Q2 2019 Earnings Call

Welcome to the Regeneron Pharmaceuticals, Q2, 2019 earnings Conference call. My name is John and I'll be your operator for today's call.

John: Welcome to the Regeneron Pharmaceuticals Q2 2019 Earnings Conference Call. My name is John, and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question and answer session. During the question and answer session, if you do have a question, press star, then one on your touchtone phone. Please note the conference is being recorded. And now, I'll turn the call over to Justin Holko.

At this time all participants are only mode. Later, we will conduct a question and answer session.

During the question answer session. If you drop a question press Star then one on your Touchtone phone.

Please note the conference is being recorded.

And I will now turn the call over to Justin Holdco.

Thank you John .

Justin Holko: Thank you, John. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron Pharmaceuticals and welcome to the second quarter 2019 conference call. An archive of this webcast will be available on our website. Joining me today are Dr. Leonard Schleifer, founder, president, and chief executive officer; Dr. George Yancopoulos, founding scientist, president, and chief scientific officer; Marion McCourt, Senior Vice President and Head of Commercial; and Bob Landry, Executive Vice President and Chief Financial Officer.

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

Thank you for your interest in Regeneron Pharmaceuticals, and welcome to the second quarter 2019 conference call.

An archive of this webcast will be available on our web site.

Joining me today are Dr. letter Swiper, founder, President and Chief Executive Officer.

Dr., George Yancopoulos founding scientist, President and Chief Scientific Officer.

Marrying the core senior 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 today.

Justin Holko: After our prepared remarks, we will open the call for Q&A. I would also like to remind you that our remarks made on the call today include four forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and businesses, Financial Forecast and Guidance, Development Programs and Related Anticipated Milestones, Collaborations, Finances, Regulatory Matters, Payer Coverage and Reimbursement Issues, Intellectual Property, and Pending Litigation and Compensation. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement. A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarterly period ended June 30, 2019, which was filed with the SEC today.

I would also like to remind you that our remarks made on the call. Today include forward looking statements Barbara General.

Such statements May include but are not limited to those related to regeneron and its products and businesses.

Financial forecast and guidance development programs and related anticipated milestones.

Collaborations finances regulatory matters payer coverage and reimbursement issues intellectual property and pending litigation the competition.

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

A more complete description of these and other material risks can be found in regenerons filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarterly period ended June Thirtyth 2019, which has been filed with the FCC today.

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

Justin Holko: Regeneron does not undertake any obligation to update publicly any forward-looking statements, whether as a result of new information, future events, or otherwise. In addition, please note that GAAP and non-GAAP measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and reconciliation of those measures to GAAP is available in our financial results press release, which can be accessed on our website. 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. Len Schleifer.

In addition, please note that GAAP and non-GAAP measures will be best cost on today's call.

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

Once our call concludes Bob Landry and the IR team will be available to answer further questions.

With that let me turn the call over to our President and Chief Executive Officer, Dr. lunch Lifer.

Leonard S. Schleifer: Thank you, Justin. Before we begin, I'd like to extend a warm welcome to Justin, who joined us earlier this summer after completing a 19-year training program at Merck and has immediately hit the ground running here at Regeneron. We're thrilled to have him as part of the team, and we worked hard to make his first quarter straight forward. Thanks to everyone for joining the call and turning to our business. We had a great quarter, actually, marked by top and bottom line growth, as well as important advances across our innovative R&D engine. Sales of Regeneron products, including those recorded by our partners, grew 32% compared to the second quarter of 2018. ILEA global net sales grew 13% to $1.9 billion, including U.S. ILEA net sales growth of 17% to $1.16 billion.

[laughter]. Thank you Justin before we begin I'd like to extend a warm welcome to Justin who joined US early this summer.

After completing a 19 year training program at Merck and has immediately hit the ground running here at Regeneron.

With thrilled to have him as part of the team and we work hard to make his first quarter, hey straight forward way.

Thanks to everyone for joining the call and turning to our business, we had a great quarter actually marked by top and bottom line growth as well as important advances across our innovative R&D engine.

Sales of Regeneron products, including those recorded by our partners grew 32% compared to the second quarter of 2018.

I lead a global net sales grew 13% to 1.9 billion, including U.S. I Leant net sales growth of 17% to 1.16 billion.

Leonard S. Schleifer: The Diabetic Retinopathy approval in May continues to build upon ILEA's leadership position in treating retinal diseases, including wet, age-related macular degeneration, diabetic macular edema, and retinal vein occlusion. We are also pleased to announce that our antibody collaboration with Sanofi achieved profitability this quarter. We expect profits to continue to increase, driven by growth in Dupixen, as well as disciplined cost management across the collaboration to stem losses from Praluent by better aligning investments with revenue.

The diabetic retinopathy approval in May continues to build upon I leave his leadership position in treating retinal diseases, including wet age related macular degeneration, diabetic macular edema and retinal vein occlusion.

We are also pleased to announce that our antibody collaboration with Sanofi with Sanofi achieved profitability. This quarter, we expect profits to continue to increase driven by growth in dupixent as well as disciplined cost management across the cloud collaboration to stem losses comprised by better aligning investments with revenues.

Leonard S. Schleifer: Depiction is fulfilling its potential to improve the lives of patients by transforming the treatment of a variety of type 2 allergic diseases. Global net sales are now annualizing at more than $2 billion. Patient initiations in the U.S. are growing, and many ex-U.S. launches are just beginning. Building on this commercial momentum, in June, we received FDA approval for dupixent in chronic rhinosinusitis with nasal polyposis. In the EU, Dupixent was approved in May for severe asthma in adults and adolescents, and, as we announced this morning, was just approved for atopic dermatitis in adolescent patients. We also announce today the strong positive results of our phase 3 study in children aged 6 to 11 with severe atopic dermatitis. We are enthusiastic about the current and future prospects for Dupixent as a treatment directed at the underlying cause of allergic disease.

Dupixent is fulfilling its potential to improve the lives of patients.

By transforming the treatment of a variety of type two allergic diseases.

Global net sales are now annualizing at more than $2 billion.

Patient initiation in the U.S., a growing and many X U.S. launches are just beginning.

Building on this commercial momentum in June we received FDA approval for Dupixent in chronic rhinosinusitis with nasal polyposis in the E. U depicts and was approved in may for severe asthma in adults and adolescents and as we announced this morning was just approved for a topic dermatitis in adolescent patients.

We also announced today a strong positive results of our phase three study in children age six to 11 with severe atopic dermatitis.

We are enthusiastic about the current and future prospects of the picks and as the treatment directed at the underlying cause of allergic diseases.

Leonard S. Schleifer: Additionally, we are making significant progress towards our goal of building a leading presence in immuno-oncology. The U.S. and EU approvals for libtio and advanced cutaneous squamous cell carcinoma are just the beginning. Our clinical efforts, which now include multiple different immuno-oncology programs, are studying a wide variety of potential drug candidates in several difficult-to-treat cancers, including non-small cell lung cancer, basal cell carcinoma, cervical cancer, ovarian cancer, non-Hodgkin's lymphoma, multiple myeloma, and prostate cancer. Beyond oncology, we continue to move novel programs forward throughout early and late stage George will speak to a few of these programs, and additional data readouts are expected later this year. We've made critical advances that have led both to top-line and bottom-line growth, but we recognize that these advances may be overshadowed by the current policy debates on the affordability and accessibility of innovative... We continue to work with policymakers to develop responsible solutions that address affordability and accessibility while preserving incentives to develop transformative treatments of the future. Now, I'll turn the call over to George.

Additionally, we are making significant progress towards our goal of building a leading presence in immuno oncology.

The U.S. and EU approvals for live tie up an advanced cutaneous squamous cell carcinoma adjust the beginning of clinical ethics, which now include multiple different immuno oncology programs are studying a wide variety of potential drug candidates in several difficult to treat cancers, including non small cell lung cancer, the basal cell carcinoma cervical cancer ovarian cancer.

Non hodgkin's lymphoma, multiple myeloma and prostate cancer.

Beyond oncology, we continue to move novel programs forward throughout early and late stage development George will speak to a few of these programs and additional data read outs are expected later this year.

[noise], we've made critical advances that have led both to topline and bottomline growth, but we recognize that these advances may be overshadowed by the current policy debates on the affordability and accessibility of innovative medicines.

We continue to work with policymakers to develop responsible solutions that address affordability and accessibility, while preserving incentives to develop transformative treatments of the future.

Now I'll turn the call over to George.

George D. Yancopoulos: Thanks, Len. Let me begin with ILEA, the market leader based on its ability to improve vision across multiple retinal diseases, along with its safety profile established by over 25 million injectors. In addition to ILEA's indication for the treatment of wet AMD, for macular edema following retinal vein occlusion, and for diabetic macular edema, or DME, the FDA label for ILEA was expanded in May to include diabetic retinopathy without centrally involved DME, based on the Panorama study. In this diabetic retinopathy setting, our updated label shows that ILEA demonstrated an 85 to 100% reduction in the incidence of vision-threatening complications.

Thanks Glenn.

Let me begin with I leave the market leader based on its ability to improve patient across multiple retinal diseases long with its safety profile established by over 25 million injections.

In addition to an indication for the treatment of wet AMD.

For Mac in or do you not following retinal vein occlusion and for diabetic macular edema or D. I mean, you have to label Friday. It was expanded in May to include diabetic retinopathy without essentially involved I mean based on the Panorama study.

In this diabetic retinopathy setting our updated label shows that I leave demonstrated an 85% to 100% reduction in the incidence of visions threatening complications.

George D. Yancopoulos: In addition, we are awaiting FDA action on our resubmitted filing for the ILEA pre-filled syringe. In terms of future innovation in retinal disease, we are planning to initiate clinical programs with a higher dose formulation of Flibriset in wet AMD and in DME by the end of 2019. These studies will test a higher dose of filbicep in 12- and 16-week regimens compared to the recommended ILEA regimen of 2 mg every 8 weeks.

In addition, we are waiting at the action on our re submitted filings with the idea of Prefilled syringe.

In terms of our future innovation and retinal disease.

We are planning to initiate clinical programs with a higher dose formulation of fibrosis in wet AMD be an Indian and by the end of 2019.

These studies will test the higher dose of Aflibercept in 12, and 16 week regimen.

Compared to the recommended idea regimen of two milligram every eight weeks.

Beyond Aflibercept, we're continuing preclinical development of a new that yet Walker.

George D. Yancopoulos: Beyond the flu receptor, we are continuing preclinical development of a new VEGF gene therapy and other novel approaches, including with our new collaborators at El Nilo. I'd like to now turn to Dupixit, a breakthrough therapy that is already benefiting many patients in a wide variety of atopic and or allergic diseases. As Len mentioned, we achieved several important regulatory milestones.

Gene therapy, and other novel approaches, including with our new collaborators at El Nio.

I'd like to now turn to depicts a breakthrough therapy. There is already benefiting many patients in a wide variety of a topic and or allergic diseases.

As Lynn mentioned, we achieved several important regulatory milestones.

George D. Yancopoulos: Beyond the highlighted approvals, an opinion by the European Committee for Medicinal Products for Human Use, or CHMP, for chronic rhinocerositis with nasal polyposis is anticipated by the end of 2019. And just this morning, we announced positive results from the phase three trial in severe pediatric atopic dermatitis patients aged 6 to 11 years, which we intend to submit to regulators in the coming months. I would like to remind you of the tremendous unmet need in this population.

Beyond the highlighted approvals an opinion by the European Committee for medicinal products for human use or C. H MP for chronic rhinosinusitis with nasal polyposis is anticipated by the end of 2019.

And just this morning, we announced positive results of the phase three trial in severe pediatric atopic dermatitis patients.

Age six to 11 years, which we intend to submit to regulators in the coming months.

I would like to remind you of the tremendous unmet need Ms population.

George D. Yancopoulos: On average, the children in our study had nearly 60% of their bodies covered with lesions and had suffered from this disease for most of their lives, leaving the children and their families devastated and without much hope. Not only did Dupixent dramatically reduce skin involvement, as measured by EZscore, by an average of about 80 percent, but it also improved measures of anxiety, depression, and health-related quality of life for both the children and their families. The study also confirmed Dupixent's established safety profile and, once again, numerically reduced skin infections. We are deeply committed to bringing PIXEN to patients suffering from a range of type 2 inflammatory diseases driven by the interleukin-4 and interleukin-13 pathways. With that goal in mind, we are actively enrolling patients in phase 3 studies for eosinophilic esophagitis and chronic obstructive pulmonary disease, or COPD. As a reminder, we are also exploring the effectiveness of Dupixen in allergy desensitization settings, such as for grass and peanut allergies.

On average the children are study at nearly 60% of their body covered with leases had suffered from this disease for most of their lives.

Leaving the children and their families devastated and without much help.

Not only did dupixent dramatically reduce skin involvement as measured by EASI score by an average of about 80%.

It also improved measures things I'd depression, and health related quality of life.

Both the children and their families.

The study also confirmed the pyxis established safety profile and once again metrically reduced skin infections.

We are deeply committed to bringing to picks in patients suffering from a range of type two I'm, sorry diseases, driven by the interleukin four and interleukin 13 pathway.

With that goal in mind, we are actively enrolling patients in phase three studies and eastern philosophic Jive in chronic obstructive pulmonary disease or C. O P deeds.

As a reminder, we were also exploring the effectiveness of Dupixent allergy desensitization sets such as for grass and peanut allergy.

George D. Yancopoulos: While allergy immunotherapy can be effective in the long term, many patients can't complete the prolonged time course required for success because of allergic reactions, which can be severe. We recently completed a small Phase IIa trial with about 25 patients per treatment arm, testing whether dupixan could improve the safety, tolerability, and efficacy of subcutaneous immunotherapy, or SCIT, therapy for grass allergies. The preliminary results of this study showed that about 30 patients discontinued therapy in the SCID group, mostly due to clinically meaningful allergic reactions, compared to only a single patient who discontinued SCIT when combined with bupixen and not due to an allergic reaction. In the primary efficacy analysis, there was no difference in terms of reduction of allergic symptoms with SCIT or in the combination.

Well allergy immunotherapy can be effective in the long term many patients can complete the prolonged time course required for success because of allergic reactions, which can be severe.

We recently completed a small phase two a trial with about 25 patients for treatment arm testing, whether dupixent could improve the safety tolerability and efficacy of subcutaneous immunotherapy or skipped therapy for grass allergy.

The preliminary results of this study showed that about 30 patients discontinued therapy in skewed group.

Mostly due to clinically meaningful allergic reactions.

Compared to only a single patient discontinued get when combined with Dupixent and not due to an allergic reaction.

And then the primary efficacy analysis, there was no difference in terms of reduction of the allergic symptoms with scale yet we're in the combination.

George D. Yancopoulos: Thus, we are encouraged by the potential of depiction to increase the tolerability of SCID therapy, and we're looking forward to presenting the results at a future medical meeting. Earlier this quarter, we reported that Regeneron 3500, our interleukin-33 antibody, met primary and secondary endpoints in a proof-of-concept study in moderate-to-severe asthma, showing that Regeneron 3500 may provide an alternative therapeutic option for asthma. Although the Regeneron 3500 results were numerically lower than those for the Dupixent Calibrator on,

Thus, we are encouraged by the potential of Dupixent increase the tolerability of skin therapy, and we're looking forward to presenting the results at a future medical meeting.

Earlier this quarter, we report that Regeneron 3500 are interleukin 33 antibody the primary and secondary endpoints in a proof of concept study in moderate to severe asthma patients showing that regeneron 3500 may provide an alternative therapeutic option for asthma.

Although the Regeneron 3500 results were numerically lower than those for the Dupixent calibrate on.

George D. Yancopoulos: In addition, the combination of Regeneron 3500 and Duprexin did not demonstrate increased benefit compared to Duprexin monotherapy in this trial, although the study was not powered for this comparison. In addition, within the next 12 months, we are expecting interim results from the Phase II Regeneron 3500 studies in COPD and in atopic dermatitis. I will now shift gears to our immunotherapy efforts to treat cancer, starting with Lep

In addition.

The combination of Regeneron 3500, Dupixent did not demonstrate increased benefit compared to depicts a monotherapy in this trial all of the study was not powered from Paris.

In addition, the next 12 months, we expect the interim results from the Phase two Regeneron 3500 studies in C O PD and in topic dermatitis.

I will now shift gears to our immunotherapy efforts to treat cancer.

[noise], starting with with time.

George D. Yancopoulos: Last month, our PD-1 antibody was approved in the EU for adults with metastatic or locally advanced cutaneous Squamous Cell Carcinoma who are not candidates for curative surgery or curative radiation, making Leptio the first and only approved medicine of any kind for patients with advanced CSCC in the U.S. and Europe. With the goal of making Lepti available for a broader population of CFCC patients, we started a In addition to an ongoing investigator-initiated study, our study in the neoadjuvant setting is scheduled to start in the fourth quarter. Additionally, a pivotal study of leptile and basal cell carcinoma, the most common skin cancer, is expected to read out in the first half of next year. Moving on, to non-small cell lung cancer.

Last month, our PD one antibody was approved in the EU for adults with metastatic locally advanced detainees.

Squamous cell carcinoma, who are not candidates for curative surgery or cure radiation, making the time of the first and only approved medicine anytime for patients with advanced C. FCC in the U.S. and Europe .

With the goal of making the time available for a broader population of sea FCC patients. We started a phase three study and as you can see FCC.

In addition to an ongoing investigator initiated study.

Our study in the Neoadjuvant setting is scheduled to start in the fourth quarter.

In addition, Lilly a pivotal study of lepton based lacrosse now the most common skin cancer is expected to read out in the first half of next year.

Moving on to non small cell lung cancer.

We are pleased by the enrollment for all the time monotherapy phase three trial in high PDL. One expressers, we have commenced enrollment in part two of our other phase three lung cancer study, which will compare laptop plus chemotherapy chemotherapy alone regardless of PDL, one status where histology.

George D. Yancopoulos: We are pleased by the enrollment for our Leptile Monotherapy Phase 3 trial in high PD-L1 expressors. We have commenced enrollment in Part 2 of our other Phase 3 lung cancer study, which will compare Leptile plus chemotherapy to chemotherapy alone, regardless of PD-L1 status or histology. Beyond checkpoint inhibition, our investigational bispecific antibody franchise consists of two broad categories based on the T cell receptor to which the bispecifics bind. CD3 molecule or the CD28 co-stimulatory bispecific. In total, we now have four biospecifics under clinical investigation. They are CD20 by CD3, BCMA by CD3, MUX16 by CD3, and notably, the newest edition of our first Coast Cemetery by Pacific PSMA

Beyond checkpoint inhibition, our investigational by specific antibody franchise consists of two broad categories based on the T cell receptor to which to buy specific bye.

The cdthree molecule or the Cdtwenty cost inventory by specifics in total we now have more bison since under clinical investigation.

Our cdtwenty by Cdthree CCMA by Cdthree MACT 16 by Cdthree.

And notably.

The nearest edition of our first coast inventory by specific estimate by CD 28.

George D. Yancopoulos: Additional candidates are expected to enter the clinic in the upcoming months and years. In June, we presented updated efficacy and safety data for Regeneron 1979, our CD20 by CD3 bispecific. Regeneron 1979 continues to show high response rates in heavily pre-treated non-Hodgkin lymphoma patients. In particular, we observed complete responses in four out of seven diffuse large B-cell lymphoma, or DLV-CL, patients treated with Regeneron 1979 doses of 80 milligrams or higher. Notably, four of these had failed prior CAR-T therapy, and two of them achieved complete responses.

Additional candidates are expected to enter the clinic in the upcoming months in years.

In June we presented updated efficacy and safety data for Regeneron 1979, our cdtwenty by Cdthree by specific.

Regeneron 1979 continues to show high response rates in heavily pretreated non hodgkin lymphoma patients.

In particular, we observe complete responses and four out of seven diffuse large b cell lymphoma, where DLD CLL patients treated with regeneron 1979 dose of 80 milligrams or higher.

Notably more of these had failed prior car T therapy, and two of which achieved complete responses.

George D. Yancopoulos: Regeneron-1979 has demonstrated manageable tolerability with no discontinuations due to cytokine release syndrome or neurotoxicity to date. Recruitment for a potentially pivotal Phase II trial for Regeneron-1979 is now ongoing. The multi-armed study will enroll several disease-specific cohorts of relapsed refractory non-Hodgkin's lymphoma patients, including follicular lymphoma, DLBCL, and other non-Hodgkin's lymphoma subjects. Our two other CD3 bispecific antibodies, MUX16 by CD3 for platinum-resistant ovarian cancer and BCMA by CD3 for relapse Finally, recruitment is ongoing for the position.

Regeneron 1979 has demonstrated manageable tolerability with no discontinuations due to cytokine release syndrome or neurotoxicity today.

Recruitment for a potentially pivotal phase two trial for Regeneron 1979 is now ongoing multi arm study will enroll several disease specific cohorts of relapse refractory non hodgkin's lymphoma patients, including Follicular lymphoma.

Dl Bcl and other non Hodgkin's lymphoma subtype.

Our two other cdthree boxes of again by must 16 by Cdthree for platinum resistant ovarian cancer and BC made by Cdthree for relapse or refractory multiple myeloma, our clinical studies that are actively enrolling patients and plan to present preliminary BC made by C data by the end of 2019.

Finally recruitment is ongoing for the.

George D. Yancopoulos: The first co-stimulatory candidate, Regeneron 5678, which binds to prostate-specific membrane antigen, or PSMA, on tumor cells, as well as the CD28 co-stimulatory molecule on T-cells. Based on preclinical evidence, we are hoping to see synergy of our co-STIMs with Liptio in disease settings, such as prostate cancer, that have proven resistant to immunotherapy alone. If successful, this innovative approach could open up the possibility of immunotherapy to a large number of patients who do not currently have this option. In addition, we expect a number of updates related to other programs emerging from our pipeline.

First coast inventory candidate, Regeneron, 5678, which buys prostate specific membrane antigen or P.S. umang on tumor cells.

As well as the Cdtwenty and cost inventory molecule on T cells.

Based on preclinical evidence, we are hoping to see synergy of our co stems with live Thailand disease, setting such as prostate cancer.

That have proven resistant to immunotherapy alone.

If successful this innovative approach could open up the possibility of immunotherapy to a large number of patients who do not currently have this option.

In addition, we expect a number of updates related to other programs emerging for our pipeline.

By the end of 2019, we are planning to present, our C antibody data in patients with PAREXEL nocturnal chemo loving area or PNNT.

George D. Yancopoulos: By the end of 2019, we are planning to present our C5 antibody data in patients with paroxysmal nocturnal hemoglobinuria, or PNH. By the end of this year, we also expect readout of our ANG-PTL3 antibody phase 3 study in homozygous familial hypercholesterolemia, as well as a readout of our active in any antibody pivotal study in the rare disease fibrodysplasia Phase III studies of Ficinumab, our advanced candidate for osteoarthritis pain, are now fully enrolled, and data are expected during 2020. Finally, we just celebrated the fifth anniversary of the Regeneron Genetics... To date, we have sequenced 700,000 individuals, linking their exome data with detailed medical records. We continue to be excited about our ongoing efforts here, including our work to sequence the UK Biobank database in collaboration with a consortium of leading biopharma partners. Mining of the Regeneron Genetic Center Database has already discovered and or validated a number of genetic drug targets across several human diseases, which are positively impacting our current development. With that, I'll now turn the call over to Marion.

By the end of this year, we also expect Riyadh over and speed tier three antibody phase three study in homozygous familial hypercholesterolemia as well as a recap of our active in antibody pivotal study in the rare disease vibrant dysplasia, ossificans progressiva or FOP.

Phase three studies at the Sydney map, our advanced candidate for osteoarthritis pain are now fully enrolled and data are expected during 2012.

Finally, we just celebrated its fifth anniversary of the Regeneron Genetics Center.

To date, we have sequenced 700000 individuals linking direct some data with detailed medical records. We continue to be excited about our ongoing effort here, including our work to sequence. The UK Biobank database in collaboration with a consortium of leading Biopharma partners.

Mining of the Regeneron Genetics Center database has already discovered and or validated a number of generic drug targets across several human diseases, which are positively impacting our current development efforts.

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

Marion McCourt: Thank you, George. In the second quarter, we executed well across our portfolio of existing lines of business and recent launches. Starting with ILEA, global net product sales grew 13% year-over-year to $1.9 billion. In the U.S., net product sales grew 17% year-over-year and 8% quarter-over-quarter to $1.16 billion. ILEA growth is driven by share gain and market expansion, underpinned by the aging population and increase in diabetes prevalence. In the branded U.S. anti-VEGF market, our share increased to 71% of net product sales. In the quarter, a temporary shortage of the vaccine in select geographies modestly impacted ILEA net sales.

Thank you Joe rights in the second quarter, we executed well across our portfolio of existing lines of business and recent launches.

Starting with EMEA level net product sales grew 13% year over year to 1.9 billion.

Let me wrap net product sales grew 17% year over year, and 8% quarter over quarter to 1.16 billion.

Revenue growth was driven by share gains and market expansion underpinned by the aging population and increase in diabetes prevalence and the branded you are looking better market our share increased to 71% of net product sales.

In the quarter, a temporary shortage of action and select geography modestly impacted our Vms sales.

Marion McCourt: ILEA continues to help patients with diabetic eye disease, and this represents an important growth opportunity for the brand. In mid-May, the FDA approved ILEA to treat all stages of diabetic retinopathy, and our launch commenced immediately. For this indication, ILEA is the only anti-VEGF approved with two dosing options, allowing doctors to customize treatment to their patients' needs.

I'm reluctant to move to help patients with diabetic eye disease and this represents an important growth opportunity for the brand in mid men collecting approved to treat all expenses are diabetic retinopathy and launch commenced immediately for this indication.

Only sentence that decreases the true dosing options, allowing doctors to customize treatments for their patients needs.

Marion McCourt: Our comprehensive plans to develop ILEA's position in the diabetic retinopathy market are underway. We began educating both physicians and patients upon approval, encouraging early intervention for appropriate patients, and ensuring ILEA is the first-line anti-VEGF treatment. It's early days in the launch, but we're pleased with feedback from retina specialists, and we're seeing positive early interest and uptake among major practices. We are investing in ILEA's promotional platforms to advance our market-leading position across all indications, including wet AMD, DME, and diabetic retinopathy. Our expanded and realigned sales force has the dual focus of growing both the diabetic eye disease market and our core wet AMD business. Robust engagement efforts with the retinal community, messaging both ILEA's clinical and real-world experience, are well underway.

Our comprehensive plan to develop RMBS position in the diabetic retinopathy market are underway, we begin entertaining that physicians and patients upon approval encouraging early intervention for appropriate patients and ensuring idea is the first time into that Jeff treatment.

It's early days and our launch and look for user feedback from retina specialists.

And we're seeing positive early interest and uptake among major practices.

We are investing in our commercial platforms together, our market leading position across all indications, including rapid RMB, Danny I'm in diabetic retinopathy.

Our expanded and realigned sales force has a dual focus of growing both the diabetic eye disease market, our corn wet AMD business.

No, but sometimes we reference with the retinal community messaging, both clinical and real world experience are well underway.

Marion McCourt: Visual outcomes and safety remain the standards by which therapies are compared, and ILEA's rapid and sustained outcomes in improving and protecting vision are unsurpassed. We're committed to further strengthening our leadership position for ILEA through continued innovation, including in dose and delivery. Pending FDA approval, the ILEA pre-filled syringe will be launched in 2019. Now, I'd now like to turn to Liptio. The launch in cutaneous gramicell carcinoma, or CSCC, continues to gain momentum, and in the US, net product sales were $41 million for the quarter.

Digital outcomes and safety remains standards by we expect these are compared an ambulance rabbit and sustained outcomes and improving and protecting vision are unsurpassed recommitment to further strengthening our leadership position for Cambia through continued innovation, including in person delivery.

How are you going after the approval the army a prefilled syringe will be launched in 2019.

I'd now like to turn the time the margin consumable squamous cell carcinoma, or see FCC continues to gain momentum and Im your net product sales were 41 million for the quarter brand awareness within the medical community is growing demonstrated by the breadth of prescribers that major cancer centers and community practices around the country. Since launch we made further progress in establishing that time as a standard of care in advance the FCC across all lines of therapy.

Marion McCourt: Brand awareness within the medical community is growing, demonstrated by the breadth of prescribers at major cancer centers and community practices around the country. Since launch, we have made further progress in establishing Liptio as the standard of care in advanced CSCC across all lines of therapy. Market research indicates more than three times as many CSCC patients are now receiving an anti-PD-1 or PD-L1 treatment compared to before Liptio's approval. We believe libtio is poised for continued growth. We have broad payer access and QA recommendation from the National Comprehensive Cancer Network. Libtio is the only checkpoint inhibitor to have this designation from CSCC. Additionally, non-US launches in CSCC are underway, and we look forward to data that could expand the potential of our dermatologic oncology portfolio into earlier stages of CSCC and beyond. Moving to Preluant, in the second quarter, global net sales were $74 million.

Market research into more than three times as many cc patients are now.

Receiving an anti PD, one or PDL, one treatment compared to before in the prior to approval.

We believe live trial is poised for continued growth would have broad payer access.

And it's true and recommendations from the National comprehensive cancer network.

The tire is the only checkpoint inhibitor to having said designation in CST soon.

Additionally, ex us launches and CFTC are underway and we look forward to data that could expand the potential of our dermatologic oncology portfolio into earlier stages of CFTC and beyond.

Moving to calculate in the second quarter Global net sales were 74 million.

Marion McCourt: In the highly competitive U.S. market, we remain focused on patient affordability and physician ease of prescribing. We are working closely with our collaborator Sanofi to greatly improve brand profitability. Turning to Kevzara, in the second quarter, global net sales were $59 million.

A highly competitive market, we remain focused on patient affordability and simplicity ease of prescribing. We are working closely with our collaborator Sanofi to greatly improve brand profitability turning to Tim Zara and second quarter Global net sales were 59 million in the U.S. concern continues to make headway in the aisle six subcutaneous class with an estimated 47% share of new patients dispense casella, MDR acts and 29% share of total scripts akcea.

Marion McCourt: In the U.S., Kevzara continues to make headway in the IL-6 subcutaneous class with an estimated 47% share of new patients dispensed Kevzara or NDRX and 29% share of total Scripps or TRX. Now for Dipixent, which is transforming the lives of patients suffering from type 2 inflammatory diseases, atopic dermatitis, asthma, and now chronic rhinosinusitis with Global net product sales in the second quarter were $557 million, and U.S. net product sales reached $455 million, representing 151% year-over-year growth.

Now for detection, which is transforming the lives of patients suffering from a type two inflammatory diseases e-commerce dermatitis asthma, and now chronic rhinosinusitis with nasal polyps.

Global net product sales in the second quarter were 557 million in the U.S. net product sales reached 455 million, representing 151% year over year growth.

Marion McCourt: Total prescriptions, or TRX, in the US grew approximately 30% compared to the first quarter. This was driven by continued growth in approved indications, adult atopic dermatitis and asthma, as well as the launch of atopic dermatitis for adolescents. Weekly Nutibran prescriptions, or NBRX, for the second quarter averaged approximately 1,200 patients per week, up from 950 in the prior quarter. This momentum is further evidence of the positive impact of our commercialization strategy and execution across all approved indications. As we mentioned last quarter, prescribing continues to grow in adult atopic dermatitis as more moderate patients are just prescribed Duplexant, and more healthcare professionals gain brand experience. Our recent launch in adolescents is going well. As a reminder, Dupixent is the first biologic approved for adolescents, many of whom remain uncontrolled using topical therapies. Market reaction has been extremely positive.

Total prescriptions, our Trx MLS grew approximately 30% compared to the first quarter. This was driven by continued growth in approved indications adult atopic dermatitis and asthma as well as the launch and topic dermatitis for adolescents.

Weekly new to brand prescription or NBR acts for the second quarter averaged approximately 1200 patients per week up from 950 in the prior quarter.

This momentum is further evidence of the positive impact of our commercialization strategy and execution across all approved indications.

As we mentioned last quarter correct.

Prescribing continues to grow and accounting topic dermatitis as more moderate patients are.

Patients are just prescribed to Texas.

And more health care professionals game brand experience.

Our recent launch in adolescence is going well as a reminder to Texas is the first biologic for adolescents, many of whom remain uncontrolled using topical therapies.

Market reaction has been extremely positive target physicians are prescribing and excited about the results are seeing their significant uptake of our both dermatologists, an allergist and were making meaningful inroads in reaching target pediatric dermatologists and pediatric Allergist. In addition market access coverage is already at or near the levels of the adult population.

Marion McCourt: Target physicians are prescribing and excited about the results they're seeing. There's significant uptake among both dermatologists and allergists, and we're making meaningful inroads into reaching target pediatric dermatologists and pediatric allergists. In addition, market access coverage is already at or near levels in the adult population.

Marion McCourt: Asthma is a significant opportunity, and Dupixent is well positioned for continued growth. Dupixent's differentiated clinical and safety profile continues to support uptake. The asthma biologic market has expanded 13% since Dupixen's launch, demonstrating our ability to compete and grow this market. Allergists who have experience using Dupixen in atopic dermatitis now also see its benefit for their asthma patients. Prescribing among pulmonologists is also increasing, and they are highly receptive to Vixen's efficacy, use in steroid-dependent patients, and self-administration. And finally, in late June, Dupixent became the first biologic medicine approved as an add-on maintenance therapy treatment for adults with adequately controlled chronic rhinosinusitis with nasal polyps.

Asthma is a significant opportunity into six and is well positioned for continued growth to take since differentiated clinical and safety profile continues to support uptake.

Yes, no biologic market has expanded 13% since to pick since launch demonstrating our ability to compete and grow this market.

Allergens web experience using takes an entire dermatitis now office seats benefit for their asthma patients prescribing more.

Excuse me prescribing mum Pulmonologists is also increasing and they are highly receptive to nixon's efficacy using start dependent patients and self administration.

And finally, reaching to take some became the first biologic medicine approved as an add on maintenance therapy treatment for adults with an adequately controlled chronic rhinosinusitis.

Nasal polyps.

Marion McCourt: This indication is yet another first-in-class opportunity for DEPIXENT given the high unmet need. In the U.S., up to 90,000 adults with chronic rhinocyticitis with nasal polyps are considered uncontrolled despite prior surgery or systemic corticosteroid use, and about 55,000 patients are those that have had prior surgery. Importantly, many patients with this disease have other type 2 inflammatory diseases like asthma. In our two Phase III clinical trials, almost 60% of patients also had asthma, which was improved with DEPIXENT treatment. Our commercial efforts are focused on ENTs and allergists, and we're having constructive payer discussions. While early in the launch, we believe this will be a meaningful growth opportunity for DEPIXENT, and we look forward to providing future updates. In closing, we're excited about our near-term performance and confident that our ongoing commercialization efforts will drive long-term growth across core brands and ongoing launches. Now, I'll turn the call over to Bob.

This indication is yet another first in class opportunity for depicts and given the high unmet need.

In the U.S. up to 90000 adults with chronic rhinosinusitis with nasal polyps are considered uncontrolled despite prior surgery or systemic corticosteroid use and about 55000 patients by does that had a prior surgery importantly, many patients with this disease have other type two inflammatory diseases like asthma.

In our two phase three clinical trial, almost 60% of patients also had asthma, which was improved to six and treatment. Our commercial efforts are focused on MTS, an allergist and we're having constructive payer discussions while early in the launch we believe this will be a meaningful growth opportunity for dupixent and we look forward to providing future updates.

In closing we are excited about our near term performance and confidence that our ongoing commercialization efforts will drive long term growth across core brands and ongoing launches.

Now I'll turn the call over to Bob.

Robert E. Landry: Thanks Marion. For the second quarter of 2019, Regeneron executed well and delivered solid financial results on both the top and bottom line. And, as Len stated, we are pleased that the Sanofi antibody collaboration has reached commercial profitability. Total revenues for Regeneron grew 20% year-over-year to $1.93 billion, driven by continued growth of our core brands. Non-gap diluted net income per share grew 10% year-over-year to $6.02, a non-gap net income of $690 million. Our second quarter GAAP results were impacted by both the Anilam upfront payment and equity investment. In addition to Marion's earlier comments about ILEA, I want to highlight two additional items related to U.S. ILEA net sales for the quarter. First, inventory movements were immaterial in the quarter.

Thanks Marianne.

For the second quarter, 2019, Regeneron executed well and delivered solid financial results on both the top and bottom lines.

And does lend stated we are pleased that the Sanofi antibody collaboration has reached commercial profitability.

Total revenues for Regeneron grew 20% year over year to 1.93 billion driven by continued growth of our core brands idly and picks and non-GAAP diluted net income per share grew 10% year over year to $6 in two cents.

Our non-GAAP net income of $690 million.

Our second quarter GAAP results were impacted by both the El Nio them upfront payment and equity investment.

In addition to marian's earlier comments about idea I want to highlight two additional items related to us I'd leave net sales for the quarter first inventory movements were immaterial in the quarter second us highly enough sales were impacted by an increase in sales related deductions.

Robert E. Landry: Second, U.S. ILEA net sales were impacted by an increase in sales-related deductions. Moving to our Collaboration Revenue Line item. Starting with Bayer, ex-U.S. ILEA net product sales, which are reported to us by Bayer, were $715 million, representing a 7% reported and a 13% constant currency basis increase year-over-year. Total Bayer collaboration revenue for the second quarter of 2019 grew 10% year-over-year to $289 million, of which $269 million was derived from our share of net profits from ILEA sales outside the U. Total Sanofi collaboration revenue was $349 million, up 47% year-over-year. This increase was primarily driven by improved profitability in the Sanofi antibody collaboration. In the second quarter of 2019, Regeneron recognized a profit of $39 million in connection with the commercialization of non-Io antibodies, compared to a loss of $69 million in the second quarter of 2018. This profitability came from higher global net product sales of Dupixent, partly offset by an increase in commercialization-related expenses to support the ongoing Dupixent launch. Based on our current projections, we anticipate increasing profitability from the commercialization of non-IO antibodies going forward.

Moving to our collaboration revenue line items, starting with bear ex us solidly in that product sales, which are reported to us by bear were $715 million, representing a 7% reported in a 13% constant currency basis increase year over year total Bayer collaboration revenue for the second quarter of 2019 grew 10% year over year to $289 million of which $269 million was derived from our share of net profits from my list sales outside the U.S.

For the Sanofi collaboration we generated significantly improved results total Sanofi collaboration revenue was 349 million up 47% year over year. This increase was primarily driven by improved profitability in the Sanofi antibody collaboration in the second quarter 2019, Regeneron recognized profit up 39 billion in connection with the commercialization of non Io antibodies compared to a loss of 69 billion in the second quarter of 2018 profitability came from higher global net product sales of Dupixent, partly offset by an increase in commercialization related expenses to support ongoing dupixent launches.

Based on our current projections, we anticipate increasing profitability from the commercialization of non Io antibodies going forward turning now to expenses non-GAAP R&D expenses were 589 million for the second quarter of 2019 compared to $470 million for the second quarter, 2018, and essentially flat compared to the 583 million recognized in the first quarter of 2019.

Robert E. Landry: Turning now to expenses. Non-GAAP R&D expenses were $589 million for the second quarter of 2019, compared to $470 million for the second quarter of 2018, and essentially flat compared to the $583 million recognized in the first quarter of 2019, driven by continued investment in our research platform and pipeline. Our non-GAAP unreimbursed R&D expense, which is calculated as the total non-GAAP R&D expense less R&D reimbursements from our collaborators, was $423 million for second quarter 2019 compared to $286 million for the second quarter 2018 and $419 million for the first quarter 2019. The year-over-year increase is primarily driven by higher spend associated with our earlier-stage pipeline, clinical trial and manufacturing costs to support ongoing development programs, and lower Sanofi reimbursement as a result of the amended immuno-oncology discovery and development.

Driven by continued investment in our research platform and pipeline.

Our non-GAAP unreimbursed R&D expense, which is calculated as the total non-GAAP R&D expense less R&D reimbursements from our collaborators.

Was 423 million for second quarter, 2019, compared to $286 million for the second quarter 2018 in $419 million for first quarter 2019, the year over year increase is primarily driven by higher spend associated with our earlier stage pipeline clinical trial and manufacturing cost to support ongoing development programs and lower Sanofi reimbursement as a result of the amended immuno oncology discovery and development agreement.

Based on the current progress in our R&D pipeline and outlook for the remainder of the year. We are tightening our previous full year 2019 guidance for non-GAAP Unreimbursed R&D to 1.625 to 1.71 billion.

Robert E. Landry: Based on the current progress in our R&D pipeline and outlook for the remainder of the year, we are tightening our previous full year 2019 guidance for non-GAAP unreimbursed R&D to $1.625 to $1.71 billion. Non-GAAP SG&A Expense was $375 million for the second quarter of 2019, a 16% year-over-year increase driven by commercialization-related expenses to support ongoing PIXENT launches We are tightening our previous full year 2019 guidance for non-GAP SGNA from 1.53 to 1.58 billion. Sanofi reimbursement of Regeneron commercialization-related expenses, a line item found within Sanofi collaboration revenue, was $123 million for the second quarter of 2019. We are lowering and tightening our previous full year 2019 guidance for Sanofi reimbursement of Regeneron commercialization related expenses to $500 to $530 million. Turning now to tax.

Next.

non-GAAP SGN expense was 375 million for the second quarter 2019, a 16% year over year increase driven by commercialization related expenses to support ongoing dupixent launches and idly as recent launch in diabetic retinopathy.

We are tightening our previous full year 2019 guidance for non-GAAP SG 90 to 1.53 to 1.58 billion.

Sanofi reimbursement of Regeneron commercialization related expenses a line item found within Sanofi collaboration revenue was 123 million for the second quarter 2019, we are lowering and tightening our previous full year 2019 guidance for Sanofi reimbursement of regeneron commercialization related expenses to $500 million to $530 million.

Turning now to taxes for the second quarter, our GAAP effective tax rate was 14.1%. We are reaffirming our full year 2019, GAAP effective tax rate guidance of 11% to 13% to assist with modeling principally due to the old xylem $400 million upfront exclusion from non-GAAP earnings.

The full year 2019, non-GAAP tax rate will be higher than our full year 2019, GAAP effective tax rate.

Robert E. Landry: For the second quarter, our GAAP effective tax rate was 14.1%. We are reaffirming our full year 2019 GAAP effective tax rate guidance of 11 to 13%, to assist with modeling principally due to the O'Neillum $400 million upfront exclusion from non-GAAP earnings. The full-year 2019 non-GAAP tax rate will be higher than our full-year 2019 GAAP effective tax rate. Turning next to our balance sheet and cash flow, Regeneron ended the second quarter with cash and marketable securities of $5.55 billion. Through the first six months of the year, we generated free cash flow of $916 million. We calculate free cash flow as net cash provided by operating activities, less capital expenditures. Capital expenditures were $95 million for the quarter and $169 million year-to-date.

Turning next to our balance sheet and cash flow Regeneron ended the second quarter with cash and marketable securities of $5.55 billion through the first six months of the year, we generated free cash flow of 916 million, we calculate free cash flow as net cash provided by operating activities less capital expenditures.

Capital expenditures were $995 million for the quarter and $169 million year to date based on our updated capital spend plan and year to date spending levels, we are lowering and tightening our full year 2019 capital expenditure guidance to $380 million to $420 million.

In conclusion, we are very pleased with our operational and financial performance. This quarter. These financial results along with the execution on our R&D and commercial strategies position us for continued long term growth with that I'd like to turn the call back to Justin.

Robert E. Landry: Based on our updated capital expenditure plan and year-to-date spending levels, we are lowering and tightening our full year 2019 capital expenditure guidance to $380 to $420 million. In conclusion, we're very pleased with our operational and financial performance this quarter. These financial results, along with the execution of our R&D and commercial strategies, position us for continued long-term growth. With that, I'd like to turn the call back to Justin.

Thank you Bob that concludes our prepared remarks, and we'd now like to open the call for Q and a.

To ensure that we are able to address as many callers as possible. Please limit your questions to one or two questions. Please go ahead John .

And thank you we'll now begin the question and answer session. If you do have a question press Star then one on your Touchtone phone.

If you wish to hear from the queue. Please press the pound or hash key.

If using a speaker phone you may need to pick up the handset first before pressing the numbers.

Once again, if you have a question press Star then one on your Touchtone phone.

Robert E. Landry: Thank you, Bob. That concludes our prepared remarks, and we'd now like to open the call for Q&A. To ensure that we are able to address as many callers as possible, please limit your questions to one or two questions. Please go ahead, John.

And our first question is from Carter, yes.

Good morning, guys. Congrats on the Sanofi collaboration tipping over into profitability and thanks for taking the question one for George I wanted to ask around the Cdtwenty antigen loss you observed at disease progression and some of the patients responding to 1979.

John: And thank you. We will now begin the question and answer session. If you do have a question, press star then 1 on your touch-tone phone. If you wish to be removed from the queue, please press the pound sign or the hash key. If using a speakerphone, you may need to pick up the handset first before pressing the numbers. Once again, if you have a question, press star then 1 on your touch-tone phone. And our first question is from Carter Gould from UBS.

I was interested in.

Our current understanding the mechanism in play here given I believe this was rare with Rituxan and how you see this potentially ultimately influencing how 1979 maybe position in the treatment paradigm. Thank you.

I have to admit I didn't quite get your question Matt.

Okay. It was it was around the CD 20 antigen loss you saw in some of the patients.

Treated and how you see that ultimately potentially influencing how the truck is positioned to the treatment paradigm.

John: Good morning. Congratulations on the Sanofi collaboration tipping over into profitability, and thanks for taking the question. One for George. I wanted to ask about the CD20 antigen loss you observed at disease progression in some of the patients responding to 1979. I was interested in your current understanding of the mechanism in play here, given I believe this was rare with rituxan, and how you see this potentially ultimately influencing how 1979 may be positioned in the treatment paradigm. Thank you.

If it.

Potentially takes away a salvage auctions.

Right.

Well.

I think that we have seen antigen loss of both Cdtwenty and also Cdnineteen, which has occurred so far doesn't seem to have.

In these very late stage patients dramatically affected the response rates are the durability.

So we're seeing.

The rates that we responded we reported.

So it doesn't seem like it's at this point the major issue.

George D. Yancopoulos: I have to admit, I didn't quite understand your question there.

Thank you.

Our next question John .

Matthew Harrison from Morgan Stanley .

Hey, good morning, Thanks for taking my question I guess I wanted to ask on the initial VCM eight data that you expect to present towards the end of this year I mean, how should we think about relevant comparisons here is this something.

George D. Yancopoulos: It was around the CD20 antigen loss you saw in some of the patients treated and how you see that ultimately potentially influencing how the drug gets positioned in the treatment paradigm if it potentially takes away salvage options.

George D. Yancopoulos: Right, well... I think that we have seen antigen loss of both CD20 and also CD19, which has occurred. So far, it doesn't seem to have, you know, in these very late stage patients, dramatically affected the response rates or the durability. So we're seeing the rates that we responded to, and we reported, so it doesn't seem like it's at this point a major issue.

You would compare against carty against bite.

Im just wondering how we should think about that and what the goal here is thanks.

Well.

Maybe George has more comments, but I would say.

Besting is probably to wait for the data but.

The way Sanofi and Regeneron and thinking about that and this is part of the collaboration is that.

Obviously, if we can deliver anything close to what a bi specific can deliver.

John: Our next question...

Then.

The car T can deliver excuse me then a bi specific being off the shelf and the pharmaceutical like drug pricing consideration things like that should obviously have a huge advantage in the marketplace.

Leonard S. Schleifer: Matthew Harrison from Morgan Stanley Hey, good morning. Thanks for taking the question. I guess I wanted to ask about the initial BCMA data that you expect to present towards the end of this year. I mean, how should we think about relevant comparisons here? Is this something you would compare against CAR-T, against Bites? I'm just wondering how we should think about that and what the goal here is.

So we would consider.

Our competition more things like the bites and what have you.

Obviously, we have already started out with long lasting molecules.

With a well designed to have a metric we make pim straightforwardly through a proprietary approach. So we think that we can compete and what you should be looking for.

Leonard S. Schleifer: Well, maybe George has more comments, but I would say the best thing is probably to wait for the data. But the way Sanofi and Regeneron are thinking about that, and this is part of the collaboration, is that obviously if we can deliver anything close to what a bi-specific can deliver, then that a CAR-T can deliver, excuse me. Then a bi-specific being off the shelf in a pharmaceutical-like drug pricing consideration, things like that, should obviously have a huge advantage in the marketplace. So we would consider our competition more things like the bites and what have you. Obviously, we have already started out with long-lasting molecules.

So what kind of activity, we can deliver so.

Maybe we should just wait for that yeah, and I think just to add that I think that.

Obviously, we're hoping that it's going to confirm that our class of cdthree by specifics, our reproducibly sort of top of the class in terms of.

Producing the sort of efficacy that weve already seen with our CD 20 by Cdthree by specific.

And so that's what we're hoping for in addition to that we just want to point out that both with our own pipeline and obviously with our partners pipeline. There are a myriad of combination opportunities.

Leonard S. Schleifer: They're well-designed, and we make them straightforwardly through a proprietary approach. So we think that we can compete, and what you should be looking for is what kind of activity we can deliver. So maybe we should just wait for that.

So it's just sort of the beginning to show the activity with the DC made by specific we can then add to it with the right set of combinations with components that both sides in the collaboration have to offer that we're very excited about including for example, our coast tips.

Leonard S. Schleifer: Yeah, and I think, just to add, that I think that, obviously, we're hoping that it's going to confirm that our class of CD3 bispecifics are reproducibly sort of, you know, top of the class in terms of producing the sort of efficacy that we've already seen with our CD20 by CD3 bispecifics, and so that's what we're hoping for in addition to that we just want to point out that both with our own pipeline and obviously with our partners pipeline there are a myriad of combination opportunities so it's just sort of the beginning to show the activity with the BCMA by specific we can then add to it with the right set of combinations with components that both sides in the collaboration have to offer that we're very excited about including for example our co-STEMs which we have quite a few that could potentially collaborate clinically with the BCMA by CE3 pipeline.

Which we have quite a few that could potentially collaborate clinically with the DC made by Cdthree by us.

Thank you Matthew next question.

Our next question is from Terence Flynn from Goldman Sachs.

Hi, great. Thanks for taking the questions and congrats on the antibody JV profitability as well.

Maybe just two on Dupixent first on I was wondering if you could share your thoughts about the relevant size of the six to 11 year old population Europe Atopic Derm and then you know with the pace of uptake be similar or faster than what we saw with adults in your view and then on Dupi for grass allergy. Thanks for the additional data just wondering next steps there for that program. If you could give us any more color on the forward. Thank you.

So when we take the Duke married to take the the commercial question first sorry mm concerns just to clarify your question on topics that you were talking about the European populations are you talking about U.S. populations.

Leonard S. Schleifer: Thank you, Matthew. Next question?

John: Our next question is from Terence Flynn from Goldman Sachs.

John: Hi, great. Thanks for taking the questions. Congratulations on the antibiotic JV profitability as well.

Sure I mean, both would be great, but but you I know you got the you have the data. This morning from six to 11 and again I don't think you guys have characterize how big those those groups are right right. So.

Marion McCourt: Maybe just two on Dupixent. First, I was wondering if you could share your thoughts about the relevant size of the 6 to 11-year-old population here at the topic derm. And then, you know, would the pace of uptake be similar or faster than what we saw with adults, in your view?

What I wanted to share with you obviously with the topic dermatitis population in the us for adults, we said about three to 400.

George D. Yancopoulos: And then, on Doobie for grass allergies, thanks for the additional data. Just wondering what the next steps there are for that program, if you could give us any more color on that. Thank you.

Thousand patients our greatest.

We just need of therapy, and I and I just want to lend the context.

Point.

Well, we're very pleased with absolute on the different parts and pieces meeting in the lives of patients, we probably only so far reached about how.

Leonard S. Schleifer: So why don't we take the, Marion will take the commercial question first.

Marion McCourt: Sure, and Terence, just to clarify, your question indicates that you were talking about European populations, or were you talking about U.S. populations?

Hi, teens about 18% of the adult patient population.

We're excited about the adolescence launch and we're seeing nice uptake. We are early days again, a lot more work to do we haven't given a characterization and the size of the pediatric population, but certainly well in the future as we got into the data readout and preparedness for launch of Bobby indication, which certainly I can confirm what we will be preparing to launch as soon as we have the FDA approval, yes, just a slight follow up on that the uptake of the.

Leonard S. Schleifer: Both would be great, but yeah, I know you had the data this morning from 6 to 11, and again, I don't think you guys have characterized how big those groups are.

Marion McCourt: Right, right. So, you know, what I wanted to share with you is, you know, obviously, with the atopic dermatitis population in the U.S. for adults, we've said about 300,000 to 400,000 patients are at greatest need of therapy, and I just want to lend some context that, at this point, while we're very pleased with the uptake and the difference that Zupixen is making in the lives of patients, we've We're excited about the adolescence launch, and we're seeing nice uptake in the early days. Again, there is a lot more work to do. We haven't yet given a characterization of the size of the pediatric population but certainly will in the future as we get further into the data readouts and preparedness for the launch of that indication, which certainly I can confirm will be. to launch as soon as we have FDA approval.

The premium.

Thank you Chris was fairly brisk I think in some of the younger patients. So we think that market is really one of great unmet medical need and as George said. These are children. We studied that had 60% 60% of the body covered with lesions have been also its effect on the mental health. This sweeping the family the adjustability quality of life. So I think that in the severe patients we would expect a pretty brisk uptake, but it's going to obviously take some work because you are treating.

Children with a biologic, we still have to constantly educate.

And remind people what George said contradict distinction to other biologics, where you see an increase in infection. If you listen carefully George mentioned that it was actually in America. We decreased consistent that we've seen this of course are severe and moderately severe atopic dermatitis patients a deep in America decrease.

Leonard S. Schleifer: Yeah, just a slight follow-up on that. The uptake of the cream that was abused was fairly brisk, I think, in some of the younger patients. So we think that market is really one of great unmet medical need. And as George said, these are children we studied that had 60 percent, 60 percent of their bodies covered with lesions, having all sorts of effects on their mental health, their sleeping, their family, their ability, and quality of life. So I think that in severe patients, we would expect a pretty brisk uptake. But it's going to obviously take some work because you're treating children with a biologic. We still have to constantly educate and remind people what George said and make a distinction between this and other biologics where you see an increased infection.

So we think that as people get more and more and more comfortable with the safety and efficacy. This will move lower lower down into the age groups as we get approval George maybe want to turn to the gross housing what's next.

Yes, so as I mentioned, we were.

Very excited by the potential of to fixing to apparently increase the tolerability of skin therapy I may have misspoke.

Obviously, if there was 25 patients per arm and I said 30 patients discontinue is 30% of the patients discontinued on skid, which is I think is about normal.

Leonard S. Schleifer: If you're listening carefully, George mentioned that there is actually a numerically decreased consistency that we've seen this across severe and moderately severe atopic dermatitis patients, a numerical decrease. So we think that as people get more and more and more comfortable with the safety and efficacy, this will move lower and lower down into the age groups as we get approval. George, maybe you want to turn to the grass allergy and what's next?

Obviously, if you do the math that study patients assessed the exact number but in any case.

So as we noted the.

Ability of desensitization therapy to work is real but it takes time and it comes at the cost of Tolerability in many patients not being able to get through the therapy because of the severe allergic reaction. So it is obviously very exciting to see dupixent have.

George D. Yancopoulos: Yeah, so as I mentioned, we were very excited by the potential of Dupixen to apparently increase the tolerability of SCIT therapy. I may have misspoken. Obviously, if it was 25 patients per arm and I said 30 patients discontinued, it was 30% of the patients discontinued on SCIT, which I think is about normal. Obviously, if you do the math, that's about 8%. That's the exact number. But, in any case,

Such an apparent benefit out be it in an early study in small numbers.

On the Tolerability of the skin therapy, we have a number of other ongoing programs and studying allergy and I think we're going to be looking at all these together before we come up with a formal.

Our strategy of of how to go forward in this but we do think that this is a very exciting area that can make a lot of difference to a lot of people are suffering from algae. So we're pretty excited.

George D. Yancopoulos: So, as we noted, the ability of desensitization therapy to work is real, but it takes time, and it comes at the cost of tolerability, with many patients not being able to get through the therapy because of severe allergic reactions. So it is obviously very exciting to see Duprexin have such an apparent benefit, albeit in an early study in small numbers, on the tolerability of SCIT therapy. We have a number of other ongoing programs for studying allergies, and I think we're going to be looking at all of these together before we come up with a formal strategy of how to go forward in this, but we do think that this is a very exciting area that can make a lot of difference to a lot of people who are suffering from allergies, so we're pretty excited.

Great. Thank you Terence next question.

Our next question is from Robert from Cowen.

Okay, great. Thanks for taking my question and again nice results.

If you don't mind, just two questions. The first one to do be if you can just give us a sense across.

Between as much a d. and obviously chronic rhinosinusitis is obviously, just getting going but what really kind of led to the growth this quarter on a quarter over quarter basis and in asthma, where where are you getting the majority of sales is it neutral biologics or is it switching from biologics.

And then just a question on a lease whether we're hearing some reports from the field that there is now a slightly higher discounting program from Regeneron about 4% and does that Jive with what you are saying thank you.

So before Marion tackles, those questions I'll say these adjustments first call and maybe he's being nice to we said one question part of that was three and will act.

George D. Yancopoulos: Great. Thank you, Terence. Next question.

Let the Merian give you pass them and try to deal with.

George D. Yancopoulos: Our next question is from Yaron Roberts from Cowen.

I'm happy to.

George D. Yancopoulos: Great, thanks for taking my question, and again, nice results. I have, if you don't mind, just two questions.

So I'm going to start with.

And then let me first comment that.

And we believe that physicians should make this place on which anti VEGF therapy, they want to select for their patients.

Marion McCourt: The first one on DUPI, if you can just give us a sense of the differences between asthma, AD, and obviously chronic rhinocerositis is obviously just getting going, but what really kind of led to the growth this quarter on a quarter-over-quarter basis? And in asthma, where are you getting the majority of sales? Is it new to biologics?

Im certainly ilea is the E.

The standard of care for many prescribers on further I'll, just say that we're really not commenting on pricing strategy I'm happy to go into some of the other items as well I'll see if I can remember the questions. We havent given for Dupixent. We haven't it's early days for many of our indications and we haven't given a break out of business by indication because it would be premature but I think your question. There are a couple of specifics in there that I can give you you are asking for a characterization in asthma and the types of patients.

Marion McCourt: Switching from biologics.

Marion McCourt: And then just a question on ILEA, whether we're hearing some reports from the field that there is now a slightly higher discounting program from Regeneron, about $4.

Marion McCourt: Thank you.

Leonard S. Schleifer: So before Marion tackles those questions, I'll say it is Justin's first call, and maybe he's being nice to you. We said one question per person, and that was three. We'll let Marion give you a pass on that and try and deal with each other. I'm happy to.

Prescribed depicts sand and we are getting on the majority of our starts from buyer naive patients about 80% of our business in some patients who are coming on to biologic therapy, and then of course the remaining our switches.

Marion McCourt: And let me first comment that, you know, we believe that physicians should make the choice on which anti-VEGF therapy they want to select for their patients, and certainly ILEA is the standard of care for many prescribers. Further, I'll just say that we're really not commenting on pricing strategies. I'm happy to go on to some of the other items as well.

The characterization I'll give you is that certainly for physicians, who are prescribing, but allergist uncommon knowledge US now Alan is obviously had a lot of experience with it.

Leonard S. Schleifer: I'll see if I can remember the questions. We haven't given up on duplicates. We haven't.

Excellent from atopic dermatitis, but we are hearing very positive comments and differentiation of the clinical profile. The SIFI. The results. They are getting in terms of the patients ability to to breed more easily and seem to go about their their lives from the normal way that obviously, coupled with the ability for our patients T cells or have at home administration.

George D. Yancopoulos: It's early days for many of our indications, so we haven't given breakout of business by indication because it would be premature. But I think your question, there were a couple specifics in there that I can give you. You were asking for a characterization in asthma of the types of patients that are being prescribed dupixent. And we are getting the majority of our starts from bio-naive patients. About 80% of our business is patients who are coming on to biologic therapy, and then, of course, the remaining are switches. The characterization I'll give you is that, you know, certainly for the physicians who are prescribing both allergists and pulmonologists now, allergists obviously had a lot of experience with dupixent from atopic dermatitis, but we are hearing very positive comments, and it's the differentiation of the clinical profile, the safety, the results they're getting in terms of the patient's ability to breathe more easily and to, you know, to go about their lives in a normal way.

Certainly asthma was a major contributor to our performance in the quarter, but as was a topic dermatitis, we continued to see substantial growth.

And as I mentioned earlier, there's still so much unmet needs throttling down and now we're very excited to also be helping barrick as adolescent patients who are very much in need. So I think I would round it off by saying that the combination of indications the expansion of our platform with Dupixent.

But its contributing to this strong second quarter performance, yes. Thanks Man I, just maybe add one thing to emphasize you said the combination the indications that's really resonating well.

Poor people for example, who have both.

George D. Yancopoulos: That obviously coupled with the ability for patients to self- or have at-home administration. So certainly asthma was a major contributor to our performance in the quarter, but so was atopic dermatitis. We continue to see substantial growth, and, you know, as I mentioned earlier, there's still so much unmet need, certainly for adults, and now we're very excited to also be helping those adolescent patients who are very much in need. So I think I would round it all up by saying that it's the combination of indications, and the expansion of our platform with dupixent that is contributing to this strong second quarter performance.

As Mike and nasal polyps, which is very common we co existing or asthma and.

A topic dermatitis, particularly in adolescence is a common coexist and so the ability to treat these co morbidities as real advantage for our product and I think the outages in particular, who are the ones that sort of the centerpoint seeing patients who have multiple comorbidities.

Really getting that.

Thanks, Jerome next question.

Our next question is from Geoff Porges from SVB Leerink.

Thank you very much and congratulations on the quarter.

Leonard S. Schleifer: Thanks, Marion. I just want to add one thing to emphasize. You said the combination of indications. That's really responding well for people, for example, who have both asthma and nasal polyps, which is very commonly coexisting, or asthma and atopic dermatitis, particularly in adolescence, which is a common coexistence. And so the ability to treat these comorbidities is a real advantage for our product, and I think the allergists, in particular, who are the ones that sort of the center point for seeing patients who have multiple comorbidities are really getting it.

Lot of things that I could ask questions on but I'll just ask one with 10 sub par.

On August 19th.

1979 study George.

You mentioned that it's going to enroll both DLP feel and fourth killing pharma and Purdue presumably also mantle cell.

Do you envisage that it could be potentially pivotal in all those NHL sub types and will you be enrolling patients who have prior car T failures in that trial. Thanks.

George D. Yancopoulos: Thanks, Jerome. Next question?

Yes, so basically the way our total phase two study is designed is with the number of arms actually each one dedicated precisely to exactly some of those sub types that you're interested in so that yes. Each one we would consider to have pending of course, how active in the data and the durability and so forth each one would have registrational possibility.

Leonard S. Schleifer: Our next question is from Jeff Portis from SVB Learing.

George D. Yancopoulos: Thank you very much and congratulations on the quarter. There are a lot of things that I could ask questions about, but I'll just ask one with 10 subparts.

Leonard S. Schleifer: I'm- I'm at my-

George D. Yancopoulos: The 1979 study, George, you mentioned that it's going to enroll both DLBCL and follicular lymphoma and, presumably, also mantle cell. Do you envisage that it could be potentially pivotal in all those NHL subtypes and will you be enrolling patients who have prior CAR T failures in that trial?

And we also have a base.

In the pivotal phase two we certainly will have the late stage flicked lymphoma patients the laces DLP CLL patients, but also we have a program, where we're focusing a norm specifically on car T failures, where we think obviously in such a high unmet need population where people have failed everything in one sees.

George D. Yancopoulos: Yeah, so basically, the way our total phase 2 study is designed is with a number of arms actually, each one dedicated precisely to exactly some of those subtypes that you're interested in, so yes, each one we would consider to have pending, of course, how active in the data and the durability and so forth. Each one would have a registrational possibility, and we also have a, in phase 2, we certainly will have the late stage follicular lymphoma patients, the late stage DLBCL patients, but also we have a program where we're focusing an arm specifically on CAR T failures, where we think, obviously, in such a high unmet need population where people have failed everything, if one sees the sort of activities that we Thank you. Thank you.

The sort of activities that we're seeing in this very small numbers of patients so far being maintained and being durable that yes. That's that also be a separate approval opportunities.

Yes, that's true for prior Carty that George mentioned with complete responses.

What's very encouraging.

Okay.

Okay. Thanks, Jeff next question.

Our next question is from Cory Kasimov from JP Morgan.

Hey, good morning, guys. Thanks for taking my question.

I recognize this is probably difficult one to answer but its we are frequently asked it. So I'll ask you and kind of how are you broadly thinking about the longer term outlook for Leo when when you balance the possibilities of health care reform and part B exposure.

George D. Yancopoulos: The two out of four prior CARTEE that George mentioned with complete responses were very encouraging.

George D. Yancopoulos: Okay. Thank you, Jeff. Next question.

Pending competition, what AMTI and then your own new idea launches in less exposed indications. Thanks.

George D. Yancopoulos: Our next question is from Corey Kacema from J.P. Morgan. Hey, good morning, guys. Thanks for taking my question. I recognize this is probably a difficult one to answer, but it's one we're frequently asked. It's I'll ask you and kind of how you are broadly thinking about the longer term outlook for ILEA when you balance the possibilities of health care reform and Part B exposure, pending competition, wet AMD, and then your own new ILEA launches and less exposed indications? Thanks.

Yeah, well obviously.

It is a difficult question to answer and we hope you gave a good answer to it.

Our view is.

Is more qualitative.

If you look at the the brand.

We're seeing good growth in the good profits not just occurring in the United States is occurring I think it was about 13%.

Outside the United States.

For our brand mix this large in this light.

In may and we.

The class that says that the demographics that we predicted.

Leonard S. Schleifer: Yeah, well, obviously, it is a difficult question to answer, and we hope you give a good answer to it. Our view is more qualitative. If you look at the brand, we're seeing good growth, and the good growth is not just occurring in the United States; it's occurring, I think it was about 13% outside the United States. For a brand that's this large and this late in the class, that says that the demographics that we predicted would be having a positive impact, so I do think there is plenty of room for growth.

Would be having a positive impact so I do think there is plenty of room for growth.

In terms of competition obviously.

As I think it was mentioned on the call.

The end of the day vision and maintaining and improving vision is the gold standard it's what the FDA measures Dubai I think it's what most patients care most about.

And we are unsurpassed and met our long term safety I think we've given over 25 million injections, we are expecting action on our.

Leonard S. Schleifer: In terms of competition, obviously, as I think was mentioned on the call, at the end of the day, vision and maintaining and improving vision is the gold standard, it's what the FDA measures you by, I think it's what most patients care most about, and we are unsurpassed in that. Our long-term safety, I think we've given over 25 million injections, and we are expecting action on our pre-filled syringe, which we've worked hard on, to come up. The due date is coming up pretty soon. So our... Douglas Goldstein, CFP®, Financial Planners & Investments, Inc. Douglas Goldstein, CFP®, Financial Planners & Investments, Inc. So we'll have to see how that all works out.

Prefilled syringe, which we've worked hard to come up to for dates coming up pretty soon.

So.

Our enormous safety database.

Is I think kind of work in our favor. It is hard to do this and the new injecting 20, as we said now up to 25 million injections into the eye.

You have to be able to do that in a very reliable and safe way. If you look at some of the studies out there.

That have been focusing on let's say.

Dryness. There's also if you look at them at some data that is worth inspecting.

On the.

The reactions in terms of inflammation. So we'll have to see how that all sorts out plus we have the advantage of being able to give the dose.

Leonard S. Schleifer: Plus, we have the advantage of being able to give the dose monthly as well as every other month as well as all the indications. So I think we're well positioned for the near term. In terms of your question about healthcare policy and the overhang, obviously, we watch that carefully. We're very involved in Washington. We know what's really important to us.

Monthly as well as every other month was as well as all the indications. So I think we're well positioned for the near term in terms of your question about.

Healthcare policy and the overhang, obviously, we watch that carefully we're very involved in Washington.

We know what's really important to us.

Leonard S. Schleifer: We are sympathetic to the notion that some have that prices in the United States are much higher than prices for the same drugs outside the United States. But we don't think that the solution of tying prices in the United States for a drug like ILEA, where we don't control the price outside the United States, makes a lot of sense. That would be a huge negative to the biotechnology industry as a whole because so many biotechnology companies license away their rights to survive outside the United States and they don't control the prices. So we were happy to see in the Grassley-Wyden compromise that that was not in there. It almost got in there in an affirmative way that it couldn't happen. That vote was 14 to 14.

We are sympathetic to the notion.

That some have that prices in the United States are much higher than prices for the same drugs outside the United States, but we don't think that the solution of time prices in the United States for drug like Leah, where we don't control the price outside the United States makes lot of sense that would be a huge negative to the biotechnology industry as a whole because so many biotechnology companies license away there their rights for survival outside the United States and they don't control the prices. So we were happy to see in the grassley have widened.

Compromise that that was not in there.

It almost got in there and in from the way that it couldn't happen that vote was 14 and 14, we watch that carefully we're working at it and so we're hopeful.

Leonard S. Schleifer: We watched that carefully. We're working on it. And so we're hopeful that the policy debates that are taking place will not block innovation or reward the good actors. We haven't had a price increase in ILEA. So the notion of having an inflation rebate would not affect us.

That.

The policy debates that are taking place.

We will not.

Block innovation will reward the good activism, we haven't had a price increase in idea. So the notion of having an inflation rebate would not affect us. So maybe that's a qualitative summary of all the things that we worry about we worry about competition, obviously, we worry but the environments, we worry about fee.

Leonard S. Schleifer: So maybe that's a qualitative summary of all the things that we worry about. We worry about competition. Obviously, we worry about the environment. We worry about the regulatory and patent exclusivity and so forth. Next question.

The regulatory and patent exclusivity and so forth.

Next question what.

Marion McCourt: I might pick up on one thread in the question, and this was just related to ILEA and our indications and, you know, obviously the growing indications with recent launches in diabetic retinopathy. Today, 60% of our sales are now coming from wet AMD, and with the expansion of our diabetes indications, now over 30% of ILEA sales are coming from the diabetes indications, and, of course, recently including diabetic retinopathy and the balance for others.

One item I might pick up on Prevnar question and this is just related to land and our indications and obviously may be growing indications with recently launching in diabetic retinopathy.

To be 60% of our sales are now coming from rap SMB and.

With the expansion of our diabetes indications now over 30%.

Finally, our sales are coming from the diabetes indications and of course recently, including diabetic retinopathy in the balance for others.

Marion McCourt: And our next question is from Evan Seigerman from Credit Suisse.

And our next question is from Evan Seigerman from Credit Suisse.

Hi, Thank you so much for taking the question and congrats on the progress on one combo for Bob and Marianne. So Bob you had mentioned that there was some sort of a novasol shortages may have benefited ilea sales in the quarter and then more broadly speaking how are you positioning Ali in light of upcoming competitive launches.

Robert E. Landry: Hi all, thank you so much for taking the question and congratulations on the progress. One, a combo for Bob and Marion. So Bob, you had mentioned that there was some sort of an Avastin shortage that may have benefited ILEA sales in the quarter. And then, more broadly speaking, how are you positioning ILEA in light of upcoming competitive launches?

Marion McCourt: Sure, so let me make a start, and then Bob has some elements to add. So I think, first, let me talk a little bit about the second quarter. We certainly had a strong quarter. It was influenced by a few factors, and I will cover those later. You know, certainly there's market expansion in consideration. We do see growth from our wet AMD and DME indications. We began launching in diabetic retinopathy. As mentioned, we added customer-facing personnel to focus on our diabetes indications. There was a modest, what we had characterized as a modest impact from Avastin shortages in some geographies in the U.S. And then, as well, we were up against a somewhat weaker 2018 second quarter comparison. So I did want to give some relative context there.

Sure. So let me let me take a start and then Bob has elements to add.

First let me talk a little bit about the second quarter, we certainly had a strong quarter. It was influenced by a few factors and let me cover those on.

Certainly there is market expansion in consideration, we do see growth from our wet AMD D. MD any indications we began launching in diabetic retinopathy as mentioned, we added customer facing personnel to focus on our diabetes indications. There was a there was a modest what we characterize as a modest impact from the vast and shortages in some geographies in the U.S. and then as well we were up against a somewhat weaker 2018 second quarter comparison.

So I did want to give some relative context, there I think in terms of.

Marion McCourt: For Ali, as a standard of care with eight years and a mark, it's important to look at growth rates as the average of several quarters to get a true sense of what the growth profile has looked like historically and may look like in the future. And then, in terms of preparation for competitive launches, we feel very well positioned to continue to perform well in the market with ILEA. And certainly, we're very excited about the breadth of indications and the profile that Len just covered related to ILEA.

As we look forward, we do think that.

For MB as a standard of care with eight years and Mark it's important to look at growth rates.

As the average of several quarters to get a a true sense of what the the growth profile has looked like historically you may go in the future and then in terms of preparation for.

Competitive launches, we feel very well positioned to.

Continued to perform well in the market with Leah and certainly we're very excited about the breadth of indications and the profile that lend just covered related to Kenya.

Marion McCourt: Next question, please. Our next question is from Yatin Sunjia from Guggenheim Partners.

Next question please.

Our next question is from Jetsons suggest from Guggenheim partners.

George D. Yancopoulos: Hey guys, congrats on all the progress and thanks for taking my question. The question is about REGN3500, the IL-33 antibody that you have. Could you maybe talk about the development strategy there? Given that Dupree monotherapy was numerically better than IL-33 across all the endpoints that you evaluated in the asthma trial, could you maybe comment on the areas where you think IL-33 might play a differentiated role relative to Du

Hey, guys. Congrats on all the progress and thanks for taking my question.

The question is on our Ijie and 35 on the IP 30, P. antibody that you have.

Could you maybe talk about the development strategy there given that Dupi monotherapy was numerically better than they are now 33 across all the endpoints that you really add value at did indeed as much trial could you maybe comment on the areas, where you think it could be might play a differentiated differentiated enrolled additive to dupi.

Well as you say.

George D. Yancopoulos: Well, as you said, um... The hope would be that there might be particular patients who might better respond to, for example, or would like the alternative, an IL-33 as opposed to a DUPI in asthma. And of course, we're also waiting for upcoming data from our atopic dermatitis program and also from our COPD program to really understand how we're going to position this. But we do think that this could be an important alternative option for some patients with asthma, just based on the current data. And we're waiting for more data to see how it evolves.

The hope would be that there might be some particular patients who might better respond to for example, or would like the alternative denial 33 as opposed to a dupixent in asthma.

And of course, we're also waiting for upcoming data from our topic dermatitis program and also from our CBD program to really understand how we're going to position. This but we do think that this.

Could be an important alternative option for some patients and with dazzling just based on the current data and we're waiting for more data to see how.

George D. Yancopoulos: Thank you. Next question, please.

The boss.

Thank you next question please.

George D. Yancopoulos: Our next question is from Mohit Bansal of Citigroup.

Our next question is from Mohit Bansal from Citigroup.

Great. Good morning, and thank you for taking my question.

Leonard S. Schleifer: Great, good morning, and thank you for taking my question. Quick question on Proluent: given the challenges you are facing in the market, do you think there comes a point when you and your partner take a tough business decision, or do you think you can turn it around and achieve profitability for this drug in the long run? Thank you.

Quick question on Praluent.

Given that the challenges facing the market do you think there comes a point that you and your partner typical.

Is that decision or you think you can turn it around in acute profit profitability for this drug.

Leonard S. Schleifer: Yeah, obviously, this is a highly competitive space, and we don't want to get too detailed about what our strategies are. But obviously, we said we're trying to match our investments appropriately, and we do have some strategies.

Thank you.

Yes, obviously this is a highly competitive space when we don't want to get too detailed about what our strategies are obviously, we said we're trying to match our investments appropriately and we do have some strategies.

Leonard S. Schleifer: At the end of the day, heart disease is still a major killer. PCSK9 is still a terrific drug. So, maybe that's all we should say at this point.

At the end of the day heart disease is still a major killer. The pcsknine is still a terrific drug.

So maybe that's all we should say at this point.

Leonard S. Schleifer: Next question, please.

Marion McCourt: Thank you. Thank you.

Okay.

Thank you next question. Please our next question is from Kennen Mackay from RBC capital markets.

Marion McCourt: Our next question is from Kenan McKay from RBC Capital Markets.

George D. Yancopoulos: Hi, thanks for taking the question. Maybe one for George. I was wondering if you could just comment a little bit more on the high-dose Flibercept trials you're initiating and sort of how high you can go on the dose and really what the goals of the high-dose treatment are. Thank you.

Hi, Thanks for taking the question maybe one for for George I was wondering if you just comment a little bit more on the high dose overshot trials, you're initiating and sort of how how high you can go on dose and really what the goals of the high dose treatment are thank you.

Well, obviously from our earlier studies, we've seen that about 50% of patients.

George D. Yancopoulos: Well, obviously, from our earlier studies, we've seen that about 50% of patients can do well with a more prolonged dosing schedule that is on a 12-week interval. And so we imagine that if we go to a higher dose of the flu precept, we may be able to push a higher percentage of patients to either a 12-week or maybe even a 16-week regimen. So we're running the studies to actually test these longer intervals and see whether the higher doses will actually do that. We'll see.

Can do well with a.

More prolong dosing schedule that is on a 12 week interval and so we're imagining that if we go to a higher dose of Aflibercept, we may be able to push a higher percentage of patients to either a 12 week or maybe even a 16 week regimen.

So on so we are running the studies to actually test these longer intervals and see whether the higher doses will actually do that so.

We will see.

George D. Yancopoulos: Great. Next question, please.

Great next question please.

Marion McCourt: Our next question is from Alethea Young from Cantor Fitzgerald. Hey guys, thanks for taking my question. I guess I found the 18% or so number very striking about how much penetration you've had in adults. And maybe you can talk about some of the things that you're doing to drive penetration, or is it just a slow but sure process to get more people on the drug thing?

Our next question is from Olympia Young from Cantor Fitzgerald.

Hey, guys. Thanks for taking my question Congrats on a very good quarter, I guess I found the 18% or so number.

Very striking about how much penetration we've had our adult so maybe can you talk about some of the things that you're doing to drive penetration or is it just the slow but sure process to get more people on the job. Thanks.

Sure. So this I believe your question leases in reference to the comment on two Texans.

Marion McCourt: Sure, so this, I believe your question, Alicia, is in reference to the comment on dupixent in adult atopic dermatitis, and I do, yes, just to give context, but my comment is to make the point that while certainly, you know, many adults that have very, very difficult, moderate to severe disease are now being treated, there is tremendous potential for us to do more with dupixent to help appropriate adults in need of therapy And to your characterization, I do think that dupixent is gaining momentum in atopic dermatitis, certainly in other indications as well, and it's not unusual for physicians to first prescribe it to those patients who are their toughest patients, the most severe patients. We're seeing a pick-up in breadth and depth of physician prescribing of dupixent, and we also are seeing more moderate to severe patients being treated.

In adult a topic dermatitis and after I do yes, just in context, but on my comment is to make the point that while certainly.

Adults.

That had very very difficult moderate to severe disease.

We are now being treated there's tremendous potential for us to do more we to take send to help appropriate adults in need of therapy.

And see your characterization.

I do think that Dupixent is gaining momentum in atopic dermatitis, certainly in other indications as well.

And it's not unusual for physicians first chief prescribed to dose patients who are their toughest patients. The most severe patients we're seeing pick up in breadth and depth of physician prescribing of distinction and we also are seeing more moderate moderate to severe patients being treated so that's encouraging because it takes and is helping these patients in a way that we hear time and time again as transformational to their lives and as well transformational covered lives of these physicians who are treating them.

Marion McCourt: I think we have time for two more questions, John.

Marion McCourt: Our next one is from Hartaj Singh of Oppenheimer and Company.

Marion McCourt: Great, thank you for my question. I just have one question on the TIO. We had a stronger number than we expected for the second quarter.

I think we have time for two more questions John .

Our next one is from our tax thing from Oppenheimer and company.

Oh, great. Thank you for my question I just have one question on the tire.

Marion McCourt: I think PD-1 has gotten some really good data and, just from what we've heard, is being really accepted broadly. Can you just give some color on the commercial rollout and how that is progressing, and any thoughts also on the lung cancer trial that you've got ongoing? Thank you.

Had a stronger number than we expected for the second quarter.

This PD one.

Has gotten some really good data and just from what we've heard is being really accepted broadly can you just give some color on the commercial rollout how that is progressing and the ports also be on the lung cancer project you got ongoing thank you.

Marion McCourt: So I will give some comments related to commercial performance. And with LibTio, we certainly are making inroads to become the standard of care for CSCC patients, as described in our label. Approximately 90% of new patient starts in CSCC within the ENT PD-1, PD-L1 class are now going to LibTio. Furthermore, we have excellent payer coverage that has already been achieved. And furthermore, we'll have our permanent J-code on October 1st, so certainly we've made a strong start in the launch of CSCC for LibTio.

So I will give some comments by maybe to commercial performance and with much higher we certainly are making inroads to become the standard of care for.

CC patients as described in our label approximately 90% of new patient starts and CSC seen within the into PD. One PDL. One class are now going to live tile.

Further we have excellent payer coverage that has already been achieved and.

Further we will have our permanent J code on October Onest.

Certainly we've made a strong start in the launch of CSC for live tile.

Marion McCourt: About lung cancer, I guess early on there were a lot of thoughts that the PD-1 space would be commoditized, and there would be, you know, so many PD-1s, and it'd be, you know, sort of boilerplate to just make another one. I think that if one fairly looks at the data, they are not behaving the same, and that's obvious for sure in the lung cancer space, where Katrina is the unquestioned leader. And so we're very excited about the fact that we think that our PD-1 might have very good activities, already demonstrated in certain settings, so we're excited to see how it performs in the lung cancer setting and whether it will be one of the rare PD-1s that can really provide a lot of benefit to patients.

About the lung cancer I guess early on there were a lot of thought that to PD, one space, we beat kamada size and that they would be.

So many PD ones and it be.

Sort of Boilerplates, just make another one I think that if one fairly looks at the data.

These are not behaving the same.

And thats obvious for sure in the lung cancer space.

Where today is the unquestioned leader and so we're very excited about the fact that we think that.

Our PD one might have very good activities already demonstrating as we've heard and in certain settings. So we're excited to see how it's going to perform.

In the lung cancer, setting and whether it will be one of the rare PD ones that can really provide a lot of benefit to patients there.

George D. Yancopoulos: Question? From Brian Skorney.

And our last question from Brian Skorney from Baird.

George D. Yancopoulos: From Brian Skorney, from Baird.

George D. Yancopoulos: Hey, good morning guys, thanks for taking the questions. Two quick ones.

Hey, good morning, guys. Thanks for taking the question.

Two quick ones, obviously, bevacizumab, most prescribed better therapy, despite being off label.

George D. Yancopoulos: Obviously Bevacizumab is the most prescribed VEGF therapy despite being off-label. It looks like there's one company planning on actually filing a BLA next year to market a branded Bevacizumab. How do you guys think about the market impact of an active Salesforce marketing Bevacizumab versus the more passive usage right now? And then just real quickly on Regeneron 4461. I know Leptin was a pretty well-researched target about a decade ago, but it never quite realized its promise. Can you just share your thoughts on what makes targeting the receptor with your antibody attractive and how it could overcome some of the prior history? Thanks.

It looks like there is one company plan and actually filing a BLE next year to market a branded bevacizumab.

How do you guys think about the market impact of an ACO salesforce marketing bevacizumab.

Versus more Paso.

You sit right now and then just real quickly on Regeneron 4461, I know application was a pretty well researched part about a decade ago.

Never quite realize the Troms can you just share your thoughts on on what makes targeting the receptor with your antibody and attractive and how could overcome some of the prior history. Thanks.

Sure just very briefly because we're running out of time I'll take the Bevacizumab question, Georgia, We will deal with the.

Leonard S. Schleifer: Sure, just very briefly because we're running out of time, I'll take the bevacizumab question and George will deal with the question about insulin. I mean, the leptin receptor. So, in terms of bevacizumab, obviously, you can't have a biosimilar to bevacizumab in terms of approvals because it doesn't have any approvals.

Question on the insulin I mean on the lepton receptor.

So in terms of Bevacizumab, obviously, you can't have a bias similar to bevacizumab in terms of the approvals because it doesnt have any approvals. So somebody we if they want to get approvals of it's going to have to do all the different studies et cetera, and we already know that in large studies conducted independently by the government. For example, example protocol T.

Leonard S. Schleifer: We already know.

George D. Yancopoulos: And I think it is important to note that in large studies conducted independently by the government, for example, Protocol T, Bevacizumab was clearly inferior to ILEA. So I think that the use of Bevacizumab is mainly one driven by its extremely low price. So having another competition there, with or without a sales force, and the doctors are well aware of this, we wouldn't expect it to have a major impact on the market. George, on the leptin receptor.

Bevacizumab was inferior clearly inferior.

Two idea so I think that the use of Bevacizumab is mainly of one driven by its.

Off label exceedingly low price so having another competition there with about a sales force that is well aware about this we wouldn't expect to have a major impact on the market George on the.

Yes, let them. So we'll just to remind you.

George D. Yancopoulos: Well, just to remind you, one of the major problems with leptin and metroleptin as they were developed was that they elicited, unfortunately, in quite a significant percentage of patients, antibodies against leptin. And a lot of these patients are patients who actually still have endogenous leptin activity. So when the antibodies come on board, the patients end up not only neutralizing the injected leptin but their endogenous leptin, they end up being worse off than they were beforehand, and they're also left with nothing actually available to treat them because you can't give them leptin. So, of course, we are pursuing our leptin receptor-activating antibody in that setting, but it would also provide a better alternative and would allow broader usage.

One of the major problems with lepton and metal lift and as it was developed was that it was elicited unfortunately quite a significant percentage of patients.

Antibodies against the left in a lot of these patients are patients who actually still haven't done is left in.

Activity, so when the antibodies come onboard the patients end up not only neutralizing the injected left in but they are in dollars is left in the end up being worse off than they were beforehand, and they're also left with nothing to actually being available to treat them. Because you now can't give them left and so of course, we are pursuing our lepton.

Receptor activating antibody in that setting up but it would also.

Provide a better alternative and would allow broader usage. There are other settings, where one could have conceived using metreleptin, except one wouldn't have not wanted to elicit this.

George D. Yancopoulos: There are other settings where one could have conceived of using metroleptin, except one wouldn't have wanted to elicit this antibody response and have the potential to wipe out the endogenous leptin-remaining activity. And so people were reticent to explore it more broadly in other settings. So on top of that, it is one of the first examples of our new activating antibody technology that allows us to, we hope, create efficient in vivo activating antibodies for growth factors and cytokines and so forth. So for all those reasons, we're pretty excited about our leptin receptor program, but of course, we'll be starting in the same sort of array of patients where leptin is mostly used right now.

Antibody response and have the potential to wipe out the endogenous.

Lepton remaining activity and so people were reticent to explore these more broadly in other settings. So.

On top of that it is one of the first examples of our new activating antibody technology that allows us to we hope create efficient in vivo acting activating antibodies for growth factors and cytokines and so forth. So for all those reasons, we're pretty excited about our lepton receptor program.

But of course, we'll be starting in the.

In the same sort of rare patients were lepton is mostly used right now.

Justin Holko: I will now turn the call back over to Justin Holkoff for his closing remarks.

I'll now turn the call back over to Justin Hall for closing remarks.

Justin Holko: Great. Thank you everyone, and thank you again for dialing in to the call today. The IR team will be around to answer your questions later today.

Great. Thank you everyone and thank you again for dialing in to the call today. The IR team will be around to answer your questions later today.

John: Thank you, ladies and gentlemen. That concludes today's conference. Thank you for participating, and you may now disconnect.

Thank you ladies and gentlemen that concludes today's conference. Thank you for participating and you may now disconnect.