Q2 2021 Regeneron Pharmaceuticals Inc Earnings Call

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Tamia: Welcome to the Regeneran Pharmaceutical Second Quarter, 2021 Earnings Conference Call. My name is Tamia, and I will be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. Please note that this conference is being recorded. I will now turn the call over to Justin Hokko, Vice President of Investor Relations. You may begin.

Welcome to the Regeneron Pharmaceuticals second quarter 2021 earnings conference call.

My name is <unk> and I will be your operator for today's call at.

And 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'll now turn the call over to Justin Holdco, Vice President Investor Relations you may begin.

Thank you to me good morning, good afternoon, and good evening to everyone listening around the globe. Thank you for your interest and Regeneron Pharmaceuticals, and welcome to the second quarter 2021 conference call and archived on this webcast will be available on our website. Joining me today on the call are Dr. Leonard Schleifer, founder President and Chief Executive Officer, Dr George and copper.

Justin Hokko: Thank you, Tamia. Good morning, good afternoon, and good evening to everyone listening around the globe. Thank you for your interest in regenerant pharmaceuticals.

Justin Hokko: and welcome to the second quarter 2021 conference call.

Justin Hokko: of this webcast will be available on our website. Joining me today on the caller are Dr. Leonard Schleifer, founder, president, and chief executive officer; Dr. George Yankopoulos, co-founder, president, and chief scientific officer; Marian McCourt, executive vice president and head of commercial; and Bob Landry, executive vice president and chief financial officer.

And with 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 also like to remind you that remarks made on today's call include forward looking statements about regeneron and such.

Justin Hokko: After our prepared remarks, we will open the call for Q&A. I would also like to remind you that remarks made on today's call include four looking statements about regeneration. Such statements may include, but are not limited to, those related to Regeneron and

Such statements May include but are not limited to those related to regeneron and its products and business and financial forecast and guidance development programs and related anticipated milestones collaborations finances regulatory matters payer coverage and reimbursement issues intellectual property pending litigation and other proceedings as well as competition.

Justin Hokko: Products and business, financial forecasting guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation, and other programs.

Justin Hokko: proceedings as well as competition. Each forward-looking statement is subject to

Justin Hokko: that could cause actual results in events to differ materially from those projected in that state. A more complete description of these and other material risks can be found in Regenerant's filings with the United States Securities and Exchange Commission, including its Form 10Q for the period ended June 30th, 2021, which we filed with the SEC earlier today. Regeneron does not undertake any obligation to update any forward-looking statements, whether

Justin Hokko: as a result of new information, future events, or otherwise. In addition, please note that Gap and Non-Gap measures will be discussed in today's call. Information regarding our use of non-gap financial

Justin Hokko: Financial measures and reconciliation of those measures to GAAP are available in our financial results press release, which can be accessed on our website.

Justin Hokko: Once our call concludes, Bob Landry and the IR team will be available to answer further questions. With that said, let me turn the call over to our President and Chief Executive Officer, Dr. Lenton.

Leonard S. Schleifer: Thank you, Justin, and thanks to everyone joining today's call. We had an outstanding performance across the enterprise in the second quarter. Not only did our base business perform exceptional, growing growth from Ilya, Pixin, and Liptya, but we also delivered 1.25 million doses of Regen to the United States government, filling the entire supply contract with Barc We also continue to advance multiple programs across our innovative R&D pipeline with several, Starting with Ilya, global net sales were over 2.3 billion, growing 33% compared to the prior year, reflecting recovery from the COVI In the U.S., sales grew 28%.

It <unk> impact on the second quarter of 2020.

And the U S sales grew 28%.

Eylea continues to set a high bar in terms of efficacy safety and convenience.

Leonard S. Schleifer: Ilya continues to set a high bar in terms of effort, Pixson also performed exceptionally well this quarter with global sales of $1.5 billion, worth 59%. This quarter also marks the first time we have made a $1 billion, quarterly net cell. There remains considerable room for further, inline indications, as well as from potential new opportunities, such as in chronic, spontaneous urticaria, where last week we announced positive phase three studies. We have additional phase three readouts in paragonodularis, isphalic esophagitis, and pediatric atopic dermatitis lateric dermatitis, which could advance the pipeline in a product that addresses numerous oncology conditions.

2 picks and also performed exceptionally well this quarter with global sales of $1.5 billion and growth of 59%.

And this quarter also marks the first time, we incentive fee exceeded $1 billion in U S to fix and quarterly net sales.

And there remains considerable room for further growth from our in line indications as well as from potential new opportunities such as and chronic spontaneous urticaria or CSU.

And last week, we announced positive phase III study results.

We have additional phase III, readouts and Prurigo, Nigel Iris <unk> guidance and pediatric atopic dermatitis later, this year, which could advance our conviction of picks and is a pipeline and a product to address numerous inflammatory diseases.

And oncology reptile global net sales were $117 million and grew 46% with meaning meaningful growth contributions from both inside and outside the United States.

Leonard S. Schleifer: Global Net, or $117 million, and grew 46% with meaningful growth outside the United States, also announced that in a large phase three pivotal study in non-small lung cancer, litene tired, combined with standard chemotherapy, by nearly 30% compared to chemotherapy. We are eager to share these data with regulatory agencies, which, if approved, will improve humanity, the number of lung cancer eligible patients. We also began to see meaningful results from a regenerative, collaborators at Intelli, showed the first ever proof of concept in Devo Genome Editon.

We also announced this morning that and a large phase III pivotal study in non small cell lung cancer led tayo combined with standard chemotherapy reduced the risk of death, and nearly 30% compared to chemotherapy alone.

We are eager to share these data with regulatory agencies, which if approved will dramatically increase the number of lung cancer eligible patients who could be treated wood look tile.

We are also beginning to see meaningful results from our Regeneron genetics medicines pipeline with our collaborators at and Telia. We showed the first ever proof of concept.

In vivo gene.

Editing with N T L. A 2001 and investigation of CRISPR therapy, Retrans by REIT, and amyloidosis or <unk> PR amyloidosis.

Leonard S. Schleifer: TLA 2001, investigation, transthyretin amyloid, or ATPR, of concept study utilizing systemically, Bishop Technal, modification, suggest this approach could have broad applicability, of course, a wide Beyond Intelia, collaborations with Elnilum and Destin, helping to form a home generation therapies beyond our broad and diverse and The second quarter represented another landmark in our efforts to combat COVID-19, which unfortunately despite considerable rates of vaccination continues to be a major global health to serve with rise to fulfilling our entire supply We were able to secure emergency use authorization, or our lower 1.2 gram subcutaneous dose, as well as exposure prophylaxia, certain appropriate, are at high risk for disease. Utilization is increasing rapidly and currently more than 50,000 We also know, recovery study showed a 20% reduction risk of death, would not mounted their own immune response, together with supporting data from regenerative study and hospitalized patients at George, Jen Cove has the potential. So what?

This proof of concept study utilizing systemically administered CRISPR technology for genome amplification.

This approach could have broad applicability across a wide range of diseases beyond and telia collaborations with them and Ireland and vegetable are helping to form a whole new pipeline and next generation therapies beyond our broad and diverse antibody pipeline.

The second quarter represented another landmark and our efforts to combat COVID-19.

Which unfortunately, despite considerable rates of vaccination.

<unk> to be a major growth global share.

And with Ryzen cases and emerging variance.

In addition to fulfilling our entire supply contract with the United States Government, we were able to secure emergency use authorization updates.

And our lower 1.2 gram subcutaneous dose as well as for post exposure prophylaxis.

And appropriate patients who are at high risk for disease.

<unk> is increasing rapidly and currently more than 50000 doses ordered per week.

We also announced that the U K recovery study showed a 20% reduction and risk of death and hospitalized patients would not mounted their own immune response.

With these results together with supporting data from Regeneron and studied and hospitalized patients and George will discuss momentarily.

<unk> has the potential and so authorized to be the first treatment for use and a wide spectrum of COVID-19 disease settings from prevention through the hospitalized setting.

George D. Yancopoulos: in a wide spectrum of COVID-19 disease settings from prevention to life, our core business is strong and continues to be diversity, innovative pipe, conditioning regenerant well, and long-term growth. Now I will turn the call over to you. Thank you, Len.

In summary, our core business is strong and continues to diversify.

And our innovative pipeline continues to advance.

<unk> and regeneron and well long term growth.

Now I will turn the call over George.

Thank you Lynn.

We have a lot to talk about this morning, which is all possible because of our regeneron colleagues, who have been working non stop throughout this pandemic.

George D. Yancopoulos: We have a lot to talk about this morning, which is all possible because of our Regenron colleagues, who have been working nonstop throughout this pandemic. And unfortunately, the world is still in the throes of this global COVID-19 pandemic, as the numbers of infected individuals in the United States are climbing again, with nearly 100,000 Americans becoming infected every day. Therefore, I will start with Regen Cove, our monoclon antibody cocktail for COVID-19. In June, the Regen Cove Emergency Use Authorization, or EUA, was updated to include the lower 1.2 gram Regen Cove dose, with both intravenous and subcutaneous administration for non-hospitalized patients.

And unfortunately, the world is still on the throes of this global COVID-19 pandemic as.

And as the numbers of infected individuals and the United States are climbing again with nearly 100000 Americans, becoming infected every day.

Therefore, I will start.

With regeneron with reach and Cobra monoclonal antibody cocktail for COVID-19.

In June the region Cove emergency use authorization or EUA was.

<unk> to include the lower 1.2 gram reach and coke dose with both intravenous and subcutaneous administration for non hospitalized patients.

George D. Yancopoulos: This EUA was supported by Phase 3 data showing that the 1.2 gram dose reduced risk of hospitalization or death by 70%. Just last week, the EUA was further expanded to include utilization in post-exposure prophylaxis for COVID-19 in certain populations and also allows for repeated monthly dosing of RegenCo for high-risk patients, such as the immunocompromised, who are at high risk of ongoing exposure to infected individuals in the same This latest authorization makes Regen Cove the only treatment that is available for both treating infected individuals and also preventing infection in certain settings. However, we would like to emphasize that Regen Cove is not a substitute for vaccination.

This EUA, we supported by phase 3 data showing that the $1.2 gram dose reduce risk of hospitalization or death by 70%.

Just last week. The EUA was further expanded to include utilization and post exposure prophylaxis for COVID-19, and certain populations and also allows for repeated monthly dosing Newbridge and co for high risk patients such as the immuno compromised who are at high risk of ongoing exposure to infected individuals and the same institute.

<unk> setting.

This latest authorization makes region Covid only treatment that is available for both treating infected individuals and also preventing infection and certain incentives we would like to emphasize that region cope is not a substitute for vaccination.

Still under review by the FDA, our additional data, which we believe could broaden and prevention application to pre exposure prophylaxis as well as to extend the treatment paradigm to hospitalized patients. The details of part a of our phase III prophylaxis study and which we assess efficacy and safety of subcutaneous region cope and preventing.

George D. Yancopoulos: Still under review by the FDA are additional data, which we believe could broaden the prevention application to pre-exposure prophylaxis, as well as extend the treatment paradigm to hospitalized patients. The details of Part A of our Phase 3 Prophylaxis study in which we assessed the efficacy and safety of subcutaneous Regen Cope in preventing infection among previously uninfected individuals have just been published today in the New England Journal of Medicine. We believe there is an enormous unmet need to try to protect immunocompromised individuals who have not responded to the vaccine, and we hope that the FDA will agree that our data will support an authorization in this pre-exposure prophylaxis setting.

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<unk> previously uninfected individuals has just been published today and the New England Journal and Medicine.

We believe there is enormous unmet need to try to protect immunocompromised individuals who have not responded to the vaccine and we hope that the FDA will agree that our data will support and authorization and this pre exposure prophylaxis settings.

And for hospitalized patients, we recently reported that region Cove tested as part of the Oxford University basically recovery study met its primary outcome, reducing risk of death by 20% and hospitalized COVID-19 patients lacking and immune response to Sars Covid 2.

George D. Yancopoulos: For hospitalized patients, we recently reported that Regen Cove tested as part of the Oxford University Phase C Recovery Study met its primary outcome, reducing risk of death by 20% in hospitalized COVID-19 patients lacking an immune response to SARS-CoV-2. Data from our own smaller study in hospitalized COVID-19 patients showed similar conclusions, with a 35% reduction in overall mortality in this study, which was limited to earlier stage hospitalized patients with no oxygen or low These collective data from recovery and from our study in hospitalized patients have been shared with regulators. In addition, we are on track to complete the Regent Code BLA submissions in the second half of 2021.

Data from our own smaller study and hospitalized COVID-19 patients.

Showed similar conclusions with 35% reduction and overall mortality in this study, which was limited to earlier stage hospitalized patients with no oxygen or low oxygen support.

These collective data from recovery and from our study in hospitalized patients have been shared with the regulators.

In addition, we are on track to complete the region co BLA submissions and the second half of 2021.

Outside of the United States, our collaborator Roche obtained emergency or temporary pandemic use authorizations for a COVID-19 antibody cocktail.

George D. Yancopoulos: Outside of the United States, our collaborator Roche obtained emergency or temporary pandemic use authorizations for our COVID-19 antibody cocktails, known as Ronaprieve outside the United States in more than 20 countries across the European Union, India, Switzerland, and Canada, with more authorizations expected soon. Japan was the first country to grant formal regulatory approval to its antibody cocktail for COVID-19. Finally, Regen Cove retains potent activity against all known variants of interest, including Delta Varian. For patients at high risk of serious consequences, including many with an inadequate response to vaccines, Regen Cove could be an important option for patients and their physicians for the foreseeable future. Moving on, we discuss ophthalmology.

Known as Ron approved outside the United States and more than 20 countries across the European Union, India, Switzerland, and Canada with more authorizations expected soon Japan was the first country to grant formal regulatory approval to our antibody cocktail for COVID-19.

And finally region code retains potent activity against all known variants of interest, including the Delta bearing.

And for patients and high risk of serious consequences, including many with an inadequate response to vaccines reach and cove could be important option to patients to patients and their physicians for the foreseeable future.

Moving on to ophthalmology and the coming months, we expect data from the phase II study of high dose <unk> and wet AMD. This readout will consist of efficacy assessments on drawing and on other anatomical measures as well as safety on the 8 milligram and the currently approved 2 milligram and fluid recip dose and an 8 week dosing interval.

George D. Yancopoulos: In the coming months, we expect data from the phase two study of high doses of flubricep in wet AMD. This readout will consist of efficacy assessments drawing in other anatomical measures, as well as safety on the 8 milligram and the currently approved 2 milligram of phleibricep dose at an 8-week dosing interval. In the 106 patients dosed in the open label Phase 2 to date, we have not seen any concerning safety signals.

And the 106 patients dosed in the open label Phase 2 to date, we have not seen any concerning safety signals. While the smaller study will not be definitive on durability matches. The phase 2 data will help provide insight into the larger phase III studies, which are testing high dose of <unk> dosing intervals up to 12 and 16 weeks.

George D. Yancopoulos: While this smaller study will not be definitive on durability measures, the Phase 2 data will help provide insights into the larger Phase 3 studies, which are testing high doses of phlybicep dosing intervals out to 12 and 16 weeks.

I'm pleased to announce that the phase III studies and D N.

George D. Yancopoulos: I'm pleased to announce that the phase three studies in DME and AMD have completed enrollment, allowing for phase three data next year. Moving on to DuPixent in our immunology and inflammation portfolio, just last week, we announced that a phase three trial in chronic spontaneous urticaria, or CSU, met primary and all key 24-week secondary endpoints, showing Depixent reduced itch and hive activity scores by nearly half.

And AMD has completed enrollment and allowing for phase III data next year move.

Moving on to do picks and and our immunology and inflammation portfolio just last week, we announced that a phase III trial and chronic spontaneous urticaria, we're CSU met primary and all key 24 week secondary endpoints showing depicts and reduced each and higher activity scores by nearly half. This is the fifth disease.

George D. Yancopoulos: This is the fifth disease in which DuPixen demonstrated positive pivotal trial results, and efficacy in this disease raises the possibility that IL4 and IL13 are critical drivers in diseases not traditionally sought to be driven by type 2 inflammation. We plan to report results from a second trial in CSU patients who are not benefiting from the approved standard of care biologic in early 2022. This positive readout in CSU has continued to build on depictions, efficacy, and safety, demonstrated across other inflammatory diseases.

And which depicts and demonstrated positive pivotal trial results and efficacy in this disease raises the possibility that IL 4 and IL 13 are critical drivers and diseases, not traditionally thought to be driven by type 2 inflammation.

We plan to report results from a second trial and CSU patients, we're not benefiting from the approved standard of care biologic and early 2022.

This positive readout and CSU is continuing to build on depictions efficacy and safety demonstrate demonstrated across other inflammatory diseases and the.

George D. Yancopoulos: In the upcoming months, we also expect results from our confirmatory phase 3B study in adult and adolescent patients with asinophilic esophagitis, as well as read out of a phase three study in Puriigo, Nodulara. Thus far, Depyxinin is improved in patients as young as 6 years old with atopic dermatitis and 12 years old with asthma. Later this year, we will report data from a phase 3 study in preschool children, as young as 6 months, up to 5 years of age, suffering from atopic dermatitis. In asthma, we anticipate a regulatory decision in October for children age 6 to 11 years old in the United States.

The upcoming months, we also expect results from our confirmatory phase III study in adult and adolescent patients with eosinophilic esophagitis as well as readout of a phase III study in Prurigo <unk>.

Thus far and depiction and it is approved and patients as young as 6 years old and atopic dermatitis and 12 years old and asthma. Later this year, we will report data from a phase III study and preschool children as young as 6 months up to 5 years of age suffering from atopic dermatitis and asthma, we anticipate a regulatory decision in October.

For children, aged 6 to 11 years old and the United States.

Moving to our anti interleukin 33 antibody.

George D. Yancopoulos: Moving to our anti-Lucin-3 antibody, it picked up your map. Results of the Phase 2 study in COPD patients were recently published in Lancet Respiratory Medicine. Well, the trial exhibited strong trends in its primary endpoint of exacerbation reduction in the overall population, which did not meet statistical significance. However, a pre-specified subgroup analysis of former smokers with COPD is what accounted for the overall benefit, with no negative subset in the remaining population.

Pick Ya man and.

The results of the Phase 2 study and COPD patients were recently published in lancet respiratory medicine.

Well the trial exhibited strong trends and its primary endpoint of exacerbation reduction and the overall population.

Which did not meet statistical significance, a prespecified subgroup analysis of former smokers with COPD is what accounted for the overall benefit with no negative subset and the remaining population and the Prespecified former smoker subgroup.

George D. Yancopoulos: In the pre-specified former smoker subgroup, picumab demonstrated a 42% reduction in exacerbations and improvement in lung function of 0.09 liters compared to placebo, with both endpoints reaching nominal statistical significance. Moreover, the publication includes genetic analyses that support a protective role for interleucin 33 in COPD. Based on these results, we and Sanofi are assessing its potential to picumab in two phase three studies focused on the former smoker population with COPD.

Pick your Mab demonstrated a 42% reduction in exacerbations and improvement and lung function of.

<unk> 9 leaders compared to placebo with both end points, reaching nominal statistical significance.

Moreover, the publication includes genetic analyses that support a protective role for interleukin 33 in COPD and based on these results, we and saying if you are assessing the potential of the day picky Mab in 2 phase III studies focused on the former smoker population with COPD I should also remind you that we have 2 ongoing studies with phase 2.

George D. Yancopoulos: I should also remind you that we have two ongoing phase three studies with DuPICT in a complementary COPD population. We're also progressing our novel approaches to treat allergies by using cocktails of monoclonal antibodies to directly bind and inactivate allergens, which have produced robust results in Phase 2 studies. Results of the initial Phase 3 study of our antibody cocktail against Birch allergy caused by the BET V1 allergen are expected later this year. The first phase 3 study of an antibody cocktail for cat allergies caused by the FFELD1 allergen is now open for enrollment.

Ongoing phase III studies, we do pixel and a complementary <unk>.

P D population.

We're also progressing our novel approaches to treat allergies by using cocktails of monoclonal antibodies to directly bind and inactivate allergists, we have which have produced robust results in phase II studies results of the initial phase III study of our antibody cocktail against Birch LG caused by the bad day, 1 Allergan are.

<unk> later this year.

The first phase III study of an antibody cocktail for cat allergy caused by the cell D..1 LG is now opened for enrollment.

We are enthusiastic about these innovative additions to our inflammation and immunology portfolio.

George D. Yancopoulos: We are enthusiastic about these innovative additions to our inflammation and immunology portfolio. In oncology, following its recent approvals in the United States for certain first-line, non-small cell lung cancer, and certain advanced basal cell carcinoma patients, TIE was subsequently approved in the EU for these settings. Furthermore, compelling overall survival data and second-line cervical cancer patients were presented at an esmo virtual plenary in May, with regulatory submissions to the FDA and EMA planned for this year.

In oncology following its recent approvals and the United States for certain and first line non small cell lung cancer and certain advanced basal cell carcinoma patients of tie was subsequently approved in the EU for these settings further.

Furthermore, compelling overall survival data in second line cervical cancer patients were presented and and ESMO virtual plenary and may with regulatory submissions to the FDA and EMA and plan for this year.

For lung cancer, we're pleased to report today and in our phase III trial, comparing with tile plus standard chemotherapy versus chemotherapy alone. The independent data monitoring committee recommended halting the trial for efficacy at the second interim analysis.

George D. Yancopoulos: For lung cancer, we are pleased to report today that in our Phase 3 trial comparing TIO plus standard chemotherapy versus chemotherapy alone, the independent data monitoring committee recommended halting the trial for efficacy at the second interim analysis. Tile plus chemotherapy significantly improved overall survival, as well as progression-free survival compared to chemotherapy alone in first-line locally advanced or metastatic non-small cell lung cancer.

Tayo plus chemotherapy significantly improved overall survival as well as progression free survival compared to chemotherapy alone in first line and locally advanced or metastatic non small cell lung cancer.

With these data <unk> is now the second PD, 1 targeting antibody that has been able to demonstrate significant overall survival benefit both as a monotherapy as well as in combination with chemotherapy for treating advanced lung cancer with this validation of Tayo provides an important foundation for our broad and multi <unk>.

George D. Yancopoulos: With these data, Leptayo is now the second PD1 targeting antibody that has been able to demonstrate a significant overall survival benefit, both as monotherapy as well as in combination with chemotherapy for treating advanced lung cancer. With this validation, Leptia provides an important foundation for a broad and multifaceted approach to address the great unmet need that patients with cancer in general and lung cancer in particular still face. In addition to our liptyle monotherapy and chemo combination opportunities in lung cancer, we are developing several bispecifics.

<unk> approach to address the great unmet need that patients with cancer in general and lung cancer and particular still face.

In addition to our lip tie on monotherapy and chemo combination opportunities in lung cancer, we are developing several bi specifics.

Our egfr by CD 20, co stim and low Tayo combination is in dose escalation for lung and other advanced cancers are met by met by specific antibody is enrolling non small cell lung cancer patients with a broad selection of patients, including met exon 14 gene mutation gene amplification and or.

George D. Yancopoulos: Our EGFR by CD28 COSTEM and Leptio combination is in dose escalation for lung and other advanced cancers. Our met-by-met bi-specific antibody is enrolling non-small lung cancer patients with a broad selection of patients, including met-exon-14 gene mutation, gene amplification, and or elevated met protein X.

Net protein expression and as we introduced at our <unk> Investor event, our first antibody drug conjugate met by net ADC is poised to enter the clinic in the coming months with a focus on patients with net over expressing cancers, including lung cancer, where met over expression occurs and as many as 25% patients.

George D. Yancopoulos: And as we introduced at our ASCO investor event, our first antibody drug conjugate, Met by Med ADC, is poised to enter the clinic in the coming months with a focus on patients with met overexpressing cancers, including lung cancer, where met overexpression occurs in as many as 25% of patients. In terms of building on the potential of Taya with combinations in skin cancer, we recently announced new clinical data for the combination of Taya with anelam The combination demonstrated a 67% response rate in PD1 or PDL1-9A patients with potential for a more favorable safety profile than with anti-CTLA4 PD1 combinations. Plan to initiate a phase three study of phyanelomab and lip tau as a first-line treatment for advanced melanoma in 2022.

In terms of building on the potential of tire with combinations and skin cancer, We recently announced new clinical data for the combination of low tier with the aniline map, our lag 3 inhibitor and advanced melanoma at the <unk> annual meeting in June the combination demonstrated a 67% response rate and PD, 1 or PD lone naive patients with potential for.

On a more favorable safety profile than with anti <unk> 4 PD 1 combinations, we plan to initiate a phase III study of <unk> and the map and look Tau as a first line treatment for advanced melanoma.

In 2022.

Ovarian cancer is the first tumor type for which we are clinically testing 3 powerful combination approaches first on <unk> by <unk> Bispecific with lip Tayo, where we hope to share initial data next year next on <unk> by CD 28, co stim Bispecific with lip tile and third our novel combination of the <unk>, 3 and Kosta and <unk>.

George D. Yancopoulos: Well, Vyran cancer is the first tumor type for which we are clinically testing three powerful combination approaches. First, our MUXXX-X-X-Ti-Bis-specific combination with Lip-Tio, which we hope to share initial data next year. Next, our MUX-16 by CD-28, Coastim-Bis-Pacific combination with Lip-Tio.

George D. Yancopoulos: And third, our novel combination of the CD3 and Coast-M-Bis-specific, for which we have now dosed the first patient. This latter combination of two bispecifics of two different classes has the potential to be a novel and disruptive approach to the treatment of solid tumors. Rounding out my commentary on solid tumors, our PSMA by CD28 program and prostate cancer continues in dose escalation with liptya, and we hope to share initial data next year. As we mentioned previously, we are planning on introducing a PSMA by CD3 bi-specific to the clinic later this year, providing another unique experimental combination for prostate cancer treatment, a tumor viewed as non-responsive currently to available immunotherapy. Moving on to hematologic cancers, starting with lymphoma.

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And for which we have now dosed. The first patient. This latter combination of 2 bi specifics of 2 different classes has potential to be a novel and disruptive approach to the treatment of solid tumors.

Rounding out my commentary and solid tumors are P. SMA by CD 20 program and prostate cancer continues in dose escalation with lip tile and we hope to share initial data next year. As we mentioned previously we are planning on introducing a P. SMA by <unk> 3 by specific to the clinic later this year, providing another unique experimental combination.

And for prostate cancer treatment of tumor viewed as non responsive currently 2 available immunotherapies.

Moving on to hematologic cancers, and starting with <unk> lymphoma.

George D. Yancopoulos: Arjunctenetamab, our CD20 by CD3 by-specific antibody, has demonstrated encouraging efficacy and durability of responses in hard-to-treat patient populations. We have resumed enrollment in the potentially pivotal phase two program in folliculum phyloomoma and diffused large-beceal lymphoma, with lifting of the partial clinical hold following protocol amendments for a modified step-up dosing protocol. Later this year, we plan to initiate testing of the Archernextamab subcutaneous formulation, and next year we plan to initiate the Phase 3 program as well as combination trials with our lympho

<unk>, our CD 20 by CD, 3 Bispecific has demonstrated encouraging efficacy and durability of responses and hard to treat patient populations, we have resumed enrollment and on.

Our potentially pivotal phase II program, and Follicular lymphoma, and diffuse large b cell lymphoma with lifting of the partial clinical hold following protocol amendments for modified step up dosing protocol later this year, we plan to initiate testing of the next.

Next day May a subcutaneous formulation and next year, we plan to initiate the phase III program as well as combination trials with our lymphoma specific coast and by specific.

And multiple myeloma are <unk> by <unk> Bispecific is on track to complete enrollment in a potentially pivotal phase II study next year. We will also initiate studies are valuing a subcutaneous formulation and combinations with standard of care.

George D. Yancopoulos: In multiple myeloma, our BUSMA by C3 BISP specific is on track to complete enrollment in a potentially pivotal phase two study next year. We will also initiate studies about a subcutaneous formulation and combinations with standard of care. With our unique position to mix and match multiple modalities and targets, with the goal of deepening the responses we are already observing with our BCMA by C3 B-specific, we are on track to start a combination study with the Kostin Bic for multiple myeloma next year. I would like to conclude with our Regeneron, Genetics, Medicine, Eff.

With our unique position to mix and match multiple modalities and targets with the goal of deepening the responses. We are already observing with our be CMA by <unk> 3 by specific we are on track to start a combination study with the coast and by specific for multiple myeloma next year.

I would like to conclude with our Regeneron genetics medicines efforts as you know these efforts start with our Regeneron genetics center and its ability to genetically identify and validate new disease targets and is coupled with emerging gene based therapeutic solutions to address these targets, including CRISPR based technologies with <unk>.

George D. Yancopoulos: As you know, these efforts start with our Regeneron Genetic Center and its ability to genetically identify and validate new disease targets, and it's coupled with emerging gene-based therapeutic solutions to address these targets, including CRISPR-based technologies with our collaborator in Telia, S-IrNA technologies with L NILA, as well as viral gene delivery technologies we are developing in-house. The Regeneron Genetic Center continues to emerge as a world leader in human and in defining genetic variance that can either be protective or causative for human disease.

Our collaborator and Telia SA RNA technologies without an island as well as viral gene delivery technologies, we are developing in house. The Regeneron genetic center continues to emerge as a world leader and human sequencing and and defining genetic variance that can either be protective or causative for human disease.

Most recently identifying a major new gene target that protects against obesity as described and a high profile publication and science last month for this newly discovered target. We're deploying several strategies to develop new classes of potential therapeutics to fight obesity and potentially type 2 diabetes.

George D. Yancopoulos: Most recently, identifying a major new gene target that protects against obesity, as described in a high-profile publication in Science last month. For this newly discovered target, we are deploying several strategies to develop new classes of potential therapeutics to fight obesity and potentially type 2 diabetes. In terms of progress with our gene-based therapeutics approaches, together with Intellia, we recently announced positive clinical data for the first ever systemically delivered CRISB-based G knockout in human patients. In the first six patients with transthyrin amyloidosis, with TTR amelodosis, a single systemic treatment led to a dose-dependent reduction in the disease-causing protein, with no serious adverse events observed through day 28.

In terms of progress with our gene based therapeutics approaches together with the Intel you, we recently announced positive clinical data for the first ever systemically delivered CRISPR based gene knockout and human patients and the first 6 patients with transfer REIT and amyloidosis with GTR amyloidosis, a single systemic treatment.

Led to dose dependent reduction and the disease, causing protein with no serious adverse events observed through day 28. This proof of concept clinical data increases the probability of success for both our Nokia as well as our insertion CRISPR based programs unlocking the potential of many future possibilities for Intel here and.

George D. Yancopoulos: This proof-of-concept clinical data increases the probability of success for both our knockout as well as our insertion CRISPR-based programs, unlocking the potential of many future possibilities for Intellia and Regeneron. Currently, we're evaluating more than 20 preclinical programs under this collaboration, and Regeneron has the rights to develop up to 15 invivial products with Intelli. Regarding our efforts with El Nileum on an SIRNA for a novel Nash target identified by the Regeneron Genetic Center, we are hoping to see initial healthy volunteer data by the end of this year.

Regeneron.

Currently we are evaluating more than 20 preclinical programs under this collaboration and Regeneron has the rights to develop up to 15 in vivo products within <unk>.

Regarding our efforts with <unk> and island on and SA RNA for a novel Nash target identified by the Regeneron Genetics Center, we are hoping to see initial healthy volunteer data by the end of this year. This 2 part first and human study is now enrolling Nash patients. We are currently evaluating about 20 preclinical programs under this collaboration and reach.

George D. Yancopoulos: This two-part, first in human study is now enrolling Nash. We are currently evaluating about 20 preclinical programs under this collaboration, and Regenron has rights to develop up to 30 products with L Nylon. With that brief glimpse into the future of genetic medicines, I would like to turn the call over to Mary.

General and has rights to develop up to 30 products without now.

With that brief glimpse into the future of genetics medicines, I would like to turn the call over to Murray.

Thank you George our business performance and the second quarter reflects robust momentum competitive strength and focused execution across our commercial portfolio. Our inland medicines continue to thrive and our ongoing launches are progressing to plan, providing a platform for diversified growth first I'll highlight our efforts accordingly genco.

Mary: Thank you, George. Our business performance in the second quarter reflects robust momentum, competitive strength, and focused execution across our commercial portfolio. Our inline medicines continue to thrive in our ongoing launches or are progressing to plan, providing a platform for diversified growth. First, I will highlight our effort supporting Regencove, our COVID-19 antibody cocktail, which is available under emergency use authorization by the FDA. In the second quarter, U.S. net sales were 2.6 billion as a result of fulfilling our second contract with the U.S. government.

19 antibody called <unk>, which is available under emergency use authorization by the FDA and the second quarter U S. Net sales were $2.6 billion as a result of fulfilling our second contract with the U S government.

Mary: There is a significant ongoing need for effective treatments against COVID-19. As Lenz said, Regencove utilization has recently accelerated and is now trending well over 50,000 doses ordered weekly. Uptake is driven by growing recognition of the importance of antibody cocktail treatment, focused educational efforts, and competitive dynamics favoring Regencove. We continue to work closely with all key stakeholders to increase Regencove utilization and support hospitals and administration sites to reduce bottlenecks. The Regencove antibody cocktail is both FDA-authorized and NIH recommended and retains potency against known variants. We've also expanded our efforts. Following the recent post-exposure prophylaxis authorization, the first for an antibody therapy in this setting, beyond Regen Cove, our core portfolio performed very well in the second quarter.

<unk> ongoing need for effective treatments against COVID-19, as Len said free Genco of utilization has recently accelerated and is now trending well over 50000 doses ordered weakly uptick is driven by growing recognition of the importance of the antibody cocktail treatment focused educational efforts and <unk>.

<unk> of dynamics favoring the genco.

We need to work closely with all key stakeholders to increase for Genco and utilization and support hospitals and administration sites to reduce bottlenecks and free Genco antibody cocktail as both FDA authorized and NIH recommended and retains potency against known variants and we've also expanded our efforts.

And the recent post exposure prophylaxis authorization.

The first 4 and antibody therapy in this setting the army Jenkins, our corporate portfolio performed very well on the second quarter, starting with Eylea second quarter Global net sales grew 33% year over year to over $2.3 billion and the U S. Eylea net sales grew 28% year over year Q1 point.

Mary: Starting with ILEA, second quarter global net sales grew 33% year-over-year to over 2.3 billion. In the U.S., Ilea net sales grew 28% year-over-year to 1.42 billion, driven by underlying demand, category share gains, and a favorable comparison versus the second quarter of 2020. ILEA is the anti-vege of category growth leader and preferred treatment option.

And for 2 billion driven by underlying demand category share gains and a favorable comparison versus the second quarter of 2020 Eylea is the anti VEGF category growth leader and preferred treatment option. As a reminder, eylea sets a high bar for efficacy and safety with more than 40 million injections administered world.

Mary: As a reminder, Ilya sets a high bar for efficacy and safety with more than 40 million injections administered worldwide in a therapeutic category where patient vision and well-being are paramount. Ilya continues to capture market and competitive share, securing nearly 50% of the overall category and 75% of the branded category. Overall demand is improving, with increased patient flow and a return to pre-pundemic levels of new patient visits. Patients who may have delayed seeing the retina specialist are now seeking treatment.

And a therapeutic category, where patients vision and wellbeing are paramount.

<unk> continues to capture market and competitive share securing nearly 50% of the overall category and 75% other branded category overall demand is improving with increased patient flow and return to pre pandemic levels of new patient visits per.

And as you may have delayed seen the retina specialists are now seeking treatment with this backdrop, we are accelerating promotional efforts to address the significant unmet needs and diabetic eye disease, we are confident and regeneron and ongoing leadership position and retinal diseases based on <unk> competitive advantages and future opportunities, including our high dose.

Mary: With this backdrop, we are accelerating promotional efforts to address the significant unmet needs and diabetic-I disease. We are confident in Regeneron's ongoing leadership position in retinaldial diseases based on ILEA's competitive advantages and future opportunities, including our high-dose program. Turning to Libthayo, where second quarter global medicine sales grew to 117 million, and U.S. net sales grew 23% to 78 million.

Graham turning to mid tier or second quarter global net sales grew to $117 million and you.

Net sales grew 23% to $78 million as expected.

Mary: As expected, at this early stage of new indication launches, the vast majority of sales come from advanced cutaneous squamous cell carcinoma, where Leptio is the number one systemic treatment despite new in-class competition. Our launches in both advanced non-small cell lung cancer and basal cell carcinoma, or BCC, are progressing to plan. In BCC, Lib Tio brand awareness is a new cell cancer.

At this early stage of new indication launches the vast majority of sales come from advanced cutaneous squamous cell carcinoma, where lead time is the number 1 systemic treatment, despite new and class competition.

Launches in both advanced non small cell lung cancer and basal cell carcinoma, or BCC are progressing to plan and BCC led tire brand awareness is high on treating oncologists. We are encouraged by meaningful patient starts and the second quarter as <unk> becomes a standard of care, we're also making considerable progress and lung cancer.

Mary: is high among treating oncologists. We are encouraged by meaningful patient starts in the second quarter as Lib TIO becomes the standard of care.

Mary: We're also making considerable progress in lung cancer, where efforts are focused on establishing libtio and our monotherapy indication, which will be an important foundation for our potential future chemotherapy combination launch, which will be based on the data announced today. Our expanded field force is now fully deployed and securing early successes with treating physicians. We're raising brand awareness, progressing formulary positioning, and payer coverage. Lung cancer thought leaders recognized Leptio's clinical differentiation, highlighting the rapid response rates and epicsine patients with clinically stable brain metastases or high PDL1 expression. In this highly competitive market, we remain focused on differentiating Leptio and increasing physician experience. Today's exciting chemotherapy combination news has the potential to dramatically expand the patient opportunity for Liptyo in non-small cell lung cancer.

Efforts are focused on establishing the tile and our monotherapy indication.

And it will be important foundation for potential future chemotherapy combination launch, which would be based on the data announced today. Our expanded sales force is now fully deployed and securing early successes with treating physicians.

And brand awareness progressing formulary positioning and payer coverage lung cancer thought leaders recognize <unk> clinical differentiation and highlighting the rapid response rates and efficacy in patients with clinically stable brain metastases or high PD lone expression and.

This highly competitive market, we remain focused on differential with differentiating the tayo and increasing physician experience.

Today's exciting chemotherapy combination is has the potential to dramatically expand the patient opportunity for lip tayo and.

Non small cell lung cancer, turning now to <unk>, which was launched earlier this year and ultra rare homozygous familial hypercholesterolemia key thought leaders recognize the benefits of of cancer, which delivers on efficacy safety and tolerability and a market where many patients have struggled to stay on therapy and the <unk>.

Mary: Turning now to Epchiza, which was launched earlier this year in ultra-rare homozygous familial hypocholesteremia, key thought leaders recognize the benefits of Avkisa, which delivers on efficacy, safety, and tolerability in a market where many patients have struggled to stay on therapy in the face of life-threatening LDL cholesterol levels.

<unk> of life, threatening LDL cholesterol levels, we're encouraged by early initiations across switch and new to category patients and can see a future where atkins it becomes the standard of care moving to depicts and global net sales from the second quarter were $1.5 billion growing 59% compared to the prior year and.

Mary: We're encouraged by early initiations across switch and new to category patients and can see a future where Kesa becomes the standard of care. Moving to DePixant, global net sales in the second quarter were $1.5 billion, growing 59% compared to the prior year. In the U.S., net sales grew 49% to $1.15 billion, driven by broad-based growth across all approved indications. New patient starts are steadily growing and are above pre-COVID levels. In atopic dermatitis, prescribing trends are strong across the spectrum of moderate to severe disease, including adolescents and pediatric patients.

U S. Net sales grew 49% to 1.15 billion driven by broad based growth across all approved indications new patient starts are steadily growing and are above pre COVID-19 levels and atopic dermatitis prescribing trends are strong across the spectrum of moderate to severe disease.

Including adolescents and pediatric patients.

Mary: There is significant and sustained growth opportunity for DePixant in a market where it is the number one dermatologist prescribed biologic. This is based on its well-established efficacy and safety profile, broad label for patients as young as six years old, and an unmatched real-world physician and patient experience. In addition, as George outlined, we see exciting future opportunities in dermatology starting with CSU. Depixant is the leading biologic and respiratory disease company, poised to capture meaningful growth now and in the future.

Michigan and sustained growth opportunity for <unk>.

And a market where it is the number 1 dermatologists dermatologist prescribed biologic and this is based on its well established efficacy and safety profile broad label for patients as Julian and 6 years old and unmatched real world physician and patient experience and addition, as George outlined we see and exciting few.

Sure opportunity opportunities and dermatology starting with CSU.

<unk> is the leading biologic and respiratory disease poised to capture meaningful growth now and in the future or asthma results outpace recent competitive biological launches launch preparations are underway and the pediatric asthma setting with the first regulatory approval expected in the U S. This October and these are <unk>.

Mary: Our asthma results outpaced recent competitive biological launches. Launch preparations are underway in the pediatric asthma setting, with the first regulatory approval expected in the U.S. this October. In nasal polyps, there's high demand among ENTs and allergists, with patients initiated regardless of prior surgery. In summary, we delivered strong performance across our brands with current and potential future launches on track to deliver sustained growth. Now I'll turn the call over to Bob.

Polyps, there's high demand among e&ps and allergists with patients initiated regardless of prior surgery and summary, we delivered strong performance across our brands with current and potential future launches on track to deliver sustained growth now I will turn the call over to Bob.

Bob: Thanks, Marion, and good morning and afternoon.

Thanks, Marion and good morning, and afternoon to everyone listening to the call my comments today on Regeneron and financial results and outlook will be on a non-GAAP basis, where applicable and the second quarter. Our core business continued to deliver impressive year over year growth bolstered by strong execution across the company to deliver the full 125.

Bob: This afternoon to everyone listening to the call. My comments today on Regeneron's financial results and outlook will be on a non-gap basis where applicable. In the second quarter, our core business continued to deliver impressive year-over-year growth, bolstered by strong execution across the company to deliver the full 1.25 million dose contract to the U.S. government for Regencove. For the second quarter, total revenues grew 163% year over year to 5.1 billion.

Millions dos contract to the U S government for rigid Cove.

For the second quarter total revenues grew 163% year over year to $5.1 billion, excluding revenues related to the COVID-19 antibody cocktail total revenue grew 22% versus the prior year total diluted net income per share grew 260% year over year to $25.80.

Bob: Excluding revenues related to the COVID-19 antibody cocktail, total revenue grew 22% versus the prior year. Total diluted net income per share grew 260% year over year to $25.80 on net income of $2.9 billion. In the second quarter, we recognized 2.6 billion of U.S. Regencove sales, representing the vast majority of revenue related to the delivery of 1.25 million doses to the U.S. government. Due to revenue recognition rules, a residual 34 million of net product sales for doses delivered under this contract will be recorded in the third quarter. Given the delivery of these doses to the U.S. government and current utilization rates, we anticipate the current U.S. government supply will be exhausted by the end of the year.

On net income of $2.9 billion.

In the second quarter, we recognized $2.6 billion of U S. Virgin Coke sales, representing the vast majority of revenue related to the delivery of 1 to 5 million doses.

To the U S government due to revenue recognition rules, a residual 34 million of net product sales for doses delivered under this contract will be recorded in the third quarter given the delivery of these doses to the U S government and current utilization rates, we anticipate the current U S government supply will be exhausted by the end of the year, we do not.

Expect to record substantial additional sales this year and the U S and less the number of cases and related utilization continue to increase exponentially.

I will now move to collaboration revenues, which were $955 million and the second quarter of 2021 as compared to $513 million and the second quarter of 2020, let me begin with the Roche collaboration.

Bob: We do not expect to record substantial additional sales this year in the U.S. unless the number of cases and related utilization continue to exponentially increase. I will now move to collaboration revenues, which were 955 million in the second quarter of 2021, as compared to 513 million in the second quarter of 2020. Let me begin with the Roche Collaboration. X-S sales of the COVID antibody cocktail known as Rone-Apreve outside of the U.S. were 470 million, as reported to us by Roche.

Ex U S sales of the Covid antibody cocktail known as rone approved outside of the U S were $470 million as reported to us by Roche, we recorded $168 million and Roche collaboration revenue for our share of profits from Roche and sale of Rona <unk>, which is now available are approved and more than 20 countries.

With new Covid cases on the rise globally, we expect the Rona.

Continue to be a meaningful revenue contributor in 2021.

With regard to our Bayer collaboration ex U S. Eylea net product sales reported to us by Bayer were $904 million for the second quarter of 2021, representing growth of 41% on a reported basis and 31% on a constant currency basis as a result of broad market recovery and a favorable comparison versus the <unk>.

Bob: We recorded 168 million in Roche collaboration revenue for our share of profits from Roche's sale of Rone-A-Prieve, which is now available and is approved in more than 20 countries. With new COVID cases on the rise globally, we expect Rone-A-Prieve will continue to be a meaningful revenue contributor in 2021.

Prior year total Bayer collaboration revenue was $349 million of which we recorded $335 million for our share of net profit from Eylea sales outside the U S.

Bob: With regard to our Bayer collaboration, XUS ILEA net product sales reported to us by Bayer were $904 million for the second quarter of 2021, representing growth of 41% on a reported basis and 31% on a constant currency basis, as a result of broad market recovery in a favorable comparison versus the prior year. Total Bayer collaboration revenue was $349 million, of which we recorded $335 million for our share of net profits from ILEA sales outside the U.S.

Bob: Finally, total Sanofi collaboration revenue was $438 million in the second quarter of 2021. Our share of the profits from the commercialization of Pixson and Kevzar was 328 million, which nearly doubled when compared to profits of 172 million in the prior year. Other revenue was $46 million in the second quarter compared to $212 million in the prior year. The decrease is primarily related to non-recurring reimbursements from Florida in 2020 for the development of COVID-19 for Ebola treatments.

Okay and higher headcount.

Cost of goods sold increase vs. The prior year from $93 million to $514 million, primarily due to adjourn Cove manufacturing costs.

Finally, the effective tax rate was 17% and the second quarter of 2021, reflecting the impact of Virgin Cope sales, which are taxed at the U S statutory rape.

Bob: We continue to expect 2021 other revenue to be less than half of what was recorded in 2020 on a full-year basis. Moving on to our operating performance. R&D increased 11% year-over-year to 643 million, primarily due to continued clinical development costs for our Regencove antibody cocktail and higher head count to support our expanding. Next, SGNA expense increased 21% year over year to 365 million due to costs related to COVID-19-related activities, launch investments for Leptio, growth initiatives for ILEA, and higher headcount. Cost to good sold increased versus the prior year, Finally, the effective tax rate was 17% in the second quarter of 2021, reflecting the impact of Regen Co sales, which are taxed at the U.S. statutory rate, shifting the cash flow in the balance sheet.

Shifting to cash flow and the balance sheet and the second quarter of 2021, Regeneron generated 478 million and free cash flow and ended the quarter with cash and marketable securities less debt of 5.1 billion. We received the full 2.625 billion of cash associated with completion of our second rich and Coke contract with.

The U S government in July.

As the business continues its strong performance, we are reiterating our capital allocation priorities of investing and internal R&D funding strategic external R&D partnerships and returning cash to shareholders occur.

Accordingly, and July we announced the new 1.8 billion dollar expansion of our Tarrytown facilities, primarily directed toward additional internal R&D operations and capabilities. We also continue to advance our next generation technology partnerships with companies like and Telia and Alnylam, which are beginning to bear fruit as Tara.

Bob: In the second quarter of 2021, Regeneron generated $478 million in free cash flow and ended the quarter with cash and marketable securities less debt of $5.1 billion. We received the full $2.625 billion of cash associated with the completion of our second Regencove contract with the U.S. government in July. As the business continues its strong performance, we are reiterating our capital allocation priorities of investing in internal R&D, funding strategic external R&D partnerships, and returning cash to shareholders.

And gets gets selected and programs move forward into development finally, and the second quarter, we repurchased $289 million of our shares and we remain opportunistic buyers and the market.

To conclude I'd like to provide select updates tour of 2021 guidance and complete summary of our latest full year guidance is available and our press release published earlier this morning.

And we were updating our full year 2021 guidance for SG&A to be and the range of 1.54 billion to 1.62 billion. The change is related to increased efforts and the second half of <unk>.

We are also revising our full year 2021 guidance for R&D to be and the range of 2.65 billion to 2.75 billion to change is driven by lower than expected spend on Virgin cold.

Bob: Accordingly, in July, we announced the new $1.8 billion expansion of our Tarry Town facilities, primarily directed toward additional internal R&D operations and capabilities. We also continue to advance our next-generation technology partnerships with companies like Intellia and El Nilem, which are beginning to bear fruit as targets get selected and programs move forward into development. Finally, in the second quarter, we repurchased $289 million of our shares, and we remain opportunistic buyers in the market.

Finally, we now expect our full year 2021, non-GAAP effective tax rate guidance that be in the range of 14 to 16 per cent driven by higher sales and Virgin Cove, which as I said are taxed at the U S statutory right.

And conclusion regeneron performed exceptionally well on the second quarter with the core business continuing on a strong growth trajectory as we invest and are diverse and differentiated pipeline for long term sustainable growth with that I'd like to turn the call back to Justin Thank.

Bob: To conclude, I'd like to provide select updates to our 2021 guidance. A complete summary of our latest full-year guidance is available in our press release published earlier this morning. We were updating our full year 2021 guidance for SG&A to be in the range of $1.54 billion to 1.62 billion. This change is related to increased efforts in the second half for Regenia. We are also revising our full year 2021 guidance for R&D to be in the range of $2.65 billion to $2.75 billion.

Thank you Bob to me and that concludes our prepared remarks, we'd now like to open the call for Q&A to ensure we are able to address as many callers as possible. We'll answer 1 question from each color prior to moving to the next please go ahead and tomato.

Thank you.

To ask a question you would need to pressed on 1 on your telephone.

<unk>.

Dry your question and press the pound Ah half tea, please standby and while we compiled Q&A roster.

And.

Yeah first question cast on a line of Chris Raymond What Piper Sandler Your line is open.

Bob: The change is driven by lower than expected spend on Regenco. Finally, we now expect our full year 2021 non-gap effective tax rate guidance to be in the range of 14 to 16% driven by higher sales of Regencove, which, as I said, is taxed at the U.S. statutory rate. In conclusion, Regeneron performed exceptionally well in the second quarter, with the core business continuing on a strong growth trajectory as we invest in our diverse and differentiated pipeline for long-term sustainable growth.

Hey, Thanks for letting me and ask a question interest on the.

The the empower study guys Uhm, we're getting a few questions and you know the cop to Keytruda I I know it sounds it's hard to compare across trials, but.

And it's a a bit tricky because and power had both screamed and non screams.

But you you're 22 month media and O S is right on top of the the non squamous experience for Keytruda and I'm sure you know you're gonna want to save you know a lot of detailed for the full presentation, but can you maybe give us a sense of the balance here between squamous and that's why I'm as patients.

Bob: With that, I'd like to turn the call back to Jeff. Bob, to meia, that concludes our prepared remarks. We'd now like to open the call for Q&A. To ensure we are able to address as many callers as possible, we'll answer one question from each caller prior to moving to the next. Please go ahead, Tamia. Thank you.

As you said I mean, we're gonna provide the details and.

And and in future.

Location and or conferences I think it's important to note as you said, it's very difficult to compare across studies done years apart and.

Tamia: Thank you. If you would like to ask a question, you will need to press star 1 on your telephone. To withdraw your question, press the pound or hash key. Please stand by while we compile the Q&A roster. Your first question comes from the line of Chris Raymond, Whit Piper Sandler. Your line is open.

And especially when we allowed classes of patients that were not previously allowed and other studies and so forth as you pointed out the median survival numbers on right on top of each other and.

But as you also point out we had 2 different subtypes and this study I I can comment and our preliminary analyses and these remain to be fully validated and so forth and 1 of the subtypes or hazard ratio was better than what was observed with the Keytruda studies and the other 1 it was worse and and it's.

Christopher Joseph Raymond: Hey, thanks for letting me ask a question. Just on the Empower study, guys, we're getting a few questions, you know, about the comp with Ketruda. I know it's hard to compare across trials, but it's a bit tricky because Empower had both squames and non-squames. But your 22-month median OS is right on top of the non-squamous experience for Ketruda. And I'm sure, you know, you're going to want to save a lot of detail for the full presentation.

Important to point out that these things bounce around and these cross study comparisons as you know and other settings with you tried to do cross country across that'd comparisons for example, and you compare are mono therapy results.

George D. Yancopoulos: But can you maybe give us a sense of the balance here between squamous and non-squamous patients? As you said, I mean, we're going to provide the details in future publications and our conferences. I think it's important to note, as you said, it's very difficult to compare cross-studies done years apart, especially when we allowed classes of patients that were not previously allowed in other studies and so forth. As you pointed out, the median survival numbers are right on top of each other. But, as you also point out, we had two different subtypes in this study. I can comment on our preliminary analyses, and these remain to be fully validated, and so forth.

And the greater than 50 per cent PDL population it looks like our numbers are substantially better and the and the skin and particularly the CFCC comparisons they're better. So these things balance around it's always hard to do these things, but I think the important thing to point out is that in this field and lung cancer very few have hit.

And both monotherapy greater than 50 per cent and and chemo combination all comers.

Remind you that uhm Devo, James and most of the P. D. L. Once did so right now there's only 2 P. D..1 antibodies it stand alone having demonstrated overall survival benefit both and the mono therapy setting as well as now and the chemo combination setting and I think that's really well positions libtayo and across.

George D. Yancopoulos: In one of the subtypes, our hazard ratio was better than what was observed with the Kachuta studies, and in the other one, it was worse. And it's important to point out that these things bounce around in these cross-study comparisons. As you know, in other settings, if you try to do cross-country, cross-study comparisons, for example, when you compare our monotherapy results in the greater than 50% PDL population, it looks like our numbers are substantially better on the skin, and particularly in CSCC comparisons, they're better. So these things bounce around. It's always hard to do these things.

And all the studies I think it's.

The definitive conclusion is that it's a very active molecule that looks at least as active as any other agents out there.

Yeah. Thanks George question. Please.

Yeah and that question comes from a line of Cory Cats M O J P. Morgan Your line is open.

Hi, This is Gavin on for court and thanks for taking our questions just to follow up on the last question.

And terms you know the longer term outlook for Libtayo and long specifically you talked about the Iowa, Iowa combo has kind of the differentiating strategy and I'm. Just wondering if you know you're maintaining that position or with the results and hand on today that view has changed.

George D. Yancopoulos: But I think the important thing to point out is that in this field, in lung cancer, very few have hit in monotherapy greater than 50% and in chemo combination all comers, reminding you that Abdevojant and most of the PDL once did. So right now, there are only two PD1 antibodies that stand alone, having demonstrated overall survival benefit, both in the monotherapy setting, as well as now in the chemo combination setting. I think this really well positions Leptio, and across all the studies, I think the definitive conclusion is that it's a very active molecule that looks at least as active as any other agents out there. Thanks, Chuck.

Thank you.

Yeah, well, we think that certainly we should be competitive right now the opportunity.

For this class, which is obviously dominated by Keytruda right now because up until now it was the only agent that had this strong data across the spectrum of mono therapy and chemo combination.

We think that now we can be legitimate competitors here and the lung cancer space, we see our combination opportunities as future growth and differentiator opportunities, but in the short term, we expect to be a viable competitor and now with these data and and the future we hope to use the combinations to to.

Tamia: Your next question comes from a line from Corey Kazimove with AP Morgan. Your line is open.

Len Schleifer: Hi, this is Gavinon on behalf of Corey. Thanks for taking our question. Just a follow up on the last question. In terms of, you know, the longer-term outlook for Libthio in the lungs specifically, you've talked

Take the standard of care and elevate you know results to another level.

Thanksgiving Your next question please.

Your next question comes from the line up Ronnie Gal, What Bernstein. Your line is open.

Len Schleifer: about the Iyo combo?

Len Schleifer: as a kind of differentiating strategy.

Hi, Good morning question on Damien Damien <unk> and can you talk a little bit about the path to establish that antibody cocktail as a treatment for patients from you know compromised before it with me before cancer to wait and and so forth uhm unique half full authorization to begin to pursue this but we think about the <unk>.

Len Schleifer: I was wondering if, you know, you're maintaining that position, or with the results in hand today, that view has changed. Thank you.

George D. Yancopoulos: Well, we think that certainly we should be competitive right now. The opportunity for this class, which is obviously dominated by a contruder right now because, up until now, it was the only agent that had this strong data across the spectrum of monotherapies and chemo combinations. We think that now we can be legitimate competitors here in the lung cancer space. We see our combination opportunities as future growth and differentiator opportunities. But in the short term, we expect to be a viable competitor now with these data, and in the future, we hope to use combinations to take the standard of care and elevate results to another level.

Longer term beyond the card will be epidemic.

And what steps that you're making towards establishing it as a long term part of the trip and tear down and various diseases.

Yeah. As you said, we think that the immuno compromised population, which as I'm sure you all know represents 3% to 4% of the U S population that several million individuals.

A variety of studies are showing that.

Somewhere around 50% or more of these individuals do not respond day after 2 or even after 3 attempts with the vaccine and so these people are left without their own antibodies to protect them. So it's a a.

Tamia: Thanks, Gary.

Tamia: Your next question comes from the line of Ronnie Gow with Bernstein. Your line is open.

Tamia: Good morning.

Tamia: Question of the immune code.

Tamia: a little bit about the path to establish that antibody cocktail as a treatment for patients or immunocompromise before cancer treatment and so forth. You need to have full authorization

A huge unmet needs setting where these individuals will not be protected and and as we're all seeing that it's very unlikely that we will be eliminating.

Tamia: to have full authorization to begin to pursue this, but if we think about the product longer term beyond the current way of the epidemic, what steps are you making towards establishing it as a long-term part of the regimen and paradigm in Bayer's diseases?

Spread of infections through breakthrough infections, whether it was symptomatic or otherwise throughout the population and for these individuals to be able to live normal lives, they're gonna need protection and we believe that the most powerful protection is essentially providing them with these surrogate and bodies that are antibody cocktail provides we already.

George D. Yancopoulos: Yeah, as you said, we think that the immunocompromised population, which, as I'm sure you all know, represents 3 to 4% of the U.S. population, that several million individuals, a variety of studies are showing that somewhere around 50% or more of these individuals do not respond after two or even after three attempts with the vaccine. And so these people are left without their own antibodies to protect them. So it's a huge unmet need setting where these individuals will not be protected.

We have very strong data, we believe to support the notion that.

This agent can be used and chronic prevention settings, and we do intend to continue to explore future study opportunities, where we can further and hands on the already existing data that shows that after the first week or so we seem to obtain somewhere upwards of 90 per cent protection.

George D. Yancopoulos: And as we're all seeing, it's very unlikely that we will be eliminating the spread of infections through breakthrough infections, whether it's symptomatic or otherwise throughout the population. And for these individuals to be able to live normal lives, they're going to need protection. And we believe that the most powerful protection is essentially providing them with these surrogate antibodies that our antibody cocktail provides. We already have very strong data, we believe, to support the notion that this agent can be used in chronic prevention settings, and we do.

And against infection, and individuals who do not have their own antibodies.

And are being exposed to.

To the Sars Kobe to virus that I think that that is very strong data that bodes very well that this is and patel.

Potentially be a very important treatment, particularly for these immuno compromised individuals who do not have antibodies on their own.

Let me just said I bet, let's and <unk>.

And and with George said as we're working with the agency to try and convince them that our data is strong and and you know and.

George D. Yancopoulos: I intend to continue to explore future study opportunities where we can further enhance the already existing data that shows that after the first week or so, we seem to obtain somewhere upwards of 90% protection against infection in individuals who do not have their own antibodies and are being exposed to the SARS-CoV-2 virus. I think that that is very strong data that bodes very well that this is, and potentially will be, a very important treatment, particularly for these immunocompromised individuals who do not have antibodies of their own. Yeah, let me just add.

The agency, obviously has a lot on its plate and it's trying I think so too whether or not uhm. These individuals should try a third dos or not uhm of a vaccine and that has to get sorted out I think and the F. D. A has a data and as George said, we're looking at ways to enhance our day.

<unk>.

But we already believe and.

That and a preexposure prophylaxis mode, we have strong data, but it's not been authorized yet by the agency and it's under review.

George D. Yancopoulos: What's implicit in what George said is we're working with the agency to try and convince them that our data is strong. You know, the agency obviously has a lot on its plate, and it's trying, I think, to sort through whether or not these individuals should try a third dose of the vaccine. That has to get sorted out, I think, and the FDA has our data, and as George said, we're looking at ways to enhance our data, but we already believe that in a pre-exposure prophylaxis mode, we have strong data, but it's not been approved yet by the agency.

So I understand you're taking and label for chronic treatment off immunocompromised population and did you think of the data and so dense such a day. So just to be clear. The current authorization allows chronic treatment, but allows kind of treatment for people for example, who are immuno compromised, but and a.

<unk> setting working and living in the Congress setting where they are exposed to infected individuals we would like to expand that to preexposure prophylaxis for the community acquired infections that is where immuno compromised people might be able to go out and the community and have some protection.

George D. Yancopoulos: So, you might understand you're seeking a label for chronic treatment of an immunocompromised population, and then you think you have the data to obtain such a label? So just to be clear, the current authorization allows chronic treatment but allows chronic treatment for people, for example, who are immunocompromised but are in an institutional setting, working or living in a congregate setting where they're exposed to infected individuals. We would like to expand that to pre-exposure prophylaxis for community-acquired infections.

So we do have chronic dosing.

And for the immuno compromised and our current authorization, but that's restricted to this post exposure ongoing exposure.

And the known infected people setting and we're trying to expand it to protect these people and the community setting. It's we think the day too strong, but obviously, there's a lot going on and a lot of considerations as I mentioned before they need to get sorted out.

George D. Yancopoulos: That is, where immunocompromised people might be able to go out in the community and have some protection. So we do have chronic dosing. for immunocompromise in our current authorization, but that's restricted to this post-exposure or ongoing exposure in known infected people setting, and we're trying to expand that to protect these people in the community setting. We think the data are strong, but obviously there's a lot going on and a lot of considerations, as I mentioned before, that need to get sorted out.

Next question.

Your next question comes from the line of Jeffrey porches with SBB Leerink. Your line is open.

Thank you. Thank you very much so many questions.

Perhaps where I'm from Marion on Idly, a really strong result, and by the way congratulations on the spectacular corner on idly tremendous strict return to growth Murray could you talk about whether there was any ketchup and the second quarter or is this a sustainable revenue run right go.

Tamia: Your next question comes from the line of Jeffrey Porges with SVB. Lee Rink, your line is open.

<unk> forward and.

Tamia: Thank you. Thank you very much. So many questions.

Because it's curry significantly above where we were expecting and then perhaps you could just give us a little bit more color on the proportion I M. D. A N T M. A thanks.

Tamia: Perhaps one for Marion on Aaliyah, a really strong result, and by the way, congratulations on the spectacular quarter for Ilea, a tremendous return to growth, and could you talk about whether there was any catch-up in the second quarter or is this a sustainable revenue run rate going forward because it's clearly significantly above where we were expecting, and then perhaps you could just give us a little bit more color on the proportion and d and DMA. Thanks. Sure. And thank you.

Sure on them and thank you, Jeff Yeah delighted to come and we did have a very strong quarter and certainly on the performance was driven by return of market growth and are on share gains vs competition and capturing that market growth in the quarter. We did see a return of patient flow to offices.

Consistent with the free pandemic period and there also is the consideration of some patients and may have delayed it treatment coming back and so it's a combination of factors, but certainly a a very strong performance for on the App as well to your question related to future growth by indication we do continue.

Mary: Sure, and thank you, Jeff. You're delighted to comment.

Mary: We did have a very strong quarter, and certainly our ALEA performance was driven by the return of market growth and our own share gains versus competition in capturing that market growth. In the quarter, we did see a return of patient flow to offices consistent with the pre-pandemic period, and there also is the consideration of some patients who may have delayed treatment coming back in. So it's a combination of factors but certainly a very strong performance for AILIA.

Need to see diabetic eye disease, and the indications that has the highest growth trajectory. So that's balancing out our web M. D business, which is still the majority Oh roughly you know 50 per cent 50.255 per cent of overall use of Eylea.

Mary: As well, to your question related to future growth by indication, we do continue to see diabetic eye disease as the indication that has the highest growth trajectory. So that's balancing out our wet AMD business, which is still the majority. Oh, roughly, you know, 50 percent, 50 to 55 percent of overall use in Idaho.

Alright, Thanks ma'am.

Ex question please.

Question comes from a line of Iran, and wherever with Cowan Your line is open.

Great. Thanks, as well, maybe a question for it from Marion and and Uhm, Bob relating to rejoin Coke too are you in order to get the next U S. Government order I do you are you waiting for approval or or are they just waiting to exhaust our current supply and then reorder. Thank you.

Mary: Leah. Thanks, Mary. Next question, please? Your next question comes from the line of Yaron Werber with Cowan. Your line is open. Great, thanks as well.

Tamia: Great, thanks as well. Maybe questions for Marion and Bob relating to Regencove, too. Are you, in order to get the next U.S. government order, are you, waiting for approval, or are they just waiting to exhaust their current supply and then reorder? Thank you. So maybe I'll take that question.

Maybe I'll take that question.

The.

Contract, we have has been fulfilled and so the government is going to need to decide whether or not they want to have another contract or they want us to switch over to commercial and model.

Tamia: The contract we have has been fulfilled, and so the government is going to need to decide whether or not they want to have another contract or they want us to switch over to a commercial model, which could occur before or after a regular approval, as it did with Ram DeVsvia. I think a lot of that is going to depend upon the government's assessment of what they think is the most efficient way to get people to use the product.

Which could occur before or after a regular approval as it did with Devonshire I think a lot of that is going to depend upon the government's assessment of what they think is the most efficient way to get people to use the product there's been a tremendous acceleration and use our penetration in terms of.

Tamia: There has been a tremendous acceleration in use. Our penetration in terms of, addressing what we would say estimated eligible patients has gone up dramatically in some ways, from the low single digits to almost 25 to 30% more recently in terms of eligible patients getting monoclonals. If that trend continues along with the trend of, unfortunately, more cases, obviously, we're going to have to go with the direction that the government wants, another contract or a commercial switchover.

Addressing what we would say estimated eligible patients.

Has gone up dramatically to some ways and the low single digits to almost.

$25 and 30%.

More recently in terms of eligible patients getting monoclonal.

If that trend continues along with the trend of unfortunately more cases, obviously, we're going to have to.

Go with the direction of the government wants and other contract or.

Or a commercial switchover and.

Tamia: You know, capacity, of course, is always an issue, but we think we're sort of well positioned to continue to supply similar amounts that we've been able to supply. We'll have to look at, and these demands can change pretty rapidly, and of course, we do have our partner, Roche, who's got capacity that we can perhaps turn to. So a lot of moving parts, you know, and the most important. important question, which is what is the shape of the current surge in the pandemic?

Passenger you of course.

Always and issue, but we think we're sort of well positioned to continue to supply similar amounts that we've been able to supply.

And we'll have to look at at least demands can change pretty rapidly and of course, we do have our part for Roche. We've got capacity that we can perhaps turned too so a lot of moving parts your own and.

Most important of which is what is the shape of the current surge and the pandemic.

Bob: Your next question comes from the line of Terrence Flann with Goldman Sachs. Your line is open.

Thank you.

Please.

Yeah and that question comes from a line of parents plan with Goldman Sachs. Your line is open.

Great. Thanks, so much for the question and congrats on the do picks and see US. Your data I was just wondering if there's incremental SG&A, that's going to be required to launch this indication or if you'd be able to leverage our existing commercial footprint and then the corollary is just how to think about the continued ramp on profitability on the J V here into 2.

Tamia: Great, thanks so much for the question and congrats on the Dupix and CSU data. I was just wondering if there's any additional SG&A that's going to be required to launch this indication or if you'd be able to leverage your existing commercial footprint. And then the corollary is just how to think about the continued ramp-up of the JV here into 2022. Are there any other significant investments that we need to consider in our models?

22 are there any other significant investments that we need to consider and our models. Thanks.

Tamia: Thanks.

Mary: Sure, Terrence, I'll start from the commercial perspective, so yeah, we're really excited about adding, you know, potentially another indication for DePixin. CSU is a big opportunity. They're about 300,000 potential patients with disease, adults, and very, you know, very limited treatment options for them today. We will be able to always look at the impact of our educational abilities and promotion by indication, but to your very clear point, we do have a leveraging opportunity here because we're already calling on the audiences that would be required to effectively promote CSU. You know, it's premature for us to say absolutely what sort of additional effort we might need, but certainly we will be able to leverage our current footprints in all areas. Yeah, and Terrence.

She turns I'll start from the commercial perspective, so yeah, we're really excited about adding potentially another indication for depicts and C. S. U as a large opportunity either about 3 and 3000 potential patients with disease adults and and very you know very limited cheating options.

For them today, and we will be able to always look at the impact of our educational abilities and promotion by indication, but you're very clear point, we do have a leveraging opportunity here because we're already calling on the audience is that will be required to effectively promote C. S U.

You know, it's premature and for us to say, absolutely and what sort of additional effort, we might need but certainly we will be able to leverage our current footprints in all areas.

Yeah, and <unk> and so I'll, just kind of punctuate, what Murray and set on that you know clearly and you can see it and the M. D. N. A that we disclosed and you can do the couch right. Our margins are getting better with this I mean this is something that we talked about certainly you know we've had a lot of ex U S launches a lot of prelaunch expenses related to that which kind of held that back a little bit and I think you're now seeing.

Bob: Yeah, and Terrence, I'll just kind of punctuate what Marion said on that. You know, clearly, and you can see it in the MDNA that we disclosed, and you can do the Couch, right? Our margins are getting better with this. I mean, this is something that we talked about. Certainly, you know, we've had a lot of XUS launches, and a lot of pre-launch expenses related to that, which kind of held that back a little bit.

Certainly year over year, you know, you're starting to see the fruits and labor and the leverage that we've been talking about for awhile and again, you know kudos to send it to you. Another another strong ex U S quarter by them as we continue to see the indications really starting to kick in ex U S.

[noise] question. Please.

Bob: I think you're now seeing, certainly year over year, you know, he's starting to see the fruits of labor. And the leverage that we've been talking about for a while, again, kudos to Sanofi, another strong X-US quarter by them as we continue to see the, you know, indications really starting to kick in XU.

Question on a line of Ken and met K with RBC capital market. Your line, it's all back.

Alright price for taking the question and huge congratulations on the quarter really across the board commercially on and clinical and a couple of surprises. This season, maybe a question on <unk>. There was commentary from another call earlier, the 2.2 earner Susan that included conversation around some somewhat aggressive.

Tamia: Your next question comes from the line of Ken and Met Kay with RBC Capital Markets. Your line is open.

Development plans of and I need to buy a similar just wandering sort of beyond the 2023 competition and matter of pattern. If you could talk to which intellectual property you have the most competence and and and keeping the franchise going especially as it relates to the U S. Thanks, and congrats again.

Tamia: Hi, thanks for taking the question and huge congratulations on the quarter, really across the board commercially.

Tamia: and clinically with

Tamia: A couple surprises this season. Maybe a question on Princess Leia.

Tamia: There was commentary from another call earlier this

Tamia: to the earning season that included conversation around

Tamia: Some somewhat aggressive development plans for an Ae Leahy Similar. Just wondering, sort of beyond the 2003 Composition of Matter Patent, if you could talk to which intellectual

Right. It is a great question, but we're gonna have to differ on that 1 because of ongoing patent issues and what have you really can't make a comment.

Tamia: you have the most confidence in in

Sorry next question.

Tamia: in keeping this franchise going, especially as it relates to the U.S. Thanks and congrats again.

Got it thank you.

Your next question comes from the line of <unk>, what Barclay and your line and help and.

Tamia: All right, it's a great question, but we're going to have to defer on that one because of ongoing patent issues and what have you. We really can't make a comment. Sorry, next question. No, I took to get it. Thank you.

Good morning, Thanks for taking my question, obviously I wanted to kind of change changing gears a bit obviously, we've seen some pretty transformational events across our fda's addressing all farmers since your last quarterly call and you did announce a early stage program on and.

Tamia: Your next question comes from the line of Carter-Gold with Barclays.

In conjunction with on island, but just wanted to see if you teach your appetite to jump and sort of the antibody directed amyloid beta lowering game. There are few companies that innovate and iterate on antibodies as well as regeneron and so if you think about your all farmers effort going forward. If that was the point and focused on any broader color on on that space would be helpful. Thank you.

Tamia: Good morning. Thanks for taking the question. Obviously, I want to kind of change the years a bit.

Tamia: Obviously, we've seen some pretty transformational events across how FDA is addressing Alzheimer's since your last quarterly call. You did announce an early stage program. Al-Niolm, but just wanted to see if, you know, gauge your appetite to jump in sort of the antibody-directed amyloid beta-lowering game. There are few companies that innovate and iterate on antibodies as well as regeneron. And so as you think about your Alzheimer's effort going forward, if that was a point of focus in any broader context, we should let me iterator and answer that. We actually, sorry. Are you speaking like? I was just saying we should be the iterator and inventor and, Go ahead, okay. I was just going to just, sorry, I didn't hear you speaking here.

We should let me get away too and they actually.

We actually sorry.

And Joanne and we should iterate or an inventor answer that.

Okay, I was going to just sorry, and hear you speak and then yeah.

Yeah, we have a very robust effort and narrow degenerative diseases here Regeneron, we are not overly excited about some of the antibody developments and.

Necessarily getting into those type of approaches, but we have we have a lot of things that were actually very excited about it and and Neurodegenerative disease space. We think novel ways of addressing charged as well as brand new targets that hadn't been haven't been discovered elsewhere, we will be discussing these efforts.

George D. Yancopoulos: Yeah, we have a very robust effort in neurodegenerative diseases here at Regenron. We are not overly excited about some of the antibody developments and..., necessarily getting into those types of approaches. But we have a lot of things that we're actually very excited about in the neurodegenerative disease space, novel ways of addressing targets as well as brand new targets that haven't been discovered elsewhere. We will be discussing these efforts going forward in more detail over the coming months and year.

Going forward and and more detail over the coming months and year.

Next question please.

Your next question cause a friend of mine and Brian Corny with Bird Your line is open.

Hey, good morning, guys. Thanks for taking my question. Unfortunately, I kind of feel like there's going to be and evergreen question as we see Sars coke to genetic shaft, but it seems like just this week, there's been some emergence of data for the Lambda strange showing potentially increased resistance to vaccination. Just wondering if you guys have any data yet on the the antibody combo and how much activity.

Tamia: Your next question comes from the line of Brian Scornie with Baird. Your line is open.

Tamia: Hey, good morning, guys. Thanks for taking the question. Unfortunately, I kind of feel like this is getting to be an evergreen question.

So the strength.

Yeah, I I have to say that I'm not sure exactly what our results are and and quantitatively.

Tamia: SARS-COV-2 genetic shift, but it seems like just this week there's been some emerging update.

But so far every variant and every strain that we've tested we retained potency and and so far there's hopefully no reason to think that's going to change because we prospectively took advantage of this cocktail approaches so that even if 1 in and body gets minimally in fact.

Tamia: showing potentially increased resistance to vaccination. Just wondering if you guys have any data yet on the answer to that question.

Tamia: data yet on the antibody combo and how much activity might retain against the string.

George D. Yancopoulos: Yeah, I have to say that I'm not sure exactly what our results are and quantitatively, but so far, every variant and every strain that we've tested retains potency, and so far, there's hopefully no reason to think that's going to change because we prospectively took advantage of this cocktail approach so that even if one antibody gets minimally infected, the other one can take its place. So we expect to retain robust activity.

Minimally affected the other 1 can take its place. So we expect to retain robust activity that said and I think we've also announced that we have second generation.

Antibodies.

There are also entering the clinic, where we're going to continue to retain broad coverage, but I believe that.

As far as it has been tested with land and we retain potency there as well.

Great. Thanks.

George D. Yancopoulos: That said, I think we've also announced that we have second generation antibodies that are also entering the clinic where we'll continue to retain broad coverage. But I believe that, you know, as far as it's been tested with Lambda, we retain potency there as well.

Your net question comes from the line of Jeff Meacham with Bank of America. Your line is open.

Hey, guys. Thanks for the thanks for the question I just wanted to ask on on commercial the Pio you just wanted to see what sort of success or what and metrics you can give us commercially with the initial first line long mono therapy and roll out as well as.

Tamia: Your next question comes from the line of Jeff Meacham with Bank of America. Your line is open.

Tamia: Hey guys, thanks for the question. I just wanted to ask about the commercial.

Tamia: Tayo, just wanted to see what

The the Derby indication as well to see how that's going early and then laughed. Thanks.

Tamia: What sort of success or what metrics you can give us commercially with the initial first-line lung monotherapy rollout as well as

Tamia: the Derm indication as well to see how that's going early in the launch. Thanks.

So just happy to sell 4 libtayo with our first long indication and mono.

Mary: Sure, Jeff, happy to. So for Liptayo, with our first lung indication in mono, you know, as expected, that is the smaller indication, so we're really excited about the, you know, chemotherapy combination data that was shared today. And in fact, if I quantify it, that indication, in terms of patient potential, is about four times the size of the mono indication. But what we're doing today in the market commercially is certainly working

As expected that is the smaller indications. So we're really excited about the.

Chemotherapy combination D dog that was shared today and in fact, if I quantify it that indication in terms of patient potential is about 4 times the size of the mono indication, but what we're doing today and the market commercially is certainly foundational to libtayo and our oncology.

Mary: to Libthayo and our oncology portfolio more broadly. You know, I'll comment that we are still the standard of care in Catanis, squamous cell carcinoma. That was a very effective launch.

And more broadly and I'll comment we are still be you know that.

Standard of care and cutaneous squamous cell carcinoma that was a very effective launch we now have a good competitor and that indication, but we retain our leadership the basal cell carcinoma launch is also going well and and certainly the efficacy and Tolerability safety Libtayo is paramount for those patients and we offer and I'll.

Mary: We now have a competitor in that indication, but we retain our leadership. The basal cell carcinoma launch is also going well. And certainly, the efficacy and tolerability safety of Lybtio are paramount for those patients, and we offer an alternative where the specialist. in that area do believe Liptyo as evolving to become the standard of care. It's early days in lung. I think our team is doing a really good job, and when we talk to the opinion leaders, they're most excited, as I mentioned, about our rapid action, our efficacy, even in those patients with stable brain metastases and with the high-expression PDL1 patients. So in the early days, we are right on track with where we expected to be, but there's a lot more potential and a lot more work to do.

Alternative where the specialist and that area do you believe with tile as evolving to become the standard of care. It's early days and long I think our team is doing a really good job and when we talk to the opinion leaders and most excited as I mentioned about our rapid action or efficacy.

See uhm, even on those patients with staple brain metastases and with the high expression PDL on patients. So early days when you're right on track with where we expected to day to be but there's a lot more potential and a lot more work to do.

Thanks, Marion we have time for maybe 2 or 3 more quick questions to me on.

Mary: Thanks, we have time for maybe two or three more quick questions to me. Thank you. Your next question comes from the line of Aletia Young with Cantor Fitzgerald. Your line is open.

Thank you. Your next question comes from the line of amnesia, Yeah with Cantor Fitzgerald. Your line is open [noise].

Tamia: Thank you. Your next question comes from the line of Aletia Young with Cantor Fitzgerald. Your line is open. Hey, guys. Thanks for taking my question.

Hey, guys. Thanks for taking my question and congrats on the corner I just wanted to talk a little bit about how you guys see what the therapeutic goals are for and Nash from medicine and sent to your leader and genetics and they've been a lot of ups and downs and Nash. Thanks.

Tamia: Well, I think there are a variety of goals, but our major question right now with our first program is that we believe that we have a novel approach that addresses not the steatosis component but the inflammatory component, which is something that really is not being addressed by other approaches, other targets, other agents so that if we can actually stop or reverse the inflammatory process. The inflammatory response to steatosis. That would be an entirely different and also potentially complementary approach to what anything and anybody else is doing right now.

I think there's a variety of golf, but our our major question right now with our first program is we believe that we have a novel approach that addresses not the the steatosis component, but the inflammatory.

And a component which is something that really is not being addressed by other approaches other targets other age and so that if we can actually stop or reverse the inflammatory response to the steatosis that would be an entirely different and also potentially complementary approach to what anything and anybody else.

Is doing right now I think the genetics very strongly pointed that that's what it actually shows that this genetic target effects and and that's what the protective mutations are actually showing so we're excited about looking at this opportunity, whether we can halt or even reverse inflammatory.

George D. Yancopoulos: I think the genetics very strongly point to that. That's what it actually shows that this genetic target affects, and that's what the protective mutations are actually showing. So we're excited about looking at this opportunity, whether we can halt or even reverse inflammatory signals, inflammatory processes, thus actual progression of the disease, regardless of the extent of stetosis.

Inflammatory signals inflammatory processes and first actual progression of the disease, you regardless of Steatosis.

Tamia: Please, your next question comes from the line of Mike King, which is H.C. Wainwright. Your line is open.

Ex question please.

Question comes from a line of my team, which H C. Wainwright Your line is open.

Tamia: Hey guys, thanks for squeezing me in. I'm not sure how long, um, how quickly this question could be answered, but I'm

Hey, guys. Thanks for squeezing me and I'm not sure how long.

And how quickly just quite and can be answered, but I'm just trying to get a better appreciation of what I would call the real world use a Virgin Cove.

Tamia: I am just trying to get a better appreciation of what I would call the real world.

Tamia: Use of Regenkov, you know, can you point to yourself? I think Glenn said something about 25% of patients, but I think that was just an estimate.

Can you point too I think Glenn said, something about 25 per cent of patients, but I think that was eligible I don't know if you have any market data from and real world use vs. What's been shipped and paid for <unk> and paid for by the government can we understand how that you know how that rubber band flexes, a little bit more.

Tamia: I don't know if you have any market data from real world use versus what's been shipped and paid for or shipped to and paid for shipping to.

Tamia: Shipped to and paid for by the government. Can we understand how that, you know, how that rubberband flexes a little bit more?

Leonard S. Schleifer: Sure. So, look, what we look at are the shipments from our distributor to institutions, hospitals, med centers, and clinics, emergency rooms, et cetera, et cetera. And we believe, based on some real-world data, that about 70% of the daily cases that occur are occurring in people who would be eligible for treatment, either because they're obese or they've got underlying conditions or they're elderly; we're seeing more younger and obese people, frankly, than we're seeing older people that were seen earlier in the pandemic.

Sure. So uhm look what we look at our the shipments from a distributor.

2 institutions hospitals mid centers and clinics.

Clinics emergencies et cetera et cetera.

And.

We believe based on some real world data that about 70% of the daily cases that occur.

Occurring and people who would be eligible for treatment.

Other because there OBIE.

Obese and they've got underlying conditions or their elderly more see we're seeing more younger and obese frankly, then we and elderly and that was seen earlier and the pandemic. So if you take for example that and May.

Leonard S. Schleifer: So if you take, for example, that maybe there were 100,000 new cases, maybe 70,000 of them would be eligible. So that gives you an idea. I was just looking, Mike, at this, to see what my orders were, and the vast, vast majority, I think it's around or above 90% of the institution's ordering, have our repeat orders, meaning that they're not people just stocking the stuff to have it around. They're using it, they're using it up. And that's what our field people seem to tell us. I don't know if Marion wants to maybe add any more on that or not, but I hope that helps you.

Maybe it was 100000, new cases may be 70000 of them.

Would be eligible so that gives you an idea I was just looking Mike at this to see what Ah repeat orders were and the vast vast majority I think it's around or above 90% of the institutions ordering have ah repeat orders, meaning that they're not people just stocking the stuff to her.

Have it around they're using it and they're using it up and that's what I feel people seem to tell us I don't know if Murray and wants to maybe it any more on that or not but I hope that helps you.

Mary: that that would be the characterization. I think the other thing that's important is, you know, we are continuing to educate and to, you know, help with some of the bottlenecks that have been experienced in the early days. So we are seeing growing utilization. And, you know, certainly as Len mentioned, the patient criteria who are eligible for treatment is broad to Lenn's point, you know, age-related, obesity, hypertension, diabetes, respiratory, and immune issues. So there are a lot of patients who are very much in need of treatment, and we're doing everything we can to, you know, to help them, you know, have the availability of the product.

Yeah that that would be the characterization I think the other thing. That's important is you know we are continuing to educate and to her.

Help with some of the bottlenecks that had been experienced early days. So we are seeing growing utilization and uhm certainly is Len mentioned the patient criteria, who are eligible for treatment is bright and 2 lens point each related obesity hypertension diabetes respiratory.

[noise] immune issues. So there are a lot of patients who are very much and need of treatment and we're doing everything we can to you know to help them you know have availability of product.

George D. Yancopoulos: Yeah, I'll just add a couple thoughts or points to that. During the last sort of surge, as Len said, we were probably only reaching somewhere under 1% of the potentially eligible patients. We're now well into the double digits in terms of the percentage of the eligible patients that we're probably reaching. And we've had some feedback from some of these institutions where we distribute to where they're actually low on inventory, suggesting that they're not stocking it up.

Yeah, I'll, just add a couple of thoughts or points to that is during the last and sort of Serge.

<unk> said, we were probably only reaching some honey water and 1% of the potentially eligible patients were now well into the double digits in terms of the percentage of the eligible patients that were probably reaching and we've had some feedback from some of these institutions, where we distribute to where they're actually low on inventory.

Testing that they're not stocking it up.

Leonard S. Schleifer: You know, just to add, because we're obviously all over this and get the individual stories, but the one thing that is so consistent, when patients are doing poorly and then they're treated with Regen Cove, within a day, two days, they see a remarkable difference in patient status that has truly been rewarding for those on the front line.

And and the other thing just to add because we obviously are all over this and get the individual stories, but the 1 thing that is so consistent when patients are doing poorly and then they're treated with <unk> within a day 2 days, they see and remarkable difference and the patient status that will truly has been rewarding for those on the front line.

Tamia: To Mia, we're going to have to cut it after one more question.

To me and we're going to have to cut it after 1 more question our.

Tamia: Our final question comes from the line of Yattin Senegia with Guggenheim Partners. Your line is open.

Our final question comes from the line of furniture with Guggenheim Partners. Your line is open.

Tamia: Hey guys, thank you for squeezing me in. Just a question on the Intellia collaboration. Can you just share your views on the gene editing space, your vision, or where you see the new indications and, obviously, the strategic goal of the broad collaboration that you have with Intellia?

Hey, guys. Thank you uhm for squeezing mean, just a question on the and tell Ya collaboration can you just share your views on the gene therapy, Jean editing space, you know your vision and all.

Where do you see them and then new indications and obviously this strategy code off the broad collaboration that you have it and tell you. Thank you.

George D. Yancopoulos: Obviously, these first results in humans are incredibly exciting, both in terms of the percent knockdown and also in terms of, thus far in these early days, the observed safety. And as we said, we have two types of broad, collaborative program areas with Intellia, both of which we think are greatly bolstered in terms of confidence based on these initial results. We have a series of programs which similarly involve systemic-based approaches to achieve G knockdown.

Yeah, obviously, these first and human results are incredibly and exciting both in terms of the per cent knocked down and also in terms of fuss for and these are only day is the observed safety and as we said we have 2 types.

Abroad.

Collaborative program areas within Tele and both of which we think are are greatly bolstered in terms of confidence based on these initial results. We have a series of programs, which similarly involve systemic based approaches to achieve G knocked out. So obviously those are.

George D. Yancopoulos: So obviously, those chances of success are greatly bolstered by what we've seen with these first human results. But we also have, I think, just as exciting, if not even more exciting, a CRISPR-based gene insertion program that we're very excited about. And since it depends on essentially overlapping technologies, this program and its chance of success have been greatly, very important, increased based on the results we've seen to date. So we think that with the fact that we have so many programs ongoing in our collaboration with Intelia, more than 20 programs under evaluation, and we have the ability to move forward quite a few of these. We're very excited that this could really change the practice of medicine and really bring CRISPR-based gene therapy to patients and to the world. So nothing can be more exciting from medicine. gene medicine

Chances of success on greatly bolstered by what we've seen with these first and human results, but we also have and and just as it that even more exciting a crisper base Jean insertion program that we're very excited and bad and since it depends on essentially overlapping technologies This program and its chance.

Success is greatly bin.

Increase based on the results we've seen to date. So we think that with the fact that and we have so many programs ongoing and our collaboration with and telling them more than 20 programs under evaluation and then we have the ability.

To move forward quite a few of these were very excited that this could really change the practice and medicine and really bring Christopher based gene therapy and.

2 patients into the world So nothing to be more exciting from Eugene Medicine point of view.

Tamia: Thank you, everyone. Thanks for hanging in there a little longer today. Bob Landry and the IR team are around today to answer any further questions. We wish you

Thank you everyone. Thanks for hanging and they're a little longer today Landry and the I R team are around today to answer any further questions. We wish you a good and of the week and enjoy the rest of the summer. Please stay safe out there. Thank you.

Tamia: end of the week and enjoy the rest of the summer; please stay.

Tamia: Summer, please stay safe out there. Thank you. This concludes today's conference call. Thank you for joining us.

This concludes today's conference call. Thank you for participating you may now disconnect.

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

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Tamia: and and Thee I'ma and....