD regulatory matters .

Speaker #4: 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 .

Speaker #4: 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 .

Speaker #4: And finally , Chris will detail our financial results and guidance . We 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 .

Speaker #4: Worldwide net product sales for Dupixent increased by 26% and Libtayo by 24% . At constant exchange rates , while Eylea HD in the United States grew by 10% .

George Yancopoulos: grew by 10%. Regeneron Pharmaceuticals 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 U.S., Dupixent 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. Dupixent has now proved the U.S. 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 U.S.

Speaker #4: The general . 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 and geographic regions in the United States .

Speaker #4: Dupixent net product sales grew 28% compared to the third quarter of last year , while maintaining its leadership position in both new and prescription share and total prescription share across all indications approved prior to this year , Dupixent is now approved in the United States to treat eight distinct diseases driven by underlying type two 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 .

Speaker #4: Dupixent approved indications can 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 .

George Yancopoulos: alone, positioning it to remain a strong growth driver over the near, medium, and long term. Global Libtayo 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 Libtayo 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 Libtayo in high-risk adjuvant cutaneous squamous cell carcinoma, making Libtayo the first and only PD-1 antibody indicated for this setting. While it only has been a few weeks since approval, our launch is already off to a great start, and we look forward to treating the up to 10,000 addressable patients in the U.S. who could benefit from this medicine. Moving to EYLEA and EYLEA HD, affordability issues continue to dampen branded anti-VEGF category growth.

Speaker #4: Global Libtayo net product sales were 365 million , up 24% on a constant currency basis compared to the third quarter of last year .

Speaker #4: In the US . Net product sales grew 12% , with Libtayo continues to be the market leading immunotherapy for advanced non-melanoma skin cancers .

Speaker #4: While building share in lung cancer . Earlier this month , the FDA approved Libtayo in high risk adjuvant cutaneous squamous cell carcinoma , making Libtayo the first and only PD one antibody indicated for this setting .

Speaker #4: 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 .

Speaker #4: Moving to Eylea and Eylea 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 .

George Yancopoulos: 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. 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, EYLEA 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 prefilled syringe administration are needed to fully unlock EYLEA HD's commercial potential.

Speaker #4: 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 .

Speaker #4: We remain committed to matching future donations to this fund through the end of the year . Despite affordability headwinds , Eylea HD had a strong performance in the third quarter , with US net product sales reaching 431 million and all time high , driven by robust physician unit demand growth , partially offset by a lower net price .

Speaker #4: We continue to believe that future product enhancements , such as a four week dosing interval , the inclusion of macular edema following retinal vein occlusion , or rvo , and a prefilled syringe administration are needed to fully unlock eylea's HD commercial potential .

George Yancopoulos: Earlier this month, we were notified by Catalent Indiana LLC, an affiliate of Novo Nordisk, that the FDA classified their facility as Official Action Indicated, or OAI. 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 prefilled syringe supplemental BLA with the sole approvability issue relating to unresolved inspection findings at Catalent. We continue to execute on our previously announced plan to submit an application to add an alternate prefilled 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 EYLEA HD BLA with a PDUFA date in late December.

Speaker #4: 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 oh , and to date , the issues identified during the July 2025 inspection have not been completely resolved .

Speaker #4: 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 catalyst .

Speaker #4: 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 .

Speaker #4: We have also been diligently working with an alternate vial filler and have already submitted an application to include them in the Eylea HD bla with a Purdue Pharma date in late December .

George Yancopoulos: 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 Pharmaceuticals.

Speaker #4: This would provide an additional opportunity for the FDA to approve the SPLA for every four week dosing , and rvo given . We believe there are no other outstanding review issues for this application .

Speaker #4: 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 .

Speaker #4: 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 .

George Yancopoulos: Finally, I'd like to take a moment to address our ongoing progress toward reaching an agreement with the U.S. 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 Pharmaceuticals 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.

Speaker #4: 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 .

Speaker #4: 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 .

Speaker #4: 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 .

George Yancopoulos: 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 advancements 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 Pharmaceuticals highlighted the importance of prioritizing biotech manufacturing and innovation in the United States. Regeneron Pharmaceuticals 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.

Speaker #4: 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 advancements in medicine while improving affordability for US patients .

Speaker #4: Furthermore , we agree that investing in US 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 .

Speaker #4: 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 .

George Yancopoulos: We remain optimistic about finding common ground with the administration that strikes the right balance between achieving our shared priorities while advancing Regeneron Pharmaceuticals' mission of harnessing the power of science to deliver life-changing medicine to patients. In closing, Regeneron Pharmaceuticals' 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.

Speaker #4: We remain optimistic about finding common ground with the University , with the administration . Excuse me , 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 .

Speaker #4: 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 .

Speaker #4: The commercial team remains focussed on maximizing growth drivers from our in-line 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 .

Speaker #4: With that , I'll now turn the call over to George . Thank you .

Marion McCourt: 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. We have 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 U.S. We are anticipating the FDA's acceptance of our submission for allergic fungal rhinosinusitis, 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.

Speaker #3: Lynn .

Speaker #4: Over the .

Speaker #5: 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 C5 program , our Cat and Birch allergy programs , as well as in our rare disease programs .

Speaker #5: 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 two inflammation , potentially adding to its existing approvals for eight diseases in the United States .

Speaker #5: We are anticipating the FDA's acceptance of our submission for allergic fungal rhinosinusitis , or Afrs , in patients aged six years and older based on positive data that we plan to present shortly .

Speaker #5: This represents yet another potential opportunity for expanding Dupixent's label , moving to our IL 33 antibody ipilimumab , which was studied in COPD , for which it met its primary endpoint in one of two replicate phase three trials , we and Sanofi are contemplating another phase three trial for the Mab in COPD , pending feedback from regulators in ipilimumab .

Marion McCourt: Moving to our IL-33 antibody, inapicamab, which was studied in COPD, for which it met its primary endpoint in one of two replicate phase 3 trials. We and Sanofi are contemplating another phase 3 trial for inapicamab in COPD, pending feedback from regulators. Inapicamab development is also advancing in other respiratory diseases, most notably our ongoing phase 3 studies in chronic rhinosinusitis with nasal polyps, where our genetic evidence is compelling. Moving to our innovative and multipronged allergy programs. As previously announced, our phase 3 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.

Speaker #5: Development is also advancing other respiratory diseases , most notably our ongoing phase three studies in chronic rhinosinusitis with nasal polyps , where our genetic evidence is compelling .

Speaker #5: Moving to our innovative and multi-pronged allergy programs as previously announced , our phase three 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 .

Speaker #5: 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 .

Marion McCourt: 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 3 studies for these programs. In the U.S. alone, these therapies could help approximately 1.6 million people suffering from severe cat allergies and 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 limoceltamab and Dupixent. The first three patients have responded remarkably, with greater than 90% rapid reductions in the allergy-causing immunoglobulin E levels following a short course of limoceltamab treatment, which are then maintained and continue to decrease with ongoing Dupixent maintenance.

Speaker #5: 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 three studies for these programs in the US alone , these therapies can help approximately 1.6 million people suffering from severe cat allergies .

Speaker #5: 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 .

Speaker #5: Combining Linvoseltamab and Dupixent . The first three patients have responded remarkably with greater than 90% rapid reductions in the allergy causing immunoglobulin E levels .

Speaker #5: Following a short course of Linvoseltamab 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 .

Marion McCourt: 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 Libtayo, 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 showed a notable 68% reduction in risk of disease recurrence or death. This approval expands and extends Libtayo's leading position in non-melanoma skin cancers. Moving to Thanilumab, our LAG-3 antibody study in combination with Libtayo.

Speaker #5: The first of which is expected to enter clinical trial next year, alongside several other promising novel candidates in immunology and inflammation. Moving on to oncology and starting with Libtayo, which was recently FDA approved as the first and only immunotherapy for the adjuvant treatment of high-risk cutaneous squamous cell carcinoma.

Speaker #5: Following surgery and radiation . Based on the only successful clinical trial in this setting , the see post-trial data that showed a notable 68% reduction in risk of disease recurrence or death .

Speaker #5: This approval expands and extends the leading position in non-melanoma skin cancers . Moving to Fianlimab . Our Lag three antibody studied in combination with Libtayo , our pivotal trial in metastatic melanoma is ongoing with enrollment for our progressive , progression free survival cohort completing in last January , and results are now anticipated in the first half of the coming year .

Marion McCourt: 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. Linezytif, our BCMA by CD3 bispecific, has been approved in the United States and the EU for relapse refractory multiple myeloma. Linezytif has the potential for best-in-class efficacy in this late-line setting compared to the other approved BCMA 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 Linezytif in earlier lines of myeloma and even in precursor settings as a monotherapy or in limited combinations.

Speaker #5: Due to slower rates of event accrual , our BCmA by CD3 bispecific has been approved in the United States and the EU for relapsed refractory multiple myeloma has the potential for best in class efficacy in this late line setting compared to the other approved BCmA by C3 Bispecifics with almost double the rates of complete responses as reported in the respective label .

Speaker #5: This is the basis for our enthusiasm for studying in early lines of myeloma , and even in precursor settings . As a monotherapy or in limited combinations consistent with this , we've recently presented promising phase two results in high risk smoldering myeloma patients with 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 .

Marion McCourt: Consistent with this, we've recently presented promising phase two results in high-risk smoldering myeloma patients with Linezytif monotherapy, demonstrating a 100% objective response rate in 19 evaluable patients, with all six patients who have been followed for at least one year achieving a molecular complete response. A phase three 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 Linezytif 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 Linezytif 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.

Speaker #5: A phase three 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 .

Speaker #5: In addition , we have observed rapid normalization with monotherapy in previously treated light chain amyloidosis . Patients , including patients who had previously received and failed a darzalex containing combination chemotherapy .

Speaker #5: Finally , I would like to highlight that little 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 .

Marion McCourt: Altogether, these data give us confidence in terms of pursuing Linezytif as a monotherapy or in simplified combination in early lines and precursor settings of myeloma. Though I won't go into detail on Undernextamab today, I want to highlight that our phase three study evaluating Undernextamab as first-line monotherapy against the standard of care in follicular lymphoma patients is fully enrolled. Similarly to Linezytif, Undernextamab demonstrated potentially best-in-class efficacy in late-line patients, driving our enthusiasm for this approach in the earlier line settings. I'd also like to remind you that in the leading cohort for this phase three study in first-line follicular lymphoma, Undernextamab monotherapy demonstrated a 100% complete response rate, further reinforcing the potential of Undernextamab in this setting. Moving on to our C5 and complement inhibitor programs.

Speaker #5: All together, these data give us confidence in terms of pursuing Zivic as a monotherapy or in simplified combination. In early lines and precursor settings of myeloma, though I won't go into detail on our next to Mab.

Speaker #5: Today , I want to highlight that our phase three study , evaluating Odronextamab as first line monotherapy against the standard of care in follicular lymphoma patients is fully enrolled similarly to had demonstrated potentially best in class efficacy in late line patients , driving our enthusiasm for this approach in the early line settings .

Speaker #5: I would also like to remind you that in the lead in cohort for this phase three study , in first line follicular lymphoma or monotherapy , demonstrated a 100% complete response rate .

Speaker #5: Further reinforcing the potential of odronextamab . 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 shrna , may provide the best in class disease control with the best in class convenience for PNH patients .

Marion McCourt: Let me remind you that in paroxysmal nocturnal hemoglobinuria, or PNH, where de-blockade of C5 seems critical to prevent breakthrough hemolysis and potentially catastrophic events, the leading 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 in generalized myasthenia gravis, in the third quarter, we announced positive phase three results for our C5 SRNA, SIMDISERIN.

Speaker #5: We have also just initiated our first in-human study of our siRNA 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.

Speaker #5: Moving on to our C5 program in generalized myasthenia gravis in the third quarter, we announced positive Phase 3 results for our C5 shRNA.

Speaker #5: Some disarray in this shrna conveniently dosed subcutaneously every three months shows statistically significant results for the primary endpoint improvement in the Mg-adl score compared to placebo and numerically better results compared to other C5 inhibitor therapies .

Marion McCourt: 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 SIMDISERIN as a potential best-in-class treatment option for this debilitating neuromuscular disorder. We are planning on submitting a U.S. regulatory application for SIMDISERIN monotherapy in the first quarter of 2026, pending FDA discussions with global submissions to follow. Finally, 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 three study in geographic atrophy, with initial results expected by the end of 2026.

Speaker #5: In cross-trial comparisons , the convenience advantage for patients currently being treated with regular intravenous infusions , together with its efficacy and safety profile positions , some as a potential best in class treatment option for this debilitating neuromuscular disorder .

Speaker #5: We are planning on submitting a U.S. regulatory application for some decent monotherapy in the first quarter of 2026, pending FDA discussions, with global submissions to follow.

Speaker #5: Finally , for our C5 program , in terms of our efforts at ophthalmology , we're hoping to complete enrollment in the first quarter of 2026 for the lead in cohort of our first phase three study in geographic atrophy , with initial results expected by the end of 2026 .

Marion McCourt: Additionally, in ophthalmology, I'd like to note that we are initiating a clinical trial in active non-infectious uveitis of an intramedullary 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 in other anticoagulation indications are set to launch in the coming months.

Speaker #5: Additionally , ophthalmology . I'd like to note that we are initiating a clinical trial in active noninfectious uveitis of an intravitreally 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 .

Speaker #5: Turning to our anti-coagulation efforts , and in particular to our factor 11 program involving two different antibodies designed to tailor anticoagulation therapy for each individual patient's needs .

Speaker #5: Pivotal studies in post-operative venous thromboembolism following total knee replacement surgery are in progress , with data anticipated in 2027 . Pivotal studies in other anticoagulation indications are set to launch in the coming months .

Marion McCourt: On November 10, 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 XI 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 Alnylam, I'd like to highlight our ongoing clinical studies, including our PNPLA3 and SID B siRNAs in MASH, our SOD and HTT siRNAs in amyotrophic lateral sclerosis and Huntington's disease. In addition, we plan to begin clinical trials for our alpha-synuclein siRNA for Parkinson's disease and our MAPTau siRNA for Alzheimer's in the coming months.

Speaker #5: On November 10th , we will kick off a new investor 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 11 antibodies in catheter associated thrombosis and in a provoked subclinical GI bleeding study .

Speaker #5: Upcoming Regeneron roundtables will spotlight our opportunities in hematologic and solid tumor oncology , obesity , and other areas , moving to our growing siRNA portfolio .

Speaker #5: Coming out of our research collaboration with El Nino , I'd like to highlight our ongoing clinical studies , including our Pnpla3 and Cideb siRNAs in Nash are Sod HTTP , siRNAs in Amyotrophic Lateral Sclerosis and Huntington's Disease , and in addition , we plan to begin clinical trials for our alpha synuclein Shrna and and our tau Shrna for Alzheimer's in the coming months .

Marion McCourt: 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 Garitussimab in our phase 3 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 formation, 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 U.S. regulatory submission by the end of 2025. We are also providing new hope for children suffering from another ultra-rare genetic disorder, in which the absence of the OTOP gene results in profound genetic hearing loss.

Speaker #5: 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 Daratumumab in our phase three Optima trial in Fibrodysplasia Ossificans , Progressiva , or FOP .

Speaker #5: Individuals suffering from this tragic genetic disorder progressively replaced their muscle and soft tissue with abnormal bone formation encasing themselves in a horrific osseous cage .

Speaker #5: 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 .

Speaker #5: 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 OTC gene results in profound genetic hearing loss .

Marion McCourt: 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 Pharmaceuticals has delivered a quarter filled with positive clinical readouts, advancing our pipeline and reinforcing our leadership in scientific innovation, from groundbreaking advances 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 Marion.

Speaker #5: 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 .

Speaker #5: 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 US regulatory submission this year .

Speaker #5: 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 addressing some of the most common medical conditions to transformative innovation in the ultra ultra rare disease space .

Speaker #5: With that , let me turn it over to Marian .

Chris Fenimore: 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 EYLEA HD and EYLEA, total combined third quarter U.S. net sales were $1.11 billion, comparable on a sequential basis, as a decrease in EYLEA net sales was offset by an increase in EYLEA HD net sales. EYLEA HD net sales grew 10% quarter over quarter to $431 million, again, growing faster than any other innovative medicine in the category. EYLEA HD unit demand grew 18% quarter over quarter, which was partially offset by ongoing competitive pricing pressures within the category. As EYLEA HD grew, EYLEA's third quarter U.S.

Speaker #6: Thanks , George . Our third quarter performance highlights the strength of Regeneron's commercial portfolio . Today's results demonstrate our ability to drive growth of in-line brands and to accelerate launch opportunities , delivering our transformative medicines to even more patients .

Speaker #6: Beginning with Eylea and Eylea . Total combined third quarter US net sales were 1.11 billion , comparable on a sequential basis . As a decrease in Eylea net sales was offset by an increase in Eylea HD net sales , Eylea HD net sales grew 10% quarter over 3:45 .31 million , again growing faster than any other innovative medicine in the category .

Speaker #6: Iliad unit demand grew 18% quarter over quarter , which was partially offset by ongoing competitive pricing pressures within the category as I league grew , Eylea's third quarter US net sales decreased 10% quarter over 5:45 .81 million , reflecting a commensurate decline in unit demand driven by the ongoing conversion to Eylea HD .

Chris Fenimore: net sales decreased 10% quarter over quarter to $681 million, reflecting a commensurate decline in unit demand driven by the ongoing conversion to EYLEA HD, patient affordability issues, and competitive dynamics. We expect a similar demand decline in the fourth quarter for EYLEA, along with ongoing pricing pressure. Together, EYLEA HD and EYLEA lead the branded anti-VEGF category based on best-in-class efficacy, safety, and with EYLEA HD durability. EYLEA HD now represents approximately 40% of Regeneron's U.S. retina franchise. Looking ahead to the fourth quarter for EYLEA 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 Dupixent. Third quarter worldwide net sales reached $4.9 billion, growing 26% on a constant currency basis compared to the prior year.

Speaker #6: Patient affordability issues and competitive dynamics . We expect a similar demand decline in the fourth quarter for Eylea , along with ongoing pricing pressure .

Speaker #6: Together , Eylea HD and Eylea lead the branded anti-VEGF category based on best in class efficacy , safety , and with Eylea HD durability and Eylea HD now represents approximately 40% of Regeneron's US retina franchise .

Speaker #6: Looking ahead to the fourth quarter for Eylea HD , we anticipate sequential demand growth to moderate to high single digits as we await label enhancements .

Speaker #6: Once approved , we believe these enhancements have the potential to generate a significant positive inflection in demand . Now to Dupixent third quarter worldwide net sales reached 4.9 billion , growing 26% on a constant currency basis compared to the prior year in the US .

Chris Fenimore: In the U.S., Dupixent's net sales reached $3.6 billion, reflecting 28% year-over-year growth. Dupixent leads the market across all established indications, including atopic dermatitis, asthma, nasal polyps, and eosinophilic esophagitis. In addition, Dupixent is the main beneficiary of competitive market growth efforts based on its proven efficacy, safety, ease of access, and ability to address unmet patient needs. Our recent launches in COPD, chronic spontaneous urticaria, and bullous pemphigoid are progressing very well. Across all launches, Dupixent's differentiated clinical profile and growing physician experience are driving strong uptake. In COPD, prescribers see Dupixent's benefits across a range of appropriate patient types, and recent market research found pulmonologists expected to substantially increase their prescribing of Dupixent over the next 12 months. Additionally, there has been rapid uptake among chronic spontaneous urticaria patients as both dermatologists and allergists embrace Dupixent.

Speaker #6: Dupixent net sales reached 3.6 billion , reflecting 28% year over year growth . Dupixent leads the market across all established indications , including atopic dermatitis , asthma , nasal polyps and eosinophilic esophagitis .

Speaker #6: In addition , dupixent 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 .

Speaker #6: Our recent launches in COPD , chronic spontaneous urticaria , and bullous pemphigoid are progressing very well across all launches . Dupixent differentiated clinical profile and growing physician experience are driving strong uptake in COPD prescribers .

Speaker #6: See Dupixent benefits across a range of appropriate patient types and recent market research found pulmonologists expected to substantially increase their prescribing of dupixent over the next 12 months in lung cancer .

Speaker #6: Excuse me ? Additionally , there has been rapid uptake among chronic spontaneous urticaria patients as both dermatologists and allergists embrace dupixent in bullous pemphigoid .

Chris Fenimore: In bullous pemphigoid, Dupixent is the first biologic 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, Libtayo delivered $365 million worldwide net sales, growing 24% on a constant currency basis compared with the prior year. In the U.S., Libtayo net sales grew 12% year-over-year to $219 million based on strong demand across all approved indications. In non-melanoma skin cancers, Libtayo's strong performance is based on established market leadership and ongoing category growth. We are making encouraging early progress with U.S.

Speaker #6: Depiction is the first biologic medicine addressing a critical unmet need . Physicians are eager to . Transition elderly patients off steroid therapy , which depicts an offering them a safer and more effective alternative .

Speaker #6: In summary , Dupixent continues to transform the lives of patients across indications , geographies and age groups from as young as six months .

Speaker #6: 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, Libtayo delivered $365 million in worldwide net sales, growing 24% on a constant currency basis compared with the prior year.

Speaker #6: In the U.S., Libtayo net sales grew 12% year over year to $219 million, based on strong demand across all approved indications in non-melanoma skin cancers.

Speaker #6: Libtayo strong performance is based on established market leadership and ongoing category growth . We are making encouraging early progress with us , launch in adjuvant Cscc where physicians are already embracing Libtayo as a new treatment option .

Chris Fenimore: launch in adjuvant cutaneous squamous cell carcinoma, where physicians are already embracing Libtayo as a new treatment option. We estimate that up to 10,000 eligible patients may benefit from Libtayo in this setting. In lung cancer, Libtayo is now the second most commonly prescribed immunotherapy for newly diagnosed patients. Physicians increasingly recognize Libtayo as an important treatment option based on clinical experience, versatility as a monotherapy or in combination with chemotherapy, and an increasing body of clinical evidence, including recent five-year survival data. Outside the U.S., Libtayo 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, Linezytif, 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.

Speaker #6: We estimate that up to 10,000 eligible patients may benefit from Libtayo in this setting . And now in lung cancer , Libtayo is now the second most commonly prescribed immunotherapy for newly diagnosed patients .

Speaker #6: Physicians increasingly recognize Libtayo as an important treatment option based on clinical experience . Versatility as a monotherapy or in combination with chemotherapy and an increasing body of clinical evidence , including recent five year survival data outside the US , Libtayo sales reached 146 million , growing 47% year over year on a constant currency basis , supported by sustained demand and ongoing launches in international markets .

Speaker #6: Moving to our new hematology therapy , 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 .

Chris Fenimore: While we expect modest revenue contribution in this heavily pretreated population, Linezytif 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 Pharmaceuticals delivered ongoing growth across EYLEA HD, Dupixent, and Libtayo, 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.

Speaker #6: While we expect modest revenue contribution in this heavily pretreated population, it is an important therapeutic advance to the hematology community. We look forward to additional clinical data supporting its potential use in earlier treatment settings.

Speaker #6: In summary , in the third quarter , Regeneron delivered ongoing growth across Eylea HD , Dupixent and limb and made important progress in several launches .

Speaker #6: 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 .

[Analyst]: Thank you, Marion. My comments today on Regeneron Pharmaceuticals' 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 Dupixent sales growth and continued growth in net sales of Libtayo globally and EYLEA HD in the U.S., partially offset by lower net sales of EYLEA in the U.S. and lower Bayer 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 Pharmaceuticals' share of profits grew 34% versus the prior year, driven by volume growth for Dupixent and improving collaboration margins.

Speaker #3: Thank you . Marion ,

Speaker #7: 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 .

Speaker #7: Sanofi collaboration revenue driven by strong Dupixent sales growth and continued growth in net sales of Libtayo globally and Eylea HD in the US , partially offset by lower net sales of Eylea in the US and lower Bayer collaboration revenue .

Speaker #7: Third quarter diluted net income per share was $11.83 on net income of 1.3 billion . Beginning with Sanofi , collaboration revenues were approximately 1.6 billion , of which 1.5 billion related to our share of collaboration profits .

Speaker #7: 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 .

[Analyst]: 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 Bayer, third quarter net sales of EYLEA and EYLEA 8mg outside the U.S. were $854 million, inclusive of $232 million of EYLEA 8mg sales. Total Bayer 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.

Speaker #7: 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.

Speaker #7: Dupixent's continued strength has enabled a rapid reimbursement of the development balance. In 2025, we now expect this balance to be fully reimbursed by no later than the end of the third quarter of 2026.

[Analyst]: The increase from the prior year was driven by higher royalty income from Alaris and growth in our share of profits from Arcolist. Now to our operating expenses. R&D expense was $1.3 billion in the third quarter, reflecting continued investments to support Regeneron Pharmaceuticals' innovative late-stage pipeline, including our pivotal programs for Linezytif and Ortsfono in 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%.

[Analyst]: The lower gross margin versus the prior year reflects a changing product mix and higher ongoing investments to support our manufacturing operations. Regeneron Pharmaceuticals 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.

[Analyst]: 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 % 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 Pharmaceuticals' 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.

Ryan Crowe: 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?

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

[Analyst]: Hey, thanks so much. It seems like your team has retooled your commercial strategy on EYLEA, 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? Are you seeing more price erosion on EYLEA, or are we also seeing that discounting on high dose? Maybe just lastly, should we continue to see volume gains and revenue gains ahead of the label enhancement potentially mid-year? Thanks so much.

George Yancopoulos: 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. I'm not sure we're able to really help you out there. Marion, I don't know if you want to add anything.

Hey uh thanks so much. Uh, it seems like your team is reto your commercial strategy on Aaliyah. Um, 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 Roshan Amgen and are you seeing more price erosion on a 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 uh potentially mid year. Thanks so much.

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

George Yancopoulos: We do see that until we get these enhancements in place, we can't see a significant upswing.

Well, you I think you may have set the record for the number of questions. We're not going to answer because in that because we don't want to it's Marion would be love to but I I think that there's so many competitive issues ongoing there in terms of our strategy on the ground, our rebates and so forth. Um so I'm I'm not sure we're able to really help you out there. Marin I don't know if you want to add anything. Oh I I think I will, I will just add that when we look at the Ali HD performance in the quarter, the favorability that we're seeing certainly is related to Aliyah, HD the product and the science and you know Retina Specialists see the clinical efficacy. The safety and now durability with Aliyah HD and that is making a big difference.

we do see that um, uh,

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

Until we get these enhancements in place. We can't uh I think see a significant upswing. Yeah.

George Yancopoulos: Thanks, Len and Marion. Let's move to the next question, please, Shannon.

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

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

To the next question, please Shannon.

[Analyst]: Morning, guys. Thanks for the question. I guess for Chris or Len, you know I'm utilizing the balance sheet, and you guys haven't historically done larger scale BD. It seems like that's going to be the case going forward. 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.

Our next question comes from the line of Jeffrey meechum with City. Your line is now open

George Yancopoulos: Yeah, it's a 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. 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, as I said during RMOs, 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. I think you do highlight one piece of the whole puzzle that we do not have adequate positioning in, which is the filling. I'm pleased to say that we would expect our filling plant to come, which we've invested quite a bit in, Jeff.

Morning guys. Uh, thanks for the question. Uh, I guess for 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 but in manufacturing, what's the appetite to further? Expand your 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.

George Yancopoulos: It's now ready to go, and we expect it to come online during the coming year. That's a great question, and it should help us sort of control all aspects of this standard biologics manufacturing.

Ryan Crowe: Okay, thanks, Len. Shannon, next question, please.

We expected to come online during the coming year. So that that's a great question and it should help us sort of control all aspects of the standard uh biologics manufacturing. Okay, thanks Len, Shannon next question. Please

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

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

[Analyst]: Thanks for taking the question. It's just maybe a question on EYLEA HD. Marion, I think I've heard you talk a lot about the importance of these labeling enhancements, and Len, I just heard your comment about share and how important they are. I think we've come to understand maybe the primary need here is, 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. Just maybe, Marion, as you've seen this market evolve, can you talk about how that, you know, clinic inventory policies have evolved over time and especially how private equity in this space may be influencing this? Is this really more of a, you know, as you're looking for share with, you know, clinics that don't necessarily have, you know, relatively aggressive inventory policies? Thanks.

Um, thanks for taking the question. Um, just maybe a question on Ivia HD. Um, Mary and I think I’ve heard you talk a lot about the importance of these labeling enhancements. And Len, I heard your comment.

Um, about share and how important it is that they are. But, um, you know, I think, um, you know,

We've come to understand maybe the primary need here is in 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 1 drug

Chris Fenimore: 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. I'm not an expert in inventory, but I can share with you that EYLEA HD is a newer branded product in the category, two years in the market now. Certainly availability, not only inventory-wise, but payer coverage-wise. 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. Of course, with EYLEA HD, they're getting, for appropriate patients, the ability to have durability that is very, very important for the patients and their caretakers.

But, um, just maybe Mary. And as you seen this Market evolved, can you talk about how um that you know, Clinic inventory policies have evolved over time and especially how private equity in the space may be influencing this, or is this really more of a you know as you're as you're looking for share with, you know, with clinics that don't necessarily have, you know, you know, relatively aggressive inventory policies. Thanks.

So um Chris my comment would be that the you know the retina community and certainly retina kol's.

Ryan Crowe: Okay, thanks, Marion. Next question, please.

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 IA HD is a newer branded product in the category 2 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. Um and then of course, with Aaliyah HD, they're getting for appropriate patients. The ability to have durability. That is very, very important for the patients and their caretakers.

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

Okay. Thanks Mary. And next question, please.

[Analyst]: 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 Dupixent in 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.

Our next question comes from the line of parents Flynn with mortgage. Only your line is now open.

Marion McCourt: 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.

Hi. Thanks for taking the question. Uh, George you mentioned, uh, it sounds like likely you and Santa Fe are are going to do another phase 3 trial here for uh Isle 33 and COPD. Can you just talk about any new insights? You might have learned that drove the differential outcome in the prior to phase 3 trials. And then what you think, you can change your optimized in a third trial here to uh, improve the likelihood of success. Thank you.

Ryan Crowe: Okay, thanks so much, George. Next question, please.

Well, due to competitive issues, I'm not going to really comment on um most of your questions there. And 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.

Chris Fenimore: Our next question comes from the line of Tyler Van Buren with TD Cowen. Your line is now open.

Okay, thanks so much. George next question, please.

[Analyst]: 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? A quick follow-up would be, is this the same alternate filler that you used for the recent Libtayo adjuvant cutaneous squamous cell carcinoma approval?

Our next question comes from the line of Tyler van Burren with TD Cowen, your line is now open.

George Yancopoulos: 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. 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 RVO Q4, that would really be perfect, and we could get it all wrapped up in late November. If it turns out that they have to go to December to get the filler approved, hopefully, that would be as far as they'd have to go. 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. I suspect that if they got through that in December, then we could rapidly resubmit or maybe

Great. Thanks. Good morning. Congratulations, on the quarter. Uh, can you elaborate on the probability of the late? December decision on the rvo and every 4 week dosing filing with the new filler resulting in an approval and and just a quick, follow-up would be is is this the same alternate filler that you use for the recent flip to add event? Cutaneous Guam cell, carcinoma approval,

No, it's a different filler. Um, it's a complicated sort of timeline here, uh, because the, uh, the new filler, uh, has to undergo its review and probably an inspection and review. Um, and it's unclear when that would get done. Ideally, if that could get done before our November, uh, timeline for the approval, uh, for the PUA day for the RVO Q4, that would really, uh, be perfect and we could get it all wrapped up in, uh, late November.

Leonard Schleifer: 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. We think we've had very good discussions about label and indications, and all that's fine. You know it's not over till it's over, obviously. 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 the 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.

Operator: Yes. Thanks, Glenn. Complicated situation. Let's move to the next question, please.

Uh, to uh, get the filler in place. So we think we've had very good discussions about label and indications and all that is fine. Um, but you know, it's not over till it's over, obviously. But the 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 that's the to date that we can tell you.

Ryan Crowe: Our next question comes from the line of Evan Seigerman with BMO Capital Markets. Your line is now open.

Yes, thanks Lauren complicated situation. Let's move to the next question, please.

George Yancopoulos: 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 and ensure that products that should be approved get approved and get to patients as quickly as possible? Thank you.

Council on the line of Evans. Sermon with BMO Capital markets, do you let us know? Open

Leonard Schleifer: Yeah, that's a very pointed question. 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. 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 in 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.

Hi guys, thank you so much for taking my question. This taking a step back. Can you walk me through somebody internal changes you made with your regulatory manufacturing teams to prevent the crls that we've seen in recent and ensure that the products that should be approved to get approved and get the patients as quickly as possible. Thank you.

Yeah, that's a very pointed question. Um, and I I I really want to address it head on

The issues that we have had.

Leonard Schleifer: 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. Then you have to do stability testing and all that and quality testing, all of that for a given filler. That takes quite a bit of time, quite a bit of resources. In summary, I don't want to sound offensive 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.

Have not been internal regulatory problems. Um, we have a terrific relationship with the FDA, our regulatory team includes people who used to work at the FDA we or people who've been in the industry doing this for decades. Uh, there's no shortage of expertise or relationships uh, on a regulatory front, we've certainly asked that question board always ask 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 um we would have expected to have that by now but we got delayed dramatically during Co because of supply chain issues and Manufacturing. As I said we hope that filling will come online. Um uh next year in terms of um getting backups and what have you? It's a relatively complicated situation. We've been working on backup.

For quite a long time. Now, the problem as you might imagine is that um, for good reason, the FDA is very, uh, finicky about showing where you make, they'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 and quality testing all of all that for a given filler and that takes quite a bit of time, quite a bit of reason.

Resources.

Leonard Schleifer: 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?" They just don't talk about the CRLs that they get, and we know that they're out there. I'm not sure that we're worse off in that regard. Wherever we are, I'm not happy about it, and we're not happy about it. We're trying to rectify the situation. I hope that gives you a glimpse into our thinking.

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

Um, so in summary, um, I don't want to sound offensive at all. We have looked at this, it is not a regulatory problem for us. It is in some respects, a manufacturing, uh, issue in terms of getting online. Our own filling, um, um, having backup fillers in places complicated. We're trying to do that. Um, and um, but our biggest problem, frankly is the FDA has now paid quite a bit of attention, close attention. And I might point out that the biggest companies in the world, have had the same issue with fillers where even with the same filler, and they've called us to know, how's it going? And but they just don't talk about this crl's that they get, um, and we know that they're out there. So I'm not sure that we're, uh, 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, uh, into our thinking

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

Okay, I'll put in the next question, please.

George Yancopoulos: 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 two study for the antibodies in AFib. 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 large into registrationals in that and other large indications and really accelerate that program. Thanks.

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

Uh, hey, good morning. Thanks for taking my question. Um, just on the pipeline front on the factor 11, uh, antibody program. Um, I I don't want you to front run your round table but um, I know you guys recently started a large Phase 2 study for for the antibodies in a-fib. Uh, so I'm just curious what you guys are looking for out of that study and and maybe out of other.

Factor 11s and development, uh, to move into large into registrations, uh, in that and other large indications, and really accelerate that program. Thanks.

Leonard Schleifer: The phase two study is a run-in study into what we anticipate to be our phase three pivotal program there. We are in pivotal programs in other settings where anticoagulation can be important. 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.

Leonard Schleifer: 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 staff indication, where right now, use of anticoagulants is very limited because of the bleeding concerns. That's what's really limiting the utilization of anticoagulants more widely across many, many, many more settings. 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. We think there's a lot of opportunities here beyond staff.

At risk. We think that frankly in some ways, um, decreases in bleeding risk are going to be frankly, more important, um, than in some cases, the anti-coagulation effect as long as you have anti-coagulation effect, but if you have really a safe way of achieving it, we think there's a plethora of settings where these 2 antibodies can respectively, find their place, uh, and particularly in places, maybe even much larger than the staff indication. Where, right now, um, use of anti-coagulants is very limited because of the bleeding concerns. That's what's really limiting the utilization of anti-coagulants, um, more widely across many, many, many, many more settings. And so, we think that our approach using 2 antibodies, is going to allow us to really customize and tailor, 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. Well, providing a different antibody,

Leonard Schleifer: 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.

Operator: In the future, you'll be having a roundtable to tell them about that.

With maybe higher anti-coagulation 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

Current is right now.

Leonard Schleifer: Correct. November 10.

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

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

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

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

George Yancopoulos: Great. Good morning. Thanks for taking the question. Len, you highlighted the sort of meager matching thus far with the foundation, and you framed it remaining committing to that funding until the end of the year, which I guess alludes 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?

Our next question comes from the line of carter gold with caner, your line is now open.

Leonard Schleifer: 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. It's a good question, though.

Great. Uh, good morning. Thanks for taking the question. Uh Len. You highlighted, the sort of the meager matching thus far for the the, with the foundation. And you sort of, uh, you know, 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 uh, any other people uh, match your uh your 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. Uh 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.

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

Good question, though.

Ryan Crowe: Our next question comes from the line of Cory Kasimov with Evercore. Your line is now open.

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

George Yancopoulos: Hey, good morning, guys. Thanks for taking the question. On the heels of your positive Phase 3 data for SIMDISERIN, I'm interested. Can you outline how you see the commercial opportunity evolving for GMG and what your plans are in Europe with this asset? Thank you.

Our next question comes from the line of Corey kasimov with evercore, your line is now open.

Leonard Schleifer: George, could you just remind everybody what’s out there and what the limitations of the current therapies are? I'm not sure everybody's on the same page on that.

Hey, good morning guys. Thanks for taking the question. So on the heels of your positive phase 3 data for some deran. Um, I'm interested a few outline, how you see the commercial opportunity evolving for GMG and and what your plans, uh, are in Europe with this asset. Thank you, thank you.

Before we get to that.

Marion McCourt: Right. 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. In terms of the FCRN class, those are given via also intravenous infusion approaches right now, or ultimately, they may move to large volume subcutaneous approaches that are also somewhat difficult to self-administer. In any case, the issues also have to do with safety and efficacy.

Because I'm not sure everybody's on the same page on that.

Right. Well, right now, there are 2 major classes um, that are being utilized in this space. 1, of course, is the C5 class. The other is the fcrn class in terms of the C5 class. Um,

Marion McCourt: 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. In cross study comparison, our agent seems to have, in terms of the standard measure that is being used to evaluate these, the best cross trial efficacy that's stable and continuous throughout the dosing period. 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.

As we know most of those are administered, uh, using these large intravenous infusions, which are very inconvenient for the patients, um, and in terms of the fcrn class, those are given via also intravenous confusions approaches right now or ultimately, they may move to large volume. Uh, subcutaneous approaches. There are also somewhat difficult to self-administer, but in any case, um, the issues also have to do with safety and efficacy. Um, the thing that's exciting about our program is unlike the fcrn which either when you use weekly treatment um you get less benefits at least cross studies from these standard scores or with the episodic treatment where you have a you

Marion McCourt: They both result potentially concerns with efficacy, in the case of the C5s, 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. 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. 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.

Concerns, uh, with efficacy, uh, in the case of the c5's mostly I mean in Chicago infection. Um, as you've probably seen with the fcrn class uh with longer usage, they've seen serious infections, for example,

Marion McCourt: 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. 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?

Um, um, um, uh, Resurgence of EBV, and Evo, even fatally, BV infections. So those are concerns with, um, 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 3 months, nothing like that has 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. Then 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, uh, and the fact that we don't completely inhibit, uh,

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

Operator: Thanks, George and Marion. Let's move to the next question, please, Shannon.

The target uh in this class, there is the long-term opportunity that we may be able to show that we may have um better safety for patients as well here. So it's a very exciting profile. Uh uh I think to potentially be able to deliver it for these classes for these class of patients who are really needing, uh, 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 um, 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 launched ready and we do feel for this really important category and patience with unmet need um that we potentially have a very highly differentiated um product to bring into the marketplace.

Ryan Crowe: Our next question comes from the line of Simon Baker with Rothschild & Co., Redburn. Your line is now open.

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

[Analyst]: 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 intravitreally 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 obviously would be a much bigger indication. Any thoughts on where this could go? It'd be much appreciated. Thank you.

Our next question comes from the line of Simon Baker with Ross Child and Company, Redbarn. Your line is now open.

Leonard Schleifer: I didn't hear what you said about glaucoma. What in glaucoma?

Thank you very much for taking my question. My, my first ever questioned on the call, um, I just wanted to go back to your comments, George on. Um, intro virtually delivered CD3. Um, you're trying to initially in, um, uvi to. So I just wonder what the scope of your ambition was uh, in that setting given the uh, the role of T-cell infiltration in glaucoma, which helps to be uh a much bigger indication, any thoughts on on where this could go be much appreciated, thank you.

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

I didn't hear what you said about glaucoma. What in what internet glaucoma.

Leonard Schleifer: Yeah. We're very excited about our CD3 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 blockers, partial agonists to date. We think that going into the eye in uveitis, which a lot of data suggests that most, if not all, of these uveitis diseases are related to T cells. If we can block the T cells locally because the doses that we're going to be using are very low, they're not going to be having systemic effects. You could have really profound benefit in this high unmet need without subjecting patients to any sort of global or systemic immunosuppression. We really think this is a very novel, very different approach to active non-infectious uveitis. We think this is the perfect setting to try our CD3 antibody.

So the the there's some evidence that glaucoma is uh caused in greater or lesser part by T Cell infiltration in the eye. So I just wondered if, if using CD3 antibodies in this in this setting was potentially in Encompass of that indication as well as uvit.

Yeah. So

Leonard Schleifer: We have been working a lot on glaucoma. I'm glad that you brought it up. I believe, based on our Regeneron Genetics Center, which are world leaders in understanding the genetic basis of disease, we've uncovered the most important drivers genetically of glaucoma. We will be rolling out in the very near future our strategy and our programs in a very near clinical program in glaucoma as well. I'm glad you brought it up. I'm glad you're interested in it. These are going to be two very different, distinct programs. We're going to have our CD3 program for non-infectious 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.

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 block, or partial Agonist to date. Um, we think that going into the eye in uvit which a lot of data suggests that most if not the 1, all of these UV ideas, these 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 could have really profound benefits in this High unmet need, without subjecting patients to any sort of global or systemic, uh, you know, suppression. So, we really think this is a very novel, very different approach to, uh, active non-infectious uvit. Uh, we think this is the perfect setting to try our CD3 antibody. Um,

Leonard Schleifer: The way we think about it, one could be the EYLEA for uveitis. The other could be the EYLEA for glaucoma. Stay tuned.

Operator: Thank you, George. Very exciting. I think we have time for three more questions, Shannon.

Abilities. Uh, 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 AHA for uveitis. The other could be the IA for glaucoma, so stay tuned.

Ryan Crowe: Our next question comes from the line of Alexandria Hammond with Wolfe Research. Your line is now open.

Thank you, George, very exciting. I think we have time for 3. More questions. Shannon.

[Analyst]: Thanks for taking the question. On the upcoming LEPTILEG phase three readout, it seems like the goal is to outperform Opdualag. Could you share your confidence in demonstrating a static benefit against Keytruda? As a follow-up, can you tell us a little bit more about the open-label phase three trial you have ongoing against Opdualag? Is it just another show of confidence that your combo can be more potent than the currently approved option?

Our next question comes from the line of Alexandria. Hammond with wolf research, your line is now open.

Marion McCourt: A lot of questions in there. 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. 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, with the minimal expectation that if we have Opdualag-like activity, we power the study so that we can win in both PFS, but also where Opdualag failed in OS. If, as you mentioned, we have better data than Opdualag, then obviously, we will significantly win even more than that.

Thanks for taking the question on the upcoming live tile lag 3 readout. It seems like the goal is to outperform Abdul lag, but could you share your confidence in demonstrating a static benefit against Cuda? As a follow-up, can you tell us a little bit more about the open label space through trial you have ongoing against Abdul lag? 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, um,

Our study is ongoing, as you said, we are trying our combination versus katuda, our hope is that the katiyar will behave as it has more or less historically, and our hope is that remember, we have 2 arms in the study of low dose in the high dose that the 2 arms at least 1 of them will behave better than the katuda arm. Um, what the way we power the study is that, uh, uh, we powered it to not only hit PFS and Os and

Marion McCourt: We powered the study for a minimal Opdualag-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 will see whether or not we end up having better efficacy than Keytruda, better efficacy cross study comparison than Opdualag, and so forth. We continue to be excited, obviously, about this program. There is obviously a high need here. There was very exciting earlier trial data using our FeNLMab antibody. We are anxiously but excited about awaiting the data readout next year.

And with the minimal expectation. That if we have Abdullah like activity, we power the study so that we can wean in both PFS, but also where Abdullah failed in OS. If as you mentioned, we have better data than Abdullah then obviously, we will significantly win even more than that. So we powered the study.

Operator: Yeah. First half of next year is the timing on that. Shannon, next question, please.

Ryan Crowe: Our next question comes from the line of Chris Schott with JP Morgan. Your line is now open.

For a minimal of dual leg life benefit. But so as to have a large enough OS signal, so that we will win with comparable data there. Um, of course, the data will speak for itself. We'll see whether or not we end up having better efficacy than, uh, katuda better efficacy cross study comparison, then Abdullah, uh, and so forth. But we continue to be excited obviously about this program because obviously a high need here. Uh, there was very exciting earlier, uh, trial data using our Fiat antibody and so, um, we are anxiously but excited about awaiting, uh, the data readout next year. Yeah. First half of next year is the timing on that. Um, chat. Our next question, please.

George Yancopoulos: Great. Thanks so much. Just a quick one on the launch of Linezytif. How is that progressing versus expectations? Can you 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 it seems to be shaping up here? Is there an ability to pull that forward or accelerate that at all in terms of working with the FDA, etc.? Thank you.

Our next question comes from the line of Chris shot with JP Morgan. Your line is now open,

Not great. Thanks so much. Just a, just a quick 1.

On the launch of uh, lynville salt map.

Chris Fenimore: I can take the first portion on the launch, and then I'm sure George will come in on the rest. 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, with formulary listings, pathway inclusion, REMS requirements, and payer coverage. We are pleased with what we're seeing so far. Certainly, the enthusiasm of the hematology community for Linezytif is high, keeping in mind this is the fifth line setting for multiple myeloma patients, so a heavily pretreated population. To George for earlier lines.

Who's 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 the profile that that seems to be shaping up here? Is that is there an ability to pull that forward or accelerate that all in terms of working with FDA Etc. Thank you.

so I can take the first portion on the launch and then I'm sure George will come in on the rest but um, certainly

Marion McCourt: 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 Linezytif would be the choice based on all the available data out there. 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 premalignant 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. The data really is stunning and unprecedented.

But as I mentioned, the progress has been very, very good. Um, we've seen the, you know, the typical indicators. When you have a successful launch, ongoing physician feedback has been very favorable of formulary listings. Pathway inclusion, Rems requirements payer coverage. So, um, we are pleased with the we're seeing so far and certainly the enthusiasm of the hematology Community for Linda ific 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 1 looks at the totality of the data, um, certainly, you know it if it was me or somebody that I cared about uh, giving the late stage patients, uh, any of these treatments? I think Leno ific would be the choice, uh, based on all the available data out there. And importantly, what this says, if it looks like it has uh, the potential for impressively more benefit in the late line patients that, of course suggests that it should have

Marion McCourt: We're having high rates of seeing molecular complete responses in smoldering in amyloidosis, which is a premalignant 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. In later line settings with new combinations that we're also trying, unprecedented levels of activity. We think that this program really has the potential to change the face of treatment for this disease indication in all of its manifestations, whether it be premalignant precursor settings, whether it's early line disease, whether it's second line disease, or whether it's for the late-stage patients. I think this is an exciting time for the field. I just want to remind you that in many ways, our Undernextamab program is quite similar, in that particularly in follicular lymphoma, where we look like we have the best late line data.

And the data really is stunning and unprecedented. Um, we're having

Um, a high rates of seeing molecular complete responses in smoldering in, um, Emily dosis which is, um, um, a premalignant 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 were also trying unprecedented levels of activity. So, we think that this program really has the potential to change the face of treatment for, um, this, uh, disease indications in all of its manifestations, whether it be premalignant precursor settings, whether it's early line disease, whether it's second line disease or whether it's for, uh, 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 our journey next to May our program is quite similar um, in that particular in follicular lymphoma.

Marion McCourt: We're going aggressively in earlier line disease. 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 hematologic oncology space in their respective settings.

Where we look like we have the best latte line data.

We're going aggressively in earlier line disease, and once again, we've released the data lead in cohorts of phase, 3s as monotherapy and so forth. Once again unprecedented, uh, efficacy in these small initial cohorts that we're looking at, which really get us excited that these by specifics really have the chance.

Leonard Schleifer: Let me just say that before we go to the next question. One is, I think, inherent in 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. 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 registrational trials for Linezytif, including, as George outlined, a broad registration program in front line or even earlier myeloma patients, all for transplant eligible and ineligible. This is a big space. It's a $30 billion market potential. Darzalex alone is annualizing at $15 billion. You saw some cross-study data that suggests that we can outperform.

To really change, uh the hemoglobin oncology space in their respective settings. So let me let me just say that before we go to the next question 1 is I think inherent in what George is saying. There is that all by specifics, not created equal, the team spends, an enormous amount of time with all the technology at hand to select and create by specifics that we think are different um fundamentally different. And that's why we think we're seeing better data. Um I just also want to emphasize we're making a huge commitment here. We expect to conduct conduct as many as 10 registration or trials for the limit ific um and and including as George outlined a broad registration program in Frontline or even earlier uh uh Myoma patients. Both for transplant eligible. And ineligible um this is a big space. It's a 30 billion dollar market uh potential. Jaws Alexa alone is annualizing at 15 billion dollars, uh you saw some cost study data that's

Leonard Schleifer: We've had some success where Darzalex has already failed in the IgA space. We've had some success in cross-study comparisons in the smoldering. I think this is pretty exciting, as George outlined. It's a huge commitment. We expect 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?

Suggest that uh, um, we can, uh, outperform. Um, we've had some success where it does. Lex is already failed in the, uh, in uh, in the IGA space. And we've had some success um and cause study comparisons uh in the uh um smoldering. So I think this is pretty exciting as George outlines. It's a huge commitment. You expect to suspend a lot and go very, uh, as fast as we can. Somebody asked about, can we accelerate

Operator: You meant the amyloidosis, not IgA.

Leonard Schleifer: Sorry.

Operator: Go ahead.

Leonard Schleifer: I meant amyloidosis. Thank you.

Operator: Thank you, Glenn and George. We also look forward to having a Regeneron roundtable on Linezytif in December of this year. Let's move to our final question, Shannon.

With the FDA, we are certainly going to talk with them and advise that we think we have the best program. How can we work together? You meant the omalo dose is not IGA. Anyway, go ahead. Thank you.

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

Glenn and George. We also look forward to having a regeneron Roundtable on loif in December of this year. Um so let's move to our final question, Shannon.

[Analyst]: Good morning. Thanks for taking my question. You spoke to novel targets here in INI in 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 versus vision improvements, and whether you need to evaluate against current agents? Just remind us on the INI side when we might hear about these novel targets. Thank you.

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

Good morning. Thanks for taking my question. Um, you spoke to

Marion McCourt: 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. As I said, we have data from the cohort A from our phase 3 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, we'll know whether there's a real opportunity there or not from that data.

Novel targets in INI and ophthalmology on the GA program in particular. Can you speak to what the FDA may be looking for and potential study designs? Whether it's slowing J. lesion growth versus 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, um, and planned our, um, pivotal readout study, uh, for Geographic. Atrophy, we are able to go against Placebo. Um, and we're primarily looking at, uh, slowing down of growth together. With, of course, Vision, um, control. Um, and as I said, we have data from our um the the cohort a from our phase 3 trial where we expect readouts

Marion McCourt: 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 obviously are related INI and ophthalmology program. You'll be hearing it roll out over the next couple of months with hopefully a new clinical program initiating next year.

That data.

Operator: Okay. Appreciate everyone's patience. We went a little over time. I appreciate your interest in Regeneron Pharmaceuticals. 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 Pharmaceuticals is available to answer any remaining questions you may have. Thank you once again and have a great day.

Um, I think that, uh, in terms of our ini programs, I think you'll probably be hearing about 1 of the first 1 additional ones. Additionally, to the C3 program, which obviously are related ini and aamal program, they'll be hearing it roll out over the next couple months with uh, hopefully a new clinical program initiating uh uh next year.

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

Okay. Appreciate everyone's patience. We want a little over time um and appreciate your interest in regeneron apologize to those who remain in the community who do not have a chance, we 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.

Today's conference call, thank you for your participation. You may now disconnect