Q2 2024 Regeneron Pharmaceuticals Inc Earnings Call

August 1, 2024

Speaker Change: They keep singin' like everybody was dancin' in the moonlight Dancin' in the moonlight, everybody's feelin' warm and bright It's such a sight

Operator: Welcome to the Regeneron Pharmaceuticals Second Quarter 2024 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 call is being recorded. I will now turn the call over to Ryan Crowe, Senior Vice President Investor Relations. You may begin. Thank you, Shannon. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron, and welcome to our second quarter 2024 earnings conference call. An archive and transcript of this call will be available on the Regeneron Investor Relations website shortly after the call ends. 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, Senior Vice President and Chief Financial Officer.

Shannon: Welcome to the Regeneron Pharmaceuticals second quarter 2024 earnings conference call. My name is Shannon and I will be your operator for today's call.

Ryan Crowe: 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 call is being recorded. I will now turn the call over to Ryan Crowe, Senior Vice President, Investor Relations. You may begin.

Unknown Executive: Later, we will conduct a question and answer session. Thank you, Shannon. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron, and welcome to our second quarter 2024 earnings conference call. An archive and transcript of this call will be available on the Regeneron Investor Relations website shortly after the call ends. 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, Senior Vice President and Chief Financial Officer.

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 and welcome to our Second Quarter 2024 Earnings Conference Call. An archive and transcript of this call will be available on the Regeneron Investor Relations website shortly after the call ends. 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, Senior Vice President and Chief Financial Officer.

Ryan Crowe: An archive and transcript of this call will be available on the Regeneron Investor Relations website shortly after the call ends.

Speaker Change: Joining me on today's call are Dr. Leonard Schleifer, Board Co-Chair, Co-Founder, President, and Chief Executive Officer.

Ryan Crowe: 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, Senior Vice President and Chief Financial Officer. After our prepared remarks, the remaining time will be available for your questions. We anticipate today's call will last approximately 60 minutes. I would like to to remind you that remarks made on today's call may include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and business, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement.

Speaker Change: Dr. George Yancopoulos, Board Co-Chair, Co-Founder, President and Chief Scientific Officer Marion McCourt, Executive Vice President of Commercial and Chris Fenimore, Senior Vice President and Chief Financial Officer

Unknown Executive: After our prepared remarks, the remaining time will be available for your questions. We anticipate today's call will last approximately 60 minutes. 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 Change: After our prepared remarks, the remaining time will be available for your questions. We anticipate today's call will last approximately 60 minutes.

Speaker Change: I would like to remind you that remarks made on today's call may include forward-looking statements about Regeneron.

Ryan Crowe: I would like to to remind you that remarks made on today's call may include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and business, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found with Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q with the quarter ended June 30, 2024, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our quarterly results press release and our corporate presentation--both of which can be accessed on the Regeneron Investor Relations website. Once our call concludes, Chris and the Investor Relations 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. Thanks, Ryan. In my remarks today, I'd like to briefly review some of the key performance drivers for the quarter and then discuss near-term pipeline opportunities.

Speaker Change: Such statements may include, but are not limited to, those related to Regeneron and its products and business, financial forecasts and guidance,

Speaker Change: Development Programs and Related Anticipated Milestones, Collaborations, Finances, Regulatory Matters, Payor Coverage and Reimbursement Issues, Intellectual Property, Pending Litigation and Other Proceedings, and Competition.

Ryan Crowe: Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found with Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q with the quarter ended June 30, 2024, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our quarterly results press release and our corporate presentation--both of which can be accessed on the Regeneron Investor Relations website. Once our call concludes, Chris and the Investor Relations team will be available to answer any further questions.

Speaker Change: 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 Change: 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 , where the quarter ended June 30, 2024, which was filed with the SEC this morning.

Unknown Executive: Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise. In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP. Once our call concludes, Chris and the Investor Relations team will be available to answer any further questions. In my remarks today, I'd like to briefly review some of the key performance drivers for the quarter and then discuss near-term pipeline opportunities.

Speaker Change: Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise. In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call.

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 accessed on the Regeneron Investor Relations website. Once our call concludes, Chris and the Investor Relations team will be available to answer any further questions.

Speaker Change: Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP.

Speaker Change: is available in our quarterly results press release and our corporate presentation, both of which can be accessed on the Regeneron Investor Relations website.

Speaker Change: Once our call concludes, Chris and the Investor Relations team will be available to answer any further questions.

Speaker Change: With that, let me turn the call over to our President and Chief Executive Officer, Dr. Leonard Schleifer. Len.

Ryan Crowe: With that, let me turn the call over to our President and Chief Executive Officer, Dr. Leonard Schleifer.

Leonard Schleifer: Thanks, Ryan. Thanks to everyone joining today's call.

Ryan Crowe: Thanks, Ryan. Thanks to everyone joining today's call. Regeneron continued its track record of strong execution, highlighted by double-digit revenue and earning growth in the second quarter, along with important advances across our broad pipeline. For my remarks today, I'd like to briefly review some of the key performance drivers for the quarter and then discuss near-term pipeline opportunities.

Leonard S. Schleifer: Thanks, Ryan. Thanks to everyone joining today's call. Regeneron continued its track record of strong execution, highlighted by double-digit revenue and earning growth in the second quarter, along with important advances across our broad pipeline. For my remarks today, I'd like to briefly review some of the key performance drivers for the quarter and then discuss near-term pipeline opportunities. ILEA HD generated $304 million in its third full quarter on the U.S. market and continues to outperform recent launches in the anti-VEGF category. Net product sales for ILEA HD and ILEA combined were $1.53 billion, representing a 2.3% growth compared to the prior year.

Leonard S. Schleifer: Thanks, Ryan. Thanks to everyone joining today's call.

Ryan Crowe: Regeneron continued its track record of strong execution, highlighted by double-digit revenue and earning growth in the second quarter, along with important advances across our broad pipeline. For my remarks today, I'd like to briefly review some of the key performance drivers for the quarter and then discuss near-term pipeline opportunities. ILEA HD generated $304 million in its third full quarter on the U.S. market and continues to outperform recent launches in the anti-VEGF category. Net product sales for ILEA HD and ILEA combined were $1.53 billion, representing a 2.3% growth compared to the prior year.

Leonard S. Schleifer: Regeneron continued its track record of strong execution, highlighted by double-digit revenue and earning growth in the second quarter, along with important advances across our broad pipeline. For my remarks today, I'd like to briefly review some of the key performance drivers for the quarter and then discuss near-term pipeline opportunities. After my remarks, George will provide further updates on our pipeline; Marian will then review our commercial performance and finally, Chris will detail our quarterly financial results and discuss updates to our full year guidance. Second quarter 2024 total revenues grew 12% to $3.55 billion, primarily driven by sales of EYLEA HD in the United States, higher Sanofi collaboration revenues, reflecting the continued strong performance of DUPIXENT as well as robust growth for LIBTAYO. generated $304 million in its third full quarter on the U.S. market and continues to outperform recent launches in the anti-VEGF category. Net product sales for ILEA HD and ILEA combined were $1.53 billion, representing a 2.3% growth compared to the prior year.

Unknown Executive: ILEA HD generated $304 million in its third full quarter on the U.S. market and continues to outperform recent launches in the anti-VEGF category. Net product sales for ILEA HD and ILEA combined were $1.53 billion, representing a 2.3% growth compared to the prior year.

Leonard Schleifer: For my remarks today, I'd like to briefly review some of the key performance drivers for the quarter and then discuss near-term pipeline opportunities.

Speaker Change: After my remarks, George will provide further updates on our pipeline, Marion will then review our commercial performance, and finally Chris will detail our quarterly financial results and discuss updates to our full year guidance.

Leonard S. Schleifer: Second quarter 2024 total revenues grew 12% to $3.55 billion, primarily driven by sales of EYLEA HD in the United States; higher Sanofi collaboration revenues, reflecting the continued strong performance of DUPIXENT; as well as robust growth for LIBTAYO. EYLEA HD generated $304 million in its third full quarter on the U.S. markets and continues to outperform recent launches in the anti-VEGF category. Net product sales for EYLEA HD and EYLEA combined were $1.53 billion, representing a 2.3% growth compared to the prior year. We are encouraged that despite increased competition in the anti-VEGF space, we have achieved a strong ILEA HD launch trajectory while maintaining our category leading combined ILEA HD and ILEA market share of 45 percent. In June, the European Commission approved Dupixent for COPD in patients with raised blood eosinophils, marking the first global regulatory approval for Dupixent in COPD. This approval enables PICSEN to address the approximately 220,000 eosinophilic COPD patients in the EU that are currently uncontrolled on maximum inhaled triple therapy.

Unknown Executive: We are encouraged that despite increased competition in the anti-VEGF space, we have achieved a strong ILEA HD launch trajectory while maintaining our category leading combined ILEA HD and ILEA market share of 45 percent. In June, the European Commission approved Dupixent for COPD in patients with raised blood eosinophils, marking the first global regulatory approval for Dupixent in COPD. This approval enables PICSEN to address the approximately 220,000 eosinophilic COPD patients in the EU that are currently uncontrolled on maximum inhaled triple therapy.

Speaker Change: We are encouraged that despite increased competition in the anti-VEGF space, we have achieved a strong ILEA HD launch trajectory while maintaining our category-leading combined ILEA HD and ILEA market share of 45%.

Leonard S. Schleifer: We are encouraged that despite increased competition in the anti-VEGF space, we have achieved a strong EYLEA HD launch trajectory while maintaining our category leading combined EYLEA HD and EYLEA market share of 45%. Our efforts to bring an EYLEA HD pre-filled syringe United States market, we made a high priority and we're tracking towards a potential pre-filled syringe launch by early 2025. In summary, we'll continue to position EYLEA HD as the new standard of care for retinal diseases based on its differentiated clinical profile, coupled with strong familiarity and satisfaction among retinal specialists. DUPIXENT global revenues grew 29% on a constant currency basis to $3.65 billion, reflecting string growth across all approved indications, age groups and geographies. In June, the European Commission approved DUPIXENT for COPD in patients with raised blood eosinophils, marking the first global regulatory approval for DUPIXENT in COPD. This approval enables DUPIXENT to address the approximately 220,000 eosinophilic COPD patients in the EU that are currently uncontrolled on maximum inhaled triple therapy.

Speaker Change: In summary, we continue to position ILEA-HT as the new standard of care for retinal diseases based on its differentiated clinical profile coupled with strong familiarity and satisfaction among retinal specialists.

Speaker Change: To PIXEN global revenues grew 29% on a constant currency basis to $3.56 billion, reflecting strong growth across all approved indications, age groups, and geographies.

Leonard S. Schleifer: DUPIXENT global revenues grew 29% on a constant currency basis to $3.65 billion, reflecting string growth across all approved indications, age groups and geographies. In June, the European Commission approved DUPIXENT for COPD in patients with raised blood eosinophils, marking the first global regulatory approval for DUPIXENT in COPD. This approval enables DUPIXENT to address the approximately 220,000 eosinophilic COPD patients in the EU that are currently uncontrolled on maximum inhaled triple therapy. We continue to work with the FDA regarding its ongoing review for this indication and expect their decision by the September 27th PDUFA date. We, and our partner Sanofi, are prepared for a U.S. launch that many pulmonologists, respiratory key opinion leaders, and their patients have been eagerly anticipating. We are also pleased with the progress we have made in establishing an international commercial footprint to support Liptio and other future products following our purchase of full global rights to Liptio from Sanofi in mid-2022.

Unknown Executive: We continue to work with the FDA regarding its ongoing review for this indication and expect their decision by the September 27th PDUFA date. We, and our partner Sanofi, are prepared for a U.S. launch that many pulmonologists, respiratory key opinion leaders, and their patients have been eagerly anticipating. We are also pleased with the progress we have made in establishing an international commercial footprint to support Liptio and other future products following our purchase of full global rights to Liptio from Sanofi in mid-2022.

Speaker Change: We continue to work with the FDA regarding its ongoing review for this indication and expect their decision by the September 27th for due for date.

Leonard S. Schleifer: The approval also represents the first biologic approved to treat this disease. We continue to work with the FDA regarding its ongoing review for this indication and expect their decision by the September 27th PDUFA date. We, and our partner Sanofi, are prepared for a U.S. launch that many pulmonologists, respiratory key opinion leaders and their patients have been eagerly anticipating. There is a high unmet need in COPD with tag to inflammation, with approximately 300,000 eligible patients in the United States. And our potential launch represents a significant driver for DUPIXENT's continued growth. LIBTAYO global net product sales were $297 million in the second quarter, an increase of 43% on a constant currency basis. Despite intense competition, LIBTAYO has maintained its leadership position in non-melanoma skin cancers while making impressive inroads in non-small cell lung cancer. We are also pleased with the progress we have made in establishing an international commercial footprint to support LIBTAYO and other future products following our purchase of full global rights to LIBTAYO from Sanofi in mid-2022.

Speaker Change: Despite intense competition, Lib Tile has maintained its leadership position in non-melanoma skin cancers while making impressive inroads in non-small cell lung cancer.

Leonard S. Schleifer: LIBTAYO global net product sales were $297 million in the second quarter, an increase of 43% on a constant currency basis. Despite intense competition, LIBTAYO has maintained its leadership position in non-melanoma skin cancers while making impressive inroads in non-small cell lung cancer. We are also pleased with the progress we have made in establishing an international commercial footprint to support LIBTAYO and other future products following our purchase of full global rights to LIBTAYO from Sanofi in mid-2022. During its review of the Limbo-Celtamed BLA, the FDA informed us that the third-party fill-finish manufacturer for Limbo-Celtamed had unresolved findings from an approval inspection for another company's product candidate. In closing, our pipeline continues to generate innovative and differentiated opportunities and now has over 35 programs in clinical development spanning several distinct therapeutic areas. Our commercial team is executing well with our in-market products and is building momentum in competitive categories. Finally, we continue to prudently deploy capital with the goal of delivering long-term value to shareholders. With that, I'll turn the call over to George.

Speaker Change: We are also pleased with the progress we have made in establishing an international commercial footprint to support Liptio and other future products following our purchase of full global rights to Liptio from Sanofi in mid-2022.

Unknown Executive: During its review of the Limbo-Celtamed BLA, the FDA informed us that the third-party fill-finish manufacturer for Limbo-Celtamed had unresolved findings from an approval inspection for another company's product candidate. In closing, our pipeline continues to generate innovative and differentiated opportunities and now has over 35 programs in clinical development spanning several distinct therapeutic areas. Our commercial team is executing well with our in-market products and is building momentum in competitive categories. Finally, we continue to prudently deploy capital with the goal of delivering long-term value to shareholders. With that, I'll turn the call over to George.

Speaker Change: During its review of the Limvoseltamib BLA, the FDA informed us that the third-party fill-finish manufacturer for Limvoseltamib had unresolved findings from approval inspection for another company's product candidate.

Speaker Change: While we now believe these findings have been resolved, a re-inspection will be required, and therefore we anticipate any potential FDA approval for limoseltamib is likely to be delayed beyond the August 22nd PDUPA date.

Leonard S. Schleifer: Regarding LINVOSELTAMAB--a BCMAxCD3 bispecific for relapsed, refractory multiple myeloma--during its review of the LINVOSELTAMAB BLA, the FDA informed us that the third-party fill-finish manufacturer for LINVOSELTAMAB had unresolved findings from approval inspection for another company's product candidate. While we now believe these findings have been resolved, a re-inspection will be required and therefore, we anticipate that a potential FDA for LINVOSELTAMAB is likely to be delayed beyond the August 22nd PDUFA date. The FDA has not informed us of any approvability issues for LINVOSELTAMAB related to safety, efficacy or the status of our ongoing confirmatory trial. While broadly on our pipeline, we are excited about several upcoming readouts later this year or in 2025, to further inform programs that could support significant long-term growth opportunities--which George will discuss in a moment. In closing, our pipeline continues to generate innovative and differentiated opportunities and now has over 35 programs in clinical development, spanning several distinct therapeutic areas. Our commercial team is executing well with our in-market products and is building momentum in competitive categories. Finally, we continue to prudently deploy capital with the goal of delivering long-term value to shareholders. With that, I'll turn the call over to George.

Speaker Change: The FDA has not informed us of any approvability issues for Limboseltamib related to safety, efficacy, or the status of our ongoing confirmatory trial.

Leonard S. Schleifer: The FDA has not informed us of any approvability issues for LINVOSELTAMAB related to safety, efficacy or the status of our ongoing confirmatory trial. While broadly on our pipeline, we are excited about several upcoming readouts later this year or in 2025, to further inform programs that could support significant long-term growth opportunities--which George will discuss in a moment.

Leonard S. Schleifer: In closing, our pipeline continues to generate innovative and differentiated opportunities and now has over 35 programs in clinical development, spanning several distinct therapeutic areas. Our commercial team is executing well with our in-market products and is building momentum in competitive categories. Finally, we continue to prudently deploy capital with the goal of delivering long-term value to shareholders. With that, I'll turn the call over to George.

Speaker Change: Our commercial team is executing well with our in-market products and is building momentum in competitive categories.

Leonard S. Schleifer: With that, I'll turn the call over to George.

Speaker Change: With that, I'll turn the call over to George.

George Yancopoulos: Thank you, Len. Starting with DUPIXENT, regarding COPD, data from our second confirmatory trial notice was featured as a late-breaking presentation at the American Thoracic Society Conference and simultaneously published in the New England Journal of Medicine. In NOTUS, DUPIXENT reduced exacerbations by 34% while significantly improving lung function, confirming the unprecedented results from the previously reported Phase III BOREAS trial. Based on data from NOTUS and BOREAS, DUPIXENT was recently approved by the European regulatory authorities for eosinophilic COPD patients uncontrolled on maximal standard of care inhaled therapy. Additional submissions are under review with other regulatory authorities around the world, including in the U.S., China and Japan. Beyond COPD, later this year, we are looking forward to data readouts from phase three studies of duprexin in chronic spontaneous urticaria and bullous pemphiglia. Seven years after its initial FDA approval, and with approval in seven different indications around the world, PIXEN continues to deliver potential new approvals for additional important disease indications. Regarding our small pilot study to potentially eliminate severe food allergies using our innovative approach that combines dupreximab and limbosaltamab, our BSMA by C3 bi-specific, we continue to expect to see initial data by the end of this year.

George: Starting with Dupixen, regarding COPD, data from our second confirmatory trial, NOTICE, was featured as a late-breaking presentation at the American Thoracic Society conference and simultaneously published in the New England Journal of Medicine.

George: Additional submissions are under review with other regulatory authorities around the world, including in the U.S., China, and Japan.

George D. Yancopoulos: Beyond COPD, later this year, we are looking forward to data readouts from phase three studies of duprexin in chronic spontaneous urticaria and bullous pemphiglia. Seven years after its initial FDA approval, and with approval in seven different indications around the world, PIXEN continues to deliver potential new approvals for additional important disease indications. Regarding our small pilot study to potentially eliminate severe food allergies using our innovative approach that combines dupreximab and limbosaltamab, our BSMA by C3 bi-specific, we continue to expect to see initial data by the end of this year.

George Yancopoulos: Beyond COPD, later this year, we are looking forward to data readouts from Phase III studies of DUPIXENT in chronic spontaneous urticaria and bullous pemphigoid. Seven years after its initial FDA approval and with approval in seven different indications around the world, DUPIXENT continues to deliver potential new approvals for additional important disease indications. Regarding our small pilot study to potentially eliminate severe food allergies using our innovative approach that combines DUPIXENT and LINVOSELTAMAB--our BSMA xCD3 bispecific--we continue to expect to see initial data by the end of this year. Study readouts and regulatory submissions for our second therapeutic candidate for this devastating disease are expected in the second half of next year. These results strengthen our view that Phenomab and Lentile may be the most promising immunotherapy combination in clinical development. As we recently announced, we are looking forward to the Phase 3 readout in this melanoma setting next year, which could position phenylmab and liptal as a new standard of care in melanoma and, eventually, potentially other cancer settings.

George Yancopoulos: Beyond COPD, later this year, we are looking forward to data readouts from Phase III studies of DUPIXENT in chronic spontaneous urticaria and bullous pemphigoid. Seven years after its initial FDA approval and with approval in seven different indications around the world, DUPIXENT continues to deliver potential new approvals for additional important disease indications. Regarding our small pilot study to potentially eliminate severe food allergies using our innovative approach that combines DUPIXENT and LINVOSELTAMAB--our BSMA xCD3 bispecific--we continue to expect to see initial data by the end of this year. On ITEPEKIMAB, our IL-33 antibody in development for certain COPD patients, our two Phase III studies are now fully enrolled. Study readouts and regulatory submissions for our second therapeutic candidate for this devastating disease are expected in the second half of next year.

George: Beyond COPD, later this year, we are looking forward to data readouts from phase 3 studies of duprexin in chronic spontaneous urticaria and bullous pemphigoid.

George: Seven years after its initial FDA approval, and with approval in seven different indications around the world, PIXEN continues to deliver potential new approvals for additional important disease indications.

George D. Yancopoulos: Study readouts and regulatory submissions for our second therapeutic candidate for this devastating disease are expected in the second half of next year. These results strengthen our view that Phenomab and Lentile may be the most promising immunotherapy combination in clinical development. As we recently announced, we are looking forward to the Phase 3 readout in this melanoma setting next year, which could position phenylmab and liptal as a new standard of care in melanoma and, eventually, potentially other cancer settings.

George Yancopoulos: Regarding our small pilot study to potentially eliminate severe food allergies using our innovative approach that combines DUPIXENT and LINVOSELTAMAB--our BSMA xCD3 bispecific--we continue to expect to see initial data by the end of this year. On ITEPEKIMAB, our IL-33 antibody in development for certain COPD patients, our two Phase III studies are now fully enrolled. Study readouts and regulatory submissions for our second therapeutic candidate for this devastating disease are expected in the second half of next year.

George: Moving to Oncology and starting with Pheanlamab or LAG-3 antibody in combination with Liptile.

George: These results strengthen our view that Phenylmab and Lentio may be the most promising immunotherapy combination in clinical development.

George Yancopoulos: On ITEPEKIMAB, our IL-33 antibody in development for certain COPD patients, our two Phase III studies are now fully enrolled. Study readouts and regulatory submissions for our second therapeutic candidate for this devastating disease are expected in the second half of next year. Moving to oncology and starting with FIANLIMAB, our LAG-3 antibody, in combination with LIBTAYO. At the upcoming ESMO meeting in September, we look forward to presenting longer term follow up on the metastatic melanoma cohorts for our first in-human study. Responses have continued to deepen with the proportion of complete responders and median progression-free survival continuing to improve. These results strengthen our view that FIANLIMAB and LIBTAYO may be the most promising immunotherapy combination in clinical development. As we recently announced, we are looking forward to the Phase III readout in this melanoma setting next year, which could position FIANLIMAB and LIBTAYO as a new standard of care in melanoma and eventually, potentially, other cancer settings.

George: As we recently announced, we are looking forward to the Phase 3 readout in this melanoma setting next year, which could position phenylamab and liptal as a new standard of care in melanoma, and eventually, potentially other cancer settings.

George Yancopoulos: Moving to oncology and starting with FIANLIMAB, our LAG-3 antibody, in combination with LIBTAYO. At the upcoming ESMO meeting in September, we look forward to presenting longer term follow up on the metastatic melanoma cohorts for our first in-human study. Responses have continued to deepen with the proportion of complete responders and median progression-free survival continuing to improve. These results strengthen our view that FIANLIMAB and LIBTAYO may be the most promising immunotherapy combination in clinical development. As we recently announced, we are looking forward to the Phase III readout in this melanoma setting next year, which could position FIANLIMAB and LIBTAYO as a new standard of care in melanoma and eventually, potentially, other cancer settings. Dose Expansion Cohorts Testing EGFR by CD28 plus Liftyl continue to enroll in various solid tumors, including non-small cell lung cancer with or without EGFR mutations, micro-satellite stable colorectal cancer, head and neck squamous cell carcinoma, and, On to our PSMA by CD28 co-stimulatory bispecific, which has already demonstrated promising activity in late-line prostate cancer when We have now initiated combination treatment of our PSMA by CD28 co-stim bispecific with our PSMA by CD3 bispecific. Developing limosultamib in earlier-aligned myeloma settings presents an important opportunity for us to help patients and their physicians in these diseases, which currently have complex treatment paradigms.

George: At the ASCO conference, we presented results for our EGFR by CD28 bispecific in combination with Leptio.

George: In microsatellite-stable colorectal cancer, a tumor historically unresponsive to immunotherapy, EGFR by CD28 in combination with Liptio demonstrated encouraging anti-tumor activity, with an overall response rate of 20% in patients without liver metastases.

George: Regarding safety, to date, we have not observed severe immune-related adverse events with this agent at our recommended phase 2 dose.

George D. Yancopoulos: Dose Expansion Cohorts Testing EGFR by CD28 plus Liftyl continue to enroll in various solid tumors, including non-small cell lung cancer with or without EGFR mutations, micro-satellite stable colorectal cancer, head and neck squamous cell carcinoma, and, On to our PSMA by CD28 co-stimulatory bispecific, which has already demonstrated promising activity in late-line prostate cancer when We have now initiated combination treatment of our PSMA by CD28 co-stim bispecific with our PSMA by CD3 bispecific. Developing limosultamib in earlier-aligned myeloma settings presents an important opportunity for us to help patients and their physicians in these diseases, which currently have complex treatment paradigms.

George: Dose Expansion Cohorts testing EGFR by CD28 plus Liptio continue to enroll in various solid tumors including non-small cell lung cancer with or without EGFR mutations, microsatellite stable colorectal cancer,

George Yancopoulos: As we recently announced, we are looking forward to the Phase III readout in this melanoma setting next year, which could position FIANLIMAB and LIBTAYO as a new standard of care in melanoma and eventually, potentially, other cancer settings. Additionally, we hope to gain insights into the anti-tumor activity of this combination in non-small cell lung cancer later this year. We're also advancing FIANLIMAB development to earlier lines of therapy, with proof of concepts in perioperative non-small cell lung cancer and perioperative melanoma now underway, with additional indications likely to follow.

George: head and neck, squamous cell carcinoma, and others.

George: which based on preclinical studies may maintain the efficacy of CERV with a leptile combination that may improve the safety and tolerability profile. We're also testing PSMA by C28 in other cancers.

George Yancopoulos: Additionally, we hope to gain insights into the anti-tumor activity of this combination in non-small cell lung cancer later this year. We're also advancing FIANLIMAB development to earlier lines of therapy, with proof of concepts in perioperative non-small cell lung cancer and perioperative melanoma now underway, with additional indications likely to follow. On to bispecifics with solid tumors. Our costimulatory bispecific antibodies are being tested in numerous studies, including as monotherapies as well as in combination with CD3 bispecifics and with LIBTAYO. At the ASCO Conference, we presented the results for our EGFRxCD20 bispecific in combination with LIBTAYO in microsatellite stable colorectal cancer, tumor historically unresponsive to immunotherapy, EGFRxCD20 in combination with LIBTAYO demonstrated encouraging anti-tumor activity with an overall response rate of 20% in patients without liver metastases. Regarding safety, to date, we have not observed severe immuno-related adverse events with this agent in our recommended Phase II dose. Dose expansion cohorts testing EGFRxCD20 plus LIBTAYO continue to enroll in various solid tumors, including non-small cell lung cancer with or without EGFR mutations, microsatellite stable colorectal cancer, head and neck squamous cell carcinoma and others. On to our PSMAxCD28 costimulatory bispecific, which has already demonstrated promising activity in late-line prostate cancer when combined with LIBTAYO. We have now initiated combination treatment of our PSMAxCD28 costim bispecific with our PSMAxCD3 bispecific, which based on pre-clinical studies, may maintain efficacy observed with the LIBTAYO combination but may improve the safety and tolerability profile. We're also testing PSMAxCD28 in other cancers. Next, to our bispecifics for hematology/oncology. LINVOSELTAMAB, our BCMAxCD3 bispecific, at an oral presentation at the European Hematologic Association Conference, we presented updated pivotal data which continued to demonstrate a potentially best-in-class profile in late-line myeloma, in terms of efficacy, safety, dosing as well as hospitalization burden. As we expected, responses continued to deepen with longer follow up. At 14-month median follow up of 117 patients, 50% achieved a complete response or better within objective overall response rate of 71%. Additional studies of LINVOSELTAMAB are now also underway in earlier stages of myeloma and in precursor conditions such as smoldering myeloma and monoclonal gammopathy of undetermined significance or MGUS. Developing LINVOSELTAMAB in earlier-line myeloma settings presents an important opportunity for us to help patients and their physicians in these diseases, which currently have complex treatment paradigms.

George Yancopoulos: On to bispecifics with solid tumors. Our costimulatory bispecific antibodies are being tested in numerous studies, including as monotherapies as well as in combination with CD3 bispecifics and with LIBTAYO. At the ASCO Conference, we presented the results for our EGFRxCD20 bispecific in combination with LIBTAYO in microsatellite stable colorectal cancer, tumor historically unresponsive to immunotherapy, EGFRxCD20 in combination with LIBTAYO demonstrated encouraging anti-tumor activity with an overall response rate of 20% in patients without liver metastases. Regarding safety, to date, we have not observed severe immuno-related adverse events with this agent in our recommended Phase II dose. Dose expansion cohorts testing EGFRxCD20 plus LIBTAYO continue to enroll in various solid tumors, including non-small cell lung cancer with or without EGFR mutations, microsatellite stable colorectal cancer, head and neck squamous cell carcinoma and others.

George: We presented updated pivotal data which continue to demonstrate a potentially best-in-class profile in late-line myeloma in terms of efficacy, safety, dosing, as well as hospitalization burden. As we expected, responses continued to deepen with longer follow-up.

George Yancopoulos: At the ASCO Conference, we presented the results for our EGFRxCD20 bispecific in combination with LIBTAYO in microsatellite stable colorectal cancer, tumor historically unresponsive to immunotherapy, EGFRxCD20 in combination with LIBTAYO demonstrated encouraging anti-tumor activity with an overall response rate of 20% in patients without liver metastases. Regarding safety, to date, we have not observed severe immuno-related adverse events with this agent in our recommended Phase II dose. Dose expansion cohorts testing EGFRxCD20 plus LIBTAYO continue to enroll in various solid tumors, including non-small cell lung cancer with or without EGFR mutations, microsatellite stable colorectal cancer, head and neck squamous cell carcinoma and others. On to our PSMAxCD28 costimulatory bispecific, which has already demonstrated promising activity in late-line prostate cancer when combined with LIBTAYO. We have now initiated combination treatment of our PSMAxCD28 costim bispecific with our PSMAxCD3 bispecific, which based on pre-clinical studies, may maintain efficacy observed with the LIBTAYO combination but may improve the safety and tolerability profile. We're also testing PSMAxCD28 in other cancers. Next, to our bispecifics for hematology/oncology. LINVOSELTAMAB, our BCMAxCD3 bispecific, at an oral presentation at the European Hematologic Association Conference, we presented updated pivotal data which continued to demonstrate a potentially best-in-class profile in late-line myeloma, in terms of efficacy, safety, dosing as well as hospitalization burden. As we expected, responses continued to deepen with longer follow up. At 14-month median follow up of 117 patients, 50% achieved a complete response or better within objective overall response rate of 71%. Additional studies of LINVOSELTAMAB are now also underway in earlier stages of myeloma and in precursor conditions such as smoldering myeloma and monoclonal gammopathy of undetermined significance or MGUS. Developing LINVOSELTAMAB in earlier-line myeloma settings presents an important opportunity for us to help patients and their physicians in these diseases, which currently have complex treatment paradigms.

George Yancopoulos: the ASCO Conference, we presented the results for our EGFRxCD20 bispecific in combination with LIBTAYO in microsatellite stable colorectal cancer, tumor historically unresponsive to immunotherapy, EGFRxCD20 in combination with LIBTAYO demonstrated encouraging anti-tumor activity with an overall response rate of 20% in patients without liver metastases. Regarding safety, to date, we have not observed severe immuno-related adverse events with this agent in our recommended Phase II dose. Dose expansion cohorts testing EGFRxCD20 plus LIBTAYO continue to enroll in various solid tumors, including non-small cell lung cancer with or without EGFR mutations, microsatellite stable colorectal cancer, head and neck squamous cell carcinoma and others. On to our PSMAxCD28 costimulatory bispecific, which has already demonstrated promising activity in late-line prostate cancer when combined with LIBTAYO. We have now initiated combination treatment of our PSMAxCD28 costim bispecific with our PSMAxCD3 bispecific, which based on pre-clinical studies, may maintain efficacy observed with the LIBTAYO combination but may improve the safety and tolerability profile. We're also testing PSMAxCD28 in other cancers. Next, to our bispecifics for hematology/oncology. LINVOSELTAMAB, our BCMAxCD3 bispecific, at an oral presentation at the European Hematologic Association Conference, we presented updated pivotal data which continued to demonstrate a potentially best-in-class profile in late-line myeloma, in terms of efficacy, safety, dosing as well as hospitalization burden. As we expected, responses continued to deepen with longer follow up. At 14-month median follow up of 117 patients, 50% achieved a complete response or better within objective overall response rate of 71%. Additional studies of LINVOSELTAMAB are now also underway in earlier stages of myeloma and in precursor conditions such as smoldering myeloma and monoclonal gammopathy of undetermined significance or MGUS. Developing LINVOSELTAMAB in earlier-line myeloma settings presents an important opportunity for us to help patients and their physicians in these diseases, which currently have complex treatment paradigms.

George Yancopoulos: Regarding safety, to date, we have not observed severe immuno-related adverse events with this agent in our recommended Phase II dose. Dose expansion cohorts testing EGFRxCD20 plus LIBTAYO continue to enroll in various solid tumors, including non-small cell lung cancer with or without EGFR mutations, microsatellite stable colorectal cancer, head and neck squamous cell carcinoma and others.

George: Additional studies of limosultamib are now also underway in earlier stages of myeloma and in precursor conditions, such as smoldering myeloma and monoclonal gammopathy of unknown significance, or MGUS.

George Yancopoulos: On to our PSMAxCD28 costimulatory bispecific, which has already demonstrated promising activity in late-line prostate cancer when combined with LIBTAYO. We have now initiated combination treatment of our PSMAxCD28 costim bispecific with our PSMAxCD3 bispecific, which based on pre-clinical studies, may maintain efficacy observed with the LIBTAYO combination but may improve the safety and tolerability profile. We're also testing PSMAxCD28 in other cancers. Next, to our bispecifics for hematology/oncology. LINVOSELTAMAB, our BCMAxCD3 bispecific, at an oral presentation at the European Hematologic Association Conference, we presented updated pivotal data which continued to demonstrate a potentially best-in-class profile in late-line myeloma, in terms of efficacy, safety, dosing as well as hospitalization burden. As we expected, responses continued to deepen with longer follow up. At 14-month median follow up of 117 patients, 50% achieved a complete response or better within objective overall response rate of 71%. Additional studies of LINVOSELTAMAB are now also underway in earlier stages of myeloma and in precursor conditions such as smoldering myeloma and monoclonal gammopathy of undetermined significance or MGUS. Developing LINVOSELTAMAB in earlier-line myeloma settings presents an important opportunity for us to help patients and their physicians in these diseases, which currently have complex treatment paradigms.

George Yancopoulos: LINVOSELTAMAB, our BCMAxCD3 bispecific, at an oral presentation at the European Hematologic Association Conference, we presented updated pivotal data which continued to demonstrate a potentially best-in-class profile in late-line myeloma, in terms of efficacy, safety, dosing as well as hospitalization burden. As we expected, responses continued to deepen with longer follow up. At 14-month median follow up of 117 patients, 50% achieved a complete response or better within objective overall response rate of 71%. Additional studies of LINVOSELTAMAB are now also underway in earlier stages of myeloma and in precursor conditions such as smoldering myeloma and monoclonal gammopathy of undetermined significance or MGUS. Developing LINVOSELTAMAB in earlier-line myeloma settings presents an important opportunity for us to help patients and their physicians in these diseases, which currently have complex treatment paradigms.

George: Touching on our non-oncology hematology pipeline, as highlighted previously, later this year we are anticipating proof-of-concept results for our two factor XI antibodies in the setting of prevention of venous thromboembolism after knee replacement surgery.

George Yancopoulos: Additional studies of LINVOSELTAMAB are now also underway in earlier stages of myeloma and in precursor conditions such as smoldering myeloma and monoclonal gammopathy of undetermined significance or MGUS. Developing LINVOSELTAMAB in earlier-line myeloma settings presents an important opportunity for us to help patients and their physicians in these diseases, which currently have complex treatment paradigms. Touching on our non-oncology/hematology We have also started an additional proof of concept study to further evaluate the two antibodies' profile for thrombosis prevention in patients who have a peripherally inserted catheter. As has been widely reported, Assuming a reasonable pace of enrollment, we continue to expect to report top-line results, including changes in body weight, fat mass, and muscle mass, by the second half of 2025. I will conclude with our genetics, medicines, and efforts. At the ASGCT conference, we presented updated data from our dbOto gene therapy program for genetic hearing loss due to mutations of the autoferrolin gene.

George: The study for the antibody targeting the Factor XI A2 domain is now fully enrolled and we expect to present results at a medical meeting in the second half of this year. Interim Phase II results for our second Factor XI antibody, which targets the catalytic domain, are expected by the end of this year for internal analysis.

George D. Yancopoulos: We have also started an additional proof of concept study to further evaluate the two antibodies' profile for thrombosis prevention in patients who have a peripherally inserted catheter. As has been widely reported, Assuming a reasonable pace of enrollment, we continue to expect to report top-line results, including changes in body weight, fat mass, and muscle mass, by the second half of 2025. I will conclude with our genetics, medicines, and efforts. At the ASGCT conference, we presented updated data from our dbOto gene therapy program for genetic hearing loss due to mutations of the autoferrolin gene.

George: We have also started an additional proof-of-concept study to further evaluate the two antibodies profiled for thrombosis prevention in patients who have a peripherally inserted catheter. Results of these studies will inform whether to proceed to registrational studies with one or both of these antibodies by next year.

Speaker Change: Moving to obesity. Our most advanced approach is designed to address the potential negative consequences of widespread use of GLP and GIP receptor agonists.

George Yancopoulos: Touching on our non-oncology/hematology We have also started an additional proof of concept study to further evaluate the two antibodies' profile for thrombosis prevention in patients who have a peripherally inserted catheter. As has been widely reported, Assuming a reasonable pace of enrollment, we continue to expect to report top-line results, including changes in body weight, fat mass, and muscle mass, by the second half of 2025. I will conclude with our genetics, medicines, and efforts. At the ASGCT conference, we presented updated data from our dbOto gene therapy program for genetic hearing loss due to mutations of the autoferrolin gene.

George Yancopoulos: Touching on our non-oncology/hematology pipeline. As highlighted previously, later this year, we are anticipating proof of concept results for our two Factor XI antibodies in the setting of prevention of venous thromboembolism after knee replacement surgery. The study for the antibody which targets the Factor XI A2 domain is now fully enrolled and we expect to present results at a medical meeting in the second half of this year. Interim Phase II results for our second Factor XI antibody, which targets the catalytic domain are expected by the end of this year for internal analysis. We have also started an additional proof of concept study to further evaluate the two antibodies' profile for thrombosis prevention in patients who have a peripherally inserted catheter. As has been widely reported, Assuming a reasonable pace of enrollment, we continue to expect to report top-line results, including changes in body weight, fat mass, and muscle mass, by the second half of 2025. I will conclude with our genetics, medicines, and efforts. At the ASGCT conference, we presented updated data from our dbOto gene therapy program for genetic hearing loss due to mutations of the autoferrolin gene.

George Yancopoulos: Touching on our non-oncology/hematology pipeline. As highlighted previously, later this year, we are anticipating proof of concept results for our two Factor XI antibodies in the setting of prevention of venous thromboembolism after knee replacement surgery. The study for the antibody which targets the Factor XI A2 domain is now fully enrolled and we expect to present results at a medical meeting in the second half of this year. Interim Phase II results for our second Factor XI antibody, which targets the catalytic domain are expected by the end of this year for internal analysis. We have also started an additional proof of concept study to further evaluate the two antibodies' profile for thrombosis prevention in patients who have a peripherally-inserted catheter. Results of these studies will inform whether to proceed to registrational studies with one or both of these antibodies by next year.

George Yancopoulos: We have also started an additional proof of concept study to further evaluate the two antibodies' profile for thrombosis prevention in patients who have a peripherally inserted catheter. As has been widely reported, Assuming a reasonable pace of enrollment, we continue to expect to report top-line results, including changes in body weight, fat mass, and muscle mass, by the second half of 2025. I will conclude with our genetics, medicines, and efforts. At the ASGCT conference, we presented updated data from our dbOto gene therapy program for genetic hearing loss due to mutations of the autoferrolin gene.

Speaker Change: As has been widely reported,

Speaker Change: Our myostatin antibody, when combined with some of the glutide with or without our activin A antibody, may protect against this muscle loss, as previously demonstrated in non-human primates.

George Yancopoulos: Interim Phase II results for our second Factor XI antibody, which targets the catalytic domain are expected by the end of this year for internal analysis. We have also started an additional proof of concept study to further evaluate the two antibodies' profile for thrombosis prevention in patients who have a peripherally-inserted catheter. Results of these studies will inform whether to proceed to registrational studies with one or both of these antibodies by next year.

Speaker Change: Part A of our COURAGE Phase 2 study testing a higher dose of trevoglumab or myostatin body in healthy subjects has now been successfully completed with no new safety signals identified.

George Yancopoulos: We have also started an additional proof of concept study to further evaluate the two antibodies' profile for thrombosis prevention in patients who have a peripherally-inserted catheter. Results of these studies will inform whether to proceed to registrational studies with one or both of these antibodies by next year. Moving to obesity. As has been widely reported, Assuming a reasonable pace of enrollment, we continue to expect to report top-line results, including changes in body weight, fat mass, and muscle mass, by the second half of 2025. I will conclude with our genetics, medicines, and efforts. At the ASGCT conference, we presented updated data from our dbOto gene therapy program for genetic hearing loss due to mutations of the autoferrolin gene.

Speaker Change: Part B of the study, which evaluates our muscle preservation and bias in combination with some of the glutide in obese participants, has started enrolling patients.

George Yancopoulos: Moving to obesity. Our most advanced approach is designed to address the potential negative consequences of widespread use of GLP and GLP receptor agonists. As has been widely reported, the profound weight loss caused by these agents unfortunately can also result in substantial loss of muscle, which is particularly concerning in older obese patients. Our myostatin antibody, when combined with semaglutide--with or without our anti-activin A antibody--may protect against this muscle loss, as previously demonstrated in non-human primates. Part A of our COURAGE Phase II study testing a higher dose of TREVOGRUMAB, our myostatin antibody, in healthy subjects has now been successfully completed with now new safety signals identified. Part B of the study, which evaluates our muscle preservation antibodies in combination with semaglutide in obese participants has started enrolling patients. Assuming a reasonable pace of enrollment, we continue to expect to report top-line results, including changes in body weight, fat mass and muscle mass, by the second half of 2025. I will conclude with our genetics medicines efforts. At the ASGCT conference, we presented updated data from our DB-OTO gene therapy program for genetic hearing loss due to mutations of the otoferlin gene.

Speaker Change: Assuming a reasonable pace of enrollment, we continue to expect to report top-line results, including changes in body weight, fat mass, and muscle mass, by the second half of 2025.

George Yancopoulos: Part A of our COURAGE Phase II study testing a higher dose of TREVOGRUMAB, our myostatin antibody, in healthy subjects has now been successfully completed with now new safety signals identified. Part B of the study, which evaluates our muscle preservation antibodies in combination with semaglutide in obese participants has started enrolling patients. Assuming a reasonable pace of enrollment, we continue to expect to report top-line results, including changes in body weight, fat mass and muscle mass, by the second half of 2025.

Speaker Change: I will conclude with our genetics medicine efforts.

Speaker Change: At the ASGCT conference, we presented updated data from our dbAuto gene therapy program for genetic hearing loss due to mutations of the autoferrulin gene.

George Yancopoulos: I will conclude with our genetics medicines efforts. At the ASGCT conference, we presented updated data from our DB-OTO gene therapy program for genetic hearing loss due to mutations of the otoferlin gene. The first child treated with this therapy, an 11-month old girl who was profoundly deaf at baseline, had hearing in the normal range by 24 weeks after treatment. Also, initial hearing improvements were observed in a second child, dosed at 4 years of age at a six-week of assessment, with additional follow up plan. As of July, we have dosed five patients in our study and we are on track to enroll several patients more this year. We also look forward to bringing additional otoferlin gene therapy programs to the clinic in the coming years, with the potential to address more common forms of monogenic hearing loss. Regarding our Intellia collaboration, transthyretin amyloidosis with cardiomyopathy--the world's first Phase III program for an in vivo CRISPR-based therapy--is enrolling in a rapid pace, indicating considerable interest from investigators and patients. In addition, we are also on track to be the first to use CRISPR technology to insert a corrective gene, in vivo, for a deficiency disease. Our siRNA collaboration with El Nylon has not only demonstrated successful silencing of genes in the liver but also for the first time for siRNA in the brain. This opens up opportunities for us to go after other disease-causing genes in the brain. A study of ALN, SOD, and ALS patients with SOD1 mutations has recently been initiated.

George D. Yancopoulos: The first child treated with this therapy, an 11-month-old girl who was profoundly deaf at baseline, had hearing in the normal range by 24 weeks after treatment. Additionally, initial hearing improvements were observed in a second child. Our siRNA collaboration with El Nylon has not only demonstrated successful silencing of genes in the liver but also for the first time for siRNA in the brain. This opens up opportunities for us to go after other disease-causing genes in the brain. A study of ALN, SOD, and ALS patients with SOD1 mutations has recently been initiated.

Speaker Change: The first child treated with this therapy, an 11-month-old girl who was profoundly deaf at baseline, had hearing in the normal range by 24 weeks after treatment. Also, initial hearing improvements were observed in a second child.

Speaker Change: Dosed at four years of age at a six-week assessment with additional follow-up plan. As of July , we have dosed five patients in our study and we are on track to enroll several more patients this year.

George Yancopoulos: As of July, we have dosed five patients in our study and we are on track to enroll several patients more this year. We also look forward to bringing additional otoferlin gene therapy programs to the clinic in the coming years, with the potential to address more common forms of monogenic hearing loss. Regarding our Intellia collaboration, transthyretin amyloidosis with cardiomyopathy--the world's first Phase III program for an in vivo CRISPR-based therapy--is enrolling in a rapid pace, indicating considerable interest from investigators and patients. In addition, we are also on track to be the first to use CRISPR technology to insert a corrective gene, in vivo, for a deficiency disease. Our siRNA collaboration with El Nylon has not only demonstrated successful silencing of genes in the liver but also for the first time for siRNA in the brain. This opens up opportunities for us to go after other disease-causing genes in the brain. A study of ALN, SOD, and ALS patients with SOD1 mutations has recently been initiated.

Speaker Change: We also look forward to bringing additional auditory gene therapy programs to the clinic in the coming years with the potential to address more common forms of monogenic hearing loss.

Speaker Change: Regarding our Intellia collaboration, trans-thalritin amyloidosis with cardiomyopathy.

Speaker Change: The world's first Phase III program for an in vivo CRISPR-based therapy is enrolling at a rapid pace, indicating considerable interest from investigators and patients.

George Yancopoulos: Regarding our Intellia collaboration, transthyretin amyloidosis with cardiomyopathy--the world's first Phase III program for an in vivo CRISPR-based therapy--is enrolling in a rapid pace, indicating considerable interest from investigators and patients. In addition, we are also on track to be the first to use CRISPR technology to insert a corrective gene, in vivo, for a deficiency disease--hemophilia B. As noted previously, we've enrolled initial patients in lead-in portion of this trial and first patient should be dosed soon. Our siRNA collaboration with Alnylam has not only demonstrated successful silencing of genes in the liver but also, for the first time, for siRNA in the brain. This opens up opportunities for us to go after other disease-causing genes in the brain. A study of ALN-SOD in ALS patients with SOD1 mutations recently initiated.

Speaker Change: In addition, we are also on track to be the first to use CRISPR technology to insert a corrective gene in vivo for a deficiency disease

Speaker Change: Hemophilia B. As noted previously, we have enrolled initial patients in the leading portion of this trial and first patients should be dosed soon.

George Yancopoulos: Our siRNA collaboration with Alnylam has not only demonstrated successful silencing of genes in the liver but also, for the first time, for siRNA in the brain. This opens up opportunities for us to go after other disease-causing genes in the brain. A study of ALN-SOD in ALS patients with SOD1 mutations recently initiated. Other CNS direct to siRNA programs are expected to enter the clinic shortly, including targeting HTT for Huntington's disease, synuclein for Parkinson's and tau for Alzheimer's and other neurodegenerative diseases. Additionally, with regard to our C5 program, our innovative approach involving the first combination of an antibody together with an siRNA, both targeting the same molecule, is progressing well and we are expecting to present updated data for our initial potential indication, paroxysmal nocturnal hemoglobinuria, by the end of this year. We are also looking forward to starting our Phase III program in geographic atrophy in the second half of this year. In summary, we will continue to drive forward our innovative development pipeline and anticipate reading out several pivotal and proof of concept data sets over the next 12 to 18 months. Our early research efforts continue to be productive, with multiple novel programs potentially advancing to the clinic over that same time frame. And with that, I will turn the call over to Marion. Thank you The number of physician offices ordering ILEA-HD during the second quarter increased by more than 50% compared to the prior quarter.

Speaker Change: Our siRNA collaboration with Elnilam has not only demonstrated successful silencing of genes in the liver, but also for the first time, for siRNA in the brain. This opens up opportunities for us to go after other disease-causing genes in the brain.

Unknown Executive: Other CNS-directed siRNA programs are expected to enter the clinic shortly, including targeting HTT for Huntington's disease, Sinuclein for Parkinson's, and Tau for Alzheimer's and other neurodegenerative diseases. Additionally, with regard to our C5 program, our innovative approach involving the first combination of an antibody together with an sRNA, both targeting the same molecule, is progressing well, and we are expecting to present updated data for our initial potential indication, paroxysmal nocturnal hemoglobinuria, by the end of this year.

Speaker Change: Other CNS-directed siRNA programs are expected to enter the clinic shortly, including targeting HTT for Huntington's disease, Sinuclein for Parkinson's, and Tau for Alzheimer's and other neurodegenerative diseases.

Speaker Change: Additionally, with regard to our C5 program, our innovative approach involving the first combination of an antibody together with an sRNA, both targeting the same molecule,

Speaker Change: is progressing well, and we are expecting to present updated data for our initial potential indication, paroxysmal nocturnal hemoglobinuria, by the end of this year. We're also looking forward...

Unknown Executive: We are also looking forward to, In summary, we continue to drive forward our innovative development pipeline and anticipate reading out several pivotal and proof-of-concept data sets over the next 12 to 18 months. Our early research efforts continue to be productive, with multiple novel programs potentially advancing to the clinic over that same time. The number of physician offices ordering ILEA-HD during the second quarter increased by more than 50% compared to the prior quarter.

Speaker Change: In summary, we continue to drive forward our innovative development pipeline and anticipate reading out several pivotal and proof-of-concept data sets over the next 12 to 18 months. Our early research efforts continue to be productive, with multiple novel programs potentially advancing to the clinic over that same time frame.

George Yancopoulos: Additionally, with regard to our C5 program, our innovative approach involving the first combination of an antibody together with an siRNA, both targeting the same molecule, is progressing well and we are expecting to present updated data for our initial potential indication, paroxysmal nocturnal hemoglobinuria, by the end of this year. We are also looking forward to starting our Phase III program in geographic atrophy in the second half of this year. In summary, we will continue to drive forward our innovative development pipeline and anticipate reading out several pivotal and proof of concept data sets over the next 12 to 18 months. Our early research efforts continue to be productive, with multiple novel programs potentially advancing to the clinic over that same time frame.

Speaker Change: Thank you, George. Our second quarter commercial results further solidify Regeneron's leadership across therapeutic categories.

Speaker Change: Our performance demonstrates the ongoing strength and diversity of our product portfolio, with continued growth opportunities powered by existing and upcoming product and indication launches across multiple geographies.

Speaker Change: I'll start with ILEA HD and ILEA in the U.S.

Speaker Change: ILEA HD continued its launch momentum in the second quarter, delivering net product sales of $304 million, which represents 52% sequential growth.

Speaker Change: The breadth and depth of ILEA HD prescribing continues to grow with utilization across a broad range of patients, including the treatment-naive population, which has doubled since last quarter.

Speaker Change: Physicians are also increasingly switching patients to ILEA-HD from other anti-VEGF treatments based on their positive early treatment experiences.

Speaker Change: In these switch patients, early real-world data indicate that treatment intervals are being extended with ILEA-HD.

George Yancopoulos: And with that, I will turn the call over to Marion.

Speaker Change: The number of physician offices ordering ILEA-HD during the second quarter increased by more than 50% compared to the prior quarter. We believe this suggests prescriber confidence in ILEA-HD's clinical profile, as well as in reimbursement now that the permanent J code has been well established.

Marion McCourt: Thank you, George. Our The number of physician offices ordering ILEA-HD during the second quarter increased by more than 50% compared to the prior quarter.

Marion McCourt: Thank you, George. Our second quarter commercial results further solidify Regeneron's leadership across therapeutic categories. Our performance demonstrates the ongoing strength and diversity of our product portfolio, with continued growth opportunities powered by existing and upcoming product in indication launches across multiple geographies. I'll start with EYLEA HD and EYLEA in the U.S. In the second quarter, combined net sales for both medicines grew 2.3% year-over-year to $1.53 billion. EYLEA continues its clear category leadership while EYLEA HD remained the fastest-growing medicine in this highly competitive category. EYLEA HD continued its launch momentum in the second quarter, delivering net product sales of $304 million, which represents 52% sequential growth. EYLEA HD continues to be the fastest launch of any anti-VEGF therapy since EYLEA more than a decade ago and the trajectory confirms a significant transition to EYLEA HD is underway. The breadth and depth of EYLEA HD prescribing continues to grow with utilization across a broad range of patients, including the treatment-naive population--which has doubled since last quarter. Physicians are also increasingly switching patients to EYLEA HD from other anti-VEGF treatments based on their positive early treatment experiences. In these switch patients, early real-world data indicate that treatment intervals are being extended with EYLEA HD. EYLEA HD's durability along with the same trusted efficacy, visual acuity and safety as EYLEA representing meaningful improvement for patient lives in greater efficiency for physician practices.

Marion McCourt: EYLEA continues its clear category leadership while EYLEA HD remained the fastest-growing medicine in this highly competitive category. EYLEA HD continued its launch momentum in the second quarter, delivering net product sales of $304 million, which represents 52% sequential growth. EYLEA HD continues to be the fastest launch of any anti-VEGF therapy since EYLEA more than a decade ago and the trajectory confirms a significant transition to EYLEA HD is underway. The breadth and depth of EYLEA HD prescribing continues to grow with utilization across a broad range of patients, including the treatment-naive population--which has doubled since last quarter. Physicians are also increasingly switching patients to EYLEA HD from other anti-VEGF treatments based on their positive early treatment experiences. In these switch patients, early real-world data indicate that treatment intervals are being extended with EYLEA HD. EYLEA HD's durability along with the same trusted efficacy, visual acuity and safety as EYLEA representing meaningful improvement for patient lives in greater efficiency for physician practices.

Marion McCourt: Physicians are also increasingly switching patients to EYLEA HD from other anti-VEGF treatments based on their positive early treatment experiences. In these switch patients, early real-world data indicate that treatment intervals are being extended with EYLEA HD. EYLEA HD's durability, along with the same trusted efficacy, visual acuity and safety as EYLEA, represents a meaningful improvement for patient lives in greater efficiency for physician practices. The number of physician offices ordering EYLEA HD during the second quarter increased by more than 50% compared to the prior quarter. We believe this suggests prescriber confidence in EYLEA HD's clinical profile, as well as in reimbursement now that the permanent J-code has been well-established. Of note, we recognize the importance of providing physicians with a pre-filled syringe option, and as Len mentioned, we're excited about our anticipated EYLEA HD prefilled syringe launch. In summary, we're pleased with our second quarter performance for EYLEA HD and EYLEA and remain on track to achieve our goal of establishing EYLEA HD as the new standard of care for retinal disease.

Marion McCourt: The number of physician offices ordering ILEA-HD during the second quarter increased by more than 50% compared to the prior quarter.

Marion McCourt: We believe this suggests prescriber confidence in EYLEA HD's clinical profile, as well as in reimbursement now that the permanent J-code has been well-established. Of note, we recognize the importance of providing physicians with a pre-filled syringe option, and as Len mentioned, we're excited about our anticipated EYLEA HD prefilled syringe launch. In summary, we're pleased with our second quarter performance for EYLEA HD and EYLEA and remain on track to achieve our goal of establishing EYLEA HD as the new standard of care for retinal disease. Next to Dupixent, which delivered 29% growth in the second quarter on a constant currency basis, with global net sales of $3.56 billion, we are approaching the important milestone of 1 million patients on Dupixent worldwide. In addition, there's a substantial opportunity for even more patients to benefit from Dupixent based on significant unmet need across indications, ages, and geographies. In the U.S., net sales grew 24% to $2.61 billion, driven by increased demand across all five approved indications. Dutexin continues its number one leadership position and new-to-brand prescriptions across all approved indications. Our commercial team remains laser-focused on pursuing initiatives that drive patient awareness and support prescribing.

Unknown Executive: We believe this suggests prescriber confidence in ILEA-HD's clinical profile, as well as in reimbursement now that the permanent J code has been well established. Of note, we recognize the importance of providing physicians with a prefilled syringe option, and as Len mentioned, we're excited about our anticipated ILEA-HD prefilled syringe launch. In summary, we're pleased with our second quarter performance for ILEA-HD and ILEA and remain on track to achieve our goal of establishing ILEA-HD as the new standard of care for retinal disease.

Speaker Change: In summary, we're pleased with our second quarter performance for ILEA-HD and ILEA and remain on track to achieve our goal of establishing ILEA-HD as the new standard of care for retinal disease.

Unknown Executive: Next to Dupixent, which delivered 29% growth in the second quarter on a constant currency basis, with global net sales of $3.56 billion, we are approaching the important milestone of 1 million patients on Dupixent worldwide. In addition, there's a substantial opportunity for even more patients to benefit from Dupixent based on significant unmet need across indications, ages, and geographies. In the U.S., net sales grew 24% to $2.61 billion, driven by increased demand across all five approved indications. Dutexin continues its number one leadership position and new-to-brand prescriptions across all approved indications. Our commercial team remains laser-focused on pursuing initiatives that drive patient awareness and support prescribing.

Speaker Change: Next to Dupixent, which delivered 29% growth in the second quarter on a constant currency basis with global net sales of $3.56 billion.

Marion McCourt: Next is DUPIXENT, which delivered 29% growth in the second quarter on a constant currency basis, with global net sales of $3.56 billion. We are approaching the important milestone of 1 million patients on DUPIXENT worldwide. In addition, there's substantial opportunity for even more patients to benefit from DUPIXENT, based on significant unmet need across indications, ages and geographies. In the U.S., net sales grew 24% to $2.61 billion, driven by an increased demand across all five approved indications. DUPIXENT continues its number one leadership position and new-to-brand prescriptions across all approved indications. Our commercial team remains laser-focused on pursuing initiatives that drive patient awareness and support prescribing. We continue to see increasing penetration in our blockbuster indications of atopic dermatitis, asthma and nasal polyps. Additionally, recent launches in eosinophilic esophagitis and Praga nodularis are exceeding our expectations, and new patient initiations are steadily increasing. We hear remarkable stories of patients as young as one year of age with EOE who are now thriving on Dutexin following its approval in January of this year. As George mentioned, there are two Dupixent Phase III programs reading out later this year in Chronic Spontaneous Urticaria and Bullous Pemphigoid.

Speaker Change: 6.1 billion driven by an increased demand across all five approved indications. GPICS continues its number one leadership position.

Unknown Executive: We continue to see increasing penetration in our blockbuster indications of atopic dermatitis, asthma, and nasal polyps. Additionally, recent launches in eosinophilic esophagitis and Praga nodularis are exceeding our expectations, and new patient initiations are steadily increasing. We hear remarkable stories of patients as young as one year of age with EOE who are now thriving on Dutexin following its approval in January of this year. As George mentioned, there are two Dupixent Phase III programs reading out later this year in Chronic Spontaneous Urticaria and Bullous Pemphigoid.

Marion McCourt: DUPIXENT continues its number one leadership position and new-to-brand prescriptions across all approved indications. Our commercial team remains laser-focused on pursuing initiatives that drive patient awareness and support prescribing. We continue to see increasing penetration in our blockbuster indications of atopic dermatitis, asthma and nasal polyps. Additionally, recent launches in eosinophilic esophagitis and prurigo nodularis are exceeding our expectations and new patient initiations are steadily increasing. We hear remarkable stories of patients as young as one year of age with EoE, who are now thriving on DUPIXENT following its approval in January of this year. The European Commission also recently approved DUPIXENT in COPD patients with raised blood eosinophils, with patients already getting treatment in Germany. We all recognize that there's significant unmet need worldwide among patients with this debilitating disease and DUPIXENT represents the first biologic medicine for COPD. Our U.S. team is ready for the anticipated FDA approval of DUPIXENT in COPD by late September and estimate approximately 300,000 U.S. patients may benefit from DUPIXENT and its indications. Separately, an FDA decision for DUPIXENT in adolescents with chronic rhinosinusitis and nasal polyps is expected next month.

Speaker Change: Additionally, recent launches in eosinophilic esophagitis and Praga nodularis are exceeding our expectations, and new patient initiations are steadily increasing.

Speaker Change: We hear remarkable stories of patients as young as one year of age with EOE who are now thriving on Dupixent following its approval in January of this year.

Marion McCourt: We hear remarkable stories of patients as young as one year of age with EoE, who are now thriving on DUPIXENT following its approval in January of this year. The European Commission also recently approved DUPIXENT in COPD patients with raised blood eosinophils, with patients already getting treatment in Germany. We all recognize that there's significant unmet need worldwide among patients with this debilitating disease and DUPIXENT represents the first biologic medicine for COPD. Our U.S. team is ready for the anticipated FDA approval of DUPIXENT in COPD by late September and estimate approximately 300,000 U.S. patients may benefit from DUPIXENT and its indications. Separately, an FDA decision for DUPIXENT in adolescents with chronic rhinosinusitis and nasal polyps is expected next month. As George mentioned, there are two DUPIXENT Phase III programs reading out later this year in chronic spontaneous urticaria and bullous pemphigoid. If data from these trials are positive, DUPIXENT has the potential to support even more patients with unmet need.

Marion McCourt: We hear remarkable stories of patients as young as one year of age with EoE, who are now thriving on DUPIXENT following its approval in January of this year.

Marion McCourt: The European Commission also recently approved DUPIXENT in COPD patients with raised blood eosinophils, with patients already getting treatment in Germany. We all recognize that there's significant unmet need worldwide among patients with this debilitating disease and DUPIXENT represents the first biologic medicine for COPD. Our U.S. team is ready for the anticipated FDA approval of DUPIXENT in COPD by late September and estimate approximately 300,000 U.S. patients may benefit from DUPIXENT and its indications. Separately, an FDA decision for DUPIXENT in adolescents with chronic rhinosinusitis and nasal polyps is expected next month. As George mentioned, there are two Dupixent Phase III programs reading out later this year in Chronic Spontaneous Urticaria and Bullous Pemphigoid.

Marion McCourt: The European Commission also recently approved DUPIXENT in COPD patients with raised blood eosinophils, with patients already getting treatment in Germany. We all recognize that there's significant unmet need worldwide among patients with this debilitating disease and DUPIXENT represents the first biologic medicine for COPD. Our U.S. team is ready for the anticipated FDA approval of DUPIXENT in COPD by late September and estimate approximately 300,000 U.S. patients may benefit from DUPIXENT and its indications. Separately, an FDA decision for DUPIXENT in adolescents with chronic rhinosinusitis and nasal polyps is expected next month. As George mentioned, there are two DUPIXENT Phase III programs reading out later this year in chronic spontaneous urticaria and bullous pemphigoid. If data from these trials are positive, DUPIXENT has the potential to support even more patients with unmet need.

Speaker Change: The European Commission also recently approved a PIXEN in COPD patients.

Speaker Change: with raised blood eosinophils.

Speaker Change: with patients already getting treatment in Germany.

Marion McCourt: Separately, an FDA decision for DUPIXENT in adolescents with chronic rhinosinusitis and nasal polyps is expected next month.

Marion McCourt: As George mentioned, there are two Dupixent Phase III programs reading out later this year in Chronic Spontaneous Urticaria and Bullous Pemphigoid.

Marion McCourt: As George mentioned, there are two DUPIXENT Phase III programs reading out later this year in chronic spontaneous urticaria and bullous pemphigoid. If data from these trials are positive, DUPIXENT has the potential to support even more patients with unmet need. We also made significant progress with LIBTAYO in the second quarter, with global net sales of $297 million, up 43% year-over-year on a constant currency basis. Total revenues increased 12% year-over-year to $3.5 billion, primarily driven by strong execution of the ongoing ILEA HD launch in the U.S., reflecting a reduction of approximately $190 million from the end of the first quarter. Now to our operating results, SG&A grew 19% from the prior year.

Unknown Executive: If data from these trials are positive, Dupixent has the potential to support even more patients with unmet need. We also made significant progress with Leptio in the second quarter, with global net sales of $297 million, up 43% year-over-year on a constant currency basis. Total revenues increased 12% year-over-year to $3.5 billion, primarily driven by strong execution of the ongoing ILEA HD launch in the U.S., reflecting a reduction of approximately $190 million from the end of the first quarter. Now to our operating results, SG&A grew 19% from the prior year.

Speaker Change: with chronic rhinosadicitis and nasal polyps is expected next month.

Marion McCourt: Our U.S. team is ready for the anticipated FDA approval of DUPIXENT in COPD by late September and estimate approximately 300,000 U.S. patients may benefit from DUPIXENT and its indications. Separately, an FDA decision for DUPIXENT in adolescents with chronic rhinosinusitis and nasal polyps is expected next month. As George mentioned, there are two DUPIXENT Phase III programs reading out later this year in chronic spontaneous urticaria and bullous pemphigoid. If data from these trials are positive, DUPIXENT has the potential to support even more patients with unmet need.

Speaker Change: In the U.S., net sales grew 40% to $182 million with growth across all market segments and indications.

Speaker Change: Outside the U.S., our teams are delivering excellent results with net product sales of $115 million as Regeneron continues its international expansion.

Speaker Change: Liptayo Net Product Sales in some of these international markets were favorably impacted by approximately 15 million of stocking purchases.

Speaker Change: Our Oncology team is also eagerly awaiting the potential FDA and EU decisions for Linva-Celtimab in late-stage myeloma. We believe Linva-Celtimab represents a best-in-class opportunity, and we look forward to potential launch.

Marion McCourt: We also made significant progress with LIBTAYO in the second quarter, with global net sales of $297 million, up 43% year-over-year on a constant currency basis. Strong commercial execution resulted in market share gains across both skin and lung cancers. In the U.S., net sales grew 40% to $182 million, with growth across all market segments and indications. In non-melanoma skin cancer, we continue to extend LIBTAYO leadership with increasing demand in market share. In lung cancer, LIBTAYO is recognized by physicians as an important therapy for their lung cancer patients and continues to gradually gain market share. Outside the U.S., our teams are delivering excellent results with net product sales of $115 million, as Regeneron continues its international expansion. LIBTAYO net product sales in some of these international markets were favorably impacted by approximately 15 million of stocking purchases. Our oncology team is also eagerly the potential FDA NEU decisions for LINVOSELTAMAB in late-stage myeloma. We believe LINVOSELTAMAB represent a best-in-class opportunity and we look forward to potential launch. In summary, our commercial team continues to deliver on our goal to provide Regeneron medicines to even more patients worldwide. There's meaningful growth potential within our approved indications and our robust pipeline provides both near and long-term opportunities to advance patient care. With that. I'll turn the call over to Chris. Total revenues increased 12% year-over-year to $3.5 billion, primarily driven by strong execution of the ongoing ILEA HD launch in the U.S., reflecting a reduction of approximately $190 million from the end of the first quarter. Now to our operating results, SG&A grew 19% from the prior year.

Chris: In summary, our commercial team continues to deliver on our goal to provide Regeneron medicines to even more patients worldwide. There is meaningful future growth potential within our approved indications, and our robust pipeline provides both near and long-term opportunities to advance patient care. With that, I'll turn the call over to Chris.

Chris: Total revenues increased 12% year-over-year to $3.5 billion, primarily driven by strong execution of the ongoing ILEA HD launch in the U.S., higher Sanofi collaboration revenue, and continued global sales growth from Lataio.

Speaker Change: Second quarter diluted net income per share grew 13% from the prior year to $11.56, a net income of $1.4 billion.

Marion McCourt: Outside the U.S., our teams are delivering excellent results with net product sales of $115 million, as Regeneron continues its international expansion. LIBTAYO net product sales in some of these international markets were favorably impacted by approximately 15 million of stocking purchases. Our oncology team is also eagerly the potential FDA and EU decisions for LINVOSELTAMAB in late-stage myeloma. We believe LINVOSELTAMAB represent a best-in-class opportunity and we look forward to potential launch. In summary, our commercial team continues to deliver on our goal to provide Regeneron medicines to even more patients worldwide. There's meaningful growth potential within our approved indications and our robust pipeline provides both near and long-term opportunities to advance patient care.

Speaker Change: Second quarter revenues from our Sanofi collaboration grew to $1.1 billion, primarily composed of our share of collaboration profits of $988 million, which increased by 32% compared to the prior year, driven by Dutixent's continued volume growth and improving margins.

Speaker Change: Reimbursement for manufacturing a commercial supply, the other component of Sanofi collaboration revenue, was 157 million dollars.

Speaker Change: Taking into account increased volumes offset by manufacturing efficiencies, we continue to expect reimbursement for manufacturing of commercial supply in 2024 to be comparable to 2023 on a full year basis.

Marion McCourt: In summary, our commercial team continues to deliver on our goal to provide Regeneron medicines to even more patients worldwide. There's meaningful growth potential within our approved indications and our robust pipeline provides both near and long-term opportunities to advance patient care.

Speaker Change: We continue to anticipate this balance will be fully reimbursed to Sanofi by the end of 2026.

Marion McCourt: With that. I'll turn the call over to Chris.

Speaker Change: Total buyer collaboration revenue was $375 million, of which $353 million related to our share of net profits outside the U.S.

Marion McCourt: Thank you, Marion. My comments today on Regeneron Total revenues increased 12% year-over-year to $3.5 billion, primarily driven by strong execution of the ongoing ILEA HD launch in the U.S., reflecting a reduction of approximately $190 million from the end of the first quarter. Now to our operating results, SG&A grew 19% from the prior year.

Chris Fenimore: Thank you, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis unless otherwise noted. Regeneron delivered strong double-digit top and bottom line growth in the second quarter. Total revenues increased 12% year-over-year to $3.5 billion, primarily driven by strong execution of the ongoing EYLEA HD launch in the U.S., higher Sanofi collaboration revenue and continued global sales growth from LIBTAYO. Second quarter diluted net income per share grew 13% from the prior year to $11.56 on net income of $1.4 billion. Second quarter revenues from our Sanofi collaboration grew to $1.1 billion, primarily composed of our share of collaboration profits of $988 million--which increased by 32% compared to the prior year, driven by DUPIXENT's continued volume growth and improving margins. Reimbursement from manufacturing a commercial supply, the other component of the Sanofi collaboration revenue, was $157 million. Taking into account increased volumes offset by [inaudible] efficiencies, we continue to expect reimbursement for manufacturing of commercial supplies in 2024 to be comparable to 2023 on a full year basis. The Sanofi development balance is approximately $2 billion at the end of the second quarter, reflecting a reduction of approximately $190 million from the end of the first quarter. We continue to anticipate this balance will be fully reimbursed to Sanofi by the end of 2026. Moving to Now to our operating results, SG&A grew 19% from the prior year.

Chris Fenimore: Thank you, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis unless otherwise noted.

Chris Fenimore: Regeneron delivered strong double-digit top and bottom line growth in the second quarter. Total revenues increased 12% year-over-year to $3.5 billion, primarily driven by strong execution of the ongoing EYLEA HD launch in the U.S., higher Sanofi collaboration revenue and continued global sales growth from LIBTAYO. Second quarter diluted net income per share grew 13% from the prior year to $11.56 on net income of $1.4 billion. Second quarter revenues from our Sanofi collaboration grew to $1.1 billion, primarily composed of our share of collaboration profits of $988 million--which increased by 32% compared to the prior year, driven by DUPIXENT's continued volume growth and improving margins.

Marion McCourt: Total revenues increased 12% year-over-year to $3.5 billion, primarily driven by strong execution of the ongoing ILEA HD launch in the U.S., reflecting a reduction of approximately $190 million from the end of the first quarter. Now to our operating results, SG&A grew 19% from the prior year.

Speaker Change: Now, to our operating expenses.

Speaker Change: Second quarter R&D expense grew 10% year-over-year to $1.1 billion, reflecting continued investments to support our road-bus pipeline, including late-stage oncology and hematology programs.

Chris Fenimore: Second quarter revenues from our Sanofi collaboration grew to $1.1 billion, primarily composed of our share of collaboration profits of $988 million--which increased by 32% compared to the prior year, driven by DUPIXENT's continued volume growth and improving margins. Reimbursement from manufacturing a commercial supply, the other component of the Sanofi collaboration revenue, was $157 million. Taking into account increased volumes offset by [inaudible] efficiencies, we continue to expect reimbursement for manufacturing of commercial supplies in 2024 to be comparable to 2023 on a full year basis. The Sanofi development balance is approximately $2 billion at the end of the second quarter, reflecting a reduction of approximately $190 million from the end of the first quarter. We continue to anticipate this balance will be fully reimbursed to Sanofi by the end of 2026. Moving to Now to our operating results, SG&A grew 19% from the prior year.

Chris Fenimore: Reimbursement from manufacturing a commercial supply, the other component of the Sanofi collaboration revenue, was $157 million. Taking into account increased volumes offset by manufacturing efficiencies, we continue to expect reimbursement for manufacturing of commercial supply in 2024 to be comparable to 2023 on a full year basis. The Sanofi development balance was approximately $2 billion at the end of the second quarter, reflecting a reduction of approximately $190 million from the end of the first quarter. We continue to anticipate this balance will be fully reimbursed to Sanofi by the end of 2026.

Speaker Change: We continue to make thoughtful investments to enable us to move quickly into Phase 3 programs if supported by data readouts anticipated over the next 12 to 18 months.

Chris Fenimore: The Sanofi development balance is approximately $2 billion at the end of the second quarter, reflecting a reduction of approximately $190 million from the end of the first quarter. We continue to anticipate this balance will be fully reimbursed to Sanofi by the end of 2026. Moving to Now to our operating results, SG&A grew 19% from the prior year.

Chris Fenimore: Moving to Bayer. Second quarter ex-U.S. net sales of EYLEA and EYLEA 8mg were $908 million, up 8% on a constant currency basis versus the prior year. Total Bayer collaboration revenue was $375 million, of which $353 million related to our share of net profits outside the U.S. Now, to our operating expenses, Second quarter R&D expense grew 10% year-over-year to $1.1 billion, reflecting continued investments to support our robust pipeline, including late-stage oncology and hematology programs. We continue to make thoughtful investments to enable us to move quickly into Phase III programs if supported by data readouts anticipated over the next 12 to 18 months.

Chris Fenimore: SG&A grew 19% from the prior year to $666 million in the second quarter, primarily driven by investment to support the launch of EYLEA HD as well as our ongoing international commercial expansion. Second quarter gross margin and net product sales was approximately 89%, which reflected ongoing start up costs for our fill-finish manufacturing facility. Now, to cash flow and the balance sheet. Regeneron generated approximately $1.6 billion in free cash flow through the first six months of 2024 and ended the quarter with cash and marketable securities, less debt, of approximately $14.8 billion. We repurchased approximately $900 million of our shares through the first six months of the year and had approximately $3.6 billion available for repurchases as of the end of the second quarter. Finally, we have made some minor changes to our full year 2024 financial guidance. We have updated our 2024 gross margin guidance and now expect gross margin to be approximately 89%, primarily reflecting anticipated changes in product mix as well as higher non-product specific costs, including start up costs for our fill-finish facility. A complete summary of our latest full year guidance is available in our press release issued earlier this morning. In summary, Regeneron delivered outstanding results in the second quarter and is well-positioned to continue to drive growth in the near and long-term. With that, I'll pass the call back to Ryan.

Chris Fenimore: We repurchased approximately $900 million of our shares through the first six months of the year and had approximately $3.6 billion available for repurchases as of the end of the second quarter. Finally, we have made some minor changes to our full year 2024 financial guidance. We have updated our 2024 gross margin guidance and now expect gross margin to be approximately 89%, primarily reflecting anticipated changes in product mix as well as higher non-product specific costs, including start up costs for our fill-finish facility. A complete summary of our latest full year guidance is available in our press release issued earlier this morning. In summary, Regeneron delivered outstanding results in the second quarter and is well-positioned to continue to drive growth in the near and long-term. With that, I'll pass the call back to Ryan.

Chris Fenimore: With that, I'll pass the call back to Ryan.

Unknown Executive: Thank you, Chris. Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. Hey guys, good morning.

Ryan Crow: 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 go to the first question, please?

Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. Hey guys, good morning.

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

Operator: 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 go to the first question, please? Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw you question, please press star 1-1 again.

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 go to the first question, please?

Speaker Change: Second quarter gross margin of net product sales was approximately 89%, which reflected ongoing start-up costs for our fill-finish manufacturing facility.

Speaker Change: Regeneron generated approximately $1.6 billion in free cash flow through the first six months of 2024 and ended the quarter with cash and marketable securities, less debt of approximately $14.8 billion.

Speaker Change: We repurchased approximately $900 million of our shares through the first six months of the year and had approximately $3.6 billion available for repurchases as of the end of the second corner.

Operator: Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw you question, please press star 1-1 again.

Speaker Change: Finally, we have made some minor changes to our full year 2024 financial guidance. We have updated our 2024 gross margin guidance and now expect gross margin to be approximately 89%.

Speaker Change: primarily reflecting anticipated changes in product mix as well as higher non-product specific costs including startup costs for our fill finish facility.

Operator: Our first question comes from the line of Tyler van Buren with TD Cowen. Your line is now open.

Shannon: 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 go to the first question, please?

Tyler Van Buren: Hey guys, good morning. Congratulations on a great quarter. Regarding the EYLEA franchise, I'm really encouraged to see that the overall franchise is up year-over-year and that the 45% category share is maintained quarter-over-quarter. So, do you believe that EYLEA HD is reaching a stage in maturity of its launch where it will allow the overall category share to be relatively stable in the coming quarters that will allow you to participate in the retinal disease market growth? And is the market still growing around 10% year-over-year? Our next question comes from the line of Evan Seigerman with BMO Capital Markets, Shelleya Snow. Thank you so much.

Shannon: Thank you. As a reminder, to ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again.

Speaker Change: Our first question comes from the line of Tyler Van Buren with TD Cowen. Your line is now open.

Unknown Executive: Congratulations on a great quarter. Regarding the ILEA franchise, I'm really encouraged to see that the overall performance is up year over year. And that's why the 45% category share is maintained quarter over quarter. So do you believe that ILEA HD is reaching a stage in the maturity of its launch where it will allow the overall category share to be relatively stable in the coming quarters that will allow you to participate in the retinal disease market growth? And is the market still growing around 10% year over year? Our next question comes from the line of Evan Seigerman with BMO Capital Markets, Shelleya Snow. Thank you so much.

Speaker Change: Hey guys, good morning. Congratulations on the great quarter. Regarding the ILEO franchise, I'm really encouraged to see that the overall franchise is up year over year, and that the 45% category share is maintained quarter over quarter.

Speaker Change: So Tyler, I'll take it in a couple pieces. Thank you for the question. You know, first, I did want to comment, we were very pleased to report the total net sales of 1.4, excuse me, 1.54 billion in the quarter. You know, obviously, as you mentioned, that's a, you know, 2.4% increase year over year.

Speaker Change: Additionally, I'll just comment a little bit more on ILEA HD, we certainly are very much in the launch stage. This is our third full quarter of results that we're reporting today, and certainly we're encouraged that in the quarter we had a 52% increase in net sales,

Shannon: So certainly, we are continuing to progress our launch and, you know, see it as important. Certainly, ILEA is an important source of switch patients for ILEA HD. Next, we see switches coming from furosemab, also avastin. Very pleased as well this quarter to report that we're seeing increased use of ILEA HD in naive patient populations. So all in all, we see this indicative that ILEA HD has the potential and certainly the profile to be the new standard of care.

Tyler Van Buren: So, Tyler, I'll take it Our next question comes from the line of Evan Seigerman with BMO Capital Markets, Shelleya Snow. Thank you so much.

Tyler Van Buren: Marion? So, Tyler, I'll take it in a couple

Ryan Crowe: Marion?

Marion McCourt: So, Tyler, I'll take it in a couple of pieces. Thank you for the question. First, I did want to comment, we were very pleased to report the total net sales of $1.4--excuse me, $1.54 billion in the quarter. Obviously, as you mentioned, that's a 2.4% increase year-over-year. Additionally, I'll just comment a little bit more on EYLEA HD--we certainly are very much in the launch stage, this is our third full quarter of results that we're reporting today and certainly, we're encouraged in the quarter, we had a 52% increase in net sales and certainly, that calculation represents $100 million net sales increase from the prior quarter--which is very significant in this competitive market. So certainly, we are continuing to progress our launch and [inaudible] is important. Certainly, EYLEA is an important source of switch patients for EYLEA HD. Next, we see switches coming from FARICIMAB, also AVASTIN. Very pleased as well this quarter to report that we're increased use of EYLEA HD in naive patient populations. So, all in all, we see this indicative that EYLEA HD has the potential and certainly, the profile to be the new standard of care. I think you also asked me about market growth--overall market growth. Let me cover that as well. I would say probably, at this stage in the year, we're tracking more on single-digit growth in the category in the mid-range as opposed to double-digit--which I think is what was cited in your question. That's right. Okay. Thank you, Marion. Let's move to the next question, please.

Marion McCourt: So, Tyler, I'll take it in a couple of pieces. Thank you for the question. First, I did want to comment, we were very pleased to report the total net sales of $1.4--excuse me, $1.54 billion in the quarter. Obviously, as you mentioned, that's a 2.4% increase year-over-year. Additionally, I'll just comment a little bit more on EYLEA HD--we certainly are very much in the launch stage, this is our third full quarter of results that we're reporting today. And certainly, we're encouraged in the quarter, we had a 52% increase in net sales and certainly, that calculation represents $100 million net sales increase from the prior quarter--which is very significant in this competitive market. So certainly, we are continuing to progress our launch and [inaudible] is important. Certainly, EYLEA is an important source of switch patients for EYLEA HD. Next, we see switches coming from FARICIMAB, also AVASTIN. Very pleased as well this quarter to report that we're increased use of EYLEA HD in naive patient populations. So, all in all, we see this indicative that EYLEA HD has the potential and certainly, the profile to be the new standard of care. I think you also asked me about market growth--overall market growth. Let me cover that as well. I would say probably, at this stage in the year, we're tracking more on single-digit growth in the category in the mid-range as opposed to double-digit--which I think is what was cited in your question.

Marion McCourt: So certainly, we are continuing to progress our launch and [inaudible] is important. Certainly, EYLEA is an important source of switch patients for EYLEA HD. Next, we see switches coming from FARICIMAB, also AVASTIN. Very pleased as well this quarter to report that we're increased use of EYLEA HD in naive patient populations. So, all in all, we see this indicative that EYLEA HD has the potential and certainly, the profile to be the new standard of care. I think you also asked me about market growth--overall market growth. Let me cover that as well. I would say probably, at this stage in the year, we're tracking more on single-digit growth in the category in the mid-range as opposed to double-digit--which I think is what was cited in your question.

Ryan Crowe: That's right. Okay. Thank you, Marion. Let's move to the next question, please.

Operator: Our next question comes from the line of Evan Seigerman with BMO Capital Markets, Your line's now open.

Shannon: I think you also asked me about market growth, overall market growth. Let me cover that as well. I would say probably at this stage in the year, we're tracking more on single-digit growth in the category in the mid-range, as opposed to double-digit, which I think is what was cited in your question.

Unknown Executive: Hi, guys. Thank you so much for taking my question and always congrats on the progress. Well, we have left and are going forward with a number of different programs; I believe the one that you're talking about is in combination with other weight loss agents, and that's based on results that suggest that, Thanks, George. Let's move to the next question. All right, Shannon, let's go to the next question.

Evan Seigerman: Hi, guys. Thank you so much for taking my question and always, congrats on the progress. I want to touch on your work in obesity, specifically with leptin. Can you just walk me through some of the rationale of moving this to a Phase II? I know that leptin had been controversial. Clearly, you saw some interesting data in earlier trials but why do you want to add this on top of, say, TIRZEPATIDE versus using a triple agonist that Lilly is doing on some of their other trials? Thank you so much.

Shannon: Evan Seigerman with BMO Capital Markets. Your line is now open.

Speaker Change: The reason leptin doesn't work in normal obese patients is because in those patients who have a high degree of fat and are in fact

Speaker Change: On the upswing of their obesity profile, their leptin levels are very high. They're already saturating.

Well, we have LEPTIN going forward in a number of different programs; I believe the one that you're talking about is in combination with other weight loss agents. And that's based on results that suggest that the reason LEPTIN doesn't work in normal obese patients is because in those patients who have a high degree of fat and are, in fact, on the upswing of their obesity profile, their leptin levels are very high. They're already saturating. Once you undergo profound weight loss, the leptin levels drop and you maybe getting into the range where the leptin is now providing a signal which is creating an increased desire in the individual to eat. And so, in these patients, it maybe that some of the weight loss is limited by decreases in the leptin, which is then driving increasing feeding type of behavior. So, this might be--and at least it's been shown in animal studies to be the situation where leptin might actually be playing an important role. So, as you point out, in historical studies in stably obese patients, leptin is already saturated and giving more leptin may not have a benefit. But in these studies where there are falling leptin levels, the falling in low leptin levels may lead to a food-seeking drive and giving leptin in that setting may allow further weight loss on top of that obtained with these other agents which tend to plateau at a certain point and that plateau--at least, based on animal studies--may be in part driven by these drops in the leptin. And these studies, as you know, are done in collaboration with a partnership with Lilly so, we're studying it in collaboration with their agent TIRZEPATIDE. Thanks, George. Let's move to the next question. All right, Shannon, let's go to the next question.

George Yancopoulos: Well, we have leptin going forward in a number of different programs; I believe the one that you're talking about is in combination with other weight loss agents. And that's based on results that suggest that the reason leptin doesn't work in normal obese patients is because in those patients who have a high degree of fat and are, in fact, on the upswing of their obesity profile, their leptin levels are very high. They're already saturating. Once you undergo profound weight loss, the leptin levels drop and you may be getting into the range where the leptin is now providing a signal which is creating an increased desire in the individual to eat. And so, in these patients, it may be that some of the weight loss is limited by decreases in the leptin, which is then driving increasing feeding type of behavior. So, this might be--and at least it's been shown in animal studies to be the situation where leptin might actually be playing an important role. So, as you point out, in historical studies in stably obese patients, leptin is already saturated and giving more leptin may not have a benefit. But in these studies where there are falling leptin levels, the falling in low leptin levels may lead to a food-seeking drive and giving leptin in that setting may allow further weight loss on top of that obtained with these other agents which tend to plateau at a certain point. And that plateau--at least, based on animal studies--may be in part driven by these drops in the leptin. And these studies, as you know, are done in collaboration with a partnership with Lilly so, we're studying it in collaboration with their agent TIRZEPATIDE.

Speaker Change: by decreases in the leptin, which is then driving increasing feeding type of behavior. So this might be, and at least it's been shown in animal studies, to be the situation where leptin might actually be playing an important role. So...

Shannon: A food-seeking drive.

Shannon: These studies, as you know, are done in collaboration with a partnership with Lilly, so we're studying it in collaboration with their agent, Gizepitide.

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

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

Brian Abrahams: Hey, good morning. Thanks for taking my question and congratulations on the quarter and all the progress.

Brian Abrahams: On Linvo, as you prepare for the potential launch there, I'm curious the feedback you're getting on how docs may position it relative to existing therapies, how much appreciation there is out there for the efficacy and administration advantages that you cite in your slide, and maybe you could also elaborate a little bit more on some of the issues with the third-party facility and the confidence that's resolved. Thanks.

Brian Abrahams: I'll take the third party issue and George can cover, or Marion, how people are...

George Yancopoulos: And so, in these patients, it may be that some of the weight loss is limited by decreases in the leptin, which is then driving increasing feeding type of behavior. So, this might be--and at least it's been shown in animal studies to be the situation where leptin might actually be playing an important role. So, as you point out, in historical studies in stably obese patients, leptin is already saturated and giving more leptin may not have a benefit. But in these studies where there are falling leptin levels, the falling in low leptin levels may lead to a food-seeking drive and giving leptin in that setting may allow further weight loss on top of that obtained with these other agents which tend to plateau at a certain point. And that plateau--at least, based on animal studies--may be in part driven by these drops in the leptin. And these studies, as you know, are done in collaboration with a partnership with Lilly so, we're studying it in collaboration with their agent TIRZEPATIDE.

Speaker Change: and this was a case where the FDA was inspecting our filler for a different product.

Speaker Change: That's why we called your attention to that. This is an industry-wide kind of issue. I think the FDA is, in fact, planning some sort of public...

George: hearing on these sorts of things. We're working with the FDA because this is a priority review application to see how we can resolve this in as expeditious manner as possible. George or Marion, you want to cover the... Yeah, I'll start and then I'll hand it over to Marion, but as...

George: We've summarized and we've detailed and as it will continue to be presented the efficacy data with our bi-specific continues to look like it is leading the field as

George: The data matures.

Speaker Change: and Survival in the Patients and we would.

Marion: Best in Class. In terms of how Marion believes the physician community is appreciating this data, I'll ask Marion to comment. Oh, thanks, George. And, you know, certainly we're very excited about the potential upcoming approval for Limbiceltamab.

Marion: This would be quite remarkable given what George just told you about the amount of responses we're seeing in the last line. So we're very excited about moving this forward and we'll keep you updated as we do that.

Thanks, George. Let's move to the next question. All right, Shannon, let's go to the next question.

Ryan Crowe: Thanks, George. Let's move to the next question.

Operator: Our next question is from the line of Brian Abrahams with RBC Capital Markets. Your line is open. Hey

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

Brian Abrahams: Hey, good morning. Thanks for taking my question and congratulations on the quarter and all the progress. On LINVO, as you prepare for the potential launch there, I'm curious the feedback you're getting on how docs may position it relative to existing therapies. How much appreciation there is out there for the efficacy and administration advantages that you cited in your slide? And maybe you could also elaborate a little bit more on some of the issues with the third-party facility and they're confident if that's resolved. Thanks.

Unknown Executive: I'll take the third party issue. Our next question comes from the line of Corey Kasimov with Evercore ISI. Your line is still, Yeah, so very importantly, what we've done is we've created antibodies that split the mechanism of action. One affects the activation domain, and the other the catalytic domain.

Leonard S. Schleifer: I'll take the third party issue and George can cover--or Marion--how people are thinking about a BCMA approach and where it might fit in, in the longer term. There's been a lot of third party filler-type and manufacturing issues with lots of CRLs across our--the biopharmaceutical space. As you know, we had one last year with HD EYLEA and this was a case where the FDA was inspecting our filler for a different product. And they found some observations, the observations needed to be remediated but because of the nature of the observations, a re-inspection is necessary. We believe, based on what we've been told, is that the observations have been remediated but since there's a re-inspection required, it might not get done--it's likely not to get done in time for our PDUFA date. Now, that's why we called your attention to that. This is a industry-wide kind of issue. I think the FDA is, in fact, having--planning some sort of public hearing on these sorts of things. We're working with the FDA because this is a priority review application, to see how we can resolve this in as expeditious manner as possible. George and Marion, you want to come with the--

Leonard S. Schleifer: We believe, based on what we've been told, is that the observations have been remediated but since there's a re-inspection required, it might not get done--it's likely not to get done in time for our PDUFA date. Now, that's why we called your attention to that. This is a industry-wide kind of issue. I think the FDA is, in fact, having--planning some sort of public hearing on these sorts of things. We're working with the FDA because this is a priority review application, to see how we can resolve this in as expeditious manner as possible. George and Marion, you want to come with the--

I'll Our next question comes from the line of Corey Kasimov with Evercore ISI. Your line is still, Yeah, so very importantly, what we've done is we've created antibodies that split the mechanism of action. One affects the activation domain, and the other the catalytic domain.

George Yancopoulos: I'll start and then, I'll hand it over to Marion. But as we've summarized and we've detailed and as we'll continue to be presented, the efficacy data with our bispecific continues to look like it is leading the field. As the data matures and patients continue on treatment, they continue to progress to deeper and deeper responses and we're now--we have complete response rates at 50% with, we believe, best-in-class PFS and overall survival-type numbers. Which is, obviously, really important because what cancer treatment is all about is trying to eliminate the cancer and getting long-term durable responses and survival in the patients. And we would imagine that this is exactly what patients and physicians are focused about. Other aspects of our profile--we also believe, in terms of safety and our dosing schedule and hospitalization burden also, we believe are best-in-class. In terms of how Marion believes the physician community is appreciating the data, I'll ask Marion to comment on that. Thanks, George.

George Yancopoulos: And we would imagine that this is exactly what patients and physicians are focused about. Other aspects of our profile--we also believe, in terms of safety and our dosing schedule and hospitalization burden also, we believe are best-in-class. In terms of how Marion believes the physician community is appreciating the data, I'll ask Marion to comment on that. Thanks, George. And certainly, we're very excited about the potential upcoming approval for LINVOSELTAMAB. George describes the differentiated clinical efficacy, safety, profile that will be incredibly important to physicians. We have a highly experienced hematology team in place and ready for launch.

Marion McCourt: Thanks, George. And certainly, we're very excited about the potential upcoming approval for LINVOSELTAMAB. George describes the differentiated clinical efficacy, safety, profile that will be incredibly important to physicians. We have a highly experienced hematology team in place and ready for launch. Yes. I would just add--this is Len--I would just add that we're not limiting ourselves, obviously, just to the last-line. We are trying to move this aggressively, either in monotherapy or in combinations, to much early lines of therapy. The rule of thumb has been, in cancer, that you tend to get more responses as you move to earlier lines. And this would be quite remarkable, given what George just told you about the amount of responses we're seeing in the last-line. So, we're very excited about moving this forward and we'll go--we'll keep you updated as we do that.

Leonard S. Schleifer: Yes. I would just add--this is Len--I would just add that we're not limiting ourselves, obviously, just to the last-line. We are trying to move this aggressively, either in monotherapy or in combinations, to much early lines of therapy. The rule of thumb has been, in cancer, that you tend to get more responses as you move to earlier lines. And this would be quite remarkable, given what George just told you about the amount of responses we're seeing in the last-line. So, we're very excited about moving this forward and we'll go--we'll keep you updated as we do that.

Our next question comes from the line of Corey Kasimov with Evercore ISI. Your line is still, Yeah, so very importantly, what we've done is we've created antibodies that split the mechanism of action. One affects the activation domain, and the other the catalytic domain.

Yeah, just a follow up on what Len said. Obviously, this is why we're moving to these trials in these earlier lines of therapy. Obviously, we won't be commercializing those areas until we get the results from those clinical trials. Sure. Absolutely. Our next question comes from the line of Corey Kasimov with Evercore ISI. Your line is still,

George Yancopoulos: Yeah, just a follow up on what Len said. Obviously, this is why we're moving to these trials in these earlier lines of therapy. Obviously, we won't be commercializing those areas until we get the results from those clinical trials.

Speaker Change: Our next question comes from the line of Corey Kasimov with Evercore ISI. Your line is still open.

Sure. Absolutely. Our next question comes from the line of Corey Kasimov with Evercore ISI. Your line is still,

Brian Abrahams: Sure. Absolutely.

All right, Shannon. Let's go to the next question. Our next question comes from the line of Corey Kasimov with Evercore ISI. Your line is still,

Ryan Crowe: All right, Shannon. Let's go to the next question.

Operator: Our next question comes from the line of Cory Kasimov with Evercore ISI. Your line is open,

Thank you, guys. Good morning. Yeah, so very importantly, what we've done is we've created antibodies that split the mechanism of action. One affects the activation domain, and the other the catalytic domain.

Cory Kasimov: Thank you, guys. Good morning. Thanks for taking the question. So, we're getting an increasing amount of inbound interest in your Factor XI program. Can you speak to the differences--this, I guess, probably for George--between your two antibodies? And what will be the key aspects you'll be focused on in your upcoming readouts to know you're on the right track? Thank you.

George Yancopoulos: Yeah. So, very importantly, what we've done is we've created antibodies that split the mechanism of action. One affects the activation domain; the other, the catalytic domain. We have developed, in both these classes, the only ones in class--or the best-in-class type of antibodies, which are best at actually hitting and inhibiting that target. Based on all of the science, a huge amount of genetics--in part fortified by our own Regeneron genetics efforts and so forth--it suggests that these two approaches will allow us to separate and optimize optimum efficacy and optimum safety. So, it's quite possible that we might actually move forward with both of these antibodies for different target populations, in some of which where efficacy is the primary driver and others where safety might be most important. So, they're very unique in their mechanisms of action. They really are exploring this target, both much more precisely by splitting the mechanism of action but also, more powerfully than competitors that have antibodies that can do one or the other of these things. So, we're very excited about these programs. As we said, we have some proof of concept studies ongoing and we hope, by the end of the year, to be able to announce the directions we may be taking either or both of these antibodies going forward in the future. as there were some other variables, such as discounting, etc.

Unknown Executive: We have developed in both these classes the only ones in class or the best in class type of antibodies, which are best at actually hitting and inhibiting that target. Based on all of the science, a huge amount of genetics, in part fortified by our own Regeneron genetics efforts, and so forth, it suggests that these two approaches will allow us to separate and optimize optimum efficacy and optimum safety. So it's quite possible that, as there were some other variables, such as discounting, etc.

George: Yeah.

Speaker Change: One affects the activation domain, the other the catalytic domain. We have developed in both these classes, the only ones in class or the best in class type of antibodies, which are best at actually hitting and inhibiting that target.

George: Based on all of the science, a huge amount of genetics, in part fortified by our own Regeneron genetics efforts and so forth, it suggests that these two approaches will allow us to separate and optimize optimum efficacy and optimum safety.

George Yancopoulos: So, it's quite possible that we might actually move forward with both of these antibodies for different target populations, in some of which where efficacy is the primary driver and others where safety might be most important. So, they're very unique in their mechanisms of action. They really are exploring this target, both much more precisely by splitting the mechanism of action but also, more powerfully than competitors that have antibodies that can do one or the other of these things. So, we're very excited about these programs. As we said, we have some proof of concept studies ongoing and we hope, by the end of the year, to be able to announce the directions we may be taking either or both of these antibodies going forward in the future.

George: So, it's quite possible that...

George: We might actually move forward with both of these antibodies for different target populations in some of which where efficacy is the primary driver and others where safety might be most important.

George: Both much more precisely by splitting the mechanism of action, but also more powerfully than competitors that have antibodies that can do one or the other of these things. So we're very excited about these programs. As we said, we have some proof of concept studies ongoing, and we hope by the end of the year to be able to announce the directions we may be taking either or both of these antibodies going forward in the future.

George Yancopoulos: Thanks, George. Let's move to the next question please, Shannon. as there were some other variables, such as discounting, etc.

Ryan Crowe: Thanks, George. Let's move to the next question please, Shannon.

George Yancopoulos: Our next question is from the line of Chris Raymond with Piper Sandler. Your line is now open. as there were some other variables, such as discounting, etc.

Operator: Our next question is from the line of Chris Raymond with Piper Sandler. Your line is now open. Hey, thanks. And just a quick question on EYLEA and the commercial progress. So, you guys, I think, were pretty clear in your messaging on the permanent J-code, is we should not really see an inflection that was seen maybe with VABYSMO when they got their permanent J-code as there were some other variables such as discounting, et cetera, going on with that example. But we've gotten some market feedback that access barriers remain even with the J-code change and specifically, among Medicare Advantage plans. Marion, I'm curious if you can talk about the dynamic there and how you see things playing out, with respect to access post-permanent J-code.

Operator: Our next question is from the line of Chris Raymond with Piper Sandler. Your line is now open.

Christopher J. Raymond: Hey, thanks. And just a quick question on EYLEA and the commercial progress. So, you guys, I think, were pretty clear in your messaging on the permanent J-code, is we should not really see an inflection that was seen maybe with VABYSMO when they got their permanent J-code as there were some other variables such as discounting, et cetera, going on with that example. But we've gotten some market feedback that access barriers remain even with the J-code change and specifically, among Medicare Advantage plans. Marion, I'm curious if you can talk about the dynamic there and how you see things playing out, with respect to access post-permanent J-code.

George Yancopoulos: Hey, thanks. as there were some other variables, such as discounting, etc.

Marion McCourt: Sure. I'm very, very happy to comment. So, certainly, for a portion of the market--fee-for-service Medicare patients--there's open access and freedom of prescribing for physicians. If we go to those areas of the market where there's a payer impact, our teams have successfully opened access for EYLEA HD in a way that covers over 80% of patient lives. So, certainly, significant progress has been made and we continue to work through situations where physicians might be having some utilization management or step edits. I will share that those are often easily managed when the physician and office staff provide information but overall, the takeaway message should be that EYLEA HD has very strong payer coverage and, again, 80% of the market where reimbursement is in place. Thanks, Marion. Let's move to the next question.

Ryan Crowe: Thanks, Marion. Let's move to the next question, Shannon.

Marion McCourt: Our next question comes from the line of Akash Tewari with Jeffries. Your line is now open, and many others that are irrelevant to muscle and we know are known to have a variety of other potential side effects and adverse effects. So we targeted the two muscle-specific pathways in this whole mechanism.

Operator: Thanks, Marion. Let's move to the next question, Shannon. Our next question comes from the line of Akash Tewari with Jefferies. Your line is now open.

Ryan Crowe: Thanks, Marion. Let's move to the next question, Shannon. Our next question comes from the line of Akash Tewari with Jefferies. Your line is now open.

Ryan Crowe: Thanks, Marion. Let's move to the next question, Shannon.

Speaker Change: when they got their permanent J-code as there were some other variables such as discounting etc going on with that example. But we've gotten some market feedback that you know access barriers remain you know even with the J-code change and specifically among Medicare Advantage plans.

Operator: Our next question comes from the line of Akash Tewari with Jefferies. Your line is now open.

Speaker Change: You know Medicare patients there's there's open access and freedom of prescribing for physicians. If we go to those areas of the market where there's a payer impact, our teams have successfully opened access for Ilia HD.

Hi, this is Cathy, on for Akash. and many others that are irrelevant to muscle and we know are known to have a variety of other potential side effects and adverse effects. So we targeted the two muscle-specific pathways in this whole mechanism.

Hi, this is Cathy, on for Akash. and many others that are irrelevant to muscle and we know are known to have a variety of other potential side effects and adverse effects. So we targeted the

Unknown: Hi, this is Kathy, on for Akash. So, for your myostatin program, can you talk about your preference for using a doublet versus triplet combination approach in your Phase III trials? And also, where do you think myostatin will stack up versus GIP/GLP /AMYLIN combination approaches--which could show, potentially, 90% plus fat versus muscle loss? Thank you.

Speaker Change: So certainly significant progress has been made, and we continue to work through situations where physicians might be having some utilization management or step edits. I will share that those are often easily managed.

George Yancopoulos: Yeah. Well, once again, what we focused on is creating individual reagents that allow is to best dissect the pathway and separate out which are the most important players. As you're aware, other people, for example, are using an antibody that blocks all the pathways--not only the two that we've targeted--but about 20 others that are irrelevant for muscle and we know are known to have a variety of other potential side effects and adverse effects. So, we targeted the two muscle-specific pathways in this whole mechanism. And what we want to see is which one might have the best efficacy to safety profile that we believe is very important. Once we determine that, we may move forward with either one or both of these antibodies--in combination with the weight loss agents--or we also have been developing in our pipeline, a variety of unimolecular solutions that will allow a single molecule to do whichever one of these multiple pathways we want, to attack, in addition to the weight loss pathway. So, what we're hoping to do is by dissecting the pathway as precisely and scientifically as possible, allow us to choose between the unimolecular solutions that we can have to follow on. That said, remember, it's not just a matter of amplifying the weight loss because with more weight loss, regardless of pathway you use, you can throw on the GLP-1 agonist; you can throw on GPR antagonist; you can lay on additional pathways--the more weight loss and the more rapidly it occurs, which is what patients want, out of necessity

Speaker Change: We're not sure when the physician and office staff provide information, but overall, the takeaway message should be that ILEA HD has very strong payer coverage, and again, 80% of the market where reimbursement is in place.

Speaker Change: Hi, this is Cathy on for Akash. So for your myostatin program, can you talk about your preference for using a doublet versus triplet combination approach in your phase three trials? And also where do you think myostatins will stack up versus GIF-GLP-AMLIN combination approaches, which could show potentially like 90% plus fat versus muscle loss. Thank you.

George Yancopoulos: Once we determine that, we may move forward with either one or both of these antibodies--in combination with the weight loss agents--or we also have been developing in our pipeline, a variety of unimolecular solutions that will allow a single molecule to do whichever one of these multiple pathways we want, to attack, in addition to the weight loss pathway. So, what we're hoping to do is by dissecting the pathway as precisely and scientifically as possible, allow us to choose between the unimolecular solutions that we can have to follow on. That said, remember, it's not just a matter of amplifying the weight loss because with more weight loss, regardless of pathway you use, you can throw on the GLP-1 agonist; you can throw on GPR antagonist; you can lay on additional pathways--the more weight loss and the more rapidly it occurs, which is what patients want, out of necessity

Speaker Change: Once again,

George Yancopoulos: That said, remember, it's not just a matter of amplifying the weight loss because with more weight loss, regardless of pathway you use--you can throw on the GLP-1 agonist, you can throw on GPR antagonist, you can lay on additional pathways--the more weight loss and the more rapidly it occurs, which is what patients want out of necessity because you're mimicking the starvation to get the pathway, it inevitably leads to muscle loss. Because of, why? Because of activation of these very pathways that we're looking at. So, any approach right now that focuses on rapidly causing weight loss will, of necessity--because it plugs in to evolutionary conserved pathways--of necessity, will result in profound lean body and muscle loss. Which can be a huge detriment these patients, especially the older obese patients. And by invoking these agents blocking these specific pathways, we may be able to deduce two things: we may block this associated, necessarily evolutionary conserved muscle loss that accompanies rapid and profound weight loss while also, perhaps, increasing the amount of fat loss--which is what you specifically want to lose. This is what we've now shown in pre-clinical studies, including non-human primates and studies that we're embarking on right now, should tell us whether all these pathways--which are incredibly evolutionary conserved--will indeed pertain in humans and whether we really can optimize, not only the weight loss--that's not what's important--but optimize, particularly, fat loss while maintaining the muscle. And we believe we're the only ones who are properly, precisely interrogating the pathways and we'll be able to dissect them to decide on which exactly is the best, safest pathway to give the best benefit to the patient. Okay. Thanks, George. And Shannon, next question, please.

two muscle-specific pathways in this whole mechanism.

George Yancopoulos: So, any approach right now that focuses on rapidly causing weight loss will, of necessity--because it plugs in to evolutionary conserved pathways--of necessity, will result in profound lean body and muscle loss. Which can be a huge detriment to these patients, especially the older obese patients. And by invoking these agents blocking these specific pathways, we may be able to deduce two things: we may block this associated, necessarily evolutionary conserved muscle loss that accompanies rapid and profound weight loss while also, perhaps, increasing the amount of fat loss--which is what you specifically want to lose. This is what we've now shown in pre-clinical studies, including non-human primates. And studies that we're embarking on right now should tell us whether all these pathways--which are incredibly evolutionary conserved--will indeed pertain in humans and whether we really can optimize, not only the weight loss--that's not what's important--but optimize, particularly, fat loss while maintaining the muscle. And we believe we're the only ones who are properly, precisely interrogating the pathways and we'll be able to dissect them to decide on which exactly is the best, safest pathway to give the best benefit to the patient.

George Yancopoulos: This is what we've now shown in pre-clinical studies, including non-human primates. And studies that we're embarking on right now should tell us whether all these pathways--which are incredibly evolutionary conserved--will indeed pertain in humans and whether we really can optimize, not only the weight loss--that's not what's important--but optimize, particularly, fat loss while maintaining the muscle. And we believe we're the only ones who are properly, precisely interrogating the pathways and we'll be able to dissect them to decide on which exactly is the best, safest pathway to give the best benefit to the patient.

Ryan Crowe: Okay. Thanks, George. And Shannon, next question, please.

George D. Yancopoulos: Our next question comes from the line of Chris Schott from J.P. Morgan. Your line is now open. And what we want to see is which one might have the best efficacy to safety profile, which we believe is very important. Once we determine that, thanks George.

Operator: Okay. Thanks, George. And Shannon, next question, please. Our next question comes from the line of Chris Schott from J.P. Morgan. Your line is now open.

Ryan Crowe: Okay. Thanks, George. And Shannon, next question, please.

Speaker Change: efficacy to safety profile that we believe is very important

Speaker Change: One or both of these antibodies in combination with the weight loss agents.

Operator: Our next question comes from the line of Chris Schott from J.P. Morgan. Your line is now open.

Speaker Change: Dissecting the pathway as precisely and scientifically as possible allows us to choose between the unimolecular solutions that we can have to follow on.

George: That said, remember, it's not just a matter of amplifying the weight loss, because with more weight loss, regardless of pathway you use, you can throw on, you know, the

Chris Schott: All right, great. Thanks so much for the question. Just on LINVO, DUPIXENT and food allergy--I know it's early but an exciting program. Can you help us just a bit to frame out the number of patients or percent of those with food allergy where you think this could be an appropriate treatment if the data we see later this year and going forward supports moving that combination forward? Thanks so much.

Speaker Change: Gipper Antagonists, you can lay on additional pathways

Speaker Change: The more weight loss, and the more rapidly it occurs, which is what patients want, out of necessity, because you're mimicking the starvation, cachectic pathway, it inevitably leads to muscle loss, because of why? Because of activation of these very pathways that we're looking at.

George: These agents blocking these specific pathways, we may be able to deduce two things, we may block this associated necessarily evolutionary conserved muscle loss that accompanies rapid and profound weight loss,

Speaker Change: These studies that we're embarking on right now should tell us whether all these pathways

George: which are incredibly evolutionary conserved will indeed pertain in humans and whether we really can optimize not only the weight loss, that's not what's important, but optimize particularly fat loss while maintaining the muscle.

Unknown Executive: I think that it's all Shannon, next question. Great, thanks so much for the question. Just on Linvo Dupixent in food allergy, I know it's an early, but exciting program. Can you help us just a bit to frame out the number of patients or percent of those with food allergies where you think this could be an appropriate treatment, if the data we see later this year and going forward supports moving that combination forward? Thanks so much.

George Yancopoulos: I think that it's all going to be a matter of the benefit-to-risk profile once again. And this is what, as I've said in these other programs we're focusing on. We believe, based on all the data that we've shown, that we may have a very safe way of eliminating the actual cells that are causing all these allergic responses and then very safely keep them from coming back by giving one of the world's historically most safe biologics, which is DUPIXENT. Of course, we have to prove this in patients. And so, we are starting in the most severe food allergy patients. And these patients, where they have, for example: very high unmet need, very high risk and so forth, it warrants undertaking this approach. The more effective it is but more importantly, the safer we can prove it is, then the broader the population can go. And in fact, if ultimately, we really have a safe way of eliminating all allergy-inducing cells and then preventing their rebound--now remember, particularly, most of these patients are also suffering from other allergic diseases; some of them may already be indicated for DUPIXENT so, you're giving them a drug which they'd actually be helping them anyway and is been shown to be quite safe in terms of as almost any biologic goes-- we may be able to go into milder and milder allergy patients. So, we can start--and we are starting with the most severe patients--we're seeing in these patients with a high unmet need, whether this approach is both effective but also safe--and how safe it is. And the safer it is, we can broaden wider and wider. There's also, ultimately, no need to be limited to food allergies; you can actually eliminate, essentially, all allergies from the most serious to the most mundane. But it depends on the benefit-risk and the safety, which is what we're testing in these initial studies. And for the initial studies, we've taken the most severe, food-allergic patients who have a very high unmet need and very high risk profile. Depending on how it goes there, we can broaden to milder and milder types of disease.

George Yancopoulos: And these patients, where they have, for example: very high unmet need, very high risk and so forth, it warrants undertaking this approach. The more effective it is but more importantly, the safer we can prove it is, then the broader the population can go. And in fact, if ultimately, we really have a safe way of eliminating all allergy-inducing cells and then preventing their rebound--now remember, particularly, most of these patients are also suffering from other allergic diseases; some of them may already be indicated for DUPIXENT so, you're giving them a drug which they'd actually be helping them anyway and is been shown to be quite safe in terms of as almost any biologic goes-- we may be able to go into milder and milder allergy patients. So, we can start--and we are starting with the most severe patients--we're seeing in these patients with a high unmet need, whether this approach is both effective but also safe--and how safe it is. And the safer it is, we can broaden wider and wider. There's also, ultimately, no need to be limited to food allergies; you can actually eliminate, essentially, all allergies from the most serious to the most mundane. But it depends on the benefit-risk and the safety, which is what we're testing in these initial studies. And for the initial studies, we've taken the most severe, food-allergic patients who have a very high unmet need and very high risk profile. Depending on how it goes there, we can broaden to milder and milder types of disease.

George Yancopoulos: So, we can start--and we are starting with the most severe patients--we're seeing in these patients with a high unmet need, whether this approach is both effective but also safe--and how safe it is. And the safer it is, we can broaden wider and wider. There's also, ultimately, no need to be limited to food allergies; you can actually eliminate, essentially, all allergies from the most serious to the most mundane. But it depends on the benefit-risk and the safety, which is what we're testing in these initial studies. And for the initial studies, we've taken the most severe, food-allergic patients who have a very high unmet need and very high risk profile. Depending on how it goes there, we can broaden to milder and milder types of disease.

I mean, the numbers are--get quite staggering. Shannon, next question. Great, thanks so much for the question. Just on Linvo Dupixent in food allergy, I know it's an early, but exciting program. Can you help us just a bit to frame out the number of patients or percent of those with food allergies where you think this could be an appropriate treatment, if the data we see later this year and going forward supports moving that combination forward? Thanks so much.

Leonard S. Schleifer: I mean, the numbers are--get quite staggering. Looking at--if you just look at the number of emergency room visits a year, could be hundreds of thousands or millions of people go to the emergency room for food-based allergies. Obviously, a smaller number for actual anaphylaxis but just to reinforce exactly what George says, if all it takes is an induction in BCMA to induce the process where you can get on to DUPI, DUPI is a very safe agent and we've got hundreds of thousands--approaching millions--of patients on the drug so, we know the profile of that drug. So, this is all--makes great scientific sense. We just have to take our time, do it safely and see how it develops.

Thanks, Len and George. Let's move to the next question, please, Shannon. Great, thanks so much for the question. Just on Linvo Dupixent in food allergy, I know it's an early, but exciting program. Can you help us just a bit to frame out the number of patients or percent of those with food allergies where you think this could be an appropriate treatment, if the data we see later this year and going forward supports moving that combination forward? Thanks so much.

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

Speaker Change: Our next question comes from the line of Chris Schott with J.P. Morgan. Your line is now open.

Our next question comes from the line of Tim Anderson with Wolfe Research. Your line is now open. Great, thanks so much for the question. Just on Linvo Dupixent in food allergy, I know it's an early, but exciting program. Can you help us just a bit to frame out the number of patients or percent of those with food allergies where you think this could be an appropriate treatment, if the data we see later this year and going forward supports moving that combination forward? Thanks so much.

Operator: Our next question comes from the line of Tim Anderson with Wolfe Research. Your line is now open.

Tim Anderson: Thank you very much. I have a question on EYLEA and this DOJ investigation into the marketing practices that emerged since April, where they assert that you guys violate the False Claims Act. Can you provide an update on kind of what happens from here? And specifically, in the interim and out of prudence, has Regeneron changed any of its marketing practices since April? And is that having any impact even on prescribers? I asked because on slide six, you mentioned "other market dynamics that resulted in lower volumes and lower price". I'm just wondering what those were.

George D. Yancopoulos: I think that it's all going to be a matter of the benefit-to-risk profile once again, and this is what, as I've said in these other programs, we're focused on. And so we are starting with the most severe food allergy patient. Then, the broader the population can go, and, in fact, if, ultimately, we really have a very safe way of eliminating all allergy-inducing cells and then preventing their rebound. And remember, especially most of these patients are also suffering from other allergic diseases. Some of them may already be indicated for Dupixent, so you're giving them a drug that may actually be helping them anyway and has been shown to be quite safe at almost any biological dose.

Speaker Change: I think that it's all going to be a matter of the benefit to risk profile once again, and this is what, as I've said in these other programs, we're focusing on.

Speaker Change: We believe, based on all the data that we've shown, that we may have a very safe way

George: of eliminating the actual cells

Speaker Change: Of course, we have to prove this in patients.

George: and so we are starting in the most severe food allergy patients.

George: [inaudible]

George: Some of them may already be indicated for Dupixent, so you're giving them a drug which may actually be helping them anyway and has been shown to be quite safe in terms of as almost any biologic goes. We may be able to go into milder and milder allergy patients.

George D. Yancopoulos: We may be able to go into milder and milder allergy patients. So we can start, and we are starting with the most severe patients. We're seeing in these patients with a high unmet need whether this approach is both effective but also safe, and how safe it is. And the safer it is, we can broaden it wider and wider. There's also ultimately no need to be limited to food allergies. You can actually eliminate essentially all allergies, from the most serious to the most mundane.

George: So we can start, and we are starting with the most severe patients.

George D. Yancopoulos: But it depends on the benefit-risk profile and the safety, which is what we're testing in these initial studies. And for the initial studies, we're taking the most severe food allergic patients who have a very high unmet need and a very high risk profile, as opposed to milder types of disease. I mean, the numbers are quite staggering. If all it takes is an induction and BCMA to induce the process where you can get on to DUPI, DUPI is a very safe agent. And we've got hundreds of thousands, approaching a million, of patients on the drug. So we know the profile of that drug. So this all makes great scientific sense. We just have to, excuse me, take our time, do it safely, and see how it develops. Our next question comes from the line of Tim Anderson with Wolf Research. Your line is now open.

George: Depending on how it goes there, we can broaden to...

George D. Yancopoulos: I mean, the numbers are quite staggering. If all it takes is an induction and BCMA to induce the process where you can get on to DUPI, DUPI is a very safe agent. And we've got hundreds of thousands, approaching a million, of patients on the drug. So we know the profile of that drug. So this all makes great scientific sense.

George: Milder and milder types of disease.

George: I mean, the numbers get quite staggering. Looking at...

George: If you just look at the number of emergency room visits a year, it could be hundreds of thousands and millions of people go to the emergency room for food-based allergies, obviously a smaller number for actual anaphylaxis, but just to reinforce exactly what George says, if all it takes

Speaker Change: The process we can get on to Doopie. Doopie is a very safe agent and you know we've got

George: hundreds of thousands, approaching millions of patients.

Speaker Change: on the drug. So we know the profile of that drug. So this is all makes great scientific sense. We just have to, excuse me, take our time, do it safely and see how it develops.

Unknown Executive: We just have to, excuse me, take our time, do it safely, and see how it develops. Our next question comes from the line of Tim Anderson with Wolf Research. Your line is now open.

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

Unknown Executive: Oh, thank you very much. I have a question on ILEA and this DOJ investigation into the marketing practices that emerged since April where they assert that you guys violate false claims. Can you provide an update on kind of what will happen from here? April.

George: Bye-bye.

Shannon: Can you provide an update on kind of what happens from here?

Speaker Change: And specifically, in the interim and out of prudence, has Regeneron changed any of its marketing practices since April ? And is that having any impact, you know, even on prescribers? I ask because on slide six, you mentioned

Leonard S. Schleifer: No, there's nothing--there's nothing in the marketplace related to this lawsuit. And frankly, we think there's nothing to this lawsuit. And we have not changed our practice and we intend to fight it vigorously. And I think once you see our papers in court, you'll get a much better understanding of that.

Speaker Change: Quote-unquote other market dynamics that resulted in lower volumes and lower price

Speaker Change: Let's move to the next question, please.

Speaker Change: It's not really putting to work. So my question is, is there an opportunity to leverage Regeneron's eye disease commercial presence by acquiring novel potential blockbuster therapies for severe eye disease?

Speaker Change: Yeah, it's a great question and it's one we ask every day here. Is there some opportunity that isn't resulting from our own innovation?

Speaker Change: Our next question is from the line of Salveen Richter with Goldman Sachs. Your line is now open.

Unknown Executive: Let's move to the next question, please. Our next question comes from the line of David Risinger from Leerink Partners. Your line is now open. So my question is, is there an opportunity to leverage Regeneron's eye disease commercial presence by acquiring novel potential blockbuster therapies for severe eye disease? Good morning, thanks for taking my question. On the Factor XI programs here, could you speak to the potential commercial opportunities that are represented and what the future development plans look like here? Well, as I said, we're in the stages of evaluating two classes of antibodies that are attacking this pathway in two different ways.

Ryan Crowe: Let's move to the next question, please.

Our next question comes from the line of David Risinger from Leerink Partners. Your line is now open. So my question is, is there an opportunity to leverage Regeneron's eye disease commercial presence by acquiring novel potential blockbuster therapies for severe eye disease? Good morning, thanks for taking my question. On the Factor XI programs here, could you speak to the potential commercial opportunities that are represented and what the future development plans look like here? Well, as I said, we're in the stages of evaluating two classes of antibodies that are attacking this pathway in two different ways.

Operator: Our next question comes from the line of David Risinger with Leerink Partners. Your line is now open.

Yeah, thanks very much. So, Regeneron is obviously a tremendous R&D leader but there's also substantial innovation happening outside of the company. And the company has a tremendous balance sheet that it's not really putting to work so, my question is, is there an opportunity to leverage Regeneron's eye disease commercial presence by acquiring novel potential blockbuster therapies for severe eye disease? Good morning, thanks for taking my question. On the Factor XI programs here, could you speak to the potential commercial opportunities that are represented and what the future development plans look like here? Well, as I said, we're in the stages of evaluating two classes of antibodies that are attacking this pathway in two different ways.

David Risinger: Yeah, thanks very much. So, Regeneron is obviously a tremendous R&D leader but there's also substantial innovation happening outside of the company. And the company has a tremendous balance sheet that it's not really putting to work. So, my question is, is there an opportunity to leverage Regeneron's eye disease commercial presence by acquiring novel potential blockbuster therapies for severe eye disease? And if so, does the company see any opportunities in the near to medium-term to do so? Thanks very much.

Salveen Richter: Good morning. Thanks for taking my question. On the Factor XI programs here, could you speak to the potential commercial opportunity that are represented and what the future development plans look like here? Thank you.

Yeah, it's a great question. Good morning, thanks for taking my question. On the Factor XI programs here, could you speak to the potential commercial opportunities that are represented and what the future development plans look like here? Well, as I said, we're in the stages of evaluating two classes of antibodies that are attacking this pathway in two different ways.

Leonard S. Schleifer: Yeah, it's a great question and it's one we ask every day here. Is there some opportunity that we aren't--isn't resulting from our own innovation that we should be trying to acquire? We have not seen any such large scale. Obviously, we've done some smaller scale and hundreds of millions of kind of numbers--or a few million--and whether or not we would--we could leverage any our in-line products or research capabilities, it's certainly something we think about but there's nothing that we, at the moment, for late-stage products, see an opportunity for.

Thanks, Len. Let's move to the next question, please, Shannon. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open. Good morning, thanks for taking my question. On the Factor XI programs here, could you speak to the potential commercial opportunities that are represented and what the future development plans look like here? Well, as I said, we're in the stages of evaluating two classes of antibodies that are attacking this pathway in two different ways.

Ryan Crowe: Thanks, Len. Let's move to the next question, please, Shannon.

Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open. Good morning, thanks for taking my question. On the Factor XI programs here, could you speak to the potential commercial opportunities that are represented and what the future development plans look like here? Well, as I said, we're in the stages of evaluating two classes of antibodies that are attacking this pathway in two different ways.

Operator: Our next question is from the line of Salveen Richter with Goldman Sachs. Your line is now open.

Salveen Richter: Good morning, thanks for taking my question. On the Factor XI programs here, could you speak to the potential commercial opportunity that are represented and what the future development plans look like here? Thank you. Well, as I said, we're in the stages of evaluating two classes of antibodies that are attacking this pathway in two different ways.

George Yancopoulos: Well, as I said, we're in the stages of evaluating in our Factor XI two classes of antibodies that are attacking this pathway in two different ways. We expect, I think we've already talked about, one of them will be more effective at preventing clot formation but potentially, come with slightly more serious side effect profiles. The other might be less effective but much safer. And as I said, we thought it was important to really, precisely interrogate this pathway using these two antibodies that are attacking two different parts. So, this is one enzyme--it has an activation domain and a catalytic domain. And by blocking, independently, the two different domains, we expect to deliver two different profiles, each one with the best-in-class antibody. Once we really understand those profiles, we will understand in which directions to be taking either one or both, potentially, of the antibodies. We can easily imagine taking forward the more effective one but for higher-risk patients, let's say, the less effective one into settings where you might want more safety and clot prevention is not as important. So, all of this is going to depend on these profiles and as I said, we hope to get our key data by the end of this year. And that should better define the efficacy and safety profile, how they compare to the various existing agents that are out there now and which direction to take them for which indication. So, two antibodies, two distinct profiles--we hope to better understand them based on our initial proof of concept study and from there, we'll understand where to take them and what the ultimate opportunity will be. But obviously, there's still enormous need here for agents that can block clot and thrombus formation. And so much depends on safety profiles here and we're very excited about having the opportunity to have these two very related but distinct profiles. Just to amplify a little bit of what George said, the direct oral anticoagulant market is a very, very large market.

George D. Yancopoulos: We expect, I think we've already talked about, one of them will be more effective at preventing slightly more serious side effect profiles. The other might be less effective, but much safer. And as I said, we thought it was important to really precisely interrogate this pathway using these two antibodies that are attacking two different parts. So this is one enzyme. It has an activation domain and a catalytic domain.

Speaker Change: Clock Formation

George Yancopoulos: So, this is one enzyme--it has an activation domain and a catalytic domain. And by blocking, independently, the two different domains, we expect to deliver two different profiles, each one with the best-in-class antibody. Once we really understand those profiles, we will understand in which directions to be taking either one or both, potentially, of the antibodies. We can easily imagine taking forward the more effective one but for higher-risk patients, let's say, the less effective one into settings where you might want more safety and clot prevention is not as important. So, all of this is going to depend on these profiles and as I said, we hope to get our key data by the end of this year. And that should better define the efficacy and safety profile, how they compare to the various existing agents that are out there now and which direction to take them for which indication. So, two antibodies, two distinct profiles--we hope to better understand them based on our initial proof of concept study and from there, we'll understand where to take them and what the ultimate opportunity will be. But obviously, there's still enormous need here for agents that can block clot and thrombus formation. And so much depends on safety profiles here and we're very excited about having the opportunity to have these two very related but distinct profiles.

George D. Yancopoulos: And by blocking independently the two different domains, we expect to deliver two different profiles, each one with the best-in-class antibody. Once we really understand those profiles, we will understand in which directions to be taking either one or both, potentially, of the antibodies. We can easily imagine taking forward the more effective one, but for higher-risk patients, let's say, the less effective one in settings where you might want more safety, and clot prevention is not as important.

Speaker Change: Once we really understand those profiles...

George Yancopoulos: So, all of this is going to depend on these profiles and as I said, we hope to get our key data by the end of this year. And that should better define the efficacy and safety profile, how they compare to the various existing agents that are out there now and which direction to take them for which indication. So, two antibodies, two distinct profiles--we hope to better understand them based on our initial proof of concept study and from there, we'll understand where to take them and what the ultimate opportunity will be. But obviously, there's still enormous need here for agents that can block clot and thrombus formation. And so much depends on safety profiles here and we're very excited about having the opportunity to have these two very related but distinct profiles.

George D. Yancopoulos: So all of this is going to depend on these profiles, and as I said, we hope to get our key data by the end of this year. And that should better define the efficacy and safety profile, how they compare to the various existing agents that are out there now, and which direction to take them for which indication. Two antibodies, two distinct profiles.

Speaker Change: Clack prevention is not as important.

Speaker Change: So, all of this...

George D. Yancopoulos: We hope to better understand them based on our initial proof of concept study, and from there, we'll understand where to take them and what the ultimate opportunity will be. But obviously, there's still an enormous need here for agents that can block clot and thrombus formation. So much depends on safety profiles here. And we're very excited about having the opportunity to have these two very related but distinct profiles. Just to amplify a little bit of what George said, the direct oral anticoagulant market is a very, very large market.

Speaker Change: two antibodies.

Speaker Change: We hope to better understand them based on our initial proof-of-concept study, and from there, we'll understand where to take them and what the ultimate opportunity will be. But obviously, there's still enormous need here for agents that can block clot and thrombus formation.

Speaker Change: So much depends on safety profiles here, and we're very excited about having the opportunity to have these two very related but distinct profiles.

Leonard S. Schleifer: Just to amplify a little bit of what George said, the direct oral anticoagulant market is a very, very large market. It's about a $20 billion market. If you could bring to part of that market, most of that market or some fragment of it--similar efficacy but with a better safety profile, then you really have a big opportunity here. So, that's what we're sort of focusing on. Can we deliver with one or the other antibody in the proper setting, as George was suggesting, a same or better efficacy but with a better safety profile? If we can give you that, if we can give patients that, then we will be able to really have a big, large market opportunity. And there are many settings where you don't use certain agents because of the safety profile, which could create whole new opportunities as well.

Speaker Change: Just to amplify a little bit of what George said, the direct oral anticoagulant market is a very, very large market. It's about a $20 billion market. If you could bring to part of that market, most of that market or some fragment, similar efficacy,

George D. Yancopoulos: It's about a $20 billion market. If you could bring to part of that market, most of that market, or some fragment of it, similar efficacy, but with a better safety profile, then you really have a big opportunity here. So that's what we're sort of focusing on. Can we deliver with one or the other antibody in the proper setting, as George was suggesting, same or better efficacy, but with a better safety profile? If we can give you that, if we can give patients that, then we will be able to really have a big, large market. And there are many settings where you don't use certain agents because of their safety profiles, which could create whole new opportunities.

Speaker Change: Then you really have a big opportunity here. So that's what we're sort of focusing on. Can we deliver with one or the other antibody in the proper setting as George was suggesting?

Speaker Change: Our next question is from the line of Carter Gould with Barclays. Your line is now open.

Carter Gould: Good morning. Congrats on the quarter. I appreciated the earlier commentary from Len on the pre-filled syringe effort, I guess, but for Marion and the team, just the confidence that the high-dose launch momentum won't be disrupted by the relative near-term disadvantage of Vizmo having a pre-filled syringe. And if you wanted to give more specificity on your own timelines, that would be appreciated.

George Yancopoulos: And there are many settings where you don't use certain agents because of the safety profile, which could create whole new opportunities as well.

Unknown Executive: Okay. Thank you. Let's move to the next question, please, Shannon. Well, I think I said in my prepared remarks that we're anticipating a launch in early 2025. I'm not sure what the competition is actually going to do about launch, but we're a matter of months, I think, apart if they launch ahead of us. And so I don't think that that's going to have a significant impact in the marketplace, where people are really focused, I think, on the profile of our drug, the durability of our drug, the safety experience they've had with Fliverset, the active ingredient. So we, The next question is from the line of Terence Flynn with Morgan Stanley. Your line is now open. You should think hard about it.

Ryan Crowe: Okay. Thank you. Let's move to the next question, please, Shannon.

Our next question Well, I think I said in my prepared remarks that we're anticipating a launch in early 2025. I'm not sure what the competition is actually going to do about launch, but we're a matter of months, I think, apart if they launch ahead of us. And so I don't think that that's going to have a significant impact in the marketplace, where people are really focused, I think, on the profile of our drug, the durability of our drug, the safety experience they've had with Fliverset, the active ingredient. So we, The next question is from the line of Terence Flynn with Morgan Stanley. Your line is now open. You should think hard about it.

Operator: Our next question is from the line of Carter Gould with Barclays. Your line is now open.

Good morning. Congrats on the quarter. Well, I think I said in my prepared remarks that we're anticipating a launch in early 2025. I'm not sure what the competition is actually going to do about launch, but we're a matter of months, I think, apart if they launch ahead of us. And so I don't think that that's going to have a significant impact in the marketplace, where people are really focused, I think, on the profile of our drug, the durability of our drug, the safety experience they've had with Fliverset, the active ingredient. So we, The next question is from the line of Terence Flynn with Morgan Stanley. Your line is now open. You should think hard about it.

Carter Gould: Good morning. Congrats on the quarter. I appreciated the earlier commentary from Len on the pre-filled syringe effort, I guess, but for Marion and the team--just the confidence that the high dose launch momentum won't be disrupted by the relative near-term disadvantage of VABYSMO having a pre-filled syringe. And if you wanted to give more specificity on your own timelines, that would be appreciated. Thank you.

Leonard S. Schleifer: Well, I think I said in my prepared remarks that we're anticipating a launch in early 2025. I'm not sure what the competition is actually going to do about launching but we're a matter of months, I think, apart if they launch ahead of us. And so, I don't think that that's going to have a significant impact in the marketplace. Where people are really focused, I think, on the profile of our drug, the durability of our drug, the safety experience they've had with AFLIBERCEPT, the active ingredient. So, we feel pretty confident in the ongoing launch. Thank you. We have time for two more question, please, Shannon. The next question is from the line of Terence Flynn with Morgan Stanley. Your line is now open. You should think hard about it.

Speaker Change: Thank you.

Well, I think I said in my prepared remarks.

Leonard S. Schleifer: Thank you. We have time for two more question, please, Shannon. The next question is from the line of Terence Flynn with Morgan Stanley. Your line is now open. You should think hard about it.

Ryan Crowe: Thank you. We have time for two more questions, please, Shannon.

Leonard S. Schleifer: The next question is from the line of Terence Flynn with Morgan Stanley. Your line is now open. You should think hard about it.

Operator: Our next question is from the line of Terence Flynn with Morgan Stanley. Your line is now open.

Leonard S. Schleifer: Hi, this is Chris, on for Terence. Just one question from us about EYLEA HD. Given what you have seen in the market dynamics in 2Q, how should we think about the pace of conversion for the second half of 2024? You should think hard about it.

Unknown: Hi, this is Chris, on for Terence. Just one question from us about EYLEA HD. Given what you have seen in the market dynamics in 2Q, how should we think about the pace of conversion for the second half of 2024?

Leonard S. Schleifer: You should think hard about it. That's your job. I don't know if Marion wants to have any comment there. I would just say that, as I commented earlier, we're very pleased with our progress in the EYLEA HD launch.

Leonard S. Schleifer: You should think hard about it. That's your job. I don't know if Marion wants to have any comment there.

Unknown Executive: That's your job. Thank you. Let's move to the final question. Thank you very much for taking my question. And I just want to, again, talk about ILAHD.

That's your job.

Speaker Change: that we're anticipating a launch in early 2025.

Marion McCourt: I would just say that, as I commented earlier, we're very pleased in our progress in the EYLEA HD launch.

I'm not sure what the competition is actually going to do about launching, but we're a matter of months, I think, apart if they launch ahead of us.

All right, thank you. Let's move to the final question, please, Shannon. Our next question is from the line of Mohit Bansal with Wells Fargo, Your line is now open. Thank you very much for taking my question. And I just want to, again, talk about ILAHD.

All right, thank you. Let's move to the final question, please, Shannon. Our next question is from the line of Mohit Bansal with Wells Fargo, Your line is now open.

Ryan Crowe: All right, thank you. Let's move to the final question, please, Shannon.

The safety experience they've had with the Fliverset, the active ingredients. So we we feel pretty confident in the ongoing launch.

Operator: Our last question is from the line of Mohit Bansal with Wells Fargo, Your line is now open.

Okay, thank you. We have time for two more questions, please, Shannon.

Hi, this is Chris on for Terence. Just one question from us about LEAHD. Given what you have seen in the market dynamics in 2Q, how should we think about the pace of conversion for the second half of 2024?

Mohit Bansal: Thank you very much for taking my question. And I just want to, again, talk about EYLEA HD. In terms of--Marion, if you could comment on, at this point, how much is switch versus naive patient at this point? I assume most of them are switch. Are they difficult to treat patients in the beginning? And then, when we think about going forward, do you think you're in the early innings of conversion or do you think there is some other dynamics we should think about from the pricing, as well as access point of view, as we model EYLEA HD versus standard dose EYLEA going forward? Thank you.

All right, thank you. Let's move to the final question, please, Shannon.

Our last question is from the line of Mohit Bansal with Wells Fargo. Your line is now open.

Unknown Executive: In terms of Mary, if you could comment on, at this point, how much is switching versus naive patient at this point? I assume most of them are switching. Are they difficult to treat patients in the beginning? And then when we think about going forward, do you think you're in the early innings of conversion, or do you think there is some other dynamics we should think about from the pricing as well as access point of view as we model highly HD versus standard dose ILEA going forward? Thank you.

Thank you very much for taking my question and I just want to again talk about Dial-A-HD.

versus naive patient at this point. I assume most of them are switched, and are they difficult to treat patient in the beginning? And then when we think about going forward,

Marion McCourt: So, it's always a combination of initiation for EYLEA HD of switch patients and then, of course, naive patients. So, I'd mentioned the profile today of switch patients to EYLEA HD--which is very encouraging--comes, not surprisingly, from EYLEA because it's the largest product in the category; secondarily from FARICIMAB and then, the third source of switch patients would be AVASTIN and then there's everything else. So, what's really encouraging, as I mentioned, in the quarter is that the utilization among treatment-naive patients doubled from the prior quarter. So, we'll continue to see an ongoing combination--as does every product, potentially, if it's got the right profile in the category--but the evolution of prescribing to EYLEA HD is progressing very well. Thanks, Marion. And thanks to everyone who dialed in today for your interest in Regeneron. We apologize to those remaining in the Q&A. I have a chance.

Switch Patients and then of course Naive Patients. So I'd mentioned the profile today of Switch Patients to ILEA HD which is very encouraging.

comes, not surprisingly, from ILEA, because it's the largest product in the category.

But what's really encouraging, as I mentioned in the quarter, is that

Marion McCourt: Thanks, Marion. And thanks to everyone who dialed in today for your interest in Regeneron. We apologize to those remaining in the Q&A queue that did not have a chance--that we did not have a chance to hear from. As always, the IR team is available to answer any remaining questions that you may have. Thank you once again and have a great day. This concludes today's conference call. Thank you for your participation. You may now disconnect.

Ryan Crowe: Thanks, Marion. And thanks to everyone who dialed in today for your interest in Regeneron. We apologize to those remaining in the Q&A queue that did not have a chance--that we did not have a chance to hear from. As always, the IR team is available to answer any remaining questions that you may have. Thank you once again and have a great day.

Marion McCourt: So we'll continue to see an ongoing combination, as will every product potentially if it's got the right profile in the category, but the evolution of prescribing to ILEA-HD is progressing very well. And thanks to everyone who dialed in today for your interest in Regeneron. We apologize to those remaining in the Q&A. I have a chance.

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

Thanks, Marion. And thanks to everyone who dialed in today for your interest in Regeneron. We apologize to those remaining in the Q&A queue that we did not have a chance to hear from. As always, the IR team is available to answer any remaining questions that you may have. Thank you once again, and have a great day.

Q2 2024 Regeneron Pharmaceuticals Inc Earnings Call

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