Q3 2023 Regeneron Pharmaceuticals Inc Earnings Call

November 2, 2023

Operator: Welcome to the Regeneron Pharmaceutical third quarter 2023 earnings conference call. My name is Shannon and I'll be your operator for today's call.

My name is Shannon and I'll be your operator for today's call.

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

Later, we will conduct a question and answer session. Please note that this conference is being recorded.

I will now turn the call over to Ryan Crow, Vice President Investor Relations. You may begin.

Ryan Crowe: Thank you, Shannon. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron, and welcome to our Q3 2023 earnings conference call. An archive and transcript of this webcast will be available on our Investor Relations website shortly after the call ends. Joining me on today's call are Dr. Leonard Schleifer, Board Co-Chair, Co-Founder, President, and Chief Executive Officer; Dr.

Ryan Crowe: Thank you Shannon. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron and welcome to our third quarter of 2023 earnings conference call. An archive and transcript of this webcast will be available on our Investor Relations website shortly after the call ends.

Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron and welcome to our third quarter of 2023 earnings Conference call, an archive and transcript up this webcast will be available on or Investor Relations website. Shortly after the call ends.

Joining me on today's call are Doctor Leonard Shleifer, Co-Chair, Co-Founder, President and Chief Executive Officer, Dr. George Yancapoulos, Board Co-Chair, Co-Founder, President and Chief Scientific Officer, Marion McCourt, Executive Vice President and Head of Commercial, and Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open the call for Q&A.

Operator: George Yancopoulos, Board Co-Chair, Co-Founder, President, and Chief Scientific Officer, Marion McCourt, Executive Vice President and Head of Commercial, and Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open the call for Q&A. I would like to remind you that remarks made on today's call may include forward-looking statements about Regeneron. Such statements may include but are not limited to those related to Regeneron and its products and businesses, business, financial forecast and guidance, revenue diversification, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings, and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement.

George Yancopoulos, Board Co-Chair, Co-Founder, President, and Chief Scientific Officer, Marion McCourt, Executive Vice President and Head of Commercial, and Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open the call for Q&A. I would like to remind you that remarks made on today's call may include forward-looking statements about Regeneron. Such statements may include but are not limited to those related to Regeneron and its products and businesses, business, financial forecast and guidance, revenue diversification, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings, and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement.

Marion Mccourt Executive Vice President and had a commercial. And Bob Landry Executive Vice President and Chief Financial Officer.

And Bob Landry Executive Vice President and Chief Financial Officer.

After I prepared remarks, we will open the call for Q&A.

I would like to remind you that remarks made on today's call, may include forward-looking statements about Regeneron. Such statements may include but are not limited to those related to Regeneron and its products and businesses, business financial forecasting guidance, revenue diversification, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings and competition.

programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings and competition.

Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarterly period ending September 30th 2023 which was filed with the SEC this morning.

Operator: A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarterly period ended 30 September 2023, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise. In addition, please note that GAAP and non-GAAP measures will be discussed in today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our financial results press release and our corporate presentation, both of which can be accessed on our website. Once our call concludes, Bob Landry and the Investor Relations team will be available to answer any further questions.

A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarterly period ended 30 September 2023, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise. In addition, please note that GAAP and non-GAAP measures will be discussed in today's call.

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 measures will be discussed in today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our financial results press release and our corporate presentation, both of which can be accessed on our website.

Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our financial results press release and our corporate presentation, both of which can be accessed on our website. Once our call concludes, Bob Landry and the Investor Relations team will be available to answer any further questions. With that, let me turn the call over to our President and Chief Executive Officer, Dr. Leonard Schleifer. Len?

Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to gap is available in our financial results press release, and our corporate presentation, both of which can be accessed on our website.

Once our call concludes, Bob Landry and the Investor Relations team will be available to answer any further questions.

Operator: With that, let me turn the call over to our President and Chief Executive Officer, Dr. Leonard Schleifer. Len? Thanks, Ryan. Thanks to everyone joining today's call. Regeneron delivered another strong quarter marked by continued execution across the company, which drove double-digit top-line growth and notable progress across our innovative R&D pipeline. Total revenues increased by 15% on a reported basis compared to the prior year quarter, primarily driven by Sanofi collaboration revenues, and Libtayo global net product sales, which grew by 50% and 62%, respectively. Dupixent global net product sales were $3.1 billion, up 33%, reflecting strong growth across all approved indications. Non-GAAP net income per share, diluted share, increased by 4%, including an unfavorable 77% impact from acquired IP R&D. Today, I will briefly discuss the launch of Eylea HD, the progress we continue to make across our pipeline, and our latest thinking on capital allocation.

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

Leonard Schleifer: Thanks, Ryan. Thanks to everyone joining today's call. Regeneron delivered another strong quarter marked by continued execution across the company, which drove double-digit top-line growth and notable progress across our innovative R&D pipeline. Total revenues increased by 15% on a reported basis compared to the prior year quarter, primarily driven by Sanofi collaboration revenues, and Libtayo global net product sales, which grew by 50% and 62%, respectively. Dupixent global net product sales were $3.1 billion, up 33%, reflecting strong growth across all approved indications. Non-GAAP net income per share, diluted share, increased by 4%, including an unfavorable 77% impact from acquired IP R&D. Today, I will briefly discuss the launch of Eylea HD, the progress we continue to make across our pipeline, and our latest thinking on capital allocation.

Leonard S. Schleifer: Thank Ryan and thanks to everyone joining today's call.

Regeneron delivered another strong quarter, marked by continued execution across the company, which drove double digit top line growth and notable progress across our innovative R&D pipeline.

Total revenues increased by 15 per cent on reported basis compared to the prior year quarter, primarily driven by scientific collaboration revenues and the title global net product sales, which grew by 50% and 62% respectively.

Dupixen global net product sales were 3.1 billion, up 33% reflecting strong growth across all approved indications. Non-GAAP net income per diluted share increased by 4%, including an unfavourable 77 [inaudible] impact from acquired IP R&D.

Reflecting strong claws across all approved indications non-GAAP net income per share diluted share increased by 4%, including an unfavourable 77.

That impact from acquired I P R and D.

Briefly discuss the launch of EYLEA HD, the progress we continue to make across our pipeline and our latest thinking on capital allocation. I will then hand the call over to George, Mary, and Bob who provide additional commentary on our pipeline developments, commercial execution, and our financial results for the quarter.

H D <unk>. I wish we continue to make a question of pipeline and our latest thinking on capital allocation.

I wish we continue to make a question of pipeline and our latest thinking on capital allocation.

Operator: I will then hand the call over to George, Marion, and Bob, who will provide additional commentary on our pipeline developments, commercial execution, and our financial results for the quarter. Starting with Eylea HD, which is off to a great start. We launched in late August, shortly following FDA approval, and recorded $43 million of net product sales in the final six weeks of the quarter, which compares favorably to recent launches in the retinal disease category. Importantly, revenues were driven by strong initial demand with multiple reorders by distributors before the end of the quarter. In addition, samples for Eylea HD were made available shortly after the launch, enabling prescribers and patients to trial the product. Early Eylea HD utilization has come from across the spectrum of wet age-related macular degeneration and diabetic macular edema patients, and momentum continues to build as positive real-world clinical experiences accumulate.

I will then hand the call over to George, Marion, and Bob, who will provide additional commentary on our pipeline developments, commercial execution, and our financial results for the quarter. Starting with Eylea HD, which is off to a great start. We launched in late August, shortly following FDA approval, and recorded $43 million of net product sales in the final six weeks of the quarter, which compares favorably to recent launches in the retinal disease category. Importantly, revenues were driven by strong initial demand with multiple reorders by distributors before the end of the quarter.

Then hand, the cold over the George married and Bob who provide additional commentary on a pipeline developments commercial execution and our financial results for the court.

Starting with EYLEA HD, which is off to a great start, we launched in late August shortly following FDA approval and recorded $43 million of net product sales in the final six weeks of the quarter, which compares favorably to recent launches in the retinal disease category.

Importantly, revenues were driven by strong initial demand with multiple reorders by distributors before the end of the quarter. In addition, samples for EYLEA HD were made available shortly after the launch, enabling prescribers and patients to try out the product.

In addition, samples for Eylea HD were made available shortly after the launch, enabling prescribers and patients to trial the product. Early Eylea HD utilization has come from across the spectrum of wet age-related macular degeneration and diabetic macular edema patients, and momentum continues to build as positive real-world clinical experiences accumulate.

In addition, samples for ILEA HD were made available shortly after the launch, enabling prescribers and patients to try out the product.

Early EYLEA HD utilization come from across the spectrum of [inaudible] age related [inaudible] generation and diabetic macular edema patients and momentum continues to build as positive real world clinical experiences accumulate. We have also made significant progress establishing access and reimbursement and we will continue to work on positioning EYLEA HD, the highest dose anti veg in therapy approved by the FDA as the new standard of care in these retinal diseases.

<unk> age related Mckenzie generation, and diabetic macular edema patience and amazing continues to build as positive real world clinical experiences accumulate. We have also made significant progress establishing access and reimbursement and we will continue to work on positioning Eylea HD.

Operator: We have also made significant progress establishing access and reimbursement, and we will continue to work on positioning Eylea HD, the highest dose anti-VEGF therapy approved by the FDA, as the new standard of care in these retinal diseases. Moving on to the recent progress we have made advancing our pipeline within Hematology Oncology and our CD3 bispecific platform, the BLA for Odronextamab, our CD20 by CD3 bispecific in certain lymphomas, was accepted by the FDA and granted priority review, with a 31 March PDUFA date set. We also remain on track to submit a BLA next month for Linvoseltamab, our BCMA by CD3 bispecific for multiple myeloma. With pivotal trials now underway for both programs to support potential accelerated approvals, we are preparing for two commercial launches next year. Last week, we reported a potential breakthrough for patients with profound congenital hearing loss.

We have also made significant progress establishing access and reimbursement, and we will continue to work on positioning Eylea HD, the highest dose anti-VEGF therapy approved by the FDA, as the new standard of care in these retinal diseases. Moving on to the recent progress we have made advancing our pipeline within Hematology Oncology and our CD3 bispecific platform, the BLA for Odronextamab, our CD20 by CD3 bispecific in certain lymphomas, was accepted by the FDA and granted priority review, with a 31 March PDUFA date set. We also remain on track to submit a BLA next month for Linvoseltamab, our BCMA by CD3 bispecific for multiple myeloma.

The highest dose anti veg in therapy approved by the F. D. A is the new standard of care in these retinal diseases.

Moving onto the recent progress we have made advances in our pipeline within hematology and oncology and our CD3 bispecific platform, the BLA for [inaudible] our CD20 by CD3 bispecific in certain lymphomas was accepted by the FDA and granted priority review with a March 31st PDUFA date assigned.

our CD20 by CD3 bispecific in certain lymphomas was accepted by the FDA and granted priority review with a March 31st PDUFA date assigned.

We also remain on track to submit a BLA next month for LINVOSELTAMAB, our BCMA by CD3 bispecific for multiple myeloma. With pivotal trials now under way for both programs to support potential accelerated approvals, we are preparing for two commercial launches next year.

With pivotal trials now underway for both programs to support potential accelerated approvals, we are preparing for two commercial launches next year. Last week, we reported a potential breakthrough for patients with profound congenital hearing loss.

With pivotal trials now under way for both programs to support potential accelerated approvals. We are preparing for two commercial launches next year.

Last week, we reported a potential breakthrough for patients with profound congenital hearing loss. The first patient enrolled in the phase I/II two quart clinical trial of DB-OTO an investigational self selective adenovirus associated viral gene therapy, designed to provide durable physiological hearing to individuals with profound congenital hearing loss caused by mutations in the [inaudible] gene experienced hearing improvements six weeks after treatment compared to baseline. We are looking forward to continue to follow up with this patient as well as enrollment of additional patients to further validate this gene therapy approach. While [inaudible] gene deficiency is an ultra rare condition, we are hopeful that we can expand our approach to gene therapy in the year to more common genetic causes of profound hearing loss.

Operator: The first patient enrolled in the Phase I-II core clinical trial of DB-OTO, an investigational cell-selective adenovirus-associated viral gene therapy designed to provide durable physiological hearing to individuals with profound congenital hearing loss caused by mutations in the otoferlin gene, experienced hearing improvement six weeks after treatment compared to baseline. We are looking forward to continued follow-up with this patient, as well as enrollment of additional patients to further validate this gene therapy approach. While otoferlin gene deficiency is an ultra-rare condition, we are hopeful that we can expand our approach to gene therapy in the year to more common genetic causes of profound hearing loss. Finally, regarding capital allocation, while we continue to prioritize internal R&D investment, given the strength of our balance sheet and anticipated future cash flows, we believe we have the flexibility to take additional actions to drive shareholder value.

The first patient enrolled in the Phase I-II core clinical trial of DB-OTO, an investigational cell-selective adenovirus-associated viral gene therapy designed to provide durable physiological hearing to individuals with profound congenital hearing loss caused by mutations in the otoferlin gene, experienced hearing improvement six weeks after treatment compared to baseline. We are looking forward to continued follow-up with this patient, as well as enrollment of additional patients to further validate this gene therapy approach. While otoferlin gene deficiency is an ultra-rare condition, we are hopeful that we can expand our approach to gene therapy in the year to more common genetic causes of profound hearing loss.

designed to provide durable physiological hearing to individuals with profound congenital hearing loss caused by mutations in the [inaudible] gene experienced hearing improvements six weeks after treatment compared to baseline. We are looking forward to continue to follow up with this patient

as well as enrollment of additional patients to further validate this gene therapy approach.

While [inaudible] gene deficiency is an ultra rare condition, we are hopeful that we can expand our approach to gene therapy in the year to more common genetic causes of profound hearing loss.

Finally, regarding capital allocation, while we continue to prioritize internal R&D investment, given the strength of our balance sheet and anticipated future cash flows, we believe we have the flexibility to take additional actions to drive shareholder value.

Found hearing loss.

Finally, regarding capital allocation, we continued to prioritize internal R&B investment. Given the strength of our balance sheet and anticipated future cash flows, we believe we have the flexibility to take additional actions to drive shareholder value. Beyond our ongoing share repurchase program, we continue to actively pursue emerging science and innovative platforms that compliment our core R&D strengths.

Continued to prioritize internal RMB investment given the strength of a balance sheet and anticipated future cash flows. We believe we have the flexibility to take additional actions to drive shareholder value.

Operator: Beyond our ongoing share repurchase program, we continue to actively pursue emerging science and innovative platforms that complement our core R&D strengths. In addition to the Decibel acquisition we announced last month, an expanded research collaboration with Intellia, combining our proprietary antibody-targeted viral vector delivery technologies with Intellia's CRISPR platform to jointly explore in vivo programs outside of the liver for neurological and muscular diseases. We have always managed Regeneron with a focus on generating long-term returns, and we will continue to think carefully about how to strategically deploy our capital with the goal of delivering breakthroughs to patients and value to shareholders. In closing, we had a strong third quarter. The Eylea HD launch is progressing well. Our pipeline is delivering important innovations, and we continue to look at ways to efficiently allocate capital. With that, let me turn the call over to George. Thanks, Len.

Beyond our ongoing share repurchase program, we continue to actively pursue emerging science and innovative platforms that complement our core R&D strengths. In addition to the Decibel acquisition we announced last month, an expanded research collaboration with Intellia, combining our proprietary antibody-targeted viral vector delivery technologies with Intellia's CRISPR platform to jointly explore in vivo programs outside of the liver for neurological and muscular diseases. We have always managed Regeneron with a focus on generating long-term returns, and we will continue to think carefully about how to strategically deploy our capital with the goal of delivering breakthroughs to patients and value to shareholders.

Beyond our ongoing share repurchase program, we continue to actively pursue emerging science and innovative platforms that compliment our core R&D strengths.

In addition to the [inaudible] acquisition, we announced last month an expanded research collaboration with Intellia combining our proprietary antibody targeted viral vector delivery technologies with Intellia's crystal platform to jointly explore and rebuild programs outside of the liver for neurological and muscular diseases.

Combining our proprietary antibody targeted viral vector deliberate technologies within tele as Christmas platform to jointly explore explore and rebuilt programs outside of the liver for neurological and muscular diseases.

We have always managed Regeneron with a focus on generating long term returns and we will continue to think carefully about how to strategically deploy our capital with the goal of delivering breakthroughs to patients and value to shareholders.

In closing, we had a strong third quarter. The Eylea HD launch is progressing well. Our pipeline is delivering important innovations, and we continue to look at ways to efficiently allocate capital. With that, let me turn the call over to George.

In closing, we had a strong third quarter, the EYLEA HD launch is progressing well, our pipeline is delivering important innovations, and we continue to look at ways to efficiently allocate capital. With that, let me turn the call over to George.

George Yancopoulos: Thanks, Len. I'd like to start with our recent data update for Eylea HD. At the EURETINA meeting last month, we presented the two-year results from the PULSAR study in wet AMD, which demonstrated that the vast majority of Eylea HD patients randomized to 12- and 16-week dosing intervals continued to sustain vision and anatomic improvements through 96 weeks. 78% of all Eylea HD patients were able to maintain at least every 12-week dosing intervals for the entire two-year period, with 88% assigned to at least every 12-week dosing by the end of the two-year period. Similarly, 70% of patients randomized to every 16-week dosing at baseline were able to maintain at least that interval through two years, with 78% assigned to at least every 16-week dosing at week 96.

Operator: I'd like to start with our recent data update for Eylea HD. At the EURETINA meeting last month, we presented the two-year results from the PULSAR study in wet AMD, which demonstrated that the vast majority of Eylea HD patients randomized to 12- and 16-week dosing intervals continued to sustain vision and anatomic improvements through 96 weeks. 78% of all Eylea HD patients were able to maintain at least every 12-week dosing intervals for the entire two-year period, with 88% assigned to at least every 12-week dosing by the end of the two-year period. Similarly, 70% of patients randomized to every 16-week dosing at baseline were able to maintain at least that interval through two years, with 78% assigned to at least every 16-week dosing at week 96.

George D. Yancopoulos: Thanks Leonard. I'd like to start with our recent data update for EYLEA HD.

I'd like to start with a recent data update Fry Leah HD.

At the EU retina meeting last month, we presented the two year results from the Pulsar study and wet AMD, which demonstrated that the vast majority of EYLEA HD patients randomized at 12 and 16 weeks dosing continued to sustain vision and anatomic improvements through 96 weeks. 78% of all EYLEA HD patients were able to maintain at least every 12 week dosing intervals for the entire two year period with 88% assigned to at least every 12 week dosing by the end of the two year period.

EYLEA HD patients were able to maintain at least every 12 week dosing intervals for the entire two year period with 88% assigned to at least every 12 week dosing by the end of the two year period.

Similarly, 70% of patients randomized every 16 week dosing at baseline were able to maintain at least at intervals through two years with 78% assigned to at least every 16 week dosing at week 96. Moreover, during the second year, many patients met the criteria for extension to even longer dosing intervals with 47% meeting the criteria for at least 20 weeks dosing intervals including 28% who were eligible for 24-week dosing.

Operator: Moreover, during the second year, many patients met the criteria for extension to even longer dosing intervals, with 47% meeting the criteria for at least 20-week dosing intervals, including 28% who were eligible for 24-week dosing intervals. The safety profile of Eylea HD remained consistent with Eylea. Sustaining vision and anatomic improvements while maintaining such extended dosing intervals over two years in both Wet AMD and DME is a remarkable advancement for the patients and their physicians. We believe that these results give Eylea HD the potential to become the new standard of care for these retinal diseases. Moving to our immunology and inflammation pipeline. On Dupixent and COPD, our first pivotal study, Boreas, met the primary and all two secondary endpoints in a previously unprecedented success for a biologic in a phase III study in patients with uncontrolled COPD and evidence of Type 2 inflammation.

Moreover, during the second year, many patients met the criteria for extension to even longer dosing intervals, with 47% meeting the criteria for at least 20-week dosing intervals, including 28% who were eligible for 24-week dosing intervals. The safety profile of Eylea HD remained consistent with Eylea. Sustaining vision and anatomic improvements while maintaining such extended dosing intervals over two years in both Wet AMD and DME is a remarkable advancement for the patients and their physicians. We believe that these results give Eylea HD the potential to become the new standard of care for these retinal diseases.

to even longer dosing intervals with 47% meeting the criteria for at least 20 weeks dosing intervals including 28% who were eligible for 24-week dosing.

The safety profile EYLEA HD remains consistent with EYLEA sustaining vision and anatomic improvements, while maintaining such extended dosing intervals over two years in both wet AMB and DME is a remarkable advancement to the patients and their physicians. We believe that these results give EYLEA HD the potential to become the new standard of care for these retinal diseases.

<unk> to become the new standard of care for these retinal diseases.

Moving to our immunology and inflammation pipeline. On Dupixent and COPD, our first pivotal study, Boreas, met the primary and all two secondary endpoints in a previously unprecedented success for a biologic in a phase III study in patients with uncontrolled COPD and evidence of Type 2 inflammation.

Moving to our immunology and inflammation pipeline. On DUPIXEN and COPD, our first pivotal study met the primary to secondary endpoints in previously unprecedented success for biologics in a phase III study of patients with uncontrolled COPD and evidence of type two inflammation.

Three studying patients with uncontrolled C O P D and evidence of type two information.

Operator: Based on recent feedback from the FDA, in addition to the positive results from the BOREAS study, a positive interim analysis of the replicate phase 3 NOTUS study would enable an sBLA submission. The Independent Data Monitoring Committee will conduct an interim analysis of the NOTUS study later this year. For itepekimab, our anti-IL-33 antibody, the phase 3 AERIFY-1 and AERIFY-2 studies remain on track for read-out and potential regulatory submissions in 2025. Both itepekimab and Dupixent could transform the treatment paradigm for COPD by leveraging their distinct mechanisms of action in reducing different types of inflammation that contribute to COPD disease progression, and we look forward to the results of these studies. Moving to oncology and combinations with Libtayo. We remain on target and are currently enrolling our pivotal study of Libtayo combined with our LAG-3 antibody, fianlimab, in first-line metastatic melanoma.

Based on recent feedback from the FDA, in addition to the positive results from the BOREAS study, a positive interim analysis of the replicate phase 3 NOTUS study would enable an sBLA submission. The Independent Data Monitoring Committee will conduct an interim analysis of the NOTUS study later this year. For itepekimab, our anti-IL-33 antibody, the phase 3 AERIFY-1 and AERIFY-2 studies remain on track for read-out and potential regulatory submissions in 2025.

Based on recent feedback from the FDA, in addition to the positive results from [inaudible] study, a positive interim analysis of the replicate based notice study would enable an SBLA submission. An independent data monitoring committee will conduct an interim analysis of the notice study later this year.

[inaudible] are anti IL 33 antibiotics. The phase Aerify one and two studies remain on track for rehab and potential regulatory submissions in 2025. [inaudible] and DUPIXEN could transform the treatment paradigm for COPD by leveraging their distinct mechanism of actions in reducing different types of inflammation that contribute to COPD disease progression and we look forward to the results of these studies.

<unk> <unk>, one and two studies remain on track for rehab and potential regulatory submissions in 2025, most day to pick them up and two picks and could transform the treatment paradigm for COPD. Leveraging their distinct methods of actions and reducing different types of information that contribute to COPD disease progression and we look forward to the results of these studies.

Both itepekimab and Dupixent could transform the treatment paradigm for COPD by leveraging their distinct mechanisms of action in reducing different types of inflammation that contribute to COPD disease progression, and we look forward to the results of these studies. Moving to oncology and combinations with Libtayo. We remain on target and are currently enrolling our pivotal study of Libtayo combined with our LAG-3 antibody, fianlimab, in first-line metastatic melanoma.

Leveraging their distinct methods of actions and reducing different types of information that contribute to COPD disease progression and we look forward to the results of these studies.

Moving to oncology and combinations with LIBTAYO, we remain on target and are currently enrolling our pivotal study of LIBTAYO combined with our [inaudible] antibody [inaudible] in first line metastatic melanoma. We believe this combination may provide a significant advance for patients in this setting based on our encouraging earlier stage studies.

We remain on target and are currently enrolling are pivotal study or blood taio combined with a lack of antibody. The element if first line Miss Derek melanoma. We believe this combination may provide a significant advance for patients in this setting based on our <unk>, our encouraging earlier stage studies.

Operator: We believe this combination may provide a significant advance for patients in this setting based on our encouraging earlier stage studies. At the annual ESMO meeting, we presented data from a phase 2 trial of neoadjuvant Libtayo treatment for resectable cutaneous squamous cell carcinoma, or CSCC, which demonstrated event-free survival for the vast majority, 89% of patients at one year. It is also noteworthy that of the 51% of patients who had a pathological complete response, none have since experienced disease recurrence. These results add to the growing body of evidence that Libtayo and other checkpoint inhibitors may have utility in earlier stages of CSCC and other malignancies. To further explore this, we are conducting a Libtayo trial in adjuvant CSCC for patients at heightened risk.

We believe this combination may provide a significant advance for patients in this setting based on our encouraging earlier stage studies. At the annual ESMO meeting, we presented data from a phase 2 trial of neoadjuvant Libtayo treatment for resectable cutaneous squamous cell carcinoma, or CSCC, which demonstrated event-free survival for the vast majority, 89% of patients at one year. It is also noteworthy that of the 51% of patients who had a pathological complete response, none have since experienced disease recurrence. These results add to the growing body of evidence that Libtayo and other checkpoint inhibitors may have utility in earlier stages of CSCC and other malignancies. To further explore this, we are conducting a Libtayo trial in adjuvant CSCC for patients at heightened risk.

At the annual ESMO meeting, we presented data from a phase two trial of Neo adjuvant [inaudible] treatment for [inaudible] squamous cell carcinoma, or CSCC, which demonstrated event free survival for the vast majority, 89% of patients at one year.

We presented data from a phase two trial of Neo adjuvant reptile treatment for receptacle containers squamous cell carcinoma, where CFCC, which demonstrated event free survival for the vast majority. 89% of patients at one year.

89% of patients at one year.

It is also noteworthy that of the 51% of patients who had a pathological complete response, none have since experienced disease recurrence. These results add to the growing body of evidence with LIBTAYO and other checkpoint inhibitors may have utility in earlier stages of CSCC and other malignancies.

These results add to the growing body of evidence tile and other checkpoint in Hebrews may I have utility earlier stages of CFCC another malignancies.

To further explore this, we're conducting a LIBTAYO trial in adjuvant CSCC for patients with heightened risks. We're also validating the combination of LIBTAYO with [inaudible] in adjuvant melanoma and plan to initiate a study of this combination in the Peri optic melanoma setting as well.

Operator: We're also evaluating the combination of Libtayo and fianlimab in adjuvant melanoma and plan to initiate a study of this combination in the perioperative melanoma setting as well. On to bispecifics. First, in hematology oncology, we are pleased that odronextamab, our CD20xCD3 bispecific, was recently accepted for review by both the FDA and European regulatory authorities in relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. Based on the pivotal phase II data from the ELM-2 study, we have initiated a robust OLYMPIA phase III development program investigating odronextamab as monotherapy as well as in combination with current standards of care in earlier lines of follicular lymphoma and DLBCL. We are looking forward to the pivotal data presentations from ELM-2 later this year.

We're also evaluating the combination of Libtayo and fianlimab in adjuvant melanoma and plan to initiate a study of this combination in the perioperative melanoma setting as well. On to bispecifics. First, in hematology oncology, we are pleased that odronextamab, our CD20xCD3 bispecific, was recently accepted for review by both the FDA and European regulatory authorities in relapsed/refractory follicular lymphoma and diffuse large B-cell lymphoma. Based on the pivotal phase II data from the ELM-2 study, we have initiated a robust OLYMPIA phase III development program investigating odronextamab as monotherapy as well as in combination with current standards of care in earlier lines of follicular lymphoma and DLBCL. We are looking forward to the pivotal data presentations from ELM-2 later this year.

Onto bispecifics, first in hematology oncology, we are pleased that [inaudible] our CD20 by C3 bispecific was recently accepted for review by both the FDA and European regulatory authorities in relapse refractory follicular lymphoma and [inaudible] lymphoma.

Based on the pivotal phase two data from the [inaudible] study, we have initiated a robust Olympia [inaudible] development program investigating [inaudible] as monotherapy as well as in combination with current standards of care in order of lines of follicular lymphoma, and DL. DCL. We're looking forward to the pivotal data presentations from L2 later this year.

Two later this year.

Operator: We are also on track to submit our regulatory application for Linvoseltamab, our BCMA x CD3 antibody, for relapsed refractory multiple myeloma by the end of the year. This bispecific may potentially offer best-in-class efficacy and convenience. The LINKER-MM3 confirmatory phase 3 study evaluating Linvoseltamab monotherapy compared to a standard of care regimen is enrolling, and studies in earlier lines of multiple myeloma and other plasma cell diseases will be enrolling soon. Finally, in addition to the ongoing phase 1 combination study of Odronextamab and our CD22 x CD28 co-stimulatory bispecific, we're also on track to initiate a study of Linvoseltamab with a corresponding co-stimulatory bispecific next year. Next, onto bispecifics for solid tumors, which are being investigated in combination with Libtayo and other modalities. At ESMO, we shared initial clinical data for the combination of Ubamatamab, our MUC16 x CD3 bispecific, with Libtayo in advanced ovarian cancer.

We are also on track to submit our regulatory application for Linvoseltamab, our BCMA x CD3 antibody, for relapsed refractory multiple myeloma by the end of the year. This bispecific may potentially offer best-in-class efficacy and convenience. The LINKER-MM3 confirmatory phase 3 study evaluating Linvoseltamab monotherapy compared to a standard of care regimen is enrolling, and studies in earlier lines of multiple myeloma and other plasma cell diseases will be enrolling soon.

We're also on track to submit our regulatory application for LINVOSELTAMAB, our [inaudible] antibody for relapse refractory multiple myeloma by the end of the year. This bispecific may potentially offer best-in-class efficacy and convenience. The linker MM3 confirmatory phase three study [inaudible] LINVOSELTAMAB mono therapy compared to a standard of care regimen is enrolling in studies in earlier lines with multiple myeloma and other plasma cells diseases will be enrolling soon.

mono therapy compared to a standard of care regimen is enrolling in studies in earlier lines with multiple myeloma and other plasma cells diseases will be enrolling soon.

Finally, in addition to the ongoing phase 1 combination study of Odronextamab and our CD22 x CD28 co-stimulatory bispecific, we're also on track to initiate a study of Linvoseltamab with a corresponding co-stimulatory bispecific next year. Next, onto bispecifics for solid tumors, which are being investigated in combination with Libtayo and other modalities. At ESMO, we shared initial clinical data for the combination of Ubamatamab, our MUC16 x CD3 bispecific, with Libtayo in advanced ovarian cancer.

Finally, in addition to the ongoing phase one combination study of [inaudible] in our CD22 by CD20 inventory bispecific, we're also on track to initiate a study of LINVOSELTAMAB with the corresponding [inaudible] bispecific next year.

Next, onto bispecifics for solid tumors, which are being investigated in combination with LIBTAYO and other modalities. At ESMO, we shared initial clinical data for the combination of [inaudible] bispecific with LIBTAYO in advanced ovarian cancer. It is early data. Promising durable responses were observed [inaudible] mono therapy as well as encouraging combination activity with LIBTAYO with evidence of turnaround responses after initial progression on mono therapy reunions in multiple patients upon addition of LIBTAYO. A randomized phase two expansion study is ongoing to evaluate two active monotherapy doses of [inaudible] with the lower dose also tested in combination with LIBTAYO in order to optimize dosing and evaluate the potential added activity of LIBTAYO. In addition, we're exploring [inaudible] in multiple rare cancers that are known to express high levels of [inaudible].

<unk>, we shared initial clinical data for the combination of romantic tab or muck 16 by two three by specific with Libtayo, an advanced ovarian cancer in his early data promising durable responses were observed <unk> mono therapy as well as encouraging combination activity with a child with evidence of.

Operator: In these early data, promising durable responses were observed with Ubamatamab monotherapy as well as encouraging combination activity with Libtayo, with evidence of turnaround responses after initial progression on monotherapy lead-in in multiple patients upon addition of the Libtayo. A randomized phase II expansion study is ongoing to evaluate two active monotherapy doses of Ubamatamab, with the lower dose also tested in combination with Libtayo, in order to optimize dosing and evaluate the potential added activity of Libtayo. In addition, we're exploring Ubamatamab in multiple rare cancers that are known to express high levels of MUC16. In terms of our co-stimulatory bispecifics for solid tumors, we are currently exploring multiple different CD28 co-stimulatory bispecific antibodies in early clinical trials in a variety of tumor settings in combination with Libtayo or with corresponding CD3 bispecifics.

In these early data, promising durable responses were observed with Ubamatamab monotherapy as well as encouraging combination activity with Libtayo, with evidence of turnaround responses after initial progression on monotherapy lead-in in multiple patients upon addition of the Libtayo. A randomized phase II expansion study is ongoing to evaluate two active monotherapy doses of Ubamatamab, with the lower dose also tested in combination with Libtayo, in order to optimize dosing and evaluate the potential added activity of Libtayo. In addition, we're exploring Ubamatamab in multiple rare cancers that are known to express high levels of MUC16. In terms of our co-stimulatory bispecifics for solid tumors, we are currently exploring multiple different CD28 co-stimulatory bispecific antibodies in early clinical trials in a variety of tumor settings in combination with Libtayo or with corresponding CD3 bispecifics.

turnaround responses after initial progression on mono therapy reunions in multiple patients upon addition of LIBTAYO. A randomized phase two expansion study is ongoing to evaluate two active monotherapy doses of [inaudible]

with the lower dose also tested in combination with LIBTAYO in order to optimize dosing and evaluate the potential added activity of LIBTAYO. In addition, we're exploring [inaudible] in multiple rare cancers that are known to express high levels of [inaudible].

In order to optimize dosing and evaluate the potential added activity of a child. In addition, we're exploring <unk> and multiple rare cancers that are known to express high levels of March 16th.

In terms of our [inaudible] bispecifics for solid tumors, we are currently exploring multiple different CD28 [inaudible] bispecific antibodies in early clinical trials [inaudible] in combination with LIBTAYO with corresponding C3 bispecifics. We are continuing development of [inaudible] bispecific in advanced prostate cancer, focusing on identifying the window of opportunity for maintaining the remarkable anti-tumor activity observed [inaudible] so far while minimizing serious toxicity.

Operator: We are continuing development of our PSMA x CD28 co-stimulatory bispecific in advanced prostate cancer, focusing on identifying the window of opportunity for maintaining the remarkable anti-tumor activity observed with this treatment so far while minimizing serious toxicity. In order to explore this, we've expanded enrollment in the PSMA x CD28 monotherapy cohort and will soon initiate cohorts in which investigators will have an option of adding a low dose of SUMIPLOMAB to the PSMA x CD28 treatment in certain patients. Moreover, we plan to initiate a trial combining PSMA x CD28 with PSMA x CD3, since based on preclinical data, CD28 co-stims with appropriate CD3 bispecifics may yield anti-tumor activity without severe immune-mediated adverse events. We also hope to progress an additional prostate-specific CD3 bispecific toward the clinic in the next year, which we may also combine with our PSMA co-stimulatory bispecific.

We are continuing development of our PSMA x CD28 co-stimulatory bispecific in advanced prostate cancer, focusing on identifying the window of opportunity for maintaining the remarkable anti-tumor activity observed with this treatment so far while minimizing serious toxicity. In order to explore this, we've expanded enrollment in the PSMA x CD28 monotherapy cohort and will soon initiate cohorts in which investigators will have an option of adding a low dose of SUMIPLOMAB to the PSMA x CD28 treatment in certain patients.

focusing on identifying the window of opportunity for maintaining the remarkable anti-tumor activity observed [inaudible] so far while minimizing serious toxicity.

In order to explore this, we've expanded enrollment in the PSMA mono therapy cohort and will soon initiate cohorts [inaudible] will have an option of adding a low dose of [inaudible] to the PSMA by C280 treatment in certain patients. Moreover, we plan to initiate a trial combining PSMA CD28 with PSMA CD3 since based on preclinical data CD28 [inaudible] with appropriate CD3 bispecifics may yield anti tumor activity without severe immune related adverse events.

Moreover, we plan to initiate a trial combining PSMA x CD28 with PSMA x CD3, since based on preclinical data, CD28 co-stims with appropriate CD3 bispecifics may yield anti-tumor activity without severe immune-mediated adverse events. We also hope to progress an additional prostate-specific CD3 bispecific toward the clinic in the next year, which we may also combine with our PSMA co-stimulatory bispecific.

preclinical data CD28 [inaudible] with appropriate CD3 bispecifics may yield anti tumor activity without severe immune related adverse events.

We also hope to progress an additional prostate [inaudible] bispecific towards the clinic in the next year, which we may also combine with our PSMA [inaudible] bispecific.

Operator: In terms of our MUC16 by CD28 co-stim in combination with Libtayo in ovarian cancer, we're planning on presenting initial data by the end of the year. Regarding our EGFR by CD28 co-stim in combination with Libtayo, we're planning on presenting updated dose escalation data in 2024. We will soon commence enrollment across eight tumor-specific expansion cohorts in the study, including colorectal cancer with or without liver metastases, as well as EGFR-mutant non-small cell lung cancer. Now to genetic medicines. We at Intellia recently announced expansion of our research collaboration to include Regeneron's proprietary antibody-targeted delivery technology with the goal of expanding the reach of in vivo gene editing to neurological and muscle diseases. The aim of this expanded collaboration is to address a current bottleneck in genetic medicines: the inability to deliver a genetic payload beyond the liver.

In terms of our MUC16 by CD28 co-stim in combination with Libtayo in ovarian cancer, we're planning on presenting initial data by the end of the year. Regarding our EGFR by CD28 co-stim in combination with Libtayo, we're planning on presenting updated dose escalation data in 2024. We will soon commence enrollment across eight tumor-specific expansion cohorts in the study, including colorectal cancer with or without liver metastases, as well as EGFR-mutant non-small cell lung cancer. Now to genetic medicines. We at Intellia recently announced expansion of our research collaboration to include Regeneron's proprietary antibody-targeted delivery technology with the goal of expanding the reach of in vivo gene editing to neurological and muscle diseases. The aim of this expanded collaboration is to address a current bottleneck in genetic medicines: the inability to deliver a genetic payload beyond the liver.

In terms of our [inaudible] by CD28 combination with ovarian cancer, we're planning on presenting initial data by the end of the year.

Regarding our Egfr by CD28 in combination with LIBTAYO, we're planning on presenting updated dose escalation data in 2024. We will soon commence enrollment across eight tumor specific expansion cohorts in the study, including colorectal cancer with or without liver metastases as well as Egfr mutation in non-small cell lung cancer.

Now to genetic medicines, we and Intellia recently announced expansion of our research collaboration to include Regeneron's proprietary antibody target delivery technology with the goal of expanding the reach of in vivo gene editing to neurological and muscle diseases. The aim of this expanded collaboration is to address a current bottleneck in genetic medicines, the inability to deliver genetic payload beyond the liver. Our proprietary preclinical validated antibody directed AV approach will initially test two in vivo non liver targets.

<unk> and and tell you recently announced expansion of our research collaboration to include Regeneron as proprietary antibody target delivery technology with the goal of expanding the reach of in vivo gene editing to neurological and muscle diseases. The aim of this expanded collaboration is to dress a current bottleneck.

Connecticut medicines <unk>. Ready to deliver genetic payload beyond the liver. Proprietary preclinical validated antibody directed a V approach will initially test two in vivo non liver targets.

Ready to deliver genetic payload beyond the liver. Proprietary preclinical validated antibody directed a V approach will initially test two in vivo non liver targets.

Operator: Our proprietary preclinically validated antibody-directed AAV approach will initially test two in vivo non-liver targets. Additionally, we at Intellia announced FDA clearance to start a pivotal phase 3 trial of NTLA-2001 for the treatment of ATTR amyloidosis with cardiomyopathy. The first time an investigational in vivo CRISPR-based gene therapy editing is cleared to enter late-stage clinical development in the United States. The trial is expected to initiate by year-end 2023. Moving to our Alnylam collaboration. Alnylam recently presented updated interim ALN-APP data in early-onset Alzheimer's disease. Updated data show that single doses of ALN-APP achieve sustained robust reduction in APP alpha and APP beta measured in the CSF up to 10 months after administration, as well as reduction of amyloidogenic peptides implicated in Alzheimer's disease and in cerebral amyloid angiopathy.

Our proprietary preclinically validated antibody-directed AAV approach will initially test two in vivo non-liver targets. Additionally, we at Intellia announced FDA clearance to start a pivotal phase 3 trial of NTLA-2001 for the treatment of ATTR amyloidosis with cardiomyopathy. The first time an investigational in vivo CRISPR-based gene therapy editing is cleared to enter late-stage clinical development in the United States. The trial is expected to initiate by year-end 2023. Moving to our Alnylam collaboration. Alnylam recently presented updated interim ALN-APP data in early-onset Alzheimer's disease. Updated data show that single doses of ALN-APP achieve sustained robust reduction in APP alpha and APP beta measured in the CSF up to 10 months after administration, as well as reduction of amyloidogenic peptides implicated in Alzheimer's disease and in cerebral amyloid angiopathy.

Proprietary preclinical validated antibody directed a V approach will initially test two in vivo non liver targets.

Additionally, we and Intellia announced FDA clearance to start a pivotal phase three trial of NTLA 2001 for the treatment of A2TR amyloidosis with cardiomyopathy, the first time an investigation of in vivo [inaudible] based gene therapy editing is cleared to enter a late stage clinical development in the United States. The trial is expected to initiate by year end 2023.

States. The trial is expected to an issue by year end 2023 <unk>.

Moving to our Alnylam collaboration, Alnylam recently presented updated interim ALN APP data in early onset Alzheimer's disease. Updated data showed that single doses of ALN APP achieved sustained robust reduction in APP Alpha and APP Beta measured in the CSS up to 10 months after administration as well as reduction of emetogenic peptides implicated in Alzheimer's disease and in cerebral amyloid angiopathy.

10 months after administration as well as reduction of Emetogenic peptides implicated in Alzheimer's disease, and then cerebral amyloid angiopathy.

Operator: Alnylam has also announced that a first patient has been redosed with ALN-APP in the multidose portion of the study, currently proceeding outside of the United States. We in Alnylam plan to initiate additional clinical programs for neurodegenerative diseases, including for amyotrophic lateral sclerosis, next year. Finally, I would like to highlight DB-OTO, our otoferlin gene therapy, Regeneron's first clinical program for genetic hearing loss, which we developed over the last few years in collaboration with Decibel Therapeutics, a company we recently acquired. Last week, we announced the first preliminary results from this trial. A child who received an intraocular injection of DB-OTO in one ear experienced improvements in hearing tests in that ear through week six compared to baseline, including both auditory brainstem responses as well as behavioral audiometry.

Alnylam has also announced that a first patient has been redosed with ALN-APP in the multidose portion of the study, currently proceeding outside of the United States. We in Alnylam plan to initiate additional clinical programs for neurodegenerative diseases, including for amyotrophic lateral sclerosis, next year. Finally, I would like to highlight DB-OTO, our otoferlin gene therapy, Regeneron's first clinical program for genetic hearing loss, which we developed over the last few years in collaboration with Decibel Therapeutics, a company we recently acquired.

Alnylam has also announced that the first patient has been redosed with ALN APP in the multidose portion of the study currently proceeding outside of the United States. We and Alnylam plan to initiate additional clinical programs for neurodegenerative diseases, including for amyotrophic lateral sclerosis next year.

Finally, I would like to highlight DB-OTO, our oto feral and gene therapy, Regeneron's first clinical program for genetic hearing loss, which we developed over the last few years in collaboration with Decibel Therapeutics, a company we recently acquired. Last week, we announced the first preliminary results from this trial. A child who receives an injection of GB-OTO in one year experienced improvements in hearing tests in that ear through week six compared to baseline, including both auditory brain stem responses as well as behavioral audiometry. We're looking forward to continuing evaluation of this innovative approach in the ongoing trial for the ultra rare oto feral gene related hearing loss as well as in other planned clinical programs, which include more common forms of genetic hearing loss.

Last week, we announced the first preliminary results from this trial. A child who received an intraocular injection of DB-OTO in one ear experienced improvements in hearing tests in that ear through week six compared to baseline, including both auditory brainstem responses as well as behavioral audiometry.

Seeds and interact with an injection of GB ODO in one year experienced improvements in hearing tests in that ear three weeks six compared to baseline, including both auditory brain stem responses as well as behavioral audiometry. We're looking forward to continuing evaluation of this innovative approach and the ongoing trial for the <unk>. <unk> G related hearing loss as well as in other plan clinical programs, which include more common forms of genetic hearing loss.

Operator: We are looking forward to continuing evaluation of this innovative approach in the ongoing trial for the ultra-rare otoferlin gene-related hearing loss, as well as in other planned clinical programs which include more common forms of genetic hearing loss. In conclusion, Regeneron's R&D engine continues to grow and deliver differentiated late and early-stage opportunities, and we are looking forward to progress in the remainder of this year and looking ahead to 2024. With that, I will turn it over to Marion. Thank you, George. I'm delighted to share details of our commercial performance in the third quarter, including very encouraging early signals for Eylea HD, as well as ongoing results from our inline brands. Starting with our anti-VEGF retinal franchise, Regeneron achieved $1.49 billion in total net sales for the quarter in the US. We were excited to rapidly launch Eylea HD in late August following its US.

We are looking forward to continuing evaluation of this innovative approach in the ongoing trial for the ultra-rare otoferlin gene-related hearing loss, as well as in other planned clinical programs which include more common forms of genetic hearing loss. In conclusion, Regeneron's R&D engine continues to grow and deliver differentiated late and early-stage opportunities, and we are looking forward to progress in the remainder of this year and looking ahead to 2024. With that, I will turn it over to Marion.

<unk> G related hearing loss as well as in other plan clinical programs, which include more common forms of genetic hearing loss.

In conclusion, Regeneron's R&D engine continues to grow and deliver differentiated late and early stage opportunities and we're looking forward to progress in the remainder of this year and looking ahead to 2024.

<unk> R&D engine continues to grow and delivered differentiated late and early stage opportunities and we're looking forward to progress and the remainder of this year and looking ahead to 2024.

Marion McCourt: Thank you, George. I'm delighted to share details of our commercial performance in the third quarter, including very encouraging early signals for Eylea HD, as well as ongoing results from our inline brands. Starting with our anti-VEGF retinal franchise, Regeneron achieved $1.49 billion in total net sales for the quarter in the US. We were excited to rapidly launch Eylea HD in late August following its US.

With that, I will turn it over to Marion.

Marion E. McCourt: I'm delighted to share details of our commercial performance in the third quarter including very encouraging early signals for EYLEA HD as well as ongoing results from our inline bands.

Starting with our anti [inaudible] franchise, Regeneron achieved 1.49 billion in total net sales for the quarter in the US. We were excited to rapidly launch EYLEA HD in late August following its US approval and total net sales for the quarter was $43 million.

We were excited to rapidly to Orange Eylea H D. In late August filing as soon as I put it all in total net sales for the quarter or $43 million.

Operator: Approval, and total net sales for the quarter were $43 million. Early launch indicators have been very positive. Physician enthusiasm was extremely high prior to Eylea HD launch, and that interest has translated into early use in a broad range of patient types across wet AMD and diabetic eye disease. It is noteworthy that physicians are prescribing Eylea HD in recalcitrant, switch, and naive patients. We are already hearing anecdotal case reports from physicians whose recalcitrant patients are returning. Many of these patients have now been able to achieve drying that they were unable to obtain with other products. To accelerate this early launch momentum, our highly experienced team is rapidly advancing reimbursement and market access. We have confirmed paid claims from 100% of Medicare jurisdictions, and many large payers have recently published coverage policies for Eylea HD. This includes both Medicare Advantage and commercial plans.

Approval, and total net sales for the quarter were $43 million. Early launch indicators have been very positive. Physician enthusiasm was extremely high prior to Eylea HD launch, and that interest has translated into early use in a broad range of patient types across wet AMD and diabetic eye disease. It is noteworthy that physicians are prescribing Eylea HD in recalcitrant, switch, and naive patients. We are already hearing anecdotal case reports from physicians whose recalcitrant patients are returning. Many of these patients have now been able to achieve drying that they were unable to obtain with other products.

Early launch indicators have been very positive. Physician enthusiasm was extremely high prior to EYLEA HD's launch and that interest has translated into early use in a broad range of patient types across rev MMB and diabetic eye disease. It is worthy to physicians prescribing EYELEA HD [inaudible] switch and know your patients. We're already hearing anecdotal case reports from physicians whose [inaudible] patients are returning. Many of these patients have now been able to achieve [inaudible] that they were unable to obtain with other products.

and know your patients. We're already hearing anecdotal case reports from physicians whose [inaudible] patients are returning. Many of these patients have now been able to achieve [inaudible] that they were unable to obtain with other products. To accelerate this early lunch momentum, our highly experienced team is rapidly advancing reimbursement in market access. We have confirmed paid claims from 100 per cent of Medicare jurisdictions, and many large payers have recently published coverage policy for EYLEA HD.

That they were unable to obtain with other products to accelerate this early lunch momentum are highly experienced team is rapidly advancing reimbursement in market access. We have confirmed paid claims from 100 per cent of Medicare jurisdictions, and many large payers of recently published coverage policy slightly each day.

To accelerate this early launch momentum, our highly experienced team is rapidly advancing reimbursement and market access. We have confirmed paid claims from 100% of Medicare jurisdictions, and many large payers have recently published coverage policies for Eylea HD. This includes both Medicare Advantage and commercial plans.

To accelerate this early lunch momentum, our highly experienced team is rapidly advancing reimbursement in market access. We have confirmed paid claims from 100 per cent of Medicare jurisdictions, and many large payers have recently published coverage policy for EYLEA HD. This includes both Medicare advantage and commercial plans. While early, the speed of EYLEA HD coverage is significantly outpacing recent competitive launches. In addition, we continue to be on track to have [inaudible] by April 1, 2024, which we anticipate we'll have additional updates. These early reimbursement successes

This includes both Medicare advantage and commercial plans. While early, the speed of EYLEA HD coverage is significantly outpacing recent competitive launches. In addition, we continue to be on track to have [inaudible] by April 1, 2024, which we anticipate we'll have additional updates. These early reimbursement successes

Operator: While early, the speed of Eylea HD coverage is significantly outpacing recent competitive launches. In addition, we continue to be on track to have a permanent J code by 1 April 2024, which we anticipate will drive additional uptake. These early reimbursement successes and positive physician experiences are being shared by prescribers with our team and more broadly with the retina community. These initial results bode well for the future of Eylea HD and substantiate our belief that Eylea HD will rapidly become the new standard of care across its approved indications. Eylea HD's unsurpassed safety and durability demonstrated in clinical trials, coupled with prescriber confidence in Eylea's efficacy and safety record, is expected to drive continued category leadership. In summary, while the launch is still in early days, we are pleased with our progress and look forward to providing future updates.

While early, the speed of Eylea HD coverage is significantly outpacing recent competitive launches. In addition, we continue to be on track to have a permanent J code by 1 April 2024, which we anticipate will drive additional uptake. These early reimbursement successes and positive physician experiences are being shared by prescribers with our team and more broadly with the retina community.

These early reimbursement successes and positive physician experiences are being shared by prescribers this with our team and more broadly with the retina community. These initial results bode well for the future of EYLEA HD and a substantiate our belief that EYLEA HD will rapidly become the new standard of care across its approved indications.

and positive physician experiences are being shared by prescribers this with our team and more broadly with the retina community. These initial results bode well for the future of EYLEA HD and a substantiate our belief that EYLEA HD will rapidly become the new standard of care across its approved indications.

These initial results bode well for the future of Eylea HD and substantiate our belief that Eylea HD will rapidly become the new standard of care across its approved indications. Eylea HD's unsurpassed safety and durability demonstrated in clinical trials, coupled with prescriber confidence in Eylea's efficacy and safety record, is expected to drive continued category leadership. In summary, while the launch is still in early days, we are pleased with our progress and look forward to providing future updates.

Initial results bode well for the future of Eylea H D and a substantial our beliefs that Ali a H T will rapidly become the new standard of care across its appraised indications.

EYLEA HD unsurpassed safety and durability demonstrated in clinical trials, coupled with prescriber confidence in EYLEA's efficacy and safety record is expected to drive continued category leadership.

In summary, while the launch is still in early days, we are pleased with our progress and look forward to providing future updates. [inaudible] remains the category leader with 45% [inaudible] share for the quarter in an increasingly competitive market. With over 70 million injections worldwide since launch, EYLEA continues to demonstrate a strong and consistent safety profile,

In summary, while the launch is still in early days, we are pleased with our progress and look forward to providing future updates.

Operator: EYLEA remains the category leader with 45% anti-VEGF share for the quarter in an increasingly competitive market. With over 70 million injections worldwide since launch, EYLEA continues to demonstrate a strong and consistent safety profile, a key differentiator given retinal vasculitis and intraocular inflammation events with certain new products introduced in the retinal category. With both EYLEA HD and EYLEA, our formidable retina franchise is poised for sustained leadership. Next to Dupixent, global net sales grew 33% year-over-year to $3.1 billion and US net sales grew 30% to $2.4 billion. This impressive third-quarter performance demonstrates Dupixent's clinical and safety differentiation across all approved indications, as well as its continued growth potential. In the third quarter, more than 50,000 new patients are taking Dupixent in the US alone, and there are now more than 750,000 patients on Dupixent worldwide.

EYLEA remains the category leader with 45% anti-VEGF share for the quarter in an increasingly competitive market. With over 70 million injections worldwide since launch, EYLEA continues to demonstrate a strong and consistent safety profile, a key differentiator given retinal vasculitis and intraocular inflammation events with certain new products introduced in the retinal category. With both EYLEA HD and EYLEA, our formidable retina franchise is poised for sustained leadership. Next to Dupixent, global net sales grew 33% year-over-year to $3.1 billion and US net sales grew 30% to $2.4 billion. This impressive third-quarter performance demonstrates Dupixent's clinical and safety differentiation across all approved indications, as well as its continued growth potential. In the third quarter, more than 50,000 new patients are taking Dupixent in the US alone, and there are now more than 750,000 patients on Dupixent worldwide.

<unk> remains the category leader with 45% empty bed checks, sir for the quarter in an increasingly competitive market with over 70 million injections worldwide. Since lunch I lead continues to demonstrate a strong and consistent safety profile.

[inaudible] remains the category leader with 45% [inaudible] share for the quarter in an increasingly competitive market. With over 70 million injections worldwide since launch, EYLEA continues to demonstrate a strong and consistent safety profile, a key differentiator given retinal vasculitis and intra ocular inflammation events with certain new products introduced in the retinol category. EYLEA HD and EYLEA, our formidable retina franchise is poised for sustained leadership.

a key differentiator given retinal vasculitis and intra ocular inflammation events with certain new products introduced in the retinol category. EYLEA HD, our medical retina franchise is point for sustained leadership. Next to [inaudible] global net sales grew 33 per cent year over year to $3.1 billion

a key differentiator given retinal vasculitis and intra ocular inflammation events with certain new products introduced in the retinol category. EYLEA HD and EYLEA, our formidable retina franchise is poised for sustained leadership.

Next to [inaudible] global net sales grew 33 per cent year over year to $3.1 billion and US net sales grew 30 per cent to 2.4 billion. This impressive third quarter performance demonstrates clinical and safety differentiation across all approved indications as well as its continued growth potential. In the third quarter more than 50,000 new patients are taking DUPEXIN in the US alone and there are now more than 750,000 patients on DUPEXIN worldwide. In atopic dermatitis, DUPEXIN's largest indication we continue to see more than 20 per cent growth six years post launch. Physicians have great confidence from the combination of efficacy, safety, and ease of use across all age groups, including as young as six months. Not only is it a remarkable adherence once patience begin therapy, we also see DUPEXIN as being the clear treatment of choice for new patients with moderate to severe disease with significant growth opportunity.

and US net sales grew 30 per cent to 2.4 billion. This impressive third quarter performance demonstrates clinical and safety differentiation across all approved indications as well as its continued growth potential. In the third quarter more than 50,000 new patients

The first indications as well as its continued growth potential. Third quarter more than 50000, new patients.

Third quarter more than 50000, new patients.

are taking DUPEXIN in the US alone and there are now more than 750,000 patients on DUPEXIN worldwide. In atopic dermatitis, DUPEXIN's largest indication we continue to see more than 20 per cent growth six years post launch. Physicians have great confidence from the combination of efficacy, safety, and ease of use across

Operator: In atopic dermatitis, Dupixent's largest indication, we continue to see more than 20% growth six years post-launch. Physicians have great confidence from the combination of efficacy, safety, and ease of use across all age groups, including as young as six months. Not only is there remarkable adherence once patients begin therapy, we also see Dupixent as being the clear treatment of choice for new patients with moderate to severe disease, with significant growth opportunity. In asthma, Dupixent is differentiated from all other medicines in the category based on its rapid and sustained effect on lung function, reduced exacerbations, and reduced corticosteroid use. In the US, Dupixent continues to lead new patient prescriptions, and we are quickly approaching our goal of being the number one prescribed medicine for asthma.

In atopic dermatitis, Dupixent's largest indication, we continue to see more than 20% growth six years post-launch. Physicians have great confidence from the combination of efficacy, safety, and ease of use across all age groups, including as young as six months. Not only is there remarkable adherence once patients begin therapy, we also see Dupixent as being the clear treatment of choice for new patients with moderate to severe disease, with significant growth opportunity. In asthma, Dupixent is differentiated from all other medicines in the category based on its rapid and sustained effect on lung function, reduced exacerbations, and reduced corticosteroid use. In the US, Dupixent continues to lead new patient prescriptions, and we are quickly approaching our goal of being the number one prescribed medicine for asthma.

all age groups, including as young as six months. Not only is it a remarkable adherence once patience begin therapy, we also see DUPEXIN as being the clear treatment of choice for new patients with moderate to severe disease with significant growth opportunity.

In asthma, DUPEXIN is differentiated from all other medicines in the category based on its rapid and sustained effect on lung function, reduced exacerbations, and reduced [inaudible]. In the US, DUPEXIN continues to lead new patient prescriptions and we are quickly approaching our goal of being the number one prescribed medicine for asthma.

Operator: Together with our partner Sanofi, Regeneron continues to advance recent launches in eosinophilic esophagitis and prurigo nodularis, which are already meaningfully contributing to Dupixent's growth. Since FDA approval, approximately 20,000 new patients with eosinophilic esophagitis have been initiated, and demand is also robust for prurigo nodularis, where Dupixent is rapidly becoming the standard of care within a year of approval. We also look forward to offering Dupixent to even more patients in the future, with anticipated regulatory approvals of pediatric eosinophilic esophagitis, as well as multiple near-term phase 3 data readouts on COPD, chronic spontaneous urticaria, and bullous pemphigoid. In summary, Dupixent continues to be a key driver of our growth, and we look forward to seeing its transformational benefits extending to even more patients with type 2 inflammatory diseases across indications, demographics, and geographies.

Together with our partner Sanofi, Regeneron continues to advance recent launches in eosinophilic esophagitis and prurigo nodularis, which are already meaningfully contributing to Dupixent's growth. Since FDA approval, approximately 20,000 new patients with eosinophilic esophagitis have been initiated, and demand is also robust for prurigo nodularis, where Dupixent is rapidly becoming the standard of care within a year of approval. We also look forward to offering Dupixent to even more patients in the future, with anticipated regulatory approvals of pediatric eosinophilic esophagitis, as well as multiple near-term phase 3 data readouts on COPD, chronic spontaneous urticaria, and bullous pemphigoid. In summary, Dupixent continues to be a key driver of our growth, and we look forward to seeing its transformational benefits extending to even more patients with type 2 inflammatory diseases across indications, demographics, and geographies.

Together with our partner [inaudible], Regeneron continues to [inaudible] recent launches in [inaudible], which are already meaningfully contributing to growth. Since the FDA's approval, approximately 20,000 new patients with [inaudible] esophagitis have been initiated and demand is also robust for [inaudible] where DUPEXIN is rapidly becoming the standard of care within a year of approval. We also look forward to offering DUPEXIN to even more patients in the future with anticipated regulatory approvals of pediatric as [inaudible] as well as multiple near term phase three data to read out on COPD [inaudible].

[inaudible] where DUPEXIN is rapidly becoming the standard of care within a year of approval. We also look forward to offering DUPEXIN to even more patients in the future with anticipated regulatory approvals of pediatric as [inaudible] as well as multiple near term phase three data to read out on COPD [inaudible].

In summary, DUPEXIN continues to be a key driver of our growth and we look forward to seeing its transformational benefits extended to even more patients with type two inflammatory diseases across indications, demographics, and geographies.

Operator: And finally, to Libtayo, Q3 global net sales grew 59% year-over-year on a constant currency basis to $232 million, with US net sales up 52% to $144 million. Global growth was driven by our non-melanoma skin indications coupled with increased utilization in both monotherapy and chemotherapy combination settings in lung cancer. We're working to expand access and use in many additional countries following recent regulatory approvals. We continue to see a growing number of prescribers choosing Libtayo when treating their patients. In conclusion, Regeneron's performance in the Q3 continues to deliver growth and value for patients and shareholders, with opportunity for sustained growth. We're encouraged by favorable early indicators from the Eylea HD launch and continue to deliver compelling performance from our inline brands, including Eylea, Dupixent, and Libtayo. Now I'll turn the call over to Bob. Thanks, Marion.

And finally, to Libtayo, Q3 global net sales grew 59% year-over-year on a constant currency basis to $232 million, with US net sales up 52% to $144 million. Global growth was driven by our non-melanoma skin indications coupled with increased utilization in both monotherapy and chemotherapy combination settings in lung cancer. We're working to expand access and use in many additional countries following recent regulatory approvals. We continue to see a growing number of prescribers choosing Libtayo when treating their patients. In conclusion, Regeneron's performance in the Q3 continues to deliver growth and value for patients and shareholders, with opportunity for sustained growth. We're encouraged by favorable early indicators from the Eylea HD launch and continue to deliver compelling performance from our inline brands, including Eylea, Dupixent, and Libtayo. Now I'll turn the call over to Bob.

And finally to LIBTAYO, third quarter global net sales grew 59% year over year on a constant currency basis to $232 million with US net sales up 52% to $144 million. Global growth was driven by non-melanoma skin indications coupled with increased utilization in both mono therapy and chemotherapy combination settings in lung cancer. We're working to expand access and use in many additional countries following recent regulatory approvals. We continue to see a growing number of prescribers choosing LIBTAYO when treating their patients. In conclusion, Regeneron's performance in the third quarter continued to deliver growth and value for patients and shareholders with opportunity for sustained growth. We're encouraged by favorable early indicators from the EYLEA HD launch and continue to deliver compelling performance from our inline brands, including EYLEA, DUPEXIN and LIBTAYO. Now I'll turn the call over to Bob.

<unk> mono therapy, and chemotherapy combination settings, and lung cancer or working to expand access and use and many additional countries. Following week regulatory approvals. We continue to see a growing number of prescribers choosing libtayo when treating their patients in conclusion pretty generous performance in the third quarter continue.

In conclusion, Regeneron's performance in the third quarter continued to deliver growth and value for patients and shareholders with opportunity for sustained growth. We're encouraged by favorable early indicators from the EYLEA HD launch and continue to deliver compelling performance from our inline brands, including EYLEA, DUPEXIN and LIBTAYO. Now I'll turn the call over to Bob.

To deliver growth and value for patients and shareholders with opportunity for sustained growth. We're encouraged by favorable early indicators from the earlier itchy lunch and continue to deliver compelling performance for my inline brands, including <unk> now I'll turn the call over to Bob.

Robert Landry: Thanks, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis, unless otherwise noted. Regeneron performed well in the third quarter, with execution across the business continuing to drive strong top and bottom-line growth. Third quarter 2023 total revenues increased 15% year-over-year to $3.4 billion, primarily driven by sales growth for Dupixent, coupled with improving margins within the Sanofi collaboration, as well as continued growth from Litayo.

Operator: My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis, unless otherwise noted. Regeneron performed well in the third quarter, with execution across the business continuing to drive strong top and bottom-line growth. Third quarter 2023 total revenues increased 15% year-over-year to $3.4 billion, primarily driven by sales growth for Dupixent, coupled with improving margins within the Sanofi collaboration, as well as continued growth from Litayo. Third quarter diluted net income per share grew 4% to $11.59 on net income of $1.3 billion. This included a $100 million acquired IPR&D charge incurred in the third quarter of 2023, which decreased growth by approximately 7 percentage points. Moving to collaboration revenue and starting with Bayer. Third quarter 2023 ex-US Eylea net product sales were $872 million, up 6% on a constant currency basis versus the prior year.

Robert E. Landry: Thanks Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis, unless otherwise noted.

Regeneron performed well in the third quarter with execution across the business continuing to drive strong top and bottom line growth. Third quarter 2023 total revenues increased 15% year over year to 3.4 billion primarily driven by sales growth for depiction, coupled with improving margins within the SANAFI collaboration as well as continued growth from LIBTAYO..

Strong top and bottom line growth third quarter of 2023 total revenues increased 15% year over year to three <unk> 3.4 billion.

Primarily driven by sales growth for depiction, coupled with improving margins within the <unk> collaboration as well as continued growth from reptile.

Third quarter diluted net income per share grew 4% to $11.59 on net income of $1.3 billion. This included a $100 million acquired IPR&D charge incurred in the third quarter of 2023, which decreased growth by approximately 7 percentage points. Moving to collaboration revenue and starting with Bayer. Third quarter 2023 ex-US Eylea net product sales were $872 million, up 6% on a constant currency basis versus the prior year.

Third quarter diluted net income per share grew 4% to $11.59 on net income of $1.3 billion. This included $100 million dollar acquired IP R&D charge incurred in the third quarter of 2023, which decreased growth by approximately seven percentage points.

Which decreased growth by approximately seven percentage points move.

Moving to collaboration revenue and starting with Bayer. Third quarter 2023, ex-US EYLEA net product sales were $872 million, up 6% on a constant currency basis versus the prior year. Total Bayer collaboration revenue was $377 million of which $350 million related to our share of EYLEA net profits outside the US.

Third quarter 2023, <unk> net product sales were $872 million up six per cent on a constant currency basis versus the prior year total bear collaboration revenue was 377 million of which 350 million related to our share of Eylea net profits outside the U S.

Operator: Total Bayer collaboration revenue was $377 million, of which $350 million related to our share of Eylea net profits outside the US. Total Sanofi collaboration revenue was $1.1 billion in Q3, up 50% versus the prior year, which included the final $50 million sales-based milestone. Our share of profits from the commercialization of Dupixent and Kevzara was $863 million, an increase of 57% versus Q3 of 2022, driven by Dupixent's continued volume growth and improving margins. As we guided last quarter, Q3 reimbursements for the manufacturing of commercial supplies from Sanofi, a component of Sanofi collaboration revenues, declined sequentially, primarily due to the ongoing phase-in of a new, higher-yielding manufacturing process. In Q4, we expect a continuation of this trend, with reimbursements for manufacturing of commercial supplies expected to be sequentially lower by approximately $40 million.

Total Bayer collaboration revenue was $377 million, of which $350 million related to our share of Eylea net profits outside the US. Total Sanofi collaboration revenue was $1.1 billion in Q3, up 50% versus the prior year, which included the final $50 million sales-based milestone. Our share of profits from the commercialization of Dupixent and Kevzara was $863 million, an increase of 57% versus Q3 of 2022, driven by Dupixent's continued volume growth and improving margins. As we guided last quarter, Q3 reimbursements for the manufacturing of commercial supplies from Sanofi, a component of Sanofi collaboration revenues, declined sequentially, primarily due to the ongoing phase-in of a new, higher-yielding manufacturing process. In Q4, we expect a continuation of this trend, with reimbursements for manufacturing of commercial supplies expected to be sequentially lower by approximately $40 million.

Total SANAFI collaboration revenue was $1.1 billion in the third quarter, up 50 per cent versus the prior year, which included the final $50 million sales based milestone. Our share of profits from the commercialization of DUPEXIN and CAMZARA was $863 million, an increase of 57% versus the third quarter of 2022, driven by DUPEXIN's continued volume growth and improving margins.

Our share of profits from the commercialization of depiction it comes or was $863 million, an increase of 57% versus the third quarter of 2022. Driven by to pick since continued volume growth and improving margins.

Driven by to pick since continued volume growth and improving margins.

As we guided last quarter, third quarter reimbursements for the manufacturing of commercial supplies from SANAFI, a component of SANAFI collaboration revenues declined sequentially, primarily due to the ongoing season of a new higher yielding manufacturing process.

In the fourth quarter, we expect a continuation of this trend with reimbursements from manufacturing of commercials supplies expected to be sequentially lower by approximately 40 million.

Operator: Other revenues were $138 million in Q3 2023, up 62% versus the prior year, and inclusive of $34 million of reimbursements from BARDA for ongoing development of our next-gen COVID antibody, as per the agreement announced in August 2023. Moving now to our operating expenses. Q3 2023 R&D expense grew 17% year-over-year to $954 million, representing continued investment in our expanding pipeline. R&D growth was primarily driven by higher headcount and related costs in funding our advancing late-stage pipeline, as well as increased clinical manufacturing activity. SG&A grew 14% from the prior year to $534 million in Q3, reflecting higher headcount and related costs, and higher contributions to an independent not-for-profit patient assistance organization.

Other revenues were $138 million in Q3 2023, up 62% versus the prior year, and inclusive of $34 million of reimbursements from BARDA for ongoing development of our next-gen COVID antibody, as per the agreement announced in August 2023. Moving now to our operating expenses. Q3 2023 R&D expense grew 17% year-over-year to $954 million, representing continued investment in our expanding pipeline. R&D growth was primarily driven by higher headcount and related costs in funding our advancing late-stage pipeline, as well as increased clinical manufacturing activity. SG&A grew 14% from the prior year to $534 million in Q3, reflecting higher headcount and related costs, and higher contributions to an independent not-for-profit patient assistance organization.

Other revenues were $138 million in the third quarter of 2023, up 62% versus the prior year and inclusive of $34 million reimbursements from BARDA for ongoing development of our next gen COVID antibody as per the agreement announced in August 2023.

Moving now to our operating expenses. Third quarter 2023 R&D expense grew 17% year over year to $954 million, representing continued investment in our expanding pipeline. R&D growth was primarily driven by higher head count related costs in funding our advanced late stage pipeline as well as increased clinical manufacturing activity.

States pipeline as well as increased clinical manufacturing activity.

SG&A grew 14% from the prior year to $534 million in the third quarter, reflecting higher headcount and related costs and higher contributions to an independent not-for-profit patient assistance organization.

Operator: In the third quarter, we recorded acquired IPR&D of $100 million, reflecting the payment of a development milestone to our collaborator, Alnylam, related to the phase I ALN-APP program in early-onset Alzheimer's disease. This impacted both GAAP and non-GAAP EPS by approximately $0.77. Third quarter COCM was $212 million, up 20% versus the prior year, driven by manufacturing costs associated with higher sales volumes from collaboration products, partially offset by lower Dupixent manufacturing costs. Fourth quarter COCM is expected to be the lowest quarter of the year as we continue to transition to the higher-yielding manufacturing process for Dupixent. Now to cash flow and the balance sheet. Through the third quarter of 2023, Regeneron generated approximately $3 billion in free cash flow and ended the third quarter with cash and marketable securities less debt of approximately $13 billion.

In the third quarter, we recorded acquired IPR&D of $100 million, reflecting the payment of a development milestone to our collaborator, Alnylam, related to the phase I ALN-APP program in early-onset Alzheimer's disease. This impacted both GAAP and non-GAAP EPS by approximately $0.77. Third quarter COCM was $212 million, up 20% versus the prior year, driven by manufacturing costs associated with higher sales volumes from collaboration products, partially offset by lower Dupixent manufacturing costs. Fourth quarter COCM is expected to be the lowest quarter of the year as we continue to transition to the higher-yielding manufacturing process for Dupixent. Now to cash flow and the balance sheet. Through the third quarter of 2023, Regeneron generated approximately $3 billion in free cash flow and ended the third quarter with cash and marketable securities less debt of approximately $13 billion.

In the third quarter, we recorded acquired IP R&D of 100 million, reflecting the payment of a development milestone tour collaborator Alnylam related to the phase one AON-AP program in early onset Alzheimer's disease. This impacted both GAAP and non-GAAP EPS by approximately 77 cents.

Third quarter COCM was $212 million, up 20% versus the prior year driven by manufacturing costs associated with higher sales volumes from collaboration products, partially offset by lower DUPIXEN manufacturing costs. Fourth quarter COCM is expected to be the lowest quarter of the year as

Fourth quarter COCM is expected to be the lowest quarter of the year as we continue to transition to the higher yielding manufacturing process for DUPIXEN.

we continue to transition to the higher yielding manufacturing process for DUPIXEN.

Now to cash flow and the balance sheet. Through the third quarter of 2023, Regeneron generated approximately $3 billion in free cash flow and ended the third quarter with cash and marketable securities less debt of approximately $13 billion.

Operator: We continue to deliver on our capital allocation priorities, buying back $507 million and $1.9 billion of our shares in Q3 and the first nine months of 2023, respectively, with $1.8 billion remaining authorized under our existing share repurchase program. Additionally, in Q3, we also announced and completed the acquisition of Decibel Therapeutics for approximately $100 million to strengthen our genetics medicine portfolio. As Len mentioned, we continue to evaluate opportunities to utilize our strong financial position and build upon our core competencies with the goal of delivering long-term shareholder value. Finally, we've made some minor changes to our full year 2023 financial guidance based on our year-to-date results and our latest outlook. Updating the guidance ranges for SG&A, R&D, gross margins, COCM, and capital expenditures. A complete summary of our latest full year 2023 guidance is available in our press release issued earlier this morning.

We continue to deliver on our capital allocation priorities, buying back $507 million and $1.9 billion of our shares in Q3 and the first nine months of 2023, respectively, with $1.8 billion remaining authorized under our existing share repurchase program. Additionally, in Q3, we also announced and completed the acquisition of Decibel Therapeutics for approximately $100 million to strengthen our genetics medicine portfolio. As Len mentioned, we continue to evaluate opportunities to utilize our strong financial position and build upon our core competencies with the goal of delivering long-term shareholder value.

We continue to deliver on our capital allocation priorities, buying back 507 million and 1.9 billion of our shares in the third quarter in the first nine months of 2023 respectively with 1.8 billion remaining authorized under our existing share repurchase program.

Additionally, in the third quarter, we also announced and completed the acquisition of Decibel Therapeutics for approximately 100 million to strengthen our genetics medicine portfolio.

As Len mentioned, we continue to evaluate opportunities to utilize our strong financial position and build upon our core competencies with the goal of delivering long term shareholder value.

Finally, we've made some minor changes to our full year 2023 financial guidance based on our year-to-date results and our latest outlook. Updating the guidance ranges for SG&A, R&D, gross margins, COCM, and capital expenditures. A complete summary of our latest full year 2023 guidance is available in our press release issued earlier this morning.

Finally, we've made some minor changes to our full year 2023 financial guidance based on our year-to-date results in our latest outlook, updating the guidance ranges for SG&A, R&D, gross margin, COCM, and capital expenditures. A complete summary of our latest full year 2023 guidance is available in our press release issued earlier this morning.

We've made some minor changes to our full year 2023 financial guidance based on our year to date results in our latest outlook updating the guidance ranges for SG&A R&D gross margin C. O C M and capital expenditures a complete summary of our latest full year 2000 twenty-three guidance is available in our press release issued earlier this morning.

Operator: As we approach the end of 2023, I'd like to provide some commentary on the preliminary outlook for 2024. We expect continued improvements in profitability from the Sanofi collaboration, which will continue to accelerate the paydown of the antibody development balance, which, as of 30 September 2023, was approximately $2.5 billion. Once this balance is fully repaid in the next few years, we expect a meaningful step-up in our share of Sanofi collaboration profits. Separately, for Praluent, we expect significant category and competitive pressures to negatively impact US sales in 2024. Moving to our operating expenses. Consistent with our capital allocation priorities, we continue to invest in our growing internal R&D pipeline to drive long-term growth. As you just heard from George, our pipeline continues to broaden while our infrastructure to support that growth continues to expand.

As we approach the end of 2023, I'd like to provide some commentary on the preliminary outlook for 2024. We expect continued improvements in profitability from the Sanofi collaboration, which will continue to accelerate the paydown of the antibody development balance, which, as of 30 September 2023, was approximately $2.5 billion. Once this balance is fully repaid in the next few years, we expect a meaningful step-up in our share of Sanofi collaboration profits. Separately, for Praluent, we expect significant category and competitive pressures to negatively impact US sales in 2024.

As we approach the end of 2023, I would like to provide some commentary on the preliminary outlook for 2024. We expect continued improvements in profitability from the SANAFI collaboration which will continue to accelerate the pay down at the antibody development balance, which as of September 30th, 2023 was approximately 2.5 billion.

Once this balance is fully repaid in the next few years, we expect a meaningful step up in our share of SANAFI collaboration profits. Separately for [inaudible] we expect significant category in competitive pressures that negatively impact US sales in 2024. Moving to our operating expenses. Consistent with our capital allocation priorities,

Moving to our operating expenses. Consistent with our capital allocation priorities, we continue to invest in our growing internal R&D pipeline to drive long-term growth. As you just heard from George, our pipeline continues to broaden while our infrastructure to support that growth continues to expand.

Moving to our operating expenses. Consistent with our capital allocation priorities, we continue to invest in our growing internal R&D pipeline to drive long term growth. As you just heard from George, our pipeline continues to broaden while our infrastructure to support that growth continues to expand. R&D investment in 2024 will be driven by advancing strategically important late stage programs such as our [inaudible] and LIBTAYO combination confirmatory key monk studies, including in earlier lines of therapy, our expanding collaboration in genetic medicine as well as higher clinical manufacturing costs and the continued expansion of our R&D organization. With this in mind, we expect year on year R&D growth in 2024 to be in the mid-teens compared to our anticipated 2023 spend. We also expect to make additional investments in our commercial business and G&A functions to support the launch of EYLEA HD, [inaudible] launches in our international expansion.

we continue to invest in our growing internal R&D pipeline to drive long term growth. As you just heard from George, our pipeline continues to broaden while our infrastructure to support that growth continues to expand. R&D investment in 2024 will be driven by advancing strategically important late stage programs such as our [inaudible]

Operator: R&D investment in 2024 will be driven by advancing strategically important late-stage programs such as our fianlimab and Libtayo combination, confirmatory hem-onc studies, including in earlier lines of therapy, our expanding collaboration in genetic medicines, as well as higher clinical manufacturing costs, and the continued expansion of our R&D organization. With this in mind, we expect year-on-year R&D growth in 2024 to be in the mid-teens compared to our anticipated 2023 spend. We also expect to make additional investments in our commercial business and G&A functions to support the launch of Eylea HD, our planned hem-onc launches, and our international expansion. In conclusion, Regeneron continues to deliver strong results, and our robust financial position allows us to make strategic investments to drive this growth over time. With that, I will now pass the call back to Ryan. Thank you, Bob. This concludes our prepared remarks.

R&D investment in 2024 will be driven by advancing strategically important late-stage programs such as our fianlimab and Libtayo combination, confirmatory hem-onc studies, including in earlier lines of therapy, our expanding collaboration in genetic medicines, as well as higher clinical manufacturing costs, and the continued expansion of our R&D organization. With this in mind, we expect year-on-year R&D growth in 2024 to be in the mid-teens compared to our anticipated 2023 spend.

and LIBTAYO combination confirmatory key monk studies, including in earlier lines of therapy, our expanding collaboration in genetic medicine as well as higher clinical manufacturing costs and the continued expansion of our R&D organization. With this in mind, we expect year on year R&D growth in 2024 to be in the mid-teens compared

We also expect to make additional investments in our commercial business and G&A functions to support the launch of Eylea HD, our planned hem-onc launches, and our international expansion. In conclusion, Regeneron continues to deliver strong results, and our robust financial position allows us to make strategic investments to drive this growth over time. With that, I will now pass the call back to Ryan.

to our anticipated 2023 spend. We also expect to make additional investments in our commercial business and G&A functions to support the launch of EYLEA HD, [inaudible] launches in our international expansion.

In conclusion, Regeneron continues to deliver stronger results and our robust financial position allows us to make strategic investments to drive this growth over time. With that, I will now pass the call back to Ryan.

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

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

Operator: We will now open the call for Q&A. To ensure that we are able to address as many questions as possible, we will answer one question from each caller before moving to the next. Shannon, can we please go to the first question? Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Evan Seigerman with BMO Capital Markets. Your line is now open. Hi, guys. Thank you for giving me the question and congrats on all the progress. So you have over $15 billion of cash and marketable securities on your balance sheet. Maybe, Bob, you could talk about how you think about capital allocation.

To ensure that we were able to address as many questions as possible. One question from each color before moving to the next. <unk> can we please go to the first question.

One question from each color before moving to the next. <unk> can we please go to the first question.

<unk> can we please go to the first question.

Operator: Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Evan Seigerman with BMO Capital Markets. Your line is now open.

Operator: Thank you. To ask a question, please press star one, one on your telephone and wait for your name to be announced.

To withdraw your question, please press star one, one again. Please standby while we compile the Q&A roster.

Police came out with some pals.

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

Evan Seigerman: Hi, guys. Thank you for giving me the question and congrats on all the progress. So you have over $15 billion of cash and marketable securities on your balance sheet. Maybe, Bob, you could talk about how you think about capital allocation. I know interest rates are high, but how else can you spend that money to derive even higher returns for Regeneron shareholders?

Evan Seigerman: Hi, guys. Thank you for giving me the question and congrats on all the progress. So you have over $15 billion of cash and marketable securities on your balance sheet, maybe Bob you could talk about how you think about capital allocation. I know interest rates are high but how else could you spend that money to drive even higher returns for Regeneron shareholders?

Operator: I know interest rates are high, but how else can you spend that money to derive even higher returns for Regeneron shareholders? Yeah, thanks, Evan. I mean, I know having dealt with you and certainly many of our investors, this is certainly an issue that we've been tasked to solve. Now, obviously, interest rates are a lot higher, so obviously what we're returning on that is certainly much better than the kind of the days of 2020 and 2021. But we kind of stick to our knitting here with regards to our capital allocations. I mean, George just went through a plethora of obviously pipeline progress that we're making. Again, first and foremost, we're going to make sure that that is fully funded to the extent possible on that.

Robert Landry: Yeah, thanks, Evan. I mean, I know having dealt with you and certainly many of our investors, this is certainly an issue that we've been tasked to solve. Now, obviously, interest rates are a lot higher, so obviously what we're returning on that is certainly much better than the kind of the days of 2020 and 2021. But we kind of stick to our knitting here with regards to our capital allocations. I mean, George just went through a plethora of obviously pipeline progress that we're making. Again, first and foremost, we're going to make sure that that is fully funded to the extent possible on that.

Robert E. Landry: Yeah, thanks Evan. I mean, I know, having dealt with you and certainly many of our investors, this is certainly an issue that we've been task to solve. Now obviously interest rates are a lot higher so obviously, what we're returning on that is certainly much better than kind of the days of 2020 and 2021. But you know we kind of stick to our knitting here with regards to our capital allocations. I mean, George just went through a plethora of obviously pipeline progress that we're making. Again, first and foremost, we're gonna make sure that that is fully funded to the extent possible on that. And then with regards to acquisitions, you heard with Len's intro I mean, we continue to look at a lot of opportunities. Certainly the market that is out there in the biotech tech space is not in the greatest shape as you know, so again, we think there are opportunities out there, but just because we have the means doesn't mean that we're gonna kind of push into something that may not give us an optimal result. It may not be kind of you know, we we like franchises as you've heard me say that before, so we need to make sure that it's the right fit with George and the team with regards to that, so we'll continue to do that.

To solve. Now you know obviously interest rates are a lot higher so obviously, what we're returning on that is certainly much better than they're kind of the days of 2020 and 2021, but you know we kind of stick to her knitting here with regards to our capital allocations you know I mean, George just went through a plethora of obviously pipeline progress that we're making again first and foremost we're gonna make sure that that is fully.

Now you know obviously interest rates are a lot higher so obviously, what we're returning on that is certainly much better than they're kind of the days of 2020 and 2021, but you know we kind of stick to her knitting here with regards to our capital allocations you know I mean, George just went through a plethora of obviously pipeline progress that we're making again first and foremost we're gonna make sure that that is fully.

Funded to the extent possible on that and then with regards to acquisitions. You know you heard with lens in trouble I mean, we continue to look at a lot of opportunities certainly the market that is out there on the biotech tech spaces.

Operator: Then with regards to acquisitions, you heard with Len's intro. I mean, we continue to look at a lot of opportunities. Certainly, the market that is out there on the biotech space is not in the greatest shape, as you know. So again, we think there are opportunities out there, but just because we have the means doesn't mean that we're going to kind of push into something that may not give us an optimal result. It may not be kind of we like franchises, as you've heard me say that before, so we need to make sure that it's the right fit with George and the team with regards to that. So we'll continue to do that. And you've seen our share repurchases, of which we're at $1.9 billion through nine months. We've done that at a very good price with regards to how we're buying that back.

Then with regards to acquisitions, you heard with Len's intro. I mean, we continue to look at a lot of opportunities. Certainly, the market that is out there on the biotech space is not in the greatest shape, as you know. So again, we think there are opportunities out there, but just because we have the means doesn't mean that we're going to kind of push into something that may not give us an optimal result.

not in the greatest shape as you know, so again, we think there are opportunities out there, but just because we have the means doesn't mean that we're gonna kind of push into something that may not give us an optimal result. It may not be kind of you know, we we like franchises as you've heard me say that before, so we need to make sure that it's the right fit with George and the team with regards to that, so we'll continue to do that.

It may not be kind of we like franchises, as you've heard me say that before, so we need to make sure that it's the right fit with George and the team with regards to that. So we'll continue to do that. And you've seen our share repurchases, of which we're at $1.9 billion through nine months. We've done that at a very good price with regards to how we're buying that back.

And you've seen our share repurchases of which we're at $1.9 billion through nine months. We've done that at a very good price with regards to how we're buying that back. We're very kind of scientific in our approach on that. We do think that stock continues to be undervalued given all the the pipeline progress and the catalysts that we have so we're going to continue to push that button going forward. So we're gonna stick to our knitting, but again, as Len kind of alluded to, we are looking at a lot of opportunities that are out there and if the right one makes the necessary fit then we'll move forward. And again, you kind of saw that with Checkmate and Decibels, albeit those were smaller, but again those were nice kind of franchise fits into the business.

Operator: We're very kind of scientific in our approach on that. We do think that stock continues to be undervalued given all the pipeline progress and the catalyst that we have, so we're going to continue to push that button going forward. So we're going to stick to our knitting, but again, as Len kind of alluded to, we are looking at a lot of opportunities that are out there, and if the right one makes the necessary fit, then we'll move forward. And again, you kind of saw that with Checkmate and Decibel, albeit those were smaller, but again, those were nice kind of franchise fits into the business. Thanks. Next question, please, Shannon. Our next question comes from the line of Mohit Bansal with Wells Fargo. Your line is now open. Hey, thank you for taking my question and congrats on the progress.

We're very kind of scientific in our approach on that. We do think that stock continues to be undervalued given all the pipeline progress and the catalyst that we have, so we're going to continue to push that button going forward. So we're going to stick to our knitting, but again, as Len kind of alluded to, we are looking at a lot of opportunities that are out there, and if the right one makes the necessary fit, then we'll move forward. And again, you kind of saw that with Checkmate and Decibel, albeit those were smaller, but again, those were nice kind of franchise fits into the business.

the pipeline progress and the catalysts that we have so we're going to continue to push that button going forward. So we're gonna stick to our knitting, but again, as Len kind of alluded to, we are looking at a lot of opportunities that are out there and if the right one makes the necessary fit then we'll move forward. And again, you kind of saw that with Checkmate and Decibels, albeit those were smaller, but again those were nice kind of franchise fits into the business.

We'll move forward and again, you kind of saw that with Chuck made in decibels, albeit those were smaller but again those were nice kind of franchise fits into the business.

Operator: Thanks.

Ryan Crowe: Next question, please, Shannon.

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

Ryan Crowe: Next section please Shannon.

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

Mohit Bansal: Hey, thank you for taking my question and congrats on the progress. My question is regarding the ulcerative colitis trial you are doing with Dupixent. Could you talk a little bit about the rationale behind that, and are you enriching this trial in any way on the basis of eosinophil counts or any other marker there? Thank you.

Okay your lifestyle.

Mohit Bansal: Thank you for taking my question and congrats on the progress. My question is regarding the [inaudible], could you talk a little bit about the rationale behind that and [inaudible] or any other marker there? Thank you.

Operator: My question is regarding the ulcerative colitis trial you are doing with Dupixent. Could you talk a little bit about the rationale behind that, and are you enriching this trial in any way on the basis of eosinophil counts or any other marker there? Thank you. Yeah. So as you sort of hinted at, what we have realized is that all of the diseases that we are treating with Dupixent really are interrelated diseases that reflect a systemic disorder. That is, upregulation of so-called type 2 inflammation, and in some cases, it manifests in the lungs, in some cases in the skin, in some cases in the gut, and so forth, all over the body, and in many cases, in most patients, actually, in more than one location.

My question is regarding the <unk> could you talk a little bit about the rationale behind that and <unk> and we can describe <unk> or any other <unk>. Thank you.

George Yancopoulos: Yeah. So as you sort of hinted at, what we have realized is that all of the diseases that we are treating with Dupixent really are interrelated diseases that reflect a systemic disorder. That is, upregulation of so-called type 2 inflammation, and in some cases, it manifests in the lungs, in some cases in the skin, in some cases in the gut, and so forth, all over the body, and in many cases, in most patients, actually, in more than one location.

George D. Yancopoulos: Yeah, so as you sort of hinted at, what we have realized is that all of the diseases that we are treating with DUPIXEN really are interrelated diseases that reflect a systemic disorder that is upregulation of so-called type two inflammation and in some cases it manifests in the lungs, in some cases in the skin, in some cases in the gut and so forth all over the body and in many cases, in most patients actually, in more than one location. And so in every disease that we're going after, including now as you mentioned in ulcerative colitis, we believe that there are a subset of patients who may be marked with type two inflammation in their gut. We are as you say utilizing biomarkers that might select out these patients and so we're going to see whether a subset of ulcerative colitis patients are driven by this type two inflammation that's driving all the other related manifestations of this systemic disorder.

All of the diseases that we are treating with Dupixent really are interrelated diseases that reflect a systemic disorders that is upregulation of so-called type two inflammation and in some cases it manifests in the lungs in some cases in the skin in some cases and.

and so forth all over the body and in many cases, in most patients actually, in more than one location. And so in every disease that we're going after, including now as you mentioned in ulcerative colitis, we believe that there are a subset of patients who may be marked with type two inflammation in their gut. We are as you say utilizing biomarkers that might select out these patients and so we're going to see whether a subset of ulcerative colitis patients are driven by this type two inflammation that's driving all the other related manifestations of this systemic disorder.

Operator: And so in every disease that we're going after, including now, as you mentioned, in ulcerative colitis, we believe that there are a subset of patients who may be marked with type 2 inflammation in their gut. We are, as you say, utilizing biomarkers that might select out these patients, and so we're going to see whether a subset of ulcerative colitis patients are driven by this type 2 inflammation that's driving all the other related manifestations of this systemic disorder. Thanks, George. Let's move to the next question, please, Shannon. Our next question comes from the line of Chris Raymond with Piper Sandler. Your line is now open. Yeah, thank you. Just maybe on Dupixent and COPD, I think the last time we talked to you guys on this, you were talking about the risk-reward on taking an interim look on NOTUS, just given the alpha hit.

And so in every disease that we're going after, including now, as you mentioned, in ulcerative colitis, we believe that there are a subset of patients who may be marked with type 2 inflammation in their gut. We are, as you say, utilizing biomarkers that might select out these patients, and so we're going to see whether a subset of ulcerative colitis patients are driven by this type 2 inflammation that's driving all the other related manifestations of this systemic disorder.

Type two inflammation in there got we are as you say indicated you're utilizing biomarkers that might select out these patients. And so we're going to see whether a subset of ulcerative colitis patients are driven by this type two inflammation, that's driving all the other related manifestations of this systemic disorder.

And so we're going to see whether a subset of ulcerative colitis patients are driven by this type two inflammation, that's driving all the other related manifestations of this systemic disorder.

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

Ryan Crowe: Thanks George. Move to the next question please Shannon.

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

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

Chris Raymond: Yeah, thank you. Just maybe on Dupixent and COPD, I think the last time we talked to you guys on this, you were talking about the risk-reward on taking an interim look on NOTUS, just given the alpha hit.

Mine is now.

Christopher J. Raymond: Yeah, thank you. Just maybe on DUPEXIN COPD, I think the last time we talked to you guys on this you were talking about the risk reward on taking an interim look on notice just given the alpha hit. It looks like you've decided to take that step here, but can you give us a sense of the alpha hit you are taking by doing this interim look? I mean, just looking at [inaudible] with a 30% reduction in exacerbations, it would seem to have a decent amount of room here and notice is tracking similarly, but if you can give us any more color on how you're thinking about this the risk reward of this decision and assume you're going to press release the result of that if it's gonna be the end of the year. Thanks.

Operator: Looks like you've decided to take that step here, but can you give us a sense of the alpha hit you are taking by doing this interim look? And I mean, just looking at BOREAS with the 30% reduction in exacerbations, it would seem you'd have a decent amount of room here if NOTUS is tracking similarly. But if you can give us any more color on how you're thinking about the risk-reward of this decision, and assume you're going to press release that result of that if it's going to be the end of the year. Thanks. Yeah. I'm going to kind of get into the details of the statistical niceties on how you do this. An alpha-sparing approach is what's typical for an interim analysis.

Looks like you've decided to take that step here, but can you give us a sense of the alpha hit you are taking by doing this interim look? And I mean, just looking at BOREAS with the 30% reduction in exacerbations, it would seem you'd have a decent amount of room here if NOTUS is tracking similarly. But if you can give us any more color on how you're thinking about the risk-reward of this decision, and assume you're going to press release that result of that if it's going to be the end of the year. Thanks.

It looks like you've decided to take take that the that step here, but can you give us a sense of the alpha hit you are taking by doing this interim looking.

I mean, just looking at <unk> with a 30% reduction in exacerbations. It would seem to have a decent amount of room here have noticed this tracking similarly, but. You know if you can give us any more color on how you're thinking about this the risk reward of this decision and assume you'll get a press release that result of that if it's if it's gonna be the end of the year.

You know if you can give us any more color on how you're thinking about this the risk reward of this decision and assume you'll get a press release that result of that if it's if it's gonna be the end of the year.

George Yancopoulos: Yeah. I'm going to kind of get into the details of the statistical niceties on how you do this. An alpha-sparing approach is what's typical for an interim analysis. We'll work closely with Sanofi on how to do this in the most efficient manner possible and get you the information as appropriate when it appears.

Leonard S. Schleifer: Yeah. I want to kind of get into the details of the statistical niceties and how you do this. An alpha sparing approach is what's typical for an interim analysis so we'll work closely with SANTAFI on how to do this in the most efficient manner possible and go to the information as appropriate when it appears.

Statistical Niceties and how you do this an alpha sparing approaches where it's typical for an interim now it says will work closely with Santa Fe. How to do this in the most efficient manner possible and go to the information is appropriate to appears.

Operator: We'll work closely with Sanofi on how to do this in the most efficient manner possible and get you the information as appropriate when it appears. Thanks, Len. Next question, please, Shannon. Our next question comes from the line of Colin Bristow of UBS. Your line is now open. Hey, good morning, and congrats on the quarter. Not surprisingly, we've been getting an increasing number of questions on your obesity assets, and I was wondering if you could just talk to your strategy and level of enthusiasm here and maybe frame out some of the timelines. You've got the GPR75, the leptin receptor antagonist. I think you shared some pretty provocative data at ADA on the myostatin blocker and the activin A blocker. Maybe you could just tell us your overall enthusiasm.

How to do this in the most efficient manner possible and go to the information is appropriate to appears.

Ryan Crowe: Thanks, Len. Next question, please, Shannon.

Ryan Crowe: Thanks Len. Next question please Shannon.

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

Colin Bristow: Hey, good morning, and congrats on the quarter. Not surprisingly, we've been getting an increasing number of questions on your obesity assets, and I was wondering if you could just talk to your strategy and level of enthusiasm here and maybe frame out some of the timelines. You've got the GPR75, the leptin receptor antagonist. I think you shared some pretty provocative data at ADA on the myostatin blocker and the activin A blocker. Maybe you could just tell us your overall enthusiasm. Is this something that you're going to go full force and plan to have a major presence in down the road? Just some color there would be helpful. Thank you.

Colin Nigel Bristow: Hi, good morning, and congrats on the quarter. Not surprisingly, we've been getting a an increasing number of questions on your obesity assets and I was wondering if you could just talk to your strategy and level of enthusiasm here and maybe frame out some of the time lines when you think of the GOP 75, the [inaudible] antagonist, you shared some pretty provocative data at ADA on the myostatin blocker and the [inaudible] A blocker. Maybe you could just tell us your level of enthusiasm. Is this something that you're going to go full force and plan to have a major presence in down the road. Just some color there would be helpful. Thank you.

C V V as in here and maybe frame out some of the time lines. The GOP 75, the the <unk>. Thank you shed some pretty provocative data a D. A on the the Myostatin blocker and yeah <unk>, Okay I I. Maybe you could just tell us you'll never enthusiasm is this something that you're going to go full force and plan to have a major presence in down the road. Just some kind of that'd be helpful. Thank you.

Maybe you could just tell us you'll never enthusiasm is this something that you're going to go full force and plan to have a major presence in down the road. Just some kind of that'd be helpful. Thank you.

Operator: Is this something that you're going to go full force and plan to have a major presence in down the road? Just some color there would be helpful. Thank you. Yeah. As you said, we're very excited about, I guess, two of the approaches that we've been taking in obesity. One is our unique collection of targets that we've either been the first to discover, like the GPR75 genetically identified target that came from our Regeneron Genetic Center, which is a very exciting new target for obesity, as well as our new approaches, such as our leptin receptor agonistic antibody. But one thing we're doing is moving those programs forward and understanding exactly what their potential is in the field of obesity.

George Yancopoulos: Yeah. As you said, we're very excited about, I guess, two of the approaches that we've been taking in obesity. One is our unique collection of targets that we've either been the first to discover, like the GPR75 genetically identified target that came from our Regeneron Genetic Center, which is a very exciting new target for obesity, as well as our new approaches, such as our leptin receptor agonistic antibody. But one thing we're doing is moving those programs forward and understanding exactly what their potential is in the field of obesity.

Just some kind of that'd be helpful. Thank you.

George D. Yancopoulos: Yeah, as you said, we're very excited about I guess two of the approaches that we've been taking in obesity. One is our unique collection of targets that we've either been the first to discover like the GPR 75 genetically identify target that came from our Regeneron genetic center, which is a very exciting new target for obesity, as well as our new approaches such as our [inaudible] receptor agonistic antibodies.

I guess two of the approaches that we've been taking in obesity. One is our unique collection of targets that we've either been the.

The first to discover like the G. P. R 75 genetically identify targets that came from our Regeneron genetic center, which is a very exciting new target for obesity as well as our new approaches such as a left and receptor agonistic antibodies, but.

One thing we're doing is moving those programs forward and understanding exactly what their potential is in the field of obesity. But as you said, right now the field is dominated by this these [inaudible] one agonists, also is recognizing increasing problems with this type of weight loss. Meaning that about 40% of the weight loss is due to muscle loss. That means if you lose 20 pounds, eight pounds of that approximately on average will be muscle. Most patients will never get that muscle back. This can overtime, especially when patients go off these drugs and regain the weight as fat can create potentially a very large public health problem and dilemma. So we also have been, as you pointed out, very active in the field of muscle preservation and muscle growth agents. We've developed I think some of the most exciting candidates in the field that have the ability to do this and we are certainly considering how to study these muscle preservation and muscle growth agents in combination with existing weight loss agents to see whether we can maintain or even grow muscle in the setting of weight loss, hopefully, perhaps increasing the quality of the weight loss, maybe even resulting in even greater weight loss, but most importantly, making sure that the patients in terms of their muscle and so forth do a lot better. And we will be talking about our clinical trials in this area, we hope very shortly.

Operator: But as you said, right now, the field, which is dominated by these GLP-1 agonists, also is recognizing increasing problems with this type of weight loss, meaning that about 40% of the weight loss is due to muscle loss. That means if you lose 20 pounds, 8 pounds of that, approximately, on average, will be muscle. Most patients will never get that muscle back. This can, over time, especially if patients go off these drugs and regain the weight as fat, can create potentially a very large public health problem and dilemma. So we also have been, as you pointed out, very active in the field of muscle preservation and muscle growth agents.

But as you said, right now, the field, which is dominated by these GLP-1 agonists, also is recognizing increasing problems with this type of weight loss, meaning that about 40% of the weight loss is due to muscle loss. That means if you lose 20 pounds, 8 pounds of that, approximately, on average, will be muscle. Most patients will never get that muscle back. This can, over time, especially if patients go off these drugs and regain the weight as fat, can create potentially a very large public health problem and dilemma. So we also have been, as you pointed out, very active in the field of muscle preservation and muscle growth agents.

Meaning that about 40% of the weight loss is due to muscle loss that means if you lose 20 pounds eight pounds of that approximately on average will be muscle most patients will never get that muscle back just kidding overtime, especially patients go off these drugs and regain the weight as <unk>.

can create potentially a very large public health problem and dilemma. So we also have been, as you pointed out, very active in the field of muscle preservation and muscle growth agents. We've developed I think some of the most exciting candidates in the field that have the ability to do this and we are certainly considering how to study these muscle preservation and muscle growth agents in combination with existing weight loss agents to see whether we can maintain or even grow muscle in the setting of weight loss, hopefully, perhaps increasing the quality of the weight loss, maybe even resulting in even greater weight loss, but most importantly, making sure that the patients in terms of their muscle and so forth do a lot better. And we will be talking about our clinical trials in this area, we hope very shortly.

Operator: We've developed some, I think, some of the most exciting candidates in the field that have the ability to do this, and we are certainly considering how to study these muscle preservation and muscle growth agents in combination with existing weight loss agents to see whether we can maintain or even grow muscle in the setting of weight loss, hopefully, perhaps increasing the quality of the weight loss, maybe even resulting in greater weight loss, but most importantly, making sure that the patients, in terms of their muscle and so forth, do a lot better. And we will be talking about our clinical trials in this area, we hope, very shortly. Okay. Thanks, George. Next question, please, Shannon. Our next question comes from the line of Tyler Van Buren of TD Cowen. Your line is now open. Great. Thanks, guys, and congrats on the tremendous quarterly results.

We've developed some, I think, some of the most exciting candidates in the field that have the ability to do this, and we are certainly considering how to study these muscle preservation and muscle growth agents in combination with existing weight loss agents to see whether we can maintain or even grow muscle in the setting of weight loss, hopefully, perhaps increasing the quality of the weight loss, maybe even resulting in greater weight loss, but most importantly, making sure that the patients, in terms of their muscle and so forth, do a lot better. And we will be talking about our clinical trials in this area, we hope, very shortly.

Develop some I think someone else excited candidates in the field that I had the ability to do this and we are certainly. Considering how to study these muscle preservation and muscle growth agents in combination with existing weight loss agents to see whether we can maintain or even grow muscle in the setting of weight loss, hopefully, perhaps increasing the quality of the weight loss, maybe even resolve. Even greater weight loss, but most importantly, making sure that the patients in terms of their muscle and so forth do a lot better and we will be talking about our clinical trials in this area, we hope very shortly.

Considering how to study these muscle preservation and muscle growth agents in combination with existing weight loss agents to see whether we can maintain or even grow muscle in the setting of weight loss, hopefully, perhaps increasing the quality of the weight loss, maybe even resolve. Even greater weight loss, but most importantly, making sure that the patients in terms of their muscle and so forth do a lot better and we will be talking about our clinical trials in this area, we hope very shortly.

Even greater weight loss, but most importantly, making sure that the patients in terms of their muscle and so forth do a lot better and we will be talking about our clinical trials in this area, we hope very shortly.

Ryan Crowe: Okay. Thanks, George. Next question, please, Shannon.

Ryan Crowe: Thanks George. Next question please Shannon.

Ryan Crowe: Our next question comes from the line of Tyler Van Buren of TD Cowen. Your line is now open.

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

<unk> okay.

Tyler Van Buren: Great. Thanks, guys, and congrats on the tremendous quarterly results. It's great to see the early Eylea HD sales, of course. And you mentioned that naive and switch patients are being treated, but are you seeing switches from Vabysmo specifically? And to what extent are you guys sending samples out as we think about assessing additional demand beyond sales?

Tyler Martin Van Buren: Great. Thanks guys and congrats on the tremendous quarterly results. It's great to see the early sales of course, and you mentioned that may even switch patients are being treated. Are you saying switches from [inaudible specifically and to what extent are you guys sending samples out as we think about assessing additional demand beyond sales?

Operator: It's great to see the early Eylea HD sales, of course. And you mentioned that naive and switch patients are being treated, but are you seeing switches from Vabysmo specifically? And to what extent are you guys sending samples out as we think about assessing additional demand beyond sales? Thanks, Tyler. So let me just, the first part, and the positive anecdotal case reports we're getting back really carry across the theme of better vision, better drying than they've seen with other Anti-VEGF products. They also comment on very frequently the tremendous confidence that they have in the safety of Eylea and the experience over many, many years. In terms of the switches, it's early days. We are seeing switches from Eylea, as you would expect, and of course, we're the category leader, so there are more potential patients to consider as well. But we are also hearing switches from Vabysmo.

Are you, saying switches from Buh buys most specifically and to what extent are you guys sending samples out as we think about assessing additional demand beyond sales.

Marion McCourt: Thanks, Tyler. So let me just, the first part, and the positive anecdotal case reports we're getting back really carry across the theme of better vision, better drying than they've seen with other Anti-VEGF products. They also comment on very frequently the tremendous confidence that they have in the safety of Eylea and the experience over many, many years. In terms of the switches, it's early days. We are seeing switches from Eylea, as you would expect, and of course, we're the category leader, so there are more potential patients to consider as well. But we are also hearing switches from Vabysmo.

Marion E. McCourt: Thanks Tyler. So let me address the first part. The positive anecdotal case reports we're getting back really carry across the theme of better vision, better [inaudible] than they've seen with other anti [inaudible] products. They also comment on very frequently the tremendous confidence that they have in the safety of EYLEA and the experience over many, many years.

The positive anecdotal case reports for getting back really carry across the theme of better vision better Jang then they've seen with other anti that Jeff products. They also comment on very frequently the tremendous confidence that they have in the safety of Eylea any experience that for many many years insurance.

In terms of the switches, it's early days. We are seeing switches from EYLEA, as you would expect, and of course, we're the category leaders so they're more potential patients to consider as well. But we are also hearing switches from [inaudible]. We're also switches from AVASTIN and other products in the category and the early reports have been quite encouraging.

Operator: We're hearing also switches from Avastin and other products in the category, and the early reports have been quite encouraging. To your other part of your question related to sampling, we do have a sampling program for Eylea HD. It's intended to give physicians experience with Eylea HD in an appropriate way. The program is constructed on an on-demand basis. We don't disclose the number of samples or things of that sort, and certainly, that's not what you were asking, but I can share with you that we have seen a high conversion rate from practices ordering Eylea HD samples and then subsequently placing orders of commercial products through commercial channels. Okay. Thank you, Marion. Next question, please. Our next question comes from the line of Terrence Flynn of Morgan Stanley. Your line is now open. Great. Thank you. This is Max Skor on for Terrence Flynn.

We're hearing also switches from Avastin and other products in the category, and the early reports have been quite encouraging. To your other part of your question related to sampling, we do have a sampling program for Eylea HD. It's intended to give physicians experience with Eylea HD in an appropriate way. The program is constructed on an on-demand basis. We don't disclose the number of samples or things of that sort, and certainly, that's not what you were asking, but I can share with you that we have seen a high conversion rate from practices ordering Eylea HD samples and then subsequently placing orders of commercial products through commercial channels.

To the other part of your question related to sampling, we do have a sampling program for EYLEA HD. It's intended to give physicians experience with EYLEA HD in an appropriate way. The program is constructed on an on demand basis. We don't disclose the number of samples or things of that sort and certainly that's not what you were asking but I can share with you that we have seen a high conversion rate from practices ordering EYLEA HD samples and then subsequently placing orders of commercial products through commercial channels.

<unk> the number of samples or things of that sort and certainly that's not what you were asking that I can share with you that we have seen a high conversion rate from practices ordering alea H D samples and then subsequently placing orders of commercial products or commercial channels.

Ryan Crowe: Okay. Thank you, Marion. Next question, please.

Ryan Crowe: Thank you Marion. Next question please.

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

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

Operator: Great. Thank you. This is Max Skor on for Terrence Flynn. Thank you for taking our question. Quick one from us. Could you provide an update on the timing or relative implications of the biosimilar Eylea litigation with Mylan? Thank you.

Matt Score: Great. Thank you. This is Matt Score on for Terence Flynn. Thank you for taking our question. Quick one from us, could you provide an update on the timing or relative implications of the biosimilar EYLEA litigation with [inaudible]? Thank you.

Operator: Thank you for taking our question. Quick one from us. Could you provide an update on the timing or relative implications of the biosimilar Eylea litigation with Mylan? Thank you. Yeah. So we had a trial in West Virginia, a bench trial, and we are waiting for a decision from the judge. It's out of our control, and as soon as it comes, it'll come. It's been several months, so it could come soon or not. It's one of those things where it's really beyond our ability to predict and control. Thanks, Len. Next question, Shannon. Our next question is from the line of Carter Gould with Barclays. Your line is now open. Great. Good morning, and congrats on all the progress. Maybe a follow-up from Marion. Thanks for all the color on the commercial dynamics for high-dose Eylea.

George Yancopoulos: Yeah. So we had a trial in West Virginia, a bench trial, and we are waiting for a decision from the judge. It's out of our control, and as soon as it comes, it'll come. It's been several months, so it could come soon or not. It's one of those things where it's really beyond our ability to predict and control.

Leonard S. Schleifer: Yeah, so we had a trial in West Virginia, a bench trial and we are waiting for a decision from the judge. It's out of our control and if it comes it'll come. It's been several months so it could come soon or not. It's one of those things where it's really beyond our ability to predict and control.

From the judge Mmm out of our control and.

<unk> comes it'll come it's been several months so it could come soon or not.

Of those things, where it's really beyond our ability to predict in control.

Ryan Crowe: Thanks, Len. Next question, Shannon.

Ryan Crowe: Thanks Len. Next question Shannon.

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

Carter Gould: Great. Good morning, and congrats on all the progress. Maybe a follow-up from Marion. Thanks for all the color on the commercial dynamics for high-dose Eylea. One thing you didn't touch on as much, though, is sort of how maybe some of the step-edit language has evolved. Is that sort of tracking in line with what you were seeing with standard-dose Eylea or any broader commentary on how that's tracking relative to your expectations? Thank you.

Barclays Your line itself.

Carter Lewis Gould: Great. Good morning and congrats on all the progress. Maybe a follow up for Marion, thanks for all the color on the commercial dynamics for high dose EYLEA. One thing you didn't touch on as much though is sort of how maybe some of the stuff added language has evolved as that sort of tracking in line with what you were seeing with high dose EYLEA? Any broader commentary on how that's tracking relative to your expectations. Thank you.

Operator: One thing you didn't touch on as much, though, is sort of how maybe some of the step-edit language has evolved. Is that sort of tracking in line with what you were seeing with standard-dose Eylea or any broader commentary on how that's tracking relative to your expectations? Thank you. Sure. So as a quick reminder, as we get into payer mix, I'll remind everybody that these are approximates based on typical patterns in the category. It's a little bit different when you look at a product that just launched, but about 45% of our overall business is in Medicare Fee-for-Service. And as I mentioned to you in the call today, we've made great progress there, not only in coverage, which is the first step to get coverage, but then taking the extra step to make sure that claims are being paid.

Can you. Touch on as much though is sort of how maybe some of the stuff added language has evolved as that sort of tracking in line with what you were saying with standard. And he brought a commentary on that I'd have a striking relative to your expectations. Thank you.

Touch on as much though is sort of how maybe some of the stuff added language has evolved as that sort of tracking in line with what you were saying with standard. And he brought a commentary on that I'd have a striking relative to your expectations. Thank you.

And he brought a commentary on that I'd have a striking relative to your expectations. Thank you.

Marion McCourt: Sure. So as a quick reminder, as we get into payer mix, I'll remind everybody that these are approximates based on typical patterns in the category. It's a little bit different when you look at a product that just launched, but about 45% of our overall business is in Medicare Fee-for-Service. And as I mentioned to you in the call today, we've made great progress there, not only in coverage, which is the first step to get coverage, but then taking the extra step to make sure that claims are being paid.

Marion E. McCourt: Sure. So as a quick reminder, as we get into payer mix, I'll remind everybody that these are approximate based on you typical patterns in the category. It's a little bit different when you look at a product that just launched. But about 45% of our overall business in Medicare fee for service. And as I mentioned to you in the call today, we've made great progress there, not only in coverage, which is the first step to get coverage, but then taking the extra step to make sure that claims are being paid, so we're seeing now that 100% of Medicare fee for service jurisdictions have coverage and demonstrated paid claims.

You and the call today, we've made great progress, they're not only in coverage, which is the first step to get coverage, but then taking the extra step to make sure that claims are being paid so we're seeing now that 100% of Medicare fee for service jurisdictions have coverage and demonstrated paid claims when we go over it.

Operator: So we're seeing now that 100% of Medicare Fee-For-Service jurisdictions have coverage and demonstrated paid claims. When we go over to Medicare Advantage, which is roughly about 25% of anti-VEGF category business, and commercial, which is about 20%, what we're seeing so far, and we are making good progress with payers, we're seeing that Eylea HD is being positioned consistently with Eylea and other brands in the category. And there are plans, as you know, that have a step-edit or utilization management. The good news is that Eylea HD is being positioned consistently with Eylea and other brands. We don't see a differentiation there. Okay, Marion. Thank you. Next question, Shannon, please. Our next question comes from the line of Robyn Karnauskas with Truist Securities. Your line is now open. Hi, guys. Thanks for the question. It's a question on CSU. I know it's a big opportunity.

So we're seeing now that 100% of Medicare Fee-For-Service jurisdictions have coverage and demonstrated paid claims. When we go over to Medicare Advantage, which is roughly about 25% of anti-VEGF category business, and commercial, which is about 20%, what we're seeing so far, and we are making good progress with payers, we're seeing that Eylea HD is being positioned consistently with Eylea and other brands in the category. And there are plans, as you know, that have a step-edit or utilization management. The good news is that Eylea HD is being positioned consistently with Eylea and other brands. We don't see a differentiation there.

When we go over to Medicare advantage, which is roughly about 25 per cent of anti budget category business and commercial which is about 20, what we're seeing so far and we are making good progress with payers, we're seeing that EYLEA HD is being positioned consistently with EYLEA and other brands in the category and there are plans as you know that have a [inaudible] or utilization management. The good news is that EYLEA HD is being positioned consistently with EYLEA and other brands. We don't see a differentiation there.

Cause you know that have a step that date or utilization management. The good news is get H D is being physician consistently with Eylea and other brands, we don't see a differentiation there.

Ryan Crowe: Okay, Marion. Thank you. Next question, Shannon, please.

Ryan Crowe: Marion, thank you. Next question Shannon please.

Operator: Our next question comes from the line of Robyn Karnauskas with Truist Securities. Your line is now open.

Operator: Our next question comes from the line of Robin Karnauskas with Truist Securities. Your line is now open.

Robyn Karnauskas: Hi, guys. Thanks for the question. It's a question on CSU. I know it's a big opportunity. Many patients are not controlled well with antihistamines, and you have a CRL. Is study C sufficient? Anything in particular you think the FDA is looking for? Is there a disconnect? Are they changing what they view for the BLA approval? What's your thoughts there? Thanks.

>>Robyn Kay Karnauskas - Truist Securities, Inc., Research Division: Hi, guys. Thanks for the question. Question on CSU, I know, it's a big opportunity, many patients are not controlled well with antihistamine and you have a CRL. Does the study seem sufficient, anything in particular you'd think the FDA is I'm looking for? Is there a disconnect or are they changing what they do for the [inaudible] approval? What's your thoughts there? Thanks.

Question on C. S. U I know, it's a big opportunity many patients are not control, while with antihistamine and you have a <unk>. Study see sufficient anything in particular you'd think the F. D. As I'm looking for is there a disconnect or are they changing you know how they what they do for the bar for Uhm approval, what's your thoughts Sir thanks.

Operator: Many patients are not controlled well with antihistamines, and you have a CRL. Is study C sufficient? Anything in particular you think the FDA is looking for? Is there a disconnect? Are they changing what they view for the BLA approval? What's your thoughts there? Thanks. Yeah. Well, as you know, we had one very positive study. We had a second study that actually had a P of 0.049, but for various statistical purposes, just missed meeting its predetermined statistical hurdle, but certainly, all the indicators are going in the right direction. And what the FDA indicated that they wanted to see the results of our ongoing study C, as we call it, to make their decision.

Study see sufficient anything in particular you'd think the F. D. As I'm looking for is there a disconnect or are they changing you know how they what they do for the bar for Uhm approval, what's your thoughts Sir thanks.

George Yancopoulos: Yeah. Well, as you know, we had one very positive study. We had a second study that actually had a P of 0.049, but for various statistical purposes, just missed meeting its predetermined statistical hurdle, but certainly, all the indicators are going in the right direction. And what the FDA indicated that they wanted to see the results of our ongoing study C, as we call it, to make their decision.

George D. Yancopoulos: Yeah, well as you know, we had one very positive study, we had a second study that actually had a PA 0.049, but for various statistical purposes, just missed meeting it's predetermined statistical hurdle, but certainly all the indicators are going in the right direction. And what the FDA indicated that they wanted to see the results of our ongoing study-C as we call it to make their decision. And so what we're hoping is that that study, which is in the same population of the very positive initial study, remember the second study was in these [inaudible] patients, who had failed Xolair among other therapies, but study-C is in the same population is our very first study A, very positive study, and we're hoping that if we get consistent data in that study that the FDA will consider to look favorably upon it.

Indicated that they wanted to see the results of our ongoing studies C. As we call it to make their decision and so what we're hoping is that that study, which isn't the same population of the very positive initial study remember the second study was in these <unk>.

Operator: And so what we're hoping is that that study, which is in the same population of the very positive initial study, remember, the second study was in these recalcitrant patients who had failed Xolair, among other therapies, but study C is in the same population as our very first study A, the very positive study. And we're hoping that if we get consistent data in that study, that the FDA will consider it and look favorably upon it. Okay. Thanks, George. Next question, Shannon. Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open. Good morning. Thanks for taking my question.

And so what we're hoping is that that study, which is in the same population of the very positive initial study, remember, the second study was in these recalcitrant patients who had failed Xolair, among other therapies, but study C is in the same population as our very first study A, the very positive study. And we're hoping that if we get consistent data in that study, that the FDA will consider it and look favorably upon it.

Patients, who would failed xolair among other therapies, but study C. As in the same population is our very first study a very positive study and we're hoping that if we get consistent data and that study that the F. D. A will consider it look favorably upon it.

Ryan Crowe: Okay. Thanks, George. Next question, Shannon.

Ryan Crowe: Thanks George. Next question Shannon.

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

Salveen Richter: Good morning. Thanks for taking my question. With regard to your cancer portfolio, as we look to additional data coming out at ASH and the proof of concept we've seen so far, but combination data that we're looking to with Libtayo, can you just talk to us about the optimization still required here and how you're thinking about positioning it in the context of emerging targets and competitive dynamics? Thank you.

I'll Miss actually line is Nelson.

Salveen Jaswal Richter: Good morning. Thanks for taking my question. With regards to your cancer portfolio as we look to additional data coming out at ASH and the proof of concept we've seen so far but the combination data that we're looking to with LIBTAYO, can you just talk to us about the optimizations still required here and how you're thinking about positioning it in the context of emerging targets and competitive dynamics? Thank you.

Operator: With regard to your cancer portfolio, as we look to additional data coming out at ASH and the proof of concept we've seen so far, but combination data that we're looking to with Libtayo, can you just talk to us about the optimization still required here and how you're thinking about positioning it in the context of emerging targets and competitive dynamics? Thank you. Yeah. We have a very large collection of combination opportunities that we're very excited about. The first one that we hope has a chance of really crossing the finish line in a very significant way, in a very significant population, is our combination of Libtayo in combination with fianlimab, putting together these two checkpoints: the anti-PD-1 and the anti-LAG-3. And I think in this case, we believe we have evidence that we have the best-in-class type of activity with both agents separately.

Portfolio as we look to additional data coming at it <unk>. Concept, we've seen so far but uhm combination data that we're looking to with Libtayo can you just talk to us about the optimizations tell required here and and how you're thinking about positioning it in the context of emerging targets and competitive dynamics. Thank you.

Concept, we've seen so far but uhm combination data that we're looking to with Libtayo can you just talk to us about the optimizations tell required here and and how you're thinking about positioning it in the context of emerging targets and competitive dynamics. Thank you.

George Yancopoulos: Yeah. We have a very large collection of combination opportunities that we're very excited about. The first one that we hope has a chance of really crossing the finish line in a very significant way, in a very significant population, is our combination of Libtayo in combination with fianlimab, putting together these two checkpoints: the anti-PD-1 and the anti-LAG-3. And I think in this case, we believe we have evidence that we have the best-in-class type of activity with both agents separately.

George D. Yancopoulos: Yeah, we have a very large collection of combination opportunities that we're very excited about. The first one that we hope has a chance of really crossing the finish line in a very significant way, in a very significant population is our combination of LIBTAYO in combination with [inaudible]. Putting together these two checkpoints, the anti PD one and the anti lag three and I think in this case, we believe we have evidence that we have the best-in-class type of activity with both agents separately. And as you've hopefully seen in our earlier stage clinical trials, the data suggests that when we put them together, we really can make a remarkable advance for patients in terms of the number of patients who respond and the extent of their progression free survival. And we're now as we announced in a pivotal trial where we hope that within the next year, perhaps be able to provide the results from that trial, which might confirm this remarkable advance for patients. If it works in this first line melanoma setting, it really opens up the door to a whole series of other opportunities both related to melanoma settings, such as an even earlier stage melanoma setting, such as the adjuvant perioperative settings, but we can be moving to other cancers as well with that proof of principle. So that's the nearest term LIBTAYO check point combination approach.

A very large collection of combination opportunities that we're very excited about the first one that we we hope has a chance of really crossing the finish line and a very significant way in regards to the population is our combination of <unk> in combination with the animal man, putting together these too.

Checkpoints the anti P. One on the anti leg three and I think in this case, we believe we have evidence that we have the best in class type of activity with both agents separately and as you hopefully scene in our earlier stage clinical trials. The data suggests that when we put them together, we really can make a <unk>.

Operator: As you hopefully seen in our earlier-stage clinical trials, the data suggests that when we put them together, we really can make a remarkable advance for patients in terms of the number of patients who respond, and the extent of their progression-free survival. We're now, as we announced, in a pivotal trial where we hope that we will, within the next year, perhaps be able to provide the results from that trial, which might confirm this remarkable advance for patients. If it works in this first-line melanoma setting, it really opens up the door to a whole series of other opportunities, both in related melanoma settings, such as in even earlier-stage melanoma settings, such as the adjuvant, and perioperative settings, but we could be moving to other cancers as well with that proof of principle. So that's the nearest-term Libtayo checkpoint combination approach.

As you hopefully seen in our earlier-stage clinical trials, the data suggests that when we put them together, we really can make a remarkable advance for patients in terms of the number of patients who respond, and the extent of their progression-free survival. We're now, as we announced, in a pivotal trial where we hope that we will, within the next year, perhaps be able to provide the results from that trial, which might confirm this remarkable advance for patients.

advance for patients in terms of the number of patients who respond and the extent of their progression free survival. And we're now as we announced in a pivotal trial where we hope that within the next year, perhaps be able to provide the results from that trial, which

might confirm this remarkable advance for patients. If it works in this first line melanoma setting, it really opens up the door to a whole series of other opportunities both related to melanoma settings, such as an even earlier stage melanoma setting, such as the adjuvant perioperative settings, but we

If it works in this first-line melanoma setting, it really opens up the door to a whole series of other opportunities, both in related melanoma settings, such as in even earlier-stage melanoma settings, such as the adjuvant, and perioperative settings, but we could be moving to other cancers as well with that proof of principle. So that's the nearest-term Libtayo checkpoint combination approach.

can be moving to other cancers as well with that proof of principle. So that's the nearest term LIBTAYO check point combination approach. As you know with our bispecifics the combination of opportunities there are also very exciting, either with LIBTAYO or with each other.

can be moving to other cancers as well with that proof of principle. So that's the nearest term LIBTAYO check point combination approach.

Operator: As you know, with our bispecifics, the combination opportunities there are also very exciting, either with Libtayo or with each other. And we have, in that space, shown that our individual agents, the important thing is we have now validated so many of our individual agents as having, once again, the potential for best-in-class type of activity, whether it's our agent for myeloma or our CD20 bispecific in, for example, follicular lymphoma and so forth and so on. But we're also excited about our co-stim bispecifics. We've released the data about the incredible efficacy at early stages that we see in combination with Libtayo, but that one is countered by concerns with immune-mediated adverse events that we're seeing in these patients. It is hard to dramatically increase the extent of immunotherapy benefit without having it associated with increased autoimmune-type reactions.

As you know, with our bispecifics, the combination opportunities there are also very exciting, either with Libtayo or with each other. And we have, in that space, shown that our individual agents, the important thing is we have now validated so many of our individual agents as having, once again, the potential for best-in-class type of activity, whether it's our agent for myeloma or our CD20 bispecific in, for example, follicular lymphoma and so forth and so on. But we're also excited about our co-stim bispecifics. We've released the data about the incredible efficacy at early stages that we see in combination with Libtayo, but that one is countered by concerns with immune-mediated adverse events that we're seeing in these patients. It is hard to dramatically increase the extent of immunotherapy benefit without having it associated with increased autoimmune-type reactions.

As you know with our bispecifics the combination of opportunities there are also very exciting, either with LIBTAYO or with each other. And we have, in that space, shown that our individual agents, the important thing is we have now validated so many of our individual agents as having once again the potential for best-in-class type of activity, whether it's our agent for myeloma or our CD25 bispecific in for example, [inaudible] and so forth and so on. But we're also excited about our coast in bispecifics. We've released the data about the incredible advocacy in early stages that we see in combination with LIBTAYO, but that one is countered by concerns with new mediated adverse events that we're seeing in these patients. It is hard to dramatically increase the extent of immunotherapy benefit without having associated with increased auto immune type reactions. We're working very hard on that and we think based on preclinical data that the trick may be combining our [inaudible] with our CD3 bispecifics where we don't see these dramatic potential increases in the mechanisms that may lead to immune adverse events.

Others.

And we have, in that space, shown that our individual agents, the important thing is we have now validated so many of our individual agents as having once again the potential for best-in-class type of activity, whether it's our agent for myeloma or our CD25 bispecific in for example, [inaudible] and so forth and so on. But we're also excited about our coast in bispecifics. We've released the data about the incredible advocacy in early stages that we see in combination with LIBTAYO, but that one is countered by concerns with new mediated adverse events that we're seeing in these patients. It is hard to dramatically increase the extent of immunotherapy benefit without having associated with increased auto immune type reactions. We're working very hard on that and we think based on preclinical data that the trick may be combining our [inaudible] with our CD3 bispecifics where we don't see these

<unk> 25 specific in for example, folliculin phone and so forth and so on but we're also excited about our coast and by specifics we've released the data about the incredible advocacy in early stages that we see in combination with reptiles, but that one that one is countered by. Concerns with new mediated adverse events that we're seeing these patients it is hard to dramatically increase the extent of immunotherapy benefit without having it. Uhm associated with increased auto immune type Ah reactions were working very hard on that and we think based on preclinical data that the trick maybe combining our costumes with our city three slices of it's where we don't see these.

Concerns with new mediated adverse events that we're seeing these patients it is hard to dramatically increase the extent of immunotherapy benefit without having it. Uhm associated with increased auto immune type Ah reactions were working very hard on that and we think based on preclinical data that the trick maybe combining our costumes with our city three slices of it's where we don't see these.

Uhm associated with increased auto immune type Ah reactions were working very hard on that and we think based on preclinical data that the trick maybe combining our costumes with our city three slices of it's where we don't see these.

Operator: We're working very hard on that, and we think, based on preclinical data, that the trick may be combining our COSTEMs with our CD3 bispecifics where we don't see these dramatic potential increases in the mechanisms that may lead to immune adverse events. So, in summary, our checkpoint combinations are very near-term. Our bispecifics as single agents have been validated, and hopefully will be being considered by the FDA for approval in the relatively near future. And the combinations are beginning to demonstrate exciting opportunity, and we're trying to tune that in order to try to present the best efficacy-safety profile for patients. All right. Thank you, George. Shannon, please, the next question. Our next question comes from the line of Brian Abrahams with RBC Capital Markets. Your line is now open. Hey, guys. Congrats on the good launch so far, and thanks for taking my question.

We're working very hard on that, and we think, based on preclinical data, that the trick may be combining our COSTEMs with our CD3 bispecifics where we don't see these dramatic potential increases in the mechanisms that may lead to immune adverse events. So, in summary, our checkpoint combinations are very near-term. Our bispecifics as single agents have been validated, and hopefully will be being considered by the FDA for approval in the relatively near future. And the combinations are beginning to demonstrate exciting opportunity, and we're trying to tune that in order to try to present the best efficacy-safety profile for patients.

dramatic potential increases in the mechanisms that may lead to immune adverse events. So in summary, our checkpoint combinations are very near term, our bispecifics to single agents have been validated and hopefully we will be being considered by the FDA for approval in the relatively near future and the combinations are beginning to demonstrate exciting opportunity and we're trying to tune that in order to try to present the best efficacy safety profile for patients.

dramatic potential increases in the mechanisms that may lead to immune adverse events.

So in summary, our checkpoint combinations are very near term, our bispecifics to single agents have been validated and hopefully we will be being considered by the FDA for approval in the relatively near future and the combinations are beginning to demonstrate exciting opportunity and we're trying to tune that in order to try to present the best efficacy safety profile for patients.

Summary, or check coin combinations are very near term or five specific to a single agents had been validated and hopefully will be will be being considered by the F. D. A for approval and they're relatively near future and the combinations are beginning to demonstrate exciting opportunity and we're trying to. Tune that in order to try to present, the best efficacy safety profile for patients.

Tune that in order to try to present, the best efficacy safety profile for patients.

Ryan Crowe: All right. Thank you, George. Shannon, please, the next question.

Ryan Crowe: Alright, thank you George. Shannon please, the next question.

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

Obviously capital markets. Your line is Nelson.

Brian Abrahams: Hey, guys. Congrats on the good launch so far, and thanks for taking my question. You mentioned in the press release some impact of price on Eylea. I'm just wondering if you could elaborate a little bit more on this, when you think this might stabilize, and the extent that this might affect high-dose Eylea as well. Thanks.

Brian Corey Abrahams: Hey, guys. Congrats on the good launch so far and thanks for taking my question. You mentioned in the press release some impact of price on EYLEA, I was wondering if you could elaborate a little bit more on this, when you think this might stabilize and extent that this might affect high dose EYLEA as well. Thanks.

Operator: You mentioned in the press release some impact of price on Eylea. I'm just wondering if you could elaborate a little bit more on this, when you think this might stabilize, and the extent that this might affect high-dose Eylea as well. Thanks. Sure, Brian. So I would comment that in an increasingly competitive category, there, of course, has been some pressure on Eylea. I'd also reflect that in 12 years in the market, it's really modest rebating and discounting if you look at the history of the brand. And, of course, that on a brand that has never taken a price increase. But we will continue to be very much watching uptake of Eylea HD, taking very responsible, appropriate, and thoughtful measures on pricing.

Marion McCourt: Sure, Brian. So I would comment that in an increasingly competitive category, there, of course, has been some pressure on Eylea. I'd also reflect that in 12 years in the market, it's really modest rebating and discounting if you look at the history of the brand. And, of course, that on a brand that has never taken a price increase. But we will continue to be very much watching uptake of Eylea HD, taking very responsible, appropriate, and thoughtful measures on pricing.

Marion E. McCourt: Sure Brian. So I would comment that in an increasingly competitive category, there of course, has been some pressure on EYLEA. I'd also reflect that in 12 years in the market, it's really modest rebating and discounting if you look at the history of the brand and of course that's on a brand that has never taken a price increase but we will continue to be very much watching uptake of EYLEA HD, taking very responsible and appropriate and thoughtful measures on pricing. And certainly as I reported to early days we're making some very strong progress in the marketplace in terms of making sure that physicians gain confidence in the reimbursement of EYLEA HD as they initiate patients.

Be in a very much watching uptake of Eylea H D taken Gary responsible inappropriate and thoughtful measures on pricing and certainly as I reported to early days uhm or making some very strong progress in the marketplace and changes, making sure that physicians gain confidence. <unk> and reimbursement of Eylea H D as they initiate patients.

Operator: And certainly, as I reported to you, early days, we're making some very strong progress in the marketplace in terms of making sure that physicians gain confidence in reimbursement of Eylea HD as they initiate patients. Okay. Thanks, Marion. Please move to the next question, Shannon. Our next question comes from the line of Yatin Suneja with Guggenheim. Your line is now open. Hey, guys. Thank you for taking my question. Question on Dupixent. Could you maybe share your views on the newer mechanism, example, OX40 or perhaps a longer-acting version of Dupixent on the franchise? Maybe if you can talk about your efforts in terms of lifecycle management of Dupixent. Thank you. Yeah. Maybe getting back to some of the comments that I made before.

And certainly, as I reported to you, early days, we're making some very strong progress in the marketplace in terms of making sure that physicians gain confidence in reimbursement of Eylea HD as they initiate patients.

<unk> and reimbursement of Eylea H D as they initiate patients.

Ryan Crowe: Okay. Thanks, Marion. Please move to the next question, Shannon.

Ryan Crowe: Thanks Marion. Please move to the next question Shannon.

Please please move to the next question Janet.

Operator: Our next question comes from the line of Yatin Suneja with Guggenheim. Your line is now open.

Operator: Our next question comes from the line of [inaudible] with Guggenheim, your line is now open.

Yatin Suneja: Hey, guys. Thank you for taking my question. Question on Dupixent. Could you maybe share your views on the newer mechanism, example, OX40 or perhaps a longer-acting version of Dupixent on the franchise? Maybe if you can talk about your efforts in terms of lifecycle management of Dupixent. Thank you.

Unknown: Hey, guys. Thank you for taking my question. Question on DUPIXEN, could you share your views on the mechanism for example, [inaudible] or perhaps longer acting version of DUPIXEN and the franchise, maybe if you can talk about your efforts in terms of lifecycle management of DUPIXEN. Thank you.

George Yancopoulos: Yeah. Maybe getting back to some of the comments that I made before. The collection of so-called allergic or type 2 conditions, which Dupixent addresses, are all characterized by a systemic inflammatory problem increase in the so-called type 2 inflammation, which, if you look at the science and literature, is really a vestigial pathway that largely evolved and was one of the most active parts of the immune system to fight things like fecal parasites, which are really not an issue now in the developed world. This part of the immune system should essentially, in the modern world, be entirely quiescent. It serves almost no role. The problem is it becomes unleashed abnormally to do things that it shouldn't be doing, like fighting allergens or attacking the skin, or the gut in atopic dermatitis, or eosinophilic esophagitis.

George D. Yancopoulos: Yeah, maybe getting back to some of the comments that I made before, the collection of so called allergic or type two conditions, which DUPIXEN addresses are all characterized by a systemic inflammatory problem, increase in this so called type two inflammation, which if you look at the signs and the literature it's really of a residual pathway that largely evolved and was one of the most active parts of immune system to fight things like sequel parasites, which are really not an issue now in the developed world. This part of the immune system should essentially in the modern world be entirely quiesce, it serves almost no role. The problem is it becomes unleashed abnormally to do things that it shouldn't be doing like fighting allergies or attacking the skin or the gut in atopic dermatitis or [inaudible] esophagitis.

Operator: The collection of so-called allergic or type 2 conditions, which Dupixent addresses, are all characterized by a systemic inflammatory problem increase in the so-called type 2 inflammation, which, if you look at the science and literature, is really a vestigial pathway that largely evolved and was one of the most active parts of the immune system to fight things like fecal parasites, which are really not an issue now in the developed world. This part of the immune system should essentially, in the modern world, be entirely quiescent. It serves almost no role. The problem is it becomes unleashed abnormally to do things that it shouldn't be doing, like fighting allergens or attacking the skin, or the gut in atopic dermatitis, or eosinophilic esophagitis.

The collection of so called allergic for type two conditions, which dupixent addresses. Are all characterized by. A systemic inflammatory problem. Increase in this so called type two inflammation, which if you look at the size of the literature is really of this digital pathway that largely evolved and was one of the most active parts of immune system to fight things like sequel, parasites, which are really not a new. Issue now in the developed World. This part of the immune system should essentially in the modern world be entirely <unk>. It serves almost no role the problem is it becomes unleashed.

Are all characterized by. A systemic inflammatory problem. Increase in this so called type two inflammation, which if you look at the size of the literature is really of this digital pathway that largely evolved and was one of the most active parts of immune system to fight things like sequel, parasites, which are really not a new. Issue now in the developed World. This part of the immune system should essentially in the modern world be entirely <unk>. It serves almost no role the problem is it becomes unleashed.

A systemic inflammatory problem. Increase in this so called type two inflammation, which if you look at the size of the literature is really of this digital pathway that largely evolved and was one of the most active parts of immune system to fight things like sequel, parasites, which are really not a new. Issue now in the developed World. This part of the immune system should essentially in the modern world be entirely <unk>. It serves almost no role the problem is it becomes unleashed.

Increase in this so called type two inflammation, which if you look at the size of the literature is really of this digital pathway that largely evolved and was one of the most active parts of immune system to fight things like sequel, parasites, which are really not a new. Issue now in the developed World. This part of the immune system should essentially in the modern world be entirely <unk>. It serves almost no role the problem is it becomes unleashed.

Issue now in the developed World. This part of the immune system should essentially in the modern world be entirely <unk>. It serves almost no role the problem is it becomes unleashed.

abnormally to do things that it shouldn't be doing like fighting allergies or attacking the skin or the gut in atopic dermatitis or [inaudible] esophagitis. What DDUPIXEN does uniquely is that it controls and the data now demonstrate this incredible fact that it puts this useless angry tiger back in the cage where it belongs and that is why it has this incredible profile of not only advocacy, but safety because what it's shutting down is it's shutting down a pathway that should be residual in the modern world, but becomes unleashed and attacks all different parts of the body.

abnormally to do things that it shouldn't be doing like fighting allergies or attacking the skin or the gut in atopic dermatitis or [inaudible] esophagitis.

Operator: What Dupixent does uniquely is that it controls, and the data now demonstrate this, the incredible effect that it puts this useless angry tiger back in the cage where it belongs. That is why it has this incredible profile of not only efficacy but safety, because what it's shutting down is it's shutting down a pathway that should be vestigial in the modern world but becomes unleashed and attacks all different parts of the body.

What Dupixent does uniquely is that it controls, and the data now demonstrate this, the incredible effect that it puts this useless angry tiger back in the cage where it belongs. That is why it has this incredible profile of not only efficacy but safety, because what it's shutting down is it's shutting down a pathway that should be vestigial in the modern world but becomes unleashed and attacks all different parts of the body.

What dupixent does uniquely is that he controls and the data now. Demonstrate this the incredible fact that it puts this useless angry tiger back in the Cage, where it belongs and that is why it has this incredible profile of not only advocacy, but safety because what it's shutting down is at. Shutting down a pathway that should be the schedule in the modern world, but becomes unleashed and attacks all different parts of the body.

What DUPIXEN does uniquely is that it controls and the data now demonstrate this incredible fact that it puts this useless angry tiger back in the cage where it belongs and that is why it has this incredible profile of not only advocacy, but safety because what it's shutting down is it's shutting down a pathway that should be residual in the modern world, but becomes unleashed and attacks all different parts of the body.

Demonstrate this the incredible fact that it puts this useless angry tiger back in the Cage, where it belongs and that is why it has this incredible profile of not only advocacy, but safety because what it's shutting down is at. Shutting down a pathway that should be the schedule in the modern world, but becomes unleashed and attacks all different parts of the body.

Shutting down a pathway that should be the schedule in the modern world, but becomes unleashed and attacks all different parts of the body.

Operator: We believe that any of this current competition that's ongoing doesn't share these remarkable features that give Dupixent its incredible broad efficacy across the spectrum of diseases with its unique safety profile, because all of these other approaches, including, for example, the OX40 approach and so forth, are addressing different fundamental immune pathways that are important in the immune system's function to do a lot of actually useful things in the modern world, like, for example, fighting viral infections and cancer and so forth. So Dupixent really has a very unique profile, which, if we can help explain and if all physicians and patients can understand it, makes it the perfect drug for this condition. It uniquely blocks this vestigial pathway that gets out of control inappropriately and causes disease all over the body.

We believe that any of this current competition that's ongoing doesn't share these remarkable features that give Dupixent its incredible broad efficacy across the spectrum of diseases with its unique safety profile, because all of these other approaches, including, for example, the OX40 approach and so forth, are addressing different fundamental immune pathways that are important in the immune system's function to do a lot of actually useful things in the modern world, like, for example, fighting viral infections and cancer and so forth. So Dupixent really has a very unique profile, which, if we can help explain and if all physicians and patients can understand it, makes it the perfect drug for this condition. It uniquely blocks this vestigial pathway that gets out of control inappropriately and causes disease all over the body.

We believe that any of this current competition that's ongoing doesn't share these remarkable features that give DUPIXEN it's incredible broad efficacy across the spectrum of diseases with its unique safety profile because all of these other approaches including for example, the [inaudible] 40 approach and so forth are addressing different fundamental immune pathways that are important in the immune systems function to do a lot of actually useful things in the modern world, like for example, fighting viral infections and cancer and so forth. So DUPIXEN really has a very unique profile, which if we can help explain and if all physicians and patients can understand that make it the perfect drug for this condition. It uniquely blocks this this residual pathway that gets out of control and appropriately and causes disease all over the body. DUPIXEN shuts down what should be a residual pathway and it helps disease, whether in the same patients it can be manifesting in the skin, in the lungs, and the nose, in the gut and so forth, it shuts it down without really untoward effects with regards to the ability of the body to actually fight infections and so forth. In fact, if you look at our clinical studies and some of the data that we published in many, if not most cases, you actually see unbelievably reduced infections in the setting of the DUPIXEN treatment because what you're doing is you're putting the the bad part of the immune system back under control and you're allowing the rest of the immune system to do its function.

approach and so forth are addressing different fundamental immune pathways that are important in the immune systems function to do a lot of actually useful things in the modern world, like for example, fighting viral infections and cancer and so forth. So DUPIXEN really has a very unique profile, which if we can help explain and if all physicians and patients can understand that make it the perfect drug for this condition. It uniquely blocks this this residual pathway that gets out of control and appropriately and causes disease all over the body. DUPIXEN shuts down what should be a residual pathway and it helps disease, whether in the same patients it can be manifesting in the skin, in the lungs, and the nose, in the gut and so forth, it shuts it down without really untoward effects with regards to the ability of the body to actually fight infections and so forth. In fact, if you look at our clinical studies and some of the data that we published in many, if not most cases, you actually see unbelievably reduced infections in the setting of the DUPIXEN treatment because what you're doing is you're putting the the bad part of the immune system back under control and you're allowing the rest of the immune system to do its function.

He was unique profile, which if we can help explain and if if all physicians and patients can understand that make it the perfect drug for this condition did you legally blocks. This this digital pathway that gets out of control and appropriately and causes disease all over the body. <unk> shuts down this which should be a vestigial pathway and it helps disease, whether in the same patients it can be manifesting the skin and the lungs, and the nose and the <unk>.

Operator: Dupixent shuts down this, what should be a vestigial pathway, and it helps disease, whether in the same patients. It could be manifesting in the skin, in the lungs, in the nose, in the gut, and so forth. It shuts it down without really untoward effects with regards to the ability of the body to actually fight infections and so forth. In fact, if you look at our clinical studies and some of the data that we publish, in many, if not most cases, you actually see unbelievably reduced infections in the setting of the Dupixent treatment, because what you're doing is you're putting the bad part of the immune system back under control, and you're allowing the rest of the immune system to do its function.

Dupixent shuts down this, what should be a vestigial pathway, and it helps disease, whether in the same patients. It could be manifesting in the skin, in the lungs, in the nose, in the gut, and so forth. It shuts it down without really untoward effects with regards to the ability of the body to actually fight infections and so forth. In fact, if you look at our clinical studies and some of the data that we publish, in many, if not most cases, you actually see unbelievably reduced infections in the setting of the Dupixent treatment, because what you're doing is you're putting the bad part of the immune system back under control, and you're allowing the rest of the immune system to do its function.

<unk> shuts down this which should be a vestigial pathway and it helps disease, whether in the same patients it can be manifesting the skin and the lungs, and the nose and the <unk>.

so forth, it shuts it down without really untoward effects with regards to the ability of the body to actually fight infections and so forth. In fact, if you look at our clinical studies and some of the data that we published in many, if not most cases, you actually see unbelievably reduced infections in the setting of the DUPIXEN treatment because what you're doing is you're putting the the bad part of the immune system back under control and you're allowing the rest of the immune system to do its function.

<unk> really untoward effects with regards to the ability of the body to actually fight infections and so forth. In fact, if you look at our clinical studies and some of the data that we published in many if not most cases, you actually see unbelievably reduced infections in the setting of the dupixent treatment because what you're doing. Is your. Putting the.

Is your. Putting the.

Putting the.

the bad part of the immune system back under control and you're allowing the rest of the immune system to do its function. All of these other approaches are trying to attack critical parts of the immune system that have important other functions and they don't address the widespread problem that occurs systemically and causes all of these diseases. So as you've seen already with various agents, they may work in one of DUPIXEN's indications, but they don't work, they failed in other indications. And if they work, they also often come with the concerns about safety because they're designed to be immuno suppressive, which DUPIXEN is not.

the bad part of the immune system back under control and you're allowing the rest of the immune system to do its function.

Operator: All of these other approaches are trying to attack critical parts of the immune system that have important other functions, and they don't address the widespread problem that occurs systemically and causes all of these diseases. So, as you've seen already with various agents, they may work in one of Dupixent's indications, but they don't work. They failed in other indications. And if they work, they also often come with the concerns about safety because they're designed to be immunosuppressive, which Dupixent is not. So, just a small point to what George, the eloquent, explanation of why Dupixent is such a special drug and the prediction that it would be safe because it's attacking this vestigial part of the immune system.

All of these other approaches are trying to attack critical parts of the immune system that have important other functions, and they don't address the widespread problem that occurs systemically and causes all of these diseases. So, as you've seen already with various agents, they may work in one of Dupixent's indications, but they don't work. They failed in other indications. And if they work, they also often come with the concerns about safety because they're designed to be immunosuppressive, which Dupixent is not. So, just a small point to what George, the eloquent, explanation of why Dupixent is such a special drug and the prediction that it would be safe because it's attacking this vestigial part of the immune system.

All of these other approaches are trying to attack critical parts of the immune system that have important other functions and they don't address the widespread problem that occurs systemically and causes all of these diseases. So as you've seen already with various agents, they may work in one of DUPIXEN's indications, but they don't work, they failed in other indications. And if they work, they also often come with the concerns about safety because they're designed to be immuno suppressive, which DUPIXEN is not.

Does that occur systemically and causes all of these diseases. So as you see already with various agents. They may work in one of two picks since indications, but they don't work they failed in other indications and if they <unk> if they work. They also often come with the concerns about safety because. They're designed to be immuno suppressive, which dupixent is not.

They're designed to be immuno suppressive, which dupixent is not.

Leonard S. Schleifer: So just add a small point to George's eloquent explanation of why DUPIXEN is such a special drug and the prediction that it would be safe because it's attacking the residual part of the immune system. You're looking at somewhere in the neighborhood of three quarters of a million people on the drug, maybe more than that so that demonstrated the safety that is predicted by the science, including in children, as we know as young as six months to improve where it's been demonstrating not only incredible safety, but incredible efficacy.

Operator: You're looking at somewhere in the neighborhood of three-quarters of a million people on the drug, many more than that so that have demonstrated the safety that is predicted by the science, including in children, as we know, as young as six months is approved there, where it's been demonstrating not only incredible safety but incredible efficacy. All right. Great points. Thank you. Shannon, I think we have time for two more questions, please. Our next question comes from the line of Dane Leone with Raymond James. Your line is now open. Hey, thanks for taking the questions, and congratulations on a strong quarter. Just actually really two quick ones from me. First one being, can you just comment whether you saw any impact from increased utilization of biosimilar ranibizumab during the quarter on Eylea sales?

You're looking at somewhere in the neighborhood of three-quarters of a million people on the drug, many more than that so that have demonstrated the safety that is predicted by the science, including in children, as we know, as young as six months is approved there, where it's been demonstrating not only incredible safety but incredible efficacy.

More than that so <unk> demonstrated the safety <unk>. <unk> by the science incur. Including in children, as we know as young as six months to improve. There, where it's been demonstrating Natalie incredible safety, but incredible efficacy.

<unk> by the science incur. Including in children, as we know as young as six months to improve. There, where it's been demonstrating Natalie incredible safety, but incredible efficacy.

Including in children, as we know as young as six months to improve. There, where it's been demonstrating Natalie incredible safety, but incredible efficacy.

There, where it's been demonstrating Natalie incredible safety, but incredible efficacy.

Ryan Crowe: All right. Great points. Thank you. Shannon, I think we have time for two more questions, please.

Ryan Crowe: Great points. Thank you. Shannon, I think we have time for two more questions please.

Operator: Our next question comes from the line of Dane Leone with Raymond James. Your line is now open.

Dane Leone: Hey, thanks for taking the questions, and congratulations on a strong quarter. Just actually really two quick ones from me. First one being, can you just comment whether you saw any impact from increased utilization of biosimilar ranibizumab during the quarter on Eylea sales?

Dane Vincent Leone: Thanks for taking the questions and congratulations on a strong quarter. This is actually really two quick ones from me. First one being, can you just comment whether you saw any impact from increased utilization biosimilar Ranibizumab during the quarter on EYLEA sales? A number of high volume clinics highlighted favorable margin opportunities from using more biosimilar, Ranibizumab, which seems to be essentially a transient impact and use of some of the brands, but would be interesting your commentary there. And then, we've gotten a just a lot of inbounds in terms of the ongoing patent litigation of EYLEA, could you just maybe state for us what your current expectation is for EYLEA patent life and just any thoughts you have on how the ruling that we're awaiting could actually impact your base case. Thank you.

Operator: A number of high-volume clinics had highlighted favorable margin opportunities from using more biosimilar ranibizumab, which seems to be potentially a transient impact in use of some of the brands, but would be interested in your commentary there. And then we've gotten just a lot of inbounds in terms of ongoing patent litigation of Eylea. Could you just maybe state for us what your current expectation is for Eylea patent life and just any thoughts you have on how the ruling that we're awaiting could actually impact your base case? Thank you. Yeah. So I'll cover the patents, and then Marion can cover any additional insight into the marketplace. On the patents, we're involved in litigation. There's a couple of key patents that have been involved in this case that both relate to formulation as well as dosing.

A number of high-volume clinics had highlighted favorable margin opportunities from using more biosimilar ranibizumab, which seems to be potentially a transient impact in use of some of the brands, but would be interested in your commentary there. And then we've gotten just a lot of inbounds in terms of ongoing patent litigation of Eylea. Could you just maybe state for us what your current expectation is for Eylea patent life and just any thoughts you have on how the ruling that we're awaiting could actually impact your base case? Thank you.

Favorable margin opportunities from using more biosimilar, ranibizumab, which seems to be essentially a transient and packed and use of some of the brands, but would be interested in your commentary there and then. We've gotten a just a lotta inbounds in terms of the ongoing patent litigation of Eylea could you just maybe state for US what your current expectation is for highly of patent life and and just any thoughts you have on how the ruling that were awaiting could actually impact. Your your base case. Thank you.

We've gotten a just a lotta inbounds in terms of the ongoing patent litigation of Eylea could you just maybe state for US what your current expectation is for highly of patent life and and just any thoughts you have on how the ruling that were awaiting could actually impact. Your your base case. Thank you.

Leonard Schleifer: Yeah. So I'll cover the patents, and then Marion can cover any additional insight into the marketplace. On the patents, we're involved in litigation. There's a couple of key patents that have been involved in this case that both relate to formulation as well as dosing.

Leonard S. Schleifer: Yeah, so I'll cover the patents and Marion can cover additional insight into the market place. On the patents, we're involved in litigation. There are a couple of key factors that are involved in this case that both relate to formulation as well as dosing. The base case for us is that we're assuming that the exclusivity will expire in May, but we will see what happens in the litigation which could be an upside obviously for the franchise.

Additional insight into the market place on the patterns were involved in litigation as a couple of two fat instead of involved in this case that both related to call relation as well as dosing. <unk> case is that for us is assuming that the exclusivity will expire in may, but we will see what happens in the litigation and which could be an upside obviously for the franchise.

Operator: The base case is that for us, we're assuming that the exclusivity will expire in May, but we will see what happens in the litigation, which could be an upside, obviously, for the franchise. Sure. And on the ranibizumab impact, it's relatively early in their launches, but there hasn't been a notable impact to the category. The Lucentis biosimilar shares in the low single-digit area in the Q3, and certainly, the impact has been seen more relative to Lucentis, which has declining share. But certainly, this has not extended to Eylea or Eylea HD. Thanks, Marion. We'll just take our last question, please, Shannon. Our last question is from the line of Brian Skorney with Baird. Your line is now open. Hey, thanks for taking the question.

The base case is that for us, we're assuming that the exclusivity will expire in May, but we will see what happens in the litigation, which could be an upside, obviously, for the franchise.

<unk> case is that for us is assuming that the exclusivity will expire in may, but we will see what happens in the litigation and which could be an upside obviously for the franchise.

Marion McCourt: Sure. And on the ranibizumab impact, it's relatively early in their launches, but there hasn't been a notable impact to the category. The Lucentis biosimilar shares in the low single-digit area in the Q3, and certainly, the impact has been seen more relative to Lucentis, which has declining share. But certainly, this has not extended to Eylea or Eylea HD.

Marion E. McCourt: Alright and then [inaudible] impact, it's relatively early in their launches and there hasn't been a notable impact to the category. [inaudible] biosimilar shares in the low single digits area in the third quarter and certainly the impact has been seeing more relatively [inaudible] which has declining share but certainly this is not extended to EYLEA HD.

Relatively early in their lunches and that there hasn't been a notable impact with a category. He the scientists biosimilar shares in the low single digits area, India, the third quarter and certainly the impact has been seen more relatively chili centers, which has been claiming <unk>.

Sure. That's certainly if this does not extend it to at a R. I a H D.

Ryan Crowe: Thanks, Marion. We'll just take our last question, please, Shannon.

Ryan Crowe: Thanks, Marian. We'll just take our last question please Shannon.

Operator: Our last question is from the line of Brian Skorney with Baird. Your line is now open.

Operator: Your last question from the line of Brian Skorney with Bayer. Your line is now open.

Brian Skorney: Hey, thanks for taking the question. It looks like J&J had a really good first quarter of their myeloma bispecific, so it definitely seems like there's a good demand there, but also an element of them having control of a lot of offerings for myeloma. So obviously, head-to-head superiority would always dominate in oncology, but with the initial launch of your bispecific next year, I'm just wondering what your strategy is for competing in the initial late line as a third-to-market. Do you think that there's differentiated enough data here to kind of take share, or is the focus really on generating data in earlier line of combos to kind of move up market share? Thanks.

Line is Nelson.

Brian Peter Skorney: Hey, thanks for taking my question. It looks like J&J had a really good first quarter of their myeloma bispecifics so it seems like there's a good demand there but also an element of having control of a lot of offerings for myeloma. So obviously [inaudible] in oncology, but with the initial launch of your bispecifics next year I'm just wondering what your strategy is for computing initial slate line as a third to market, do you think that there's differentiated enough data here on share or is the focus really on generating data in earlier lineup combos to kind of move up market share? Thanks.

Operator: It looks like J&J had a really good first quarter of their myeloma bispecific, so it definitely seems like there's a good demand there, but also an element of them having control of a lot of offerings for myeloma. So obviously, head-to-head superiority would always dominate in oncology, but with the initial launch of your bispecific next year, I'm just wondering what your strategy is for competing in the initial late line as a third-to-market. Do you think that there's differentiated enough data here to kind of take share, or is the focus really on generating data in earlier line of combos to kind of move up market share? Thanks. Well, of course, it's both. We do believe that data rules the best, both efficacy, safety profile, but also convenience profile.

Like next year I, just wondering what your strategy is for computer in the initial late line as a third to market do you think that there's.

Furniture that enough data here <unk>.

Chair or is the focus really on generating data in earlier lineup combos to kind of move up market share.

George Yancopoulos: Well, of course, it's both. We do believe that data rules the best, both efficacy, safety profile, but also convenience profile. We will be continuing to show our evolving and maturing data, which we believe could result in best-in-class in terms of efficacy, in terms of response rates and complete response rates, in terms of safety, in terms of the frequency of cytokine release syndrome and so forth, and in terms of differentiation in terms of mandated hospitalizations. We will be continuing to present our data.

George D. Yancopoulos: Well of course, it's both. We do believe that data rules both efficacy safety profile, but also convenience profile and we will be continuing to show our evolving and maturing data, which we believe could result in best-in-class in terms of efficacy, in terms of response rates, and complete response rates, in terms of safety, in terms of the frequency of cytokine release syndrome, and so forth, and in terms of differentiation in terms of mandated hospitalization. So we will be continuing to present our data. Of course, we'll see exactly ultimately what gets in the label and what the FDA supports but there's the potential here for best-in-class differentiation in terms of efficacy, safety, and convenience and schedule.

Operator: We will be continuing to show our evolving and maturing data, which we believe could result in best-in-class in terms of efficacy, in terms of response rates and complete response rates, in terms of safety, in terms of the frequency of cytokine release syndrome and so forth, and in terms of differentiation in terms of mandated hospitalizations. We will be continuing to present our data. Of course, we'll see exactly ultimately what gets in the label and what the FDA supports, but there's the potential here for best-in-class differentiation in terms of efficacy, safety, and convenience and schedule. Of course, as you said, we're also moving with, we think, an exciting program in earlier lines of therapy. All of this is also going to be combined with the opportunities for our future combinations.

Asked in class. In terms of efficacy in terms of response rates and complete response rates in terms of safety in terms of the frequency of of of cytokine release syndrome, and so forth in terms of differentiation in terms of mandated hospitalization. So. We will be continuing to present, our data of course, we'll see exactly ultimately what gets in the label and what the F. D. A supports but there's the potential here for best in class differentiation in terms of efficacy safety and convenience and schedule and.

In terms of efficacy in terms of response rates and complete response rates in terms of safety in terms of the frequency of of of cytokine release syndrome, and so forth in terms of differentiation in terms of mandated hospitalization. So. We will be continuing to present, our data of course, we'll see exactly ultimately what gets in the label and what the F. D. A supports but there's the potential here for best in class differentiation in terms of efficacy safety and convenience and schedule and.

We will be continuing to present, our data of course, we'll see exactly ultimately what gets in the label and what the F. D. A supports but there's the potential here for best in class differentiation in terms of efficacy safety and convenience and schedule and.

Of course, we'll see exactly ultimately what gets in the label and what the FDA supports, but there's the potential here for best-in-class differentiation in terms of efficacy, safety, and convenience and schedule. Of course, as you said, we're also moving with, we think, an exciting program in earlier lines of therapy. All of this is also going to be combined with the opportunities for our future combinations.

And of course, as you said, we're also moving with we think an exciting program in earlier of lines of therapy and all of this is also going to be combined with the opportunities for our future combinations. We have a variety of coasting bispecifics that we're excited about combining specifically with this agent in the plasma cell Dyscrasia settings. So we think it's a very exciting opportunity. As you said, unfortunately there's a large opportunity out there because there's a lot of patients that are still in need. I think that if you have the best agent for late stage patients a lot of people will want to use it and then if we figure out the best program to demonstrate how it can be utilized in earlier stage patients that can certainly enhance that opportunity, let alone if we come up with one of our magic combos that really takes it to the whole next level.

Combined with the opportunities for our future combinations, we have a variety of coasting by specifics that we're excited about combining specifically with this agent in the plasma cells Dyscrasia settings. So we think is a very exciting opportunity as you said. Fortunately you know, there's a large opportunity out there because there's a lot of patients that are still in need I think that if you have the best agent for late stage patience a lot of people who want to use it and then if we figure out the best program to demonstrate how it can be utilized an earlier stage. <unk> certainly enhanced that opportunity let alone if we come up with one of our magic combos that really takes into the whole next level.

Operator: We have a variety of co-stim bispecifics that we're excited about combining specifically with this agent in the plasma cell dyscrasia setting. So we think it's a very exciting opportunity. As you said, unfortunately, there's a large opportunity out there because there's a lot of patients that are still in need. I think that if you have the best agent for late-stage patients, a lot of people will want to use it. And then if we figure out the best program to demonstrate how it can be utilized in earlier-stage patients, that can certainly enhance that opportunity, let alone if we come up with one of our magic combos that really takes it to the whole next level. Okay. Thanks, George, and thanks to everyone who dialed in today, and for your interest in Regeneron.

We have a variety of co-stim bispecifics that we're excited about combining specifically with this agent in the plasma cell dyscrasia setting. So we think it's a very exciting opportunity. As you said, unfortunately, there's a large opportunity out there because there's a lot of patients that are still in need. I think that if you have the best agent for late-stage patients, a lot of people will want to use it. And then if we figure out the best program to demonstrate how it can be utilized in earlier-stage patients, that can certainly enhance that opportunity, let alone if we come up with one of our magic combos that really takes it to the whole next level.

Fortunately you know, there's a large opportunity out there because there's a lot of patients that are still in need I think that if you have the best agent for late stage patience a lot of people who want to use it and then if we figure out the best program to demonstrate how it can be utilized an earlier stage. <unk> certainly enhanced that opportunity let alone if we come up with one of our magic combos that really takes into the whole next level.

<unk> certainly enhanced that opportunity let alone if we come up with one of our magic combos that really takes into the whole next level.

Ryan Crowe: Okay. Thanks, George, and thanks to everyone who dialed in today, and for your interest in Regeneron. We apologize to those remaining in the queue that we did not have a chance to hear from. But as always, the investor relations team here is available to answer any remaining questions you may have. Thank you once again, and have a great day.

Ryan Crowe: Okay, thanks George and thanks to everyone who dialed in today and for your interest in Regeneron. We apologize to those remaining in the queue that we did not have a chance to hear from, but as always, the Investor Relations team here is available to answer any remaining questions you may have. Thank you once again and have a great day.

Operator: We apologize to those remaining in the queue that we did not have a chance to hear from. But as always, the investor relations team here is available to answer any remaining questions you may have. Thank you once again, and have a great day. This concludes today's conference call. Thank you for joining. You may now disconnect.

We apologize to those remaining in the queue that you did not have a chance to hear from what I was always the investor Relations team here is available to answer any remaining questions. You may have thank you once again and have a great day.

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

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Q3 2023 Regeneron Pharmaceuticals Inc Earnings Call

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