Q4 2023 Regeneron Pharmaceuticals Inc Earnings Call

February 2, 2024

Operator: Welcome to the Regeneron Pharmaceuticals 4th Quarter 2023 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.

Welcome to the Regeneron Pharmaceuticals fourth quarter 2023 earnings Conference call. My name is Shannon and I'll be your operator for today's call at.

At this time all participants are in a listen only mode.

Operator: Later, we will conduct a question and answer session. Please note that this conference is being recorded. I will now turn the call over to Ryan Crow, Senior Vice President, Investor Relations. You may begin. Good morning, good afternoon, and good evening to everyone listening around the world.

Later, we will conduct a question and answer session.

Please note that this conference is being recorded I will now turn the call over to Ryan Crow Senior Vice President Investor Relations you may begin.

Ryan Crowe: Good morning, good afternoon, and good evening to everyone listening around the world.

Ryan Crow: 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 fourth quarter 2023 earnings Conference call, an archive and transcript of this call will be available on the Regeneron Investor Relations website. Shortly after the call ends.

Ryan Crow: Thank you for your interest in Regeneron and welcome to our fourth quarter 2023 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 today 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 and Head of Commercial; Bob Landry, Executive Vice President and Chief Financial Officer; and Chris Fenimore, Senior Vice President and Controller. As many of you already know, Bob will retire from Regeneron after our form 10-K is filed next week and Chris has been appointed to become Regeneron's next CFO upon Bob's retirement. After our prepared remarks, the remaining time will be available for your questions. We anticipate today's call will last approximately 60 minutes.

Thank you for your interest in Regeneron and welcome to our fourth quarter 2023 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 today 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 and Head of Commercial; Bob Landry, Executive Vice President and Chief Financial Officer; and Chris Fenimore, Senior Vice President and Controller. As many of you already know, Bob will retire from Regeneron after our form 10-K is filed next week and Chris has been appointed to become Regeneron's next CFO upon Bob's retirement.

Ryan Crow: Joining me today are.

Ryan Crow: Joining me today 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 and Head of Commercial; Bob Landry, Executive Vice President and Chief Financial Officer; and Chris Fenimore, Senior Vice President and Controller.

Speaker Change: Doctor Leonard Schleifer Board Co Chair co founder President and Chief Executive Officer, Dr. George John Coppola Sport Co Chair co founder President and Chief Scientific Officer, Marion Mccourt Executive Vice President and head of commercial.

Bob Landry Executive Vice President and Chief Financial Officer, and Chris Fenimore, Senior Vice President and controller.

Ryan Crow: As many of you already know, Bob will retire from Regeneron after our form 10-K is filed next week and Chris has been appointed to become Regeneron's next CFO upon Bob's retirement.

Speaker Change: As many of you already know.

Speaker Change: Bob will retire from Regeneron. After our Form 10-K is filed next week and Chris has been appointed to become Regeneron next CFO upon bobs retirement.

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

Ryan Crow: I'd like to remind you that remarks made on today's call may include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and business, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payor covers and reimbursement issues, intellectual property, pending litigation and other proceedings, and competition. Each forward-looking statement is subject to risk and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-K for the year ended December 31st, 2023, which we expect to file with the SEC on Monday, February 5th.

Speaker Change: I'd like to remind you that remarks made on today's call may include forward looking statements about regeneron such statements may include but are not limited to those related to regeneron and its products and business.

Speaker Change: 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.

Speaker Change: Each forward looking statement is subject subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement.

Ryan Crow: 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-K for the year ended December 31st, 2023, which we expect to file with the SEC on Monday, February 5th.

A more complete description of these and other material risks can be found in regeneron and <unk> filings with the United States Securities and Exchange Commission, including its Form 10-K for the year ended December 31st 2023, which we expect to file with the SEC on Monday in February 5th.

Ryan Crow: 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 earnings results, press release, and our corporate presentation, both of which can be accessed on the Regeneron Investor Relations website.

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.

Speaker Change: 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 earnings.

<unk> press release, and our corporate presentation, both of which can be accessed on the regeneron Investor Relations website.

Leonard S. Schleifer: Once our call ends, Bob, Chris, and the IR team will be available to answer any further questions. With that, let me turn the call over to our President and Chief Executive Officer, Dr. Len Schleifer.

Speaker Change: Once our call and Bob Chris and the IR team will be available to answer any further questions with that let me turn the call over to our President and Chief Executive Officer, Dr. Len Schleifer Len.

Len Schleifer: Thank you, Ryan, and thank you to everyone joining today's call. The fourth quarter of 2023 capped another strong year for Regeneron, and Bob will walk you through our financial results. For my remarks today, I'd like to briefly look back on 2023 and then discuss what's to come in the year ahead. 2023 was another remarkable year for Regeneron, highlighted by several significant achievements that better position the company to deliver sustainable growth and long-term shareholder value. At the start of the year, we identified five key strategic imperatives.

Len Schleifer: Thank you Ryan and thank you to everyone joining today's call.

Fourth quarter 2023 capped another strong year food General line and Bob will walk you through our financial results for my remarks today I'd like to briefly look back at 2023, and then discuss what's to come in the year ahead.

Len Schleifer: 2023 was another remarkable year for regeneron highlighted by several significant achievements that better position the company to deliver sustainable growth and long term shareholder value.

Len Schleifer: 2023 was another remarkable year for Regeneron, highlighted by several significant achievements that better position the company to deliver sustainable growth and long-term shareholder value. At the start of the year, we identified five key strategic imperatives.

Len Schleifer: Part of the year, we did we identified five key strategic imperatives.

Leonard S. Schleifer: First, obtaining FDA approval and successfully launching EYLEA-HD. We did encounter a minor delay when we received a complete response letter in late June due to an issue at a third-party filler, but this was quickly remedied, and EYLEA-HD was granted approval in mid-August. With what we believe to be a best-in-class potential clinical profile, EYLEA-HD is poised to become the new standard of care for patients with wet, age-related macular degeneration and diabetic eye diseases. The launch is off to a great start, which Marion will discuss in a few minutes. Second, we had to defend our intellectual property related to EYLEA.

Len Schleifer: First obtaining FDA approval and successfully launching Eylea H D. We did encounter a minor delay when we received a complete response letter in late June due to an issue at a third party fill up but this was quickly remedied and Eylea H D was granted approval in mid August.

Len Schleifer: With what we believe to be a best in class potential clinical profile Eylea H D is poised to become the new standard of care for patients with wet age related macular degeneration and diabetic eye diseases. The launch is off to a great start, which maryanne will discuss in a.

Leonard S. Schleifer: Second, we had to defend our intellectual property related to EYLEA. We presented our best case and prevailed in the district court, which found that one of EYLEA's formulation patents was both valid and infringed by a biosimilar [inaudible] manufacturer. This favorable decision may have broad implications and could result in a delay of the biosimilar [inaudible] launch. Third, we and our collaborator, Sanofi, needed to continue driving DUPIXENT growth, not only by further penetrating previously-approved indications but also reaching even more patients suffering from other diseases driven by type-2 inflammation.

Maryanne: A few minutes.

Second we had to defend our intellectual property related to Eylea, we presented our best case and prevailed in district Court, which found that one of our latest formulation patents was both valid and infringed by a biosimilar a flipper set manufacturer this favorable decision.

Leonard S. Schleifer: We presented our best case and prevailed in the district court, which found that one of EYLEA's formulation patents was both valid and infringed by a biosimilar [inaudible] manufacturer. This favorable decision may have broad implications and could result in a delay of the biosimilar [inaudible] launch. Third, we and our collaborator, Sanofi, needed to continue driving DUPIXENT growth, not only by further penetrating previously-approved indications but also reaching even more patients suffering from other diseases driven by type-2 inflammation. In 2023, we did both.

We presented our best case and prevailed in the district court, which found that one of EYLEA's formulation patents was both valid and infringed by a biosimilar [inaudible] manufacturer. This favorable decision may have broad implications and could result in a delay of the biosimilar [inaudible] launch. Third, we and our collaborator, Sanofi, needed to continue driving DUPIXENT growth, not only by further penetrating previously-approved indications but also reaching even more patients suffering from other diseases driven by type-2 inflammation.

Maryanne: It may have broad implications and could result in a delay to biosimilar a flavor set launches.

Maryanne: Third, we and our collaborator Sanofi needed to continue driving to pyxis growth not only by further penetrating previously approved indications by also reaching even more patients suffering from other diseases driven by type two inflammation.

Leonard S. Schleifer: In 2023, we did both. DUPIXENT global net product sales grew by 34% on a constant currency basis to $11.6 billion. DUPIXENT led a new-to-brand prescription share in the United States across all five of its approved indications. We also had a major breakthrough in chronic obstructive pulmonary disease, or COPD. In March, we reported strong data from the BOREA study, which enrolled COPD patients with uncontrolled, moderate to severe disease and evidence of type-2 inflammation. The FDA granted breakthrough therapy designation during the summer, but it required additional evidence of efficacy to support a regulatory filing. Based on this feedback, We and Sanofi decided to conduct an interim analysis on the Replicant Notice Study, which read out similarly compelling results, enabling our December SPLA submission and a potential U.S. launch for this indication as early as mid-2024.

Maryanne: In 2023, we did vote to pixel global net product sales grew by 34% on a constant currency basis to $11 6 billion.

Leonard S. Schleifer: DUPIXENT global net product sales grew by 34% on a constant currency basis to $11.6 billion. DUPIXENT led a new-to-brand prescription share in the United States across all five of its approved indications. We also had a major breakthrough in chronic obstructive pulmonary disease, or COPD. In March, we reported strong data from the BOREA study, which enrolled COPD patients with uncontrolled, moderate to severe disease and evidence of type-2 inflammation. The FDA granted breakthrough therapy designation during the summer, but it required additional evidence of efficacy to support a regulatory filing. Based on this feedback, We and Sanofi decided to conduct an interim analysis on the Replicant Notice Study, which read out similarly compelling results, enabling our December SPLA submission and a potential U.S. launch for this indication as early as mid-2024.

Maryanne: Two picks and lead in new to brand prescription share in the United States across all five of its approved indications.

Maryanne: We also had a major breakthrough in chronic obstructive pulmonary disease or COPD.

Maryanne: In March we reported strong data from the Boreas study, which enrolled COPD patients with uncontrolled moderate to severe disease and evidence of type two inflammation.

Maryanne: The FDA granted breakthrough therapy designation during the summer, but required additional evidence of efficacy to support a regulatory filing.

Maryanne: Based on this feedback we incentive fee decided to conduct an interim analysis on the replicate noticed study, which read out similarly compelling results, enabling our December S. BLA submission and the potential U S launch for this indication as early as mid.

Maryanne: 2024.

Leonard S. Schleifer: Fourth, we continue making progress toward our long-term goal of becoming a global leader in oncology. 2023 was highlighted by our regulatory submissions for LINVOSELTAMAB, our BCMA by CD3 bispecific in myeloma, and ODRONEXTAMAB, our CD20 by CD3 bispecific in lymphoma, while continuing to advance other opportunities in solid tumors. And finally, we needed to advance our early-stage pipeline. And over the course of 2023, we presented intriguing proof-of-mechanism or proof-of-concept data across hematology and genetic medicines, as well as other areas, including obesity, with data from non-human primates. Many of these early programs, which George will run through in a few minutes, represent first or best-in-class opportunities that we believe can drive long-term growth for Regeneron. Accomplishments in 2023 have put us in a position of strength entering 2024.

Maryanne: Fourth we continued making progress toward our long term goal of becoming a global leader in oncology.

Maryanne: 2023 was highlighted by our regulatory submissions for <unk> cel to map, our bcm made by C. D. Three by specific in myeloma and <unk>, our CD 20 by CD three by specific in lymphoma.

Maryanne: Continuing to advance other opportunities in solid tumors.

Maryanne: And finally, we needed to advance our early stage pipeline and over the course of 2023, we presented intriguing proof of mechanism or proof of concept data across hematology and genetic medicines as weather as well as other areas, including obesity with data from nonhuman primates. Many.

Maryanne: These early programs, which George will run through in a few minutes represent first or best in class opportunities that we believe can drive long term growth for regeneron.

Leonard S. Schleifer: Accomplishments in 2023 have put us in a position of strength entering 2024.

Maryanne: Our accomplishments in 2023 have put us in a position of strength entering 2024 for this year one of our strategic imperatives is to continue driving commercial execution, especially the ongoing launch of Eylea H D. With the goal of access accelerating the pace of conversion from other anti.

Leonard S. Schleifer: This year, one of our strategic imperatives is to continue driving commercial execution, especially the ongoing launch of EYLEA-HD, with the goal of accelerating the pace of conversion from other anti-VEGF agents. Another important launch milestone was achieved last month when the Center for Medicare and Medicaid Services assigned a permanent J-code for EYLEA-HD that will go into effect on April 1st, 2024, at which point a potential reimbursement concern for physicians will be removed. We also need to continue to drive DUPIXENT's growth in its currently improved indications, as well as from the potential FDA approval and launch in COPD with an eosinophilic phenotype. If approved, DUPIXENT would represent the first meaningful advance in over a decade for the 300,000 patients in the United States suffering from this form of COPD and would be the first ever biologic approved for COPD.

VEGF agents.

Maryanne: Another important launch milestone was achieved last month, when the center for Medicare and Medicaid services assigned a permanent J code for Eylea H D that will go into effect on April 1st 2024 at which point a potential reimbursement concerns.

Leonard S. Schleifer: We also need to continue to drive DUPIXENT's growth in its currently improved indications, as well as from the potential FDA approval and launch in COPD with an eosinophilic phenotype. If approved, DUPIXENT would represent the first meaningful advance in over a decade for the 300,000 patients in the United States suffering from this form of COPD and would be the first ever biologic approved for COPD.

Maryanne: Physicians will be removed.

Maryanne: We also need to continue to drive new pixel growth in its currently approved indications as well as from the potential FDA approval and launch in COPD with an eosinophilic phenotype. If approved two picks and would represent the first meaningful advance in over a decade for the 300.

Maryanne: Thousands of patients in the United States suffering from this form of C. O P D and would be the first ever biologic approved for C. O P D.

Leonard S. Schleifer: In oncology this year, aside from continuing to build on the success of Liptio in non-melanoma skin cancers and non-small cell lung cancer, we're excited about the potential launches of Odonextamab and Limboceltamab, the latter of which has the potential to be the best-in-class bispecific for myeloma. We also expect to make significant advances across our pipeline in 2024, with key readouts for pheanlamab, or lag-3 antibody, in combination with libtio, in metastatic melanoma, and non-small cell lung, libtio in adjuvant cutaneous squamous cell carcinoma and our factor 11 antibodies in thrombosis which may inform pivotal studies, We also plan to initiate clinical trials in obesity, geographic atrophy, hemophilia B, and severe food allergies, in addition to expanding early studies of our CD28 co-stimulatory biospecific programs in solid and hematologic malignancies.

Maryanne: In oncology this year aside from continuing to build on the success of lip tayo non melanoma skin cancers, and non small cell lung cancer. We're excited about the potential launches of old Gen X to lab and Limbaugh South of Matt The latter of which has the potential to be the best in class.

Maryanne: <unk> Bispecific for myeloma.

Maryanne: We also expect to make significant advances across our pipeline in 2024 with key readouts for Fianna Mab or lag three antibody.

Maryanne: Combination with LIG tayo in metastatic melanoma, and non small cell lung cancer lip tayo in adjuvant cutaneous squamous cell carcinoma, and a factor 11 antibodies and sign on bonuses, which may inform pivotal studies.

Maryanne: We also plan to initiate clinical trials in obesity geographic atrophy, hemophilia B and severe food allergies. In addition to expanding early studies of ICD 28, co stimulatory bispecific programs in solid and hematologic malignancies.

Leonard S. Schleifer: In closing, we had a strong 2023 and are poised to deliver in 2024 and beyond. Our pipeline of over 30 clinical programs is delivering important and differentiated innovations. Our commercial team is executing well, and we continue to look at ways to efficiently deploy capital to drive shareholder returns over time. Before I hand it over to George, I want to take a moment to thank Bob Landry for his many contributions to Regeneron over his 10 years as our Chief Financial Officer.

Maryanne: In closing we had a strong 2023 and are poised to deliver in 2024 and beyond our pipeline of over 30 clinical programs is delivering important and differentiated innovations our commercial team is executing well and we continue to look at ways to them.

Maryanne: Patiently deploy capital to drive shareholder returns over time.

I hand, it over to George I wanted to take a moment to thank Bob Landry for his many contributions to regeneron over his 10 years as our Chief Financial Officer and.

Leonard S. Schleifer: In addition to helping fortify Regeneron's financial strength and discipline, Bob has been an incredible mentor to many of Regeneron's current and future leaders, helped drive our financial results over the past decade, and worked tirelessly to ensure we have the resources needed to help improve the lives of patients around the world. Bob, on behalf of the entire Regeneron family, thank you, and we wish you continued good health and happiness. As we first announced back in September, upon Bob's retirement next week, Chris Fenimore will become the CFO of Regeneron. We all look forward to working closely with Chris in his new role, knowing he brings a similar rigor and depth of financial knowledge that will ensure continuity and collaboration across the organization. With that, I'll now turn the call over to George. Thanks. This was really an impressive opening performance.

George: In addition to helping fortify regeneron financial strength and discipline, Bob it's been an incredible mentor to many of Regeneron its current and future leaders helped drive our financial results over the past decade and worked tirelessly to ensure we have the resources needed to help improve the lives of patients.

George: Around the world Bob on behalf of the entire regenerative family. Thank you and we wish you continued good health and happiness.

George: As we first announced back in September Pons Bob's retirement next week, Chris Panama will become the CFO of Regeneron, we all look forward to working closely with Chris in his new role knowing he brings a similar rigor in depth of financial knowledge that will ensure continuity and collaboration across the organization.

Jason.

George: With that I'll now turn the call over to George.

George: Thanks Lynn.

Jason: That was really an impressive for you I have to say.

George Damis Yancopoulos: 2023 was another year of firsts delivered by Regeneron, as well as together with our collaborators, all of which have the potential to change the practice of medicine. Starting with inflammation and immunology, as you heard from Len, we are planning yet another launch for Dupixen, this time in eosinophilic COPD, which would represent the sixth disease that this remarkable medicine is approved to treat and the fifth for which it would be first in class. Dupixent's transformative potential in COPD is based on the unprecedented results from our first phase 3 trial, BORIAS, which were then confirmed by our second phase 3 trial, NOTICE, demonstrating that Dupixent-treated patients had a 34% reduction in the annualized rate of moderate to severe COPD exacerbations compared to IL-33 blocking antibody.

2020 three was another year of first delivered by Regeneron as well as together with our collaborators all of which have the potential to change the practice of medicine.

Starting with inflammation immunology as you heard from Len, we are planning yet another launch for <unk> at this time in eosinophilic, COPD, which reference which would represent.

Jason: This remarkable medicine is approved to treat and the fifth for which you would be first in class depicting transformative potential in COPD.

Just on the unprecedented results from our first phase III trial, Boreas, which would then confirm bar second phase III trial notice demonstrating that your picks in treated patients had a 34% reduction in the annualized rate of moderate to severe COPD exacerbations.

Jason: IL 33 blocking antibody the pivotal Aerophyte, one and two studies pass an interim futility analysis last year. The studies are now on track to complete enrollment.

George Damis Yancopoulos: The pivotal ARIFI1 and 2 studies passed an interim futility analysis last year. The studies are now on track to complete enrollment in 2024 with an anticipated readout in 2025. If the phase 2 results from these studies even approach the phase 2 data reported in former smokers, where a 42% reduction in annualized exacerbation rate was observed, it has the potential to further transform the treatment paradigm for COPD. Later this year, we are planning on testing an innovative new treatment approach for severe food allergies using a combination of transient BCMA by CD3 bispecific intervention in patients receiving dupixent therapy. As many of you know, allergic responses are driven by pathologically high levels of immunoglobulin E or IgE. This is why many say the E in IgE stands for evil.

In 2024 with an anticipated readout in 2025.

Jason: If the phase III results from New studies, even approach the phase two data reported in former smokers were a 42% reduction in the annualized exacerbation rate was observed.

Jason: Mac has the potential to further transform the treatment paradigm for COPD.

Jason: Later this year, we are planning on testing an innovative new treatment approach for severe food allergies, using a combination of transient PUC made by CPT III by specific intervention in patients receiving <unk> therapy as many of you know allergic responses are driven by pathologically high levels.

Jason: Oh, the immunoglobulin a or Iga. This is why many say the E N I G E stands for evil.

George Damis Yancopoulos: About 40 years ago, it was discovered that interleukin-4 and interleukin-13 were the switch factors required for switching to IgE production, based on exciting preclinical, data including in non-human primates, as well as human data, our innovative approach has the potential to reverse severe allergies by first eliminating the long-lived plasma cells that serve as an IgE reservoir with the BCMA by CD3, followed by blocking of de novo immunoglobulin class switching to IgE with the Dupixac. We are looking forward to starting a small proof-of-concept study which will inform next steps for this program. We believe this approach has the potential to benefit the millions of people suffering from severe allergies who are at constant risk, tragically highlighted just last week by the widely reported death of yet another young person unknowingly exposed to a food allergy. Moving to oncology.

Jason: 40 years ago. It was discovered that interleukin four and interleukin 13, where the switch factors required for switching to Iga production base.

Jason: Based on exciting preclinical.

Jason: Data, including in nonhuman primates, as well as human data our innovative approach has the potential to reverse severe allergies by first eliminating the long lived plasma cells that serve as an E.

Jason: E reservoir with the PUC made by <unk>, three followed by blocking a de Novo immunoglobulin class switching to GE with the depiction.

Jason: We are looking forward to starting a small proof of concept study, which will inform next steps for this program. We believe this approach has the potential to benefit millions of people suffering from severe allergies, who are at constant risk.

Jason: Tragically hybrid highlighted just last week by the widely reported death of yet another young person unknowingly exposed to food allergy.

Jason: Moving to oncology lip tayo is the leading PD, one antibody for non melanoma skin cancer, including metastatic cutaneous squamous cell carcinoma, or SEC and basal cell carcinoma.

George Damis Yancopoulos: Leptio is the leading PD-1 antibody for non-melanoma skin cancers, including metastatic cutaneous squamous cell carcinoma, or CSCC, and basal cell carcinoma. We are looking forward to potentially expanding the currently approved CSCC indication to include adjuvant CSCC. And we expect results from potentially pivotal interim analysis in this setting in the second half of the year. Regarding leptile combinations, our most advanced is the combination with our LAG-3 antibody, Fanlamab. As a reminder, our early clinical data in three separate first-line metastatic melanoma cohorts demonstrated potential for best-in-class efficacy when compared cross-trial with the approved anti-LAG-3 PD-1 combination product, highlighted by objective response rates greater than 60% and an estimated median progression-free survival of longer than 15 months. These early clinical data suggest that the Leptile-Phenylamide combination may be one of the most exciting examples of a checkpoint inhibitor combination with clinically meaningful benefit and with a safety profile that is similar to that seen with anti-PD-1 monotherapy.

Jason: Looking forward to potentially expanding the currently approved CFCC indication to include adjuvant SEC and we expect results from potentially pivotal interim analysis.

Jason: In this setting in the second half of the year.

Jason: Regarding lip tayo combinations are most advances the combination with our lag three antibody San limit as a reminder, our early clinical data in three separate first line metastatic melanoma cohorts demonstrated potential for best in class efficacy when compare cross trial with the approved <unk>.

Jason: Anti lag three PD, one combination products highlighted by objective response rates greater than 60% an estimated median progression free survival of longer than 15 months. These early clinical data suggested that the <unk> combination maybe one of the most exciting examples of the checkpoint inhibitor combination with.

Jason: Clinically meaningful benefit and with the safety profile that is similar to that seen with anti PD one monotherapy.

George Damis Yancopoulos: We're expecting a potentially pivotal initial readout from our first-line metastatic melanoma trial by the end of this year. We also anticipate phase 2 data in non-small cell lung cancer in late 2024. On to bispecifics, starting with solid tumors. In the dose escalation trial of our EGFR by C28 co-stimulatory bispecific combined with Leptile, we observed promising activity in microsatellite-stable colorectal cancer at higher doses of the co-stimulatory bispecific. In terms of safety, so far, we have not seen an increase in immune-related adverse events with this COVID-19 vaccine.

Jason: We are expecting a potentially pivotal initial readout from our first line metastatic melanoma trial by the end of this year. We also anticipate phase II data in non small cell lung cancer in late 2024.

Onto bi specifics starting with solid tumors in the dose escalation trial of our Egfr by 328 co stimulatory Bispecific combined with lip tile, we observed promising activity in microsatellite stable colorectal cancer with higher doses of the coaster in terms of safety. So far we have.

Jason: <unk> seen an increase in immune related adverse events with this coaster.

George Damis Yancopoulos: Based on these encouraging early data, which will be presented at a scientific forum later this year, we will be initiating expansion cohorts across several solid tumors in the first half of the year. In 2024, we are also planning to provide updates for MUX16xCD3 and MUX16xCD28 programs in advanced ovarian cancer, and Next, our BISPECIFIC for hematology oncology. For livosultomab, our BCMA by CD3 BISPECIFIC for multiple myeloma, FDA acceptance of our BLA submission is expected later this month, and the EMA recently accepted our MAA submission. These submissions were supported by a potentially best-in-class profile in late-line myeloma in terms of efficacy, safety, dosing, as well as convenience. A confirmatory phase 3 study, as well as studies in earlier stages of myeloma and premalignant disease, are enrolling or will soon begin enrolling patients. For odronextramab, our CD20 by CD3 bispecific antibody for non-Hodgkin lymphoma.

Jason: Based on these encouraging early data, which will be presented at a scientific forum. Later this year, we will be initiating expansion cohorts across several solid tumors in the first half of the year.

Jason: In 2024, we are also planning to provide updates for our <unk> by <unk>, three and <unk> by CD 28 programs in advanced ovarian cancer.

Jason: Next to our Bispecific for hematology oncology for <unk> or <unk> by <unk> Bispecific for multiple myeloma FDA acceptance of our BLA submission is expected later this month.

Jason: The EMA recently accepted our MAA submission. These submissions was supported by a potentially best in class profile in late line myeloma in terms of efficacy safety dosing as well as convenience a confirmatory phase III study as well as studies in earlier stages of myeloma and pre malignant disease or <unk>.

Rolling or will soon begin enrolling patients.

Jason: Roger next to map, our CD 20 by CD three bispecific for non Hodgkin's lymphoma. The FDA decision for our BLA is expected by its March 31st <unk> date, and the decision is expected in the second half of the year.

George Damis Yancopoulos: The FDA decision for our BLA is expected by its March 31st PDUFA date, and the EU decision is expected in the second half of the year. In terms of additional recent news for our Oncology and Immunology Pipeline, this week, we announced the formation of Regeneron Cell Medicines Unit and that we are acquiring full development and commercialization rights for 270 BIOS Pipeline of Investigational Immune Cell Therapy. We have worked with 270 since 2018 on many of these programs and are excited about the opportunity to continue advancing our collective effort. After the deal closing, certain 270 employees will join Regeneron Cell Medicines and continue to work on addressing cancer and other serious diseases in novel ways, including by combining Regeneron's antibody capabilities with CAR-T therapy. Moving from Immunology and Oncology to Obesity and Metabolic Diseases. Despite all the enthusiasm surrounding GLP-1 agonists for obesity, it has been increasingly recognized that profound weight loss is accompanied by substantial muscle loss, accounting for up to as much as 40% of the weight loss.

Jason: In terms of additional recent news for our oncology and immunology pipeline. This week, we announced the formation of Regeneron cell medicines unit and that we are acquiring full development and commercialization rights for 270 bio's pipeline of investigational immune cell therapies. We have worked with 270 since 2018 on many of these.

Jason: Programs and are excited about the opportunity to continue advancing our collective efforts.

Jason: After deal closing certain $2 70 employees will join Regeneron cell medicines and continue to work on addressing cancer and other serious diseases in novel ways, including by combining regeneron antibody capabilities with car T therapies.

Jason: Moving from immunology, and oncology to obesity and metabolic diseases.

Jason: Despite all the enthusiasm surrounding <unk>, one agonists for obesity. It has been increasingly recognized that the profound weight loss is accompanied by substantial muscle loss accounting for up to as much as 40% of the weight loss. This potentially irretrievable muscle loss can be catastrophic for patients.

George Damis Yancopoulos: This potentially irretrievable muscle loss can be catastrophic for patients and may even lead to major public health concerns in the future. We have previously shown that our antibodies targeting myostatin and Activin A have the potential to preserve and grow muscle in human trials. Based on these data, as well as additional data in obese, non-human primates, we believe that inhibiting these pathways on top of GLP-1 receptor agonism has the potential to achieve comparable overall reductions in body weight, but with improved quality of weight loss, resulting in more fat loss while preserving, or actually increasing, muscle mass.

Jason: It may even lead to major public health concerns in the future. We have previously shown that our antibodies targeting milestone inactive and they have the potential to preserve and grow muscle in human trials based on these data as well as additional data in obese nonhuman primates, we believe that inhibiting these pathways on top of <unk>.

<unk> one receptor agonism has the potential to achieve comparable overall reductions in body weight.

With improved quality of the weight loss, resulting in more fat loss, while preserving or actually increasing muscle mass.

George Damis Yancopoulos: In mid-2024, we plan to start our first clinical trial to evaluate the combination of our muscle preservation antibodies in combination with semaglutide. Also, in 2024, we are anticipating proof of concept data for our Factor XI antibodies in the setting of prevention of venous thromboembolism after knee replacement surgery. Based on preclinical and healthy volunteer data, our antibody approach demonstrated more complete Factor XI blockade compared to competing approaches in development for coagulation disorders, and the program is on a rapid path to a registrational trial starting late next late this year or early next early next. We'll now conclude with our efforts in genetic medicine. Our siRNA collaboration with L. nylum has demonstrated successful silencing of genes in the liver and, for the first time with siRNA, in the brain.

Jason: In mid 2024, we plan to start our first clinical trial to evaluate the combination of our muscle preservation antibodies in combination with <unk> will also in 2024, we are anticipating proof of concept data for a factor <unk> antibodies in the setting of prevention of venous thromboembolism after knee replacement surgery.

Jason: Just on preclinical and healthy volunteer data our antibody approach demonstrated more complete factor 11 blockade compared to competing approaches in development for coagulation disorders and the program is on rapid path to a registrational trial starting.

Jason: Late late this year or next early next year, we will now conclude with our efforts in genetic medicines.

Jason: Our <unk> collaboration with on the island has demonstrated successful silencing of genes in the liver and for the first time for <unk> in the brain proof of principle was achieved for <unk> last year and we are anticipating additional data from that program this year, including from patients who have received multiple doses.

Jason: Based on the success, we are looking forward to and use RNA programs targeting.

Jason: CNS diseases entering the clinic this year, such as <unk> <unk> for ALS patients with <unk> mutations.

George Damis Yancopoulos: Proof of Principle was achieved for ALN APP last year, and we are anticipating additional data from that program this year, including from patients who have received multiple doses. Based on the success, we are looking forward to new sRNA programs targeting CNS disease entering the clinic this year, such as ALN-SOD for ALS patients with SOD1 mutation. Our collaboration with Intelia on CRISPR gene editing continues to advance, where we together produced the first example of CRISPR-based gene editing of a pathological gene in human beings. This initial program for a lead indication of TTR amyloidosis with cardiomyopathy is now the first in vivo CRISPR program clear to enter phase 3 studies in the United States.

Jason: Our collaboration with <unk> and CRISPR gene editing continues to advance where we together produce the first example of CRISPR based gene editing of a pathological gene in human beings. This initial program for our lead indication of GTR amyloidosis with cardiomyopathy is now in the.

Jason: The first in vivo CRISPR program cleared to enter phase III studies in the United States.

Jason: Together with <unk>, we also hope to be the first to use CRISPR technology to insert a corrective gene for deficiency disease. We recently achieved IND clearance for a CRISPR based gene insertion program for factor nine and initiated the lead in portion of the clinical trial to evaluate it as a potential cure for hemophilia.

George Damis Yancopoulos: Together with Intellia, we also hope to be the first to use CRISPR technology to insert a corrective gene for deficiency disease. We recently achieved ING clearance for a CRISPR-based gene insertion program for Factor IX and initiated the lead-in portion of a clinical trial to evaluate it as a potential cure for hemophilia B. Moving on, to genetic hearing loss.

Jason: <unk>.

Jason: Moving to genetic hearing loss, we were the first U S based company to announce hearing restoration in the young child suffering from genetic hearing loss after treatment with a novel gene therapy approach. We're excited by these early results for this ultra rare disease and look forward to advancing to the clinic additional programs to potentially address more common.

George Damis Yancopoulos: We were the first U.S.-based company to announce hearing restoration in a young child suffering from genetic hearing loss after treatment with our novel gene therapy approach. We are excited by these early results for this ultra-rare disease and look forward to advancing to the clinic additional programs to potentially address more common forms of monogenic hearing loss. These data represent validation of our viral-based gene therapy program, in this case, delivered to the cells of the inner ear.

Jason: <unk> of monogenic hearing loss these.

Jason: These data represent validation of our viral based gene therapy program. In this case locally delivered to the cells of the inner ear beyond. These efforts, we have made significant investments and leveraging our monoclonal and bispecific antibody expertise to use these agents to systematically deliver virally based genetic based pay.

Jason: Loads directly to specific tissues in the body not amenable to local delivery such as to muscle in the central nervous system based on encouraging preclinical data we will be progressing these approaches to the clinic in the coming years.

George Damis Yancopoulos: Beyond these efforts, we have made significant investments in leveraging our monoclonal and bispecific antibody expertise to use these agents to systematically deliver virally-based, genetically-based payloads directly to specific tissues in the body non-amenable to local delivery, such as to muscle and the central nervous system. Based on encouraging preclinical data, we will be progressing these approaches to the clinic in the coming years. Finally, concluding with another notable first-in-class program involving a combination of an siRNA with an antibody, in this case, to block the C5 complement target. Normally, one needs very high levels of infused antibody to achieve sufficient efficacy because of high target levels.

Jason: Finally, concluding with another notable first in class program involving a combination of <unk> with an antibody in this case to block the C. Five complement target <unk>.

Normally when needs very high levels of infused the antibody to achieve sufficient efficacy because of high target levels.

Regarding C five, but our CSI RNA co treatment dramatically lower C five target burden, allowing lower and more convenient antibody doses. We recently shared encouraging initial data from our phase III study in patients with <unk>, which supported our hypothesis that this combination approach could provide better efficacy than <unk>.

Jason: Troll of breakthrough hemolysis with more convenient dosing.

Jason: Based.

Jason: And building on these data we continue to enroll our phase III studies in <unk> in myasthenia Gravis. We're also planning to extend this combination approach to geographic atrophy dry AMD. While this combination is expected to have manageable systemic Texas cities, including elevated risk of infections, we believe that our approach.

George Damis Yancopoulos: But our siRNA co-treatment dramatically lowers C5 target burden, allowing lower and more convenient antibody dosing. We recently shared encouraging initial data from a phase 3 study in patients with PNH, which supported our hypothesis that this combination approach could provide better efficacy and control of breakthrough hemolysis with more convenient dosing. Peace.

Has several potential advantages over recently approved complement inhibiting agents for <unk>, which are delivered directly to the eye and have resulted in a rare but serious cases of retinal vasculitis, sometimes resulting in permanently impaired vision.

Jason: In conclusion, Regeneron R&D engine continues to grow and deliver many firsts, including differentiated early mid and late stage opportunities and we're looking forward to additional progress in 2024.

George Damis Yancopoulos: Building on these data, we continue to enroll our phase three studies in PNH and myosinia gravis. We're also planning to extend this combination approach to geographic atrophy and dry MD. While this combination is expected to have manageable systemic toxicities, including elevated risk of infections, we believe that our approach has several potential advantages over recently approved complement inhibitors for GA, which are delivered directly to the eye and have resulted in rare but serious cases of retinal vasculitis, sometimes resulting in permanently impaired vision.

Before I turn the call over Mary I would like to add my thanks, and appreciation to Bob for his many years of devoted efforts and leaderships and welcoming and look forward to adding Chris Fenimore to our leadership team.

Jason: With that I will turn it over to Mary.

Mary: Thanks George.

Mary: <unk> delivered strong results in the fourth quarter and for the year over the course of 2023, we successfully launched Eylea Hte grew depicts and across the type two inflammatory.

Mary: Amatory diseases and expanded <unk> presence in life and non melanoma skin cancers, we look forward to several potential approvals this year and new therapeutic categories, including in COPD with depictions and hematologic oncology using new treatment modalities.

Marion McCourt: In conclusion, Regeneron's R&D engine continues to grow and deliver many firsts, including differentiated early, mid, and late stage opportunities, and we are looking forward to additional progress in 2024. Before I turn the call over, Marion, I would like to add my thanks and appreciation to Bob for his many years of devoted efforts and leadership, and welcome and look forward to adding Chris Fenimore to our leadership team. With that, I will turn it over to Marion. Thank you, George.

Mary: Start with a retinal franchise in January we announced fourth quarter combined U S. Eylea HD and Eylea net product sales of $1 $4 6 billion in its first full quarter Eylea HD net product sales were $123 million based on growing demand and positive early physician experience.

Eylea HD is already being used across a broad range of patient types, including those switching from eylea other branded agents or avastin.

Well as modest but increasing use in treatment nave patients in the fourth quarter, Eylea HD and IEM together secured 49% of the anti veg, Jeff category share, despite increasing competition and changing market dynamics. This share gain was driven by the differentiated efficacy in.

Marion McCourt: Our business delivered strong results in the fourth quarter and for the year. Over the course of 2023, we successfully launched ILEA-HD, grew Dupixent across approved type 2 inflammatory diseases, and expanded Liptia's presence in lung and non-melanoma skin cancers. We look forward to several potential approvals this year in new therapeutic categories, including in COPD with dupixent and in hematologic oncology using I'll start with our retinal franchise.

Mary: Safety profile of our medicine as well as a short term disruption in compounded avastin due to a quality issue at a large supplier that has since been resolved.

Mary: Since launch we have made significant progress in securing access and reimbursement for Eylea HD more than two thirds of eligible lives are now covered with the vast majority having first line or single step edit access in Medicare fee for service, which represents approximately 45% of total category use.

Marion McCourt: In January, we announced fourth-quarter combined U.S. ILEA HD and ILEA net product sales of $1.46 billion. In its first full quarter, ILEA HD net product sales were $123 million, based on growing demand and positive early physician experience. ILEA HD is already being used across a broad range of patient types, including those switching from ILEA, other branded agents, or Vastan, as well as modest but increasing use in treatment-naive patients.

Mary: <unk> are being paid across 100% of jurisdictions using a miscellaneous J code.

Mary: Going ahead in 2024, we remind you that the first quarter is typically impacted by payer reauthorization and that Eylea HD will remain subject to a miscellaneous J code. However in late January we achieved another important launch milestone with CMS as assignment of a permanent J code friendly HD.

Mary: We will go into effect on April one.

Mary: This will provide additional reimbursement confidence for those physicians hesitant to prescribed before a permanent J code based on their negative experiences with other new disease medicines. Overall, we are very excited about the future of our retinal franchise. We continued to see physicians prescribed eylea HD and both treatment experienced.

Marion McCourt: In the fourth quarter, ILEA, HD, and ILEA together secured 49% of the anti-veg death category share despite increasing competition and changing market dynamics. This share gain was driven by the differentiated efficacy and safety profile of our medicines, as well as a short-term disruption in compounded avastin due to a quality issue at a large supplier that has since been resolved. Since launch, we've made significant progress in securing access to and reimbursement for ILEA-HD. More than two-thirds of eligible lives are now covered, with the vast majority having first-line or single-step edit access. Medicare Fee-for-Service, which represents approximately 45% of total category use, claims are being paid across 100% of jurisdictions using a miscellaneous J code.

Mary: Treatment naive settings as NBA HD is increasingly recognized as the new standard of care now.

Mary: Now did pixel fourth fourth quarter 2023, global net sales grew 31% on a constant currency basis to $3 2 billion and U S. Net sales grew 28% to $2 5 billion with more than 800000 patients on therapy worldwide. It takes is one of the most important biologic medicines for patients across the spectrum.

Mary: Diseases. Additionally continues to have significant growth potential based on new and upcoming indications.

And U S depicts it lead new to brand prescription share across all five approved indications an important leading indicator for future growth. In addition to takes it already leads total prescription share in four of five approved indications and we are approaching share leadership in biologic asthma and <unk>.

Marion McCourt: Looking ahead in 2024, we remind you that the first quarter is typically impacted by payer reauthorizations, and that ILEA HD will remain subject to a miscellaneous J code. However, in late January, we achieved another important launch milestone with CMS's assignment of a permanent J code for ILEA HD that will go into effect on April 1st. This will provide additional reimbursement confidence for those physicians hesitant to prescribe before a permanent J code based on their negative experiences with other new eye disease medications. Overall, we are very excited about the future of our retinal franchise. We continue to see physicians prescribe ILEA-HD in both treatment-experienced and treatment-naive settings, as ILEA-HD is increasingly recognized as the new standard of care. Now to Dupixent, where fourth-quarter 2023 global net sales grew 31% on a constant currency basis to $3.2 billion, and U.S. net sales grew 28% to $2.5 billion. With more than 800,000 patients on therapy worldwide, Dupixent is one of the most important biologic medicines for patients across the spectrum of diseases.

Mary: The topic dermatitis depicts since the largest indication physicians continue to prescribe detection as a therapy of choice. Despite increased competition over the course of 2023 fourth quarter depicts <unk> new to brand prescription share and modestly increase sequentially compared to the third quarter 2023, driven by its differentiate.

Mary: <unk> mechanism of action clinical results and trusted safety profile, including approval and patients as young as six months of age.

Mary: Since U S. Labor was recently updated with efficacy and safety data for patients with moderate to severe hand or foot atopic dermatitis.

Mary: <unk> is the only biologic medicine with data in the label supporting use for this subset of patients with this hard to treat disease.

Mary: Beyond atopic dermatitis, but also continues in asthma and nasal polyps both of which are already blockbuster indications. The recent launches for ascend until like esophagitis notice.

Mary: And <unk> further contributed to <unk> performance and represent indications of significant growth potential in which prior to depicts since approval had no FDA approved treatments nearly 25000 patients in the U S alone have already initiated therapy and detection.

Mary: The Fda's recent approval of detection and pediatric ele extend this indication to patients as young as one year of age where approximately 20000 children in the U S.

Marion McCourt: Additionally, it continues to have significant growth potential based on new and upcoming indications. In the U.S., Dupixent leads new-to-brand prescription share across all five approved indications, an important leading indicator for future growth. In addition, Dupixent already leads total prescription share in four or five approved indications, and we are approaching share leadership in biologic asthma. In atopic dermatitis, Dupixent's largest indication, physicians continue to prescribe Dupixent as their therapy of choice.

Mary: Being treated for EOG with unapproved therapies.

Mary: Patient Initiations also continue to accelerating <unk> solidifying depicted as the standard of care for multiple dermatologic conditions in summary depiction is delivering on its potential as one of the most important biologic medicines of our generation with significant remaining opportunity for growth, we anticipate bringing to <unk>.

To many more patients this year across approved indications the pediatric launch is already underway and we are actively preparing to launch <unk> in a scenario like COPD pending potential FDA approval later this year and finally till a tayo fourth quarter global net sales grew 43% year over year.

Marion McCourt: Despite increased competition over the course of 2023, the fourth quarter depicts a new-to-brand prescription share in AD modestly increased sequentially compared to the third quarter 2023, driven by its differentiated mechanism of action, clinical results, and trusted safety profile, including approval in patients as young as six months of age. Dupixent's U.S. label was recently updated with efficacy and safety data for patients with moderate to severe hand or foot Dupixent is the only biologic medicine with data in the label supporting use for this subset of patients with this hard-to-treat disease. Beyond atopic dermatitis, growth also continues in asthma and nasal polyps, both of which are already blockbusters. The recent launches for eosinophilic esophagitis, known as EOE, and Pragenodularis further contributed to Dupixen's performance and represent indications of significant growth potential. For EOE, which prior to Dupixen's approval had no FDA-approved treatments, nearly 25,000 patients in the U.S. alone have already initiated therapy on Dupixen. The FDA's recent approval of Dupixent and Pediatric EOE extends this indication to patients as young as one year of age, where approximately 20,000 children in the U.S. are being treated for EOE with unapproved therapy.

Mary: On a constant currency basis to $244 million with U S. Net sales of $155 million with Tayo continues to lead the category of non melanoma skin cancers, and we've made progress in penetrating the non small cell lung cancer market. In 2024, we expect continued growth across all indications advancing.

Mary: Goal to exceed $1 billion in <unk>.

Mary: Annual lift higher net sales in conclusion 2024 provides the opportunity to further build regeneron has market leading positions with our medicines and cross even more therapeutic areas now I will turn the call over to Bob.

Christopher Thomas Schott: Thank you Maryann my comments today on Regeneron <unk> financial results and outlook will be on a non-GAAP basis.

Christopher Thomas Schott: Unless otherwise noted regeneron ended 2023 with strong performance in the fourth quarter, excluding contributions from <unk> total revenues increased 14% year over year to $3 4 billion, primarily driven by sales growth and margin expansion from depicts the launch of Eylea HD and strong <unk>.

Christopher Thomas Schott: Sales growth from lip tayo.

Christopher Thomas Schott: Fourth quarter diluted net income per share was $11 86 on net income of $1 4 billion.

Christopher Thomas Schott: Moving to collaboration revenue and starting with Bayer fourth quarter 2023, ex U S. Eylea net product sales were $890 million up 4% on a constant currency basis versus the prior year total Bayer collaboration revenue was $377 million of which $345 million related to <unk>.

Marion McCourt: Patient initiations also continue to accelerate in Prague and Andaluras, solidifying PIGSEN as the standard of care for multiple dermatologic conditions. In summary, Dupixent is delivering on its potential as one of the most important biologic medicines of our generation, with significant remaining opportunity for growth. We anticipate bringing Dupixent to many more patients this year across approved indications. The pediatric EOE launch is already underway, and we are actively preparing to launch. Accident in a Cinephilic COPD Pending, Possible FDA approval later this year. And finally, to Liptio, fourth quarter global net sales grew 43% year over year on a constant currency basis to $244 million, with U.S. net sales of $155 million. Liptio continues to lead the category in non-melanoma skin cancers, and we've made progress in penetrating the non-small cell lung cancer market.

Christopher Thomas Schott: Our share of Eylea net profits outside the U S.

Christopher Thomas Schott: Total scientific collaboration revenue.

Christopher Thomas Schott: Grew 19% in the fourth quarter of 2000 $23 million to $993 million.

Christopher Thomas Schott: Excluding a $50 million.

Christopher Thomas Schott: Dollar sales milestone recorded in the fourth quarter of 2022.

Christopher Thomas Schott: Scientific collaboration revenue grew 26%.

Christopher Thomas Schott: Our share of collaboration profit was $886 million, an increase of 43% versus the fourth quarter of 2022, driven by to pick since continued volume growth and improving margins.

Christopher Thomas Schott: Reimbursements for manufacturing of commercial supply component of Santa Fe collaboration revenues declined 36% versus the prior year due to the implementation of a new higher yielding manufacturing process.

Christopher Thomas Schott: At the end of 2023, the Santa fee development balance was $2 33 billion, reflecting a net decrease of $534 million compared to the balance as of December 31 2022.

Marion McCourt: In 2024, we expect continued growth across all indications, advancing our goal to exceed $1 billion in annual Liptio net sales. In conclusion, 2024 provides the opportunity to further build Regeneron's market-leading positions with our medicines across even more therapeutic areas. Now I'll turn the call over to Bob. Thank you, Marion. My comments today on Regeneron's financial results and outlook will be on a non-gap basis, unless otherwise noted. Regeneron ended 2023 with a strong performance in the fourth quarter, excluding contributions from Ranapreve. Total revenues increased 14% year-over-year to $3.4 billion, primarily driven by sales growth and margin expansion from Depixent, the launch of ILEA HD, and strong sales growth from Liptide. Fourth quarter diluted net income per share was $11.86 on net income of $1.4 billion.

Christopher Thomas Schott: Recall. This decrease is primarily recorded as a reduction to our share of collaboration profits. We continue to expect this balance to be fully reimbursed in the next few years, which would result in a significant step up in our <unk> collaboration profits.

Christopher Thomas Schott: Other revenue was $213 million in the fourth quarter of 2023 up 66% versus the prior year, primarily driven by higher royalties from Novartis on sales of <unk>.

Christopher Thomas Schott: And an increase in our share of Arcalis profit from connect discuss.

Christopher Thomas Schott: The increase in other revenue also reflects higher reimbursements for increased shipment volumes of ex U S commercial supplies of Praluent to sign a fee.

Christopher Thomas Schott: Moving now to our operating expenses fourth quarter 2023, R&D expense grew 13% year over year to one 3 billion, which reflects continued investment in our growing pipeline.

Robert E. Landry: Moving to Collaboration Revenue and Starting with Bayer. For the fourth quarter of 2023, ex-US ILEA net product sales were $890 million, up 4% on a constant currency basis versus the prior year. Total Bayer Collaboration revenue was $377 million, of which $345 million related to our share of ILEA net profits outside the U.S. Total Santa Fe Collaboration revenue grew 19% in the fourth quarter of 2023 to $993 million, excluding a $50 million Dollar Sales Milestone recorded in the fourth quarter of 2022. Santa Fe Collaboration revenue grew 26%.

Christopher Thomas Schott: R&D growth was primarily driven by higher head count and related costs funding of our of our advancing late stage programs and increased clinical manufacturing activity.

Christopher Thomas Schott: SG&A grew 7% from the prior year to $622 million in the fourth quarter, reflecting higher head count and related costs and higher commercialization expenses, including costs to support the launch of Eylea HD in prelaunch activities for anticipated 2024, haemonchus product launches.

Christopher Thomas Schott: Fourth quarter <unk> declined 12% from the prior year quarter to $210 million recall that we are reimbursed for these costs.

Robert E. Landry: Our share of collaboration profits was $886 million, an increase of 43% versus the fourth quarter of 2022, driven by Tipixtin's continued volume growth and improving margins. Reimbursements for Manufacturing of Commercial Supply, the component of Sanofi collaboration revenues, declined 36% versus the prior year due to the implementation of a new higher yielding manufacturing process. At the end of 2023, the Sanofi development balance was $2.33 billion, reflecting a net decrease of $534 million compared to the balance as of December 31, 2022.

Christopher Thomas Schott: Now to cash flow and the balance sheets and.

Christopher Thomas Schott: In 2023, Regeneron generated $3 9 billion in free cash flow ending the year with cash and marketable securities less debt of approximately $13 5 billion.

Christopher Thomas Schott: In 2023, we repurchased over $2 2 billion of our shares with approximately $1 5 billion remaining authorized for repurchase as of December 31 2023.

Christopher Thomas Schott: Since we began repurchased repurchasing our shares in 2019, we have bought back approximately $12 billion work and plan to continue to make opportunistic repurchases.

Robert E. Landry: Recall, this decrease is primarily recorded as a reduction to our share of collaboration profits. We continue to expect this balance to be fully reimbursed in the next few years, which would result in a significant step up in our Sanofi collaboration process. Other revenue was $213 million in the fourth quarter of 2023, up 66% versus the prior year, primarily driven by higher royalties from Novartis on sales of Alaris, an increase in our share of Archelous profits from Konietzka. The increase in other revenue also reflects higher reimbursements for increased shipment volumes of ex-U.S. commercial supplies of Pralulin to Santa Fe.

Speaker Change: Now moving to our financial guidance for 2024.

Speaker Change: Note that these guidance ranges do not assume the completion of any business development transactions that were not completed as of today, including our recently announced agreement to acquire a preclinical and clinical programs from $2 70 bio.

Speaker Change: Starting with R&D expense in 2024, which is anticipated to be in the range of $4 three to $4 5 billion as George just discussed and as we highlighted at the Jpmorgan Conference. Our pipeline continues to expand with a growing number of registration, enabling studies ongoing or expected to initiate.

Speaker Change: This year. These include potentially pivotal studies for <unk> phase III studies in earlier lines of <unk>, and Linda <unk> and our C. Five programs. In addition, we expect to bring eight to 10, new molecules into the clinic in 2024.

Robert E. Landry: Moving now to our operating expenses. Fourth quarter 2023 R&D expenses grew 13% year over year to 1.03 billion, which reflects continued investment in our growing pipeline. R&D growth was primarily driven by higher headcount and related costs, funding of our advancing late-stage programs, and increased clinical manufacturing activity. SG&A grew 7% from the prior year to $622 million in the fourth quarter, reflecting higher headcount and related costs and higher commercialization expenses, including costs to support the launch of ILEA HD in pre-launch activities for an anticipated 2024 Hemonc product launch. In the fourth quarter, COCM declined 12% from the prior year quarter to $210 million.

Speaker Change: We expect 2020 for SG&A spending to be in the range of two five to $2 65 billion. This reflects increased promotional activities for the ongoing launch of Eylea HD investments to support two anticipated <unk>.

Speaker Change: <unk> product launches and higher head count to support our growing organization inclusive of our ongoing international expansion.

Speaker Change: <unk> is expected to be in the range of $850 to $910 million. This range reflects lower drug substance manufacturing costs route depiction offset by higher depicts and volumes and higher production costs for other collaboration products, including Eylea HD for Bayer.

Speaker Change: Recall, we are reimbursed for <unk> expenses and as a result, we expect reimbursement from <unk>, which are recorded as a component of scientific collaboration revenue to be slightly lower in 2024 as compared to 2023, we expect the 2020 for gross margin on net product sales to be in the range of 89%.

Robert E. Landry: Recall that we are reimbursed for these costs. Now to cash flow and the balance. In 2023, Regeneron generated $3.9 billion in free cash flow, ending the year with cash and marketable securities, less debt of approximately $13.5 billion.

Speaker Change: 91%.

Speaker Change: We also expect our effective tax rate to be in the range of 10% to 12%.

Robert E. Landry: In 2023, we repurchased over $2.2 billion of our shares with approximately $1.5 billion remaining authorized for repurchase as of December 31, 2023. Since we began repurchasing our shares in 2019, we have bought back approximately $12 billion and plan to continue to make opportunistic repurchases. Now moving to our financial guidance for 2024. Note that these guidance ranges do not assume the completion of any business development transactions that have not been completed as of today, including our recently announced agreement to acquire preclinical and clinical programs from 270- starting with R&D expense in 2024, which is anticipated to be in the range of 4.3 to 4.5 billion. As George just discussed, and as we highlighted at the J.P. Morgan Conference, our pipeline continues to expand with a growing number of registration-enabling studies ongoing are expected to initiate this year.

Finally, we expect capital expenditures to be in the range of $825 million to $950 million, which reflects expansion of our R&D facilities at our Tarrytown, New York headquarters as well as continued expansion of our manufacturing capabilities, including ongoing construction of our fill finish facility in Rensselaer New York.

Speaker Change: In addition to our full year guidance, we expect U S. Net product sales of Praluent to be lower in 2024 as compared to 2023 due to changes in payer coverage. We also expect 2024 net product sales for <unk> to be in line with 2023 revenues with nearly all 2024 revenue is expected to be.

Speaker Change: We recorded in the fourth quarter.

Finally, we anticipate other revenue in 2020 forward to be in line with 2023 with the second half is expected to be higher than our.

Speaker Change: First half.

Overall, regeneron performed well in 2023, and our continued investments position the company to drive long term shareholder value.

Robert E. Landry: These include potentially pivotal studies for pheanlamab, phase three studies in earlier lines of ojonexamab, and limbaseltamab in our C5 programs. In addition, we expect to bring eight to 10 new molecules into the clinic in 2024. We expect 2024 SG&A spend to be in the range of $2.5 to $2.65 billion. This reflects increased promotional activities for the ongoing launch of ILEA HD, investments to support two anticipated HEMON product launches, and higher headcount to support our growing organization, inclusive of our ongoing international expansion. COCM is expected to be in the range of $850 to $910 million.

Speaker Change: Before I conclude I'd like to sincerely, thank Len and George for their kind words.

Speaker Change: And an honor to serve as Regeneron CFO for these past 10 years and I have appreciated all of my interactions with each of you in the investment community I wish Chris Fenimore much success in this role and have the utmost confidence that he and the rest of the management team will continue to deliver breakthrough medicines for patients in Val.

Speaker Change: To shareholders. Thank you and I wish you all continued success with that I will pass the call back to Ryan.

Speaker Change: Thank you Bob and congratulations again.

Speaker Change: 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 you will answer one question from each caller before moving to the next <unk>.

Robert E. Landry: This range reflects lower drug substance manufacturing costs for tipixin, offset by higher tipixin volumes and higher production costs for other collaboration products, including ILEA HD for Bayhers. Recall, we are reimbursed for COCM expenses, and as a result, we expect reimbursement from Sanofi, which is recorded as a component of Sanofi collaboration revenue, to be slightly lower in 2024 as compared to 2023. We expect the 2024 gross margin on net product sales to be in the range of 89 to 91%. We also expect our effective tax rate to be in the range of 10 to 12%.

Speaker Change: <unk> can we go to the first question. Please.

Speaker Change: Thank you to ask a question. Please press star one one of your telephone and wait for your name to be announced.

Speaker Change: To withdraw your question. Please press star one again.

Speaker Change: Please stand by while we compile the Q&A roster.

Speaker Change: Our first question.

Speaker Change: Comes from the line of Tyler Van Buren with PD Cowen. Your line is now open.

Speaker Change: Yes.

Speaker Change: Great. Thanks, guys, good morning, and I'd like to say congratulations to you as well Bob what's your well during our retirement business.

Privilege to work with you.

Speaker Change: And Chris I look forward to working with you as well.

So in the opening Len mentioned accelerating the rate of conversion of patients from other agents to Eylea HD. So can you discuss the different factors at play that will accelerate the rate over the year, which I assume includes the permanent J code and also the robust sampling effort that is impacting too big sales.

Robert E. Landry: Finally, we expect capital expenditures to be in the range of $825 to $950 million, which reflects the expansion of our R&D facilities at our Tarrytown, New York headquarters, as well as continued expansion of our manufacturing capabilities, including ongoing construction of a fill-finish facility in Rensselaer, New York. In addition to our full-year guidance, we expect U.S. net product sales of Pralulent to be lower in 2024 as compared to 2023 due to changes in payer coverage. We also expect 2024 net product sales for Invozeb to be in line with 2023 revenues, with nearly all 2024 revenues expected to be recorded in the fourth quarter. Finally, we anticipate other revenue in 2024 to be in line with 2023, with the second half expected to be higher than the first half.

Speaker Change: Sure Tyler I'm happy to answer so as I mentioned, we're very encouraged by the early performance of Eylea HD in the market and a number of factors early are driving that success first its the clinical data, which is now showing in the actual market real world setting.

Speaker Change: <unk> efficacy safety and durability of Eylea HD, all very important factors as we look to the future physicians will build upon their early experience and as I mentioned that experiences coming from conversion patients from branded agents broadly avastin and also in some cases naive patients but going.

Speaker Change: Forward I would share that in addition to ongoing experience and confidence.

Speaker Change: The reimbursement.

Speaker Change: Consideration is very very important for physicians and some are hesitant to prescribe a product that doesn't have a permanent J code. So we do look forward to that occurring.

Robert E. Landry: Overall, Regeneron performed well in 2023, and our continued investments position the company to drive long-term shareholder value. Before I conclude, I'd like to sincerely thank Len and George for their kind words. It has been an honor to serve as Regeneron's CFO for these past 10 years, and I have appreciated all of my interactions with each of you in the investment community.

Speaker Change: April 1st and beyond basis based on Cms's recent update and then in addition to reimbursement contents. We've made progress certainly in payer coverage, we anticipate making more and certainly be experiencing market to date with Eylea HD has been very favorable for physicians and that is the probably the most important.

Speaker Change: Those differentiating characteristics of a product.

Speaker Change: Thanks, Marion Shannon next question please.

Speaker Change: Our next question comes from the line of Brian Abrahams with RBC capital markets. Your line is now open.

Robert E. Landry: I wish Chris Fenimore much success in this role and have the utmost confidence that he and the rest of the management team will continue to deliver breakthrough medicines for patients and value to shareholders. Thank you, and I wish you all continued success. With that, I will pass the call back to Ryan.

Brian Corey Abrahams: Hey, guys. Thanks for taking my question and it can congrats to both Bob and.

Brian Corey Abrahams: Chris.

Brian Corey Abrahams: I was wondering if you could maybe talk a little bit about the differentiation of the emerging obesity portfolio as you move into the next wave of studies I know patent filing revealed that the antibody <unk> shows very competitive weight loss in animal models. So I'm wondering where you see that differentiating most is it tolerability and five distribution or dose frequency or somewhere else.

Ryan Crow: Thank you, Bob, and congratulations again. This concludes our prepared remarks. We will now open the call for Q&A. We will answer one question from each caller before moving to the next. Shannon, can we go to the first question? Thank you. To ask a question, please press star 1-1 on your telephone and wait for your name to be announced.

Brian Corey Abrahams: I know others are pursuing myostatin as well on top of <unk>, just curious where you see your biggest competitive advantage there.

Brian Corey Abrahams: Okay.

Speaker Change: Okay, well, let me start with the latter first in terms of muscle preservation. Other people have related approaches, but we're the only ones were the ones who discovered that there are two key.

Operator: To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Tyler Van Buren with TD Cowen. Your line is now open.

Speaker Change: Like answered growth factors that control muscle size.

Speaker Change: While statin Myostatin, one we call it in Myostatin to our activin, a and what are the only ones that have specific blocking antibodies for those two.

Tyler Van Buren: Great. Thanks, guys. Good morning.

Marion McCourt: And I'd like to say congratulations to you as well, Bob, and wish you well during your retirement. It's been a privilege to work with you, and Chris, I look forward to working with you as well. So, in the opening, Len mentioned accelerating the rate of conversion of patients from other agents to ILEA HD. So, can you discuss the different factors at play that will accelerate the rate over the year, which I assume includes the permanent J code and also the robust sampling effort that is impacting on making sales?

Speaker Change: We are testing them together and individually.

And the reason why that's important is it's going to be a combination of both efficacy and safety that matters here. So we're going to see which approach does the best in terms of the muscle preservation in the face of the profound muscle loss that you can see with <unk>, one agonists treatment, but we're also going to see.

Speaker Change: The safety profile and I think that that's that's going to be so critical because safety is so important here.

Marion McCourt: Sure, Tyler, I'm happy to answer. As I mentioned, we're very encouraged by the early performance of ILEA HD in the market, and a number of factors are early driving that success. First, it's the clinical data, which is now showing in the real-world setting the efficacy, safety, and durability of ILEA HD, all very important factors. As we look to the future, physicians will build upon their early experience. And as I mentioned, that experience is coming from conversion patients, from branded agents broadly, Avastin, and also, in some cases, naive patients. But going forward, I would share that, in addition to ongoing experience and confidence, the reimbursement consideration is very, very important for physicians. And some are hesitant to prescribe a product that doesn't have a permanent J-code.

Speaker Change: Other people are just testing one of these agents alone I believe the milestone and then others are testing very broad approaches such as trying to block the receptors for these factors the problem with the receptor blockade approach is that the receptors that are used by these factors are also used by over a dollar.

Speaker Change: Other ligand that have very diverse biologic functions and you can easily imagine that by blocking so many diverse functions you might end up having all sorts of safety issues, which you're not going to want to be able to be dealing with in the setting of.

Speaker Change: A treatment thats intended to optimize obesity and body weight loss and give benefit to the patients. So our programs are very different in that we discovered the two key regulators. The two key growth factors, we have separate antibodies blocking them, both and we're valuing them separately and together.

Marion McCourt: So we do look forward to that occurring on April 1st and beyond based on CMS's recent update. And then, in addition to reimbursement confidence, we've made progress certainly in payer coverage. We anticipate making more, and certainly, the experience and market to date with ILEA-HD have been very favorable for physicians. And that is probably the most important thing, those differentiating characteristics of the product. Thanks, Marion. Shannon, next question. Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is now open. Hey guys, thanks for taking my question. And congratulations to both Bob and Chris.

Speaker Change: Either in the setting of <unk>, one receptor agonist to see what gives us the best benefit vis vis muscle preservation as well as safety profile.

Speaker Change: While we're doing that as we said we're initiating those trials. This year. We are also developing Uni molecular solutions.

Speaker Change: So whichever approach works best we hope to have the possibility.

Speaker Change: Of having a.

Speaker Change: Tethered GOP one as you put it associated with the right set of antibody molecules. So they will have the advantage of having a union molecular solution that can provide.

Speaker Change: All in one benefit in terms of providing hopefully.

Speaker Change: The best convenience profile and potentially once a month dosing together with providing not only the weight loss the profound weight loss that what is seen with <unk>, one receptor agonist, but now complemented by providing muscle <unk>, but with the safest possible approach. So we think.

Brian Corey Abrahams: I was wondering if you could maybe talk a little bit about the differentiation of the emerging obesity portfolio as you move into the next wave of studies. I know patent filing revealed that antibody-tethered GLP-1 shows very competitive weight loss in animal models. So I'm wondering where you see that differentiating most. Is it tolerability in the five distribution or dose frequency or somewhere else?

We have.

Speaker Change: The most unique program in terms of addressing all these possibilities.

Speaker Change: We are very very excited about these programs.

Speaker Change: Thanks, George Shannon next question please.

George Damis Yancopoulos: And then I know others are pursuing myostatin as well on top of GLP-1s. Just curious where you see your biggest competitive advantage there. Thanks. Okay, well, let me start with the latter first in terms of muscle preservation. Other people have related approaches, but we're the only ones who discovered that there are two key ligands, growth factors that control muscle size. Myostatin, Myostatin 1, we call it, and Myostatin 2 are active in A.

Speaker Change: Our next question comes from the line of Mohit Bansal with Wells Fargo. Your line is now open.

Mohit Bansal: Great. Thank you very much for taking my question and thank you.

Mohit Bansal: For all your help over the years.

Mohit Bansal: Maybe so.

Mohit Bansal: One question for me.

Mohit Bansal: Can you just comment on the trends in and David IGF market underlying trends I mean is the market growing.

Mohit Bansal: Our U S. A great phosphate phosphates possibilities, it's slowing down a little bit and in that context, how do you see the outlook for.

Mohit Bansal: Hydro <unk> Eylea, plus Eylea gleek forward.

Mohit Bansal: With underlying demand.

Speaker Change: Thank you.

Speaker Change: Sure Mohit so.

Mohit Bansal: Is that theory Asian between quarters and years as it relates to anti VEGF category growth overall, though the category is healthy from Macquarie standpoint.

George Damis Yancopoulos: And we're the only ones that have specific blocking antibodies for those two, and we are testing them together and individually. And the reason why that's important is that it's going to be a combination of both efficacy and safety that matters here. So we're going to see which approach does the best in terms of muscle preservation in the face of the profound muscle loss that you can see with GLP-1 agonist treatment. But we're also going to see the safety profiles, and I think that that's going to be so critical because safety is so important here. Other people are just testing one of these agents alone, I believe Myostatin, and others are testing very broad approaches, such as trying to block the receptors for these factors.

Mohit Bansal: Unfortunately based on the number of individuals with diabetes are diagnosed with diabetes.

Mohit Bansal: Brighter note aging population is good so overall, we see it as healthy healthy category growth.

Mohit Bansal: But there is variability.

Mohit Bansal: An example, there has been some decline by a couple of points between last year and this year overall.

Speaker Change: Okay next question please Shannon.

Speaker Change: Our next question comes from the line of Christopher Raymond with Piper Sandler. Your line is now open.

Christopher Joseph Raymond: Thanks Megan.

Christopher Joseph Raymond: Just another question I know you guys don't want to get too granular on your pricing strategy, but we have been struck that even with the two milligram format revenue contracted in the last couple of quarters. Our checks show that it's really not a market share issue in fact share of that format remains up around it.

George Damis Yancopoulos: The problem with the receptor blockade approach is that the receptors that are used by these factors are also used by over a dozen other ligands that have very diverse biological functions. And you can easily imagine that by blocking so many diverse functions, you might end up having all sorts of safety issues, which you're not going to want to be able to be dealing with in the setting of a treatment that's intended to optimize obesity and body weight loss and give benefit to the patient. So our programs are very different in that we discovered the two key regulators, the two key growth factors. We have separate antibodies blocking them both, and we're evaluating them separately and together in the setting of GLP-1 receptor agonists to see what gives us the best benefit vis-a-vis muscle preservation as well as a safety profile.

Christopher Joseph Raymond: An all time high so one would think that that's been price erosion, that's been driving that.

Christopher Joseph Raymond: Just understand this may be a strategy to maximize the HD launch and broad stroke can you talk about what we should be expecting in 2024 do.

Christopher Joseph Raymond: Do you expect further price erosion for that two milligram format or are things sort of leveled off.

Speaker Change: I'm not sure we werent married to get into the details.

Speaker Change: Our strategy is pricings rebates things like that but we can say could add thoughts.

Speaker Change: We view it as a very competitive marketplace.

Speaker Change: There has been some price erosion on some of the products in the marketplace. We're starting at a new point with HD and we think we priced it.

George Damis Yancopoulos: While we're doing that, as we said, we're initiating those trials this year, we are also developing unimolecular solutions. So whichever approach works best, we hope to have the possibility of having a tethered GLP-1, as you put it, associated with the right set of antibody molecules. So they will have the advantage of having a unimolecular solution that can provide an all-in-one benefit in terms of providing, hopefully, the best convenience profile and potentially once-a-month dosing together with providing not only the weight loss, the profound weight loss that one is seeing with GLP-1 receptor agonists, but now complemented by providing muscle polarization, but with the safest possible approach.

Well it was received well it was intended to match on a yearly basis.

Speaker Change: And so we think the actual price point.

Speaker Change: It's fine I don't know if Matt wants to add anything at all but we don't like to comment specifically on those competitive dynamics, yes, Chris really nothing and everyone to add to that.

Speaker Change: Okay. Alright next question please Shannon.

Shannon: Our next question comes from the line of Colin Bristow with UBS. Your line is now open.

Colin Bristow: Good morning, and thanks for taking the questions and all the best in the future.

Colin Bristow: Maybe a couple more on the muscle span staffing program I'm curious.

Colin Bristow: George what are your thoughts.

Colin Bristow: The potential concern of myostatin targeting increases or preserved muscle volume, but the muscle is less functional and then any thoughts on the.

George Damis Yancopoulos: So we think that we have the most unique program in terms of addressing all these possibilities, and we're very, very excited about these programs. Thanks, George. Shannon, next question. Our next question comes from the line of Mohit Vontal with Wells Fargo. Your line is now open.

George Shannon: The regulatory pathway you would utilized for that.

Speaker Change: These muscles by assets. Thank you.

George Shannon: The regulatory up yeah. Okay. So first of all we've done extensive work in preclinical models.

Mohit Vontal: Great. Thank you very much for taking my question and, Bob, for all your help over the years. One question for Maddie.

George Shannon: And.

Speaker Change: These antibodies have already been in humans we.

We believe that our studies are actually showing that this muscle is functional and certainly very important from both the metabolic and energy expenditure point of view.

Marion McCourt: Can you just comment on the trends in the anti-VEGF market, underlying trends? I mean, is the market growing, or are you going fast, as fast as it's been going in the past? Or is it slowing down a little bit?

Speaker Change: So so far those studies are very supportive of this whole approach.

Marion McCourt: And in that context, how do you see the outlook for hydrozilia plus ilia going forward with underlying demand? Thank you. Sure, Mohit.

Speaker Change: I should also say, there's a variety of regulatory pathways that we're pursuing here, obviously, the easiest which.

Marion McCourt: So, there is variation between quarters and years as it relates to anti-VEGF category growth. Overall, though, the category is healthy from a growth standpoint, unfortunately based on the number of individuals with diabetes or diagnosed with diabetes. On a brighter note, the aging population is good.

Would come from the possible.

Speaker Change: Results that we're seeing in the in the animal studies is if there is.

Speaker Change: Incrementally more weight loss that might suffice as a regulatory strategy. Alternatively, if its just the quality of the weight loss than we would have to show functional outcomes in terms of strength and so forth and so on so those are still early in the.

Marion McCourt: So, overall, we see it as healthy category growth, but there is variability, and, as an example, there has been some decline by a couple of points between last year and this year overall. Okay, next question, please. Our next question comes from the line of Christopher Raymond with Piper Sandler. Your line is now open.

Speaker Change: Thinking we have to see from these initial studies, but as I said, if we simply see increased weight loss that would be the simplest way forward and then you'd have more weight loss, but better body composition data and May also may be better metabolic benefits, which we also see in muscle, which could also provide additional paths to approval. So so it depends.

Speaker Change: On those results that we're going to get from the initial studies I should also mention in terms of additional programs that we have in obesity. I mean these are things that are here and now that we're doing these clinical trials and we hope to be getting results over the over the course of the next year year and a half that could really inform.

Christopher Joseph Raymond: Thanks. Maybe just another ILEA question. So I know you guys don't want to get, you know, sort of too granular on your pricing strategy, but we've been struck that even with the two milligram format, revenue contracting in the last couple quarters, our checks show that it's really not a market share issue. In fact, share of that format remains up around an all-time high.

Speaker Change: In terms of all of these questions that you have and really validate that there is real promise here, but remember we're doing a lot of other things as well and obesity that are in earlier stages. So for example.

Christopher Joseph Raymond: So you know, one would think that's price erosion, that's been driving that, you know, just understand, this may be a strategy to maximize the HD launch. In broad strokes, can you talk about what we should be expecting in 2024? Do you expect further price erosion for that two milligram format, or have things sort of leveled off? Yeah, I'm not sure we want Marion to get into the details of our strategies, pricing, rebates, things like that. But we can say, and Marion could add her thoughts, that we view it as a very competitive marketplace. There has been some price erosion on some of the products in the marketplace.

As you probably know we discovered a brand new promising target in obesity, using our Regeneron genetics center.

Speaker Change: The largest big data set on the planet in terms of human sequence linked to electronic health Records and identified in some ways one of the most exciting new targets and obesity, that's that's been ever discovered and.

Speaker Change: And we have a variety of it's called GPRS 75. It was published in a prominent paper in science about a year or so ago, and we have a variety of promising and not that far away approaches from the clinic in terms of blocking this target for weight loss and I think that we've presented at J P. Morgan early pre.

Leonard S. Schleifer: We're starting at a new point with ILEA HD. We think we priced it well. It was received well. It was intended to match on a yearly basis.

Speaker Change: Clinical data using <unk> approaches that look very exciting.

Leonard S. Schleifer: So we think the actual price point was fine. I don't know if Marion wants to add anything at all, but we don't like to comment specifically on those competitors. There's really nothing for everyone to add to that.

Speaker Change: I should also mention that in terms of smaller programs and so forth. We have things like a very exciting leptin receptor activating antibody that has had very promising human data as well. So there's a lot of things going on but I think the muscle preservation program and how it goes forward.

Marion McCourt: All right, next question, please. Our next question comes from the line of Colin Bristow with UBS, Yolani Snow. Good morning and thanks for taking the questions and all the best in the future, Bob. Maybe a couple more on the muscle-sparing myostatin program. I'm curious, George, what are your thoughts around the potential concerns of myostatin targeting? It increases or preserves muscle volume, but the muscle is less functional.

Speaker Change: He is going to be very interesting to look at it over the next year year and a half thanks, George Shannon next question.

Speaker Change: Our next question comes from the line of Kevin <unk> with BMO capital markets. Your line is now open.

Kevin: Hi, guys I have one final question for Bob So Bob you've done an outstanding job managing the financials of the business and helping drive shareholder returns over the past decade. Looking ahead, how do you believe regeneron can best use this rapidly growing cash balance to further drive investor returns in the next decade of Regeneron and thanks for everything Bob.

Colin Bristow: And then, any thoughts on the regulatory pathway that you would utilize for these muscle-sparing assets? Thank you. Regulatory. Okay, so first of all, you know, we've done extensive work in preclinical models. And, you know, these antibodies have already been in humans. We believe that our studies are actually showing that this muscle is functional and certainly very important from both the metabolic and energy expenditure point of view.

Christopher Thomas Schott: Kevin Thanks for the question and thanks for the video that we were able to show at my retirement Party was it was great.

Kevin: On that question George just laid out earlier today, you know we have so many so many opportunities with regards to our kind of research and development and again I'm going to hand, the mantle over there Chris but his number one priority within capital allocation is to make sure that that is kind of fully funded.

George Damis Yancopoulos: So, so far, those studies are very supportive of this whole approach. I should also say there's a variety of regulatory pathways that we're pursuing here. Obviously, the easiest, which would come from the possible results that we're seeing in the animal studies, is if there's Incrementally more weight loss.

Kevin: Len and George do a great job with regards to making sure what we're bringing into the clinic has opportunities and they're going to continue to do that and Theres just a lot coming particularly when I said, you know kind of 8% to 10 <unk>.

George Damis Yancopoulos: That might suffice as a regulatory strategy. Alternatively, if it's just the quality of the weight loss, then we would have to show functional outcomes in terms of strength, and so forth, and so on. So those are still early in the thinking process. We have to see from these initial studies. But as I said, if we simply see increased weight loss, that would be the simplest way forward. And then you'd have more weight loss, but better body composition data, and also maybe better metabolic benefits, which we also see in muscle, which could also provide additional paths to approval.

I'm proud on buybacks, maybe I've kind of circled the victory too much on that with regards to how much we bought back and at what price, but we have a good methodology here that Chris is ingrained with and he'll continue to do that.

Kevin: And with regards to business development I mean, just because we can doesn't mean, we're going to force something it has to be right. It has to be a franchise has to be modality as you've heard George mentioned that has to be kind of incremental to what we currently have in the clinic here with regards to <unk> and the targets, we develop and all of that so we will we will remain prudent on that.

George Damis Yancopoulos: So it depends on the results that we're going to get from the initial studies. I should also mention, in terms of additional programs that we have in obesity, I mean, these are things that are here and now that we're doing these clinical trials, and we hope to be getting results over the course of the next year, year and a half that could really inform in terms of all these questions that you have and really validate that there's real promise here. But remember, we're doing a lot of other things as well in the fight against obesity that are in earlier stages. So for example, As you probably know, we discovered a brand new promising target in obesity using our Regeneron Genetic Center, the largest big data set on the planet in terms of human sequence linked to electronic health records, and identified, in some ways, one of the most exciting new targets in obesity that's ever been discovered.

Kevin: To be proud of the free cash flow that we're generating and I Trust that Chris George Len, and the board will optimize it and put it to great views.

Speaker Change: Thank you Bob next question please Shannon.

Salveen Richter: Our next question comes from the line of <unk> Richter with Goldman Sachs. Your line is now open.

Salveen Richter: Thank you good morning, and Bobby truly will be missed and enjoy the next stage of life here.

Shannon: With regard to your GAA program can you outline what's contributing to your confidence in the systemic approach here and what data you've seen to supported given the move from animal models to phase III.

Shannon: Right.

Shannon: Okay geographic atrophy.

Shannon: Basically.

Shannon: The excitement is that as we.

Shannon: Shell data from our combination approach, we believe that we have the most effective way of blocking the.

George Damis Yancopoulos: And we have a variety of, it's called GPR-75, it was published in a prominent paper in Science about a year or so ago, and we have a variety of promising and not that far away approaches to blocking this target for weight loss, and I think that we presented at J.P. Morgan early preclinical data using siRNA approaches that looked very exciting.

Shannon: The bodies C five.

Shannon: Activity.

Shannon: The C five which is active in the eye is.

Shannon: Essentially all coming from the liver.

Shannon: And we've shown now in our <unk> studies, when we reveal the data from the first portion of our phase III program that it looked like we had the best in class activity in terms of.

George Damis Yancopoulos: I should also mention that in terms of smaller programs and so forth, we have things like a very exciting leptin receptor activating antibody that has had very promising human data as well. So, there's a lot going on, but I think the muscle preservation program and how it goes forward are going to be very interesting to look at over the next year, year and a half. George Shannon, next question. Our next question comes from the line of Evan Seigerman with BMO Capital Markets. Your line is now open.

Shannon: Decreasing <unk> five activity. So if you block it at the source then you don't have the block in the eye.

Shannon: And if you're blocking at the source then you don't suffer from all the concerns and side effects and so forth.

Shannon: That you have from having to block it in the eye. So your block it where it's coming from then you don't have to treat locally in the all you can avoid the local side effects. The concern with systemic blockade is it comes with increased risks of infection and so forth. So we will have to come up with a strategy, which we're working on to <unk>.

Evan Seigerman: Hi guys, I have one final question for Bob. Bob, you've done an outstanding job managing the financials of the business and helping drive shareholder returns over the past decade. Looking ahead, how do you believe Regeneron can best use its rapidly growing cash balance to further drive investor returns in the next decade?

Shannon: Try to mitigate that in the elderly population that suffers from GE. We believe that we may need for that and approach to identify the patients who might be at risk in those settings. Because we certainly know that for example patients with <unk> and.

Shannon: In Miami Senior Gravis, who are immuno suppressed and so forth.

Robert E. Landry: And thanks for everything, Bob. Evan, thanks for the question, and thanks for the video that we were able to show at my retirement party. You know, on that question, George just laid out earlier today, you know, we have so many opportunities with regard to our kind of research and development. And again, you know, I'm going to hand the mantle over to Chris, but his number one priority within capital allocation is to make sure that that is kind of fully funded. You know, Len and George do a great job with regard to making sure what we're bringing into the clinic has opportunities, and they're going to continue to do that. And there's just a lot coming, particularly when I said, you know, kind of 8 to 10 INDs.

Shannon: Not only with our agent, but certainly with this whole class of agents can suffer from.

Shannon: Syria systemic infections when you block C. Five so we are coming up with a way to mitigate that in part by probably selecting out patients who are at the highest risk but in terms of efficacy. The fact that you're blocking at the source should make it much more effective than trying to block it indirect.

<unk> in the eye, while avoiding all of the serious local.

Shannon: Side effects, you can get in the eye, including this horrific retinal vasculitis, which is associated with sudden and permanent blindness.

Speaker Change: Thanks, George I think we have time for two more questions.

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

Robert E. Landry: I'm proud of buybacks; maybe I've kind of circled the victory too much on that with regard to how much we bought back and at what price. But you know, we have a good methodology here that Chris is ingrained in, and he'll continue to do that. And with regard to business development, I mean, just because we can doesn't mean we're going to force something. It has to be right.

David Risinger: Yes, thanks, very much and.

David Risinger: First I wanted to offer my congrats as well and best wishes to you, both Bob and Chris So I.

David Risinger: I have a commercial question on Lindbergh sell to Matt. Please it's clearly generated best in class results in a more attractive profile for patients, but regeneron has to displace the incumbents. So could you discuss your plans to convert prescribers to inverse Seltzer mab.

Robert E. Landry: It has to be a franchise, has to be modalities. You've heard George mentioned that it has to be kind of incremental to, you know, what we currently have in the clinic here with regard to RGC and the targets we develop and all of that. So we will we will remain prudent on that, you know, continue to be proud of the free cash flow that we're generating. And I trust that Chris, George, Len, and the board will optimize it and put it to great use. Thank you, Bob. Next question, please. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open. Thank you. Good morning.

David Risinger: Q.

Speaker Change: Thank you Dave may be primary and.

Speaker Change: I'm anxious to answer, but we will of course go first so I just wanted to give a little history. There you actually ramp.

Speaker Change: We've been asked the exact question I am not sure when we were launching Eylea and we have to displace lucentis.

Speaker Change: With Roche.

Speaker Change: There are some lessons in there then it can be done with us.

Speaker Change: Starting with a really good molecule as you described.

Speaker Change: Catastrophe best in class and then strong execution.

Salveen Richter: And, Bob, you truly will be missed and enjoyed the next stage of life here. With regard to your GA program, can you outline what's contributing to your confidence in the systemic approach here and what data you've seen to support it, given the move from animal models to phase three? Okay. Okay. Geographic. So basically,

Speaker Change: At the commercial clients, we've done it we're not afraid of that.

Speaker Change: 800 pound gorilla.

Flip that gorilla, perhaps.

Speaker Change: A weight loss program.

Speaker Change: Get in there and show them, what we can do merit any comments I just wanted to put that historical perspective.

Speaker Change: Thank you David for the question and I'm going to be a bit redundant. So I'll be sure, but my comment was to say you know it always starts with the best in class molecule. That's about the science and certainly you've seen us across therapeutic areas launch into competitive categories.

George Damis Yancopoulos: The excitement is that as we have shown data from our combination approach, we believe that we have the most effective way of blocking the body's C5 activity. The C5, which is active in the eye, is essentially all coming from the liver. And we've shown now in our PNH studies, when we revealed the data from the first portion of our phase three program, that it looked like we had the best in class activity in terms of decreasing C5 activity. So if you block it at the source, then you don't have to block it in the eye. And if you block it at the source, then you don't suffer from all the concerns and side effects and so forth that you have from having to block it in the eye. So you block it where it's coming from, then you don't have to treat it locally in the eye. You can avoid these local side effects.

Speaker Change: Both in the anti VEGF category, and then more recently, bringing great products into the marketplace. So we do look forward to this opportunity and it fits quite beautifully with our oncology team are will be on Keane team and certainly we will be very ready for that launch and look forward to helping patients with Linda.

Okay, Thanks, Lynne and Marion.

Speaker Change: And last question please.

Our last question comes from the line of Carter Gould with Barclays. Your line is now open.

Christopher Thomas Schott: Great. Good morning, Thanks for taking the question I'll Echo the prior comments about Bob and best of luck, maybe just.

Christopher Thomas Schott: Just on the 270 deal Len and George how should we think about this was this more about sort of protecting the rights to the assets that you were already kind of partnered on or really around sort of getting access to that manufacturing facility and does that have implications then as we think about your business development going forward and maybe change kind of your willingness to move further down that path of cellular.

George Damis Yancopoulos: The concern with systemic blockade is that it comes with increased risks of infections and so forth. So we will have to come up with a strategy, which we're working on to try to mitigate that in the elderly population that suffers from GA. We believe that we may need an approach to identify the patients who might be at risk in those settings. Because we certainly know that, for example, patients with PNH and myasthenia gravis who are immunosuppressed and so forth, not only with our agents but certainly with this whole class of agents can suffer from serious systemic infections when you block C5. So we are coming up with a way to mitigate that in part by probably selecting out the patients who are at the highest risk, but in terms of efficacy, the fact that you block it at the source should make it much more effective than trying to block it indirectly in the eye while avoiding all of the serious local side effects you can get in the eye, including this horrific retinal vasculitis, which is associated with sudden and permanent blindness.

Speaker Change: Therapy. Thank you.

Speaker Change: I'll, let George comment on.

George Shannon: The scientific rationale, which drives pretty much everything we do.

George Shannon: Just to mention from a business development point of view, we have been a long standing partner with.

George Shannon: <unk> hundred 70, when they were still part of Bloomberg, we've invested in them both in equity and frankly.

George Shannon: So this was something that was well known George can comment how we see this fitting it yes.

George Shannon: Yes, we're excited about the existing programs, but we're even more excited about is as we know that the history of many diseases, but cancer in particular is about combination approaches and thus far even in the setting of this collaboration.

George Shannon: The car T space has been separate from the biologic space.

George Shannon: And even though we were working together as.

George Damis Yancopoulos: Thanks, George. I think we have time for two more questions. Our next question comes from the line of David Reisinger with Lee Rink Partners. Your line is now open.

George Shannon: As separate companies it was a little harder to really move forward in an expedited fashion the incredible opportunities that I believe that we have to combine what we think is the largest and most exciting portfolio of biologics in immunotherapy should gather with <unk>.

David Reisinger: Yes, thanks very much. And first, I wanted to offer my congratulations as well and best wishes to you both, Bob and Chris. So I have a commercial question about Linvaseltamib, please.

George Shannon: Cell therapy approaches nobody else has really tried that nobody else has really led that now that we're really together all in.

David Reisinger: It's clearly generated best-in-class results and a more attractive profile for patients, but Regeneron has to displace the incumbents. So could you discuss your plans to convert prescribers to InvoCeltamib? Thank you. Thank you, David. Before I answer, I'm anxious to answer, but Len will, of course, go first. No, I just wanted to give you a little history, David. You actually were around. You may even ask the exact question. I'm not sure.

With our new selected colleagues from $2 70, and near capabilities. We believe that we will now have the first opportunity to really try this new set of combination approaches against cancer that is combining our large portfolio of biologics in immunotherapy.

George Shannon: Faced with their cell therapy capabilities and expertise that brings a whole new level of combinations to the immunotherapy field. We believe we will be alone in that capability until somebody else tries to copy us and do what we're doing here and that's what we're really excited about in addition to.

Leonard S. Schleifer: When we were launching ILEA and we had to displace Lucentis by the behemoth Roche, there were some lessons in there that it can be done with starting with a really good molecule, as you described, one that returns to be best in class, and then strong execution on the commercial front. We did it. We're not afraid of the 800-pound gorilla. We hope to put that gorilla on, perhaps, a weight loss program and get in there and show them what we can do. Marion, any comments? I just wanted to put that historical perspective out there.

George Shannon: Just moving forward the existing cell therapy programs that we've been working on them for five years or more alright.

Speaker Change: Alright, Thanks, Len, and George and thanks to everyone, who dialed in today for your interest in Regeneron, we apologize to those remaining in the queue.

Speaker Change: We did not have a chance to hear from as always the Investor Relations team here at Regeneron is available to answer any remaining questions. You may have thank you once again and have a great day.

Marion McCourt: Thank you, David, for the question. I'm going to be a bit redundant, so I'll be short. But my comment was to say, you know, it always starts with the best in class molecule. It's about the science.

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

Speaker Change: Okay.

Speaker Change: [music].

Marion McCourt: And certainly, you've seen us across therapeutic areas launch into competitive categories, both in the anti-VEGF category and then more recently, bringing great products into the marketplace. So we do look forward to this opportunity. And it fits quite beautifully with our oncology team. Our oncologist will be on the team, and certainly, we will be very ready for that launch and look forward to helping patients with lymphoma. Thanks, Len and Marion. Shannon, last question. Our last question comes from the line of Carter Gould with Barclays. Your line is now open. Good morning.

Speaker Change: Okay.

Yes.

Speaker Change: Okay.

Speaker Change: Yeah.

Speaker Change: [music].

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Okay.

Speaker Change: Yes.

Speaker Change: Tim.

Speaker Change: [music].

Christopher Thomas Schott: Thanks for taking the question. I'll echo all the prior comments about Bob and best of luck. Maybe just on the 270 deal, Len and George, what should we think about this?

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Okay.

Speaker Change: Yes.

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Yes.

Leonard S. Schleifer: Was this more about sort of protecting the rights to the assets that you were already kind of partnered on, or really around sort of getting access to that manufacturing facility? And does that have implications then, as we think about your business development going forward, and maybe change your willingness to move further down that path of cellular therapies? Thank you. I'll let George comment on the scientific rationale which drives pretty much everything we do.

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Yes.

Speaker Change: [music].

Speaker Change: Okay.

Speaker Change: Yes.

Speaker Change: Okay.

George Damis Yancopoulos: Just to mention, from a business development point of view, we have been a long-standing partner with 270 when they were still part of Bluebird. We invested in them, both in equity and, frankly, in development. So this was something that was well known.

Speaker Change: Okay.

Speaker Change: Yes.

Speaker Change: Okay.

George Damis Yancopoulos: George can comment on what he sees... Yeah, we're excited about the existing program. But what we're even more excited about is, as we know, that the history of many diseases, but cancer in particular, is about combination approaches. Thus far, even in the setting of this collaboration, the CAR-T space has been separate from the biologics space. And even though we were working together as separate companies, it was a little harder to really move forward in an expedited fashion the incredible opportunities that I believe that we have to combine what we think is the largest and most exciting portfolio of biologics in immunotherapy together with cell therapy approaches. Nobody else has really tried that yet.

Speaker Change: Yeah.

Speaker Change: Okay.

Okay.

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Tim.

Speaker Change: [music].

Okay.

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Okay.

Speaker Change: Sure.

[music].

Speaker Change: Yes.

[music].

Speaker Change: Okay.

Okay.

Speaker Change: Yes.

George Damis Yancopoulos: Nobody else has really led that. Now that we're all together all in with our new selected colleagues from 270 and their capabilities, we believe that we will now have the first opportunity to really try this new set of combination approaches against cancer. That is, combining our large portfolio of biologics in the immunotherapy space with their cell therapy capabilities and expertise. That brings a whole new level of combinations to the immunotherapy field. We believe we will be alone in that capability until somebody else tries to copy us and do what we're doing here.

Speaker Change: Sure.

Speaker Change: Okay.

Speaker Change: Yes.

Speaker Change: Okay.

Okay.

Speaker Change: Okay.

Okay.

Speaker Change: Okay.

George Damis Yancopoulos: And that's what we're really excited about in addition to just moving forward with the existing cell therapy programs that we've been working on for five years or more. All right, thanks, Len and George. And thanks to everyone who dialed in today for your interest in Regeneron. We apologize to those remaining in the queue that we did not have a chance to hear from. As always, the investor relations team here at Regeneron is available to answer any remaining questions. Thank you once again, and have a great day. This concludes today's conference call. Thank you for your participation. You may now disconnect. www.regeneron.com.

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Okay.

Speaker Change: Yes.

Speaker Change: Tim.

Speaker Change: [music].

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Okay.

Yes.

Speaker Change: [music].

Speaker Change: Yeah.

Speaker Change: Okay.

Speaker Change: [music].

Speaker Change: Okay.

[music].

Speaker Change: Okay.

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