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

Thank you, Tamia. Good morning, good afternoon, and good evening to everyone listening around the globe. Thank you for your interest in Regeneron Pharmaceuticals, and welcome to the second quarter 2021 conference call. An archive of this webcast will be available on our website. Joining me today on the call are Dr. Leonard Schleifer, Founder, President, and Chief Executive Officer; Dr. George Yancopoulos, Co-Founder, President, and Chief Scientific Officer; Marion McCourt, Executive Vice President and Head of Commercial; and Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open the call for Q&A. I would also like to remind you that remarks made on today's call include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products in this financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, intellectual property, pending litigation and other proceedings as well as competition. 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 period ended June 30, 2021, which we filed with the SEC earlier today. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise. In addition, please note that GAAP and non-GAAP measures will be discussed in today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our financial results press release, 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. Len Schleifer.

Thank you, Justin, and thanks to everyone joining today's call. We had an outstanding performance across the enterprise in the second quarter. Not only did our base business perform exceptionally well with strong growth from EYLEA, Dupixent, and Libtayo, but we also delivered 1.25 million doses of REGEN-COV for the United States government, fulfilling the entire supply contract with BARDA. We also continue to advance multiple programs across our innovative R&D pipeline with several important readouts. Starting with EYLEA. Global net sales were over $2.3 billion, growing 33% compared to the prior year, reflecting recovery from the COVID pandemic impact on the second quarter of 2020. In the U.S., sales grew 28%. EYLEA continues to set a high bar in terms of efficacy, safety, and convenience. Dupixent also performed exceptionally well this quarter with global sales of $1.5 billion and growth of 59%. This quarter also marks the first time we and Sanofi exceeded $1 billion in U.S. Dupixent quarterly net sales. There remains considerable room for further growth from our in-line indications as well as from potential new opportunities, such as in chronic spontaneous urticaria with CSU where last week, we announced positive Phase III study results. We have additional Phase III readouts in prurigo nodularis, eosinophilic esophagitis, and pediatric atopic dermatitis later this year, which could advance our conviction that Dupixent is a pipeline in a product to address numerous inflammatory diseases. In oncology, the entire global net sales were $117 million and grew 46% with meaningful growth contributions from both inside and outside the United States. We also announced this morning that in a large Phase III pivotal study in non-small cell lung cancer, Libtayo, combined with standard chemotherapy, reduced the risk of death by nearly 30% compared to chemotherapy alone. We are eager to share these data with regulatory agencies, which, if approved, would dramatically increase the number of lung cancer-eligible patients who could be treated with Libtayo. We also began to see meaningful results from our Regeneron Genetics medicines pipeline. With our collaborators at Intellia, we showed the first-ever proof-of-concept in vivo genome editing with NTLA-2001, an investigation of CRISPR therapy for transthyretin amyloidosis or ATTR amyloidosis. This proof-of-concept study utilizing systemically administered CRISPR technology for genome modification suggests this approach could have broad applicability across a wide range of diseases. Beyond Intellia, our collaborations with Alnylam and Decibel are helping to form a whole new pipeline for next-generation therapies beyond our broad and diverse antibody pipeline. The second quarter represented another landmark in our efforts to combat COVID-19, which, unfortunately, despite considerable rates of vaccination, continues to be a major global health service with rising cases and emerging variants. In addition to fulfilling our entire supply contract with the United States government, we were able to secure emergency use authorization updates for our lower 1.2 gram subcutaneous dose as well as for post-exposure prophylaxis for certain appropriate patients who are at high risk for disease. Utilization is increasing readily, and currently, more than 50,000 doses are ordered per week. We also announced that the U.K. recovery study showed a 20% reduction in risk of death in hospitalized patients who do not mount their own immune response. With these results, together with supporting data from Regeneron study in hospitalized patients that George will discuss momentarily, REGEN-COV has the potential, if so authorized, to be the first treatment used in a wide spectrum of COVID-19 disease settings from prevention through the hospitalized setting. In summary, our core business is strong and continues to diversify, and our innovative pipeline continues to advance, positioning Regeneron well for long-term growth. Now I will turn the call over to George.

Thank you, Len. We have a lot to talk about this morning, which is possible because of our Regeneron colleagues who have been working nonstop throughout this pandemic. Unfortunately, the world is still in the throes of this global COVID-19 pandemic. As the number of infected individuals in the United States is climbing again with nearly 100,000 Americans becoming infected every day. Therefore, I will start with Regeneron with REGEN-COV, our monoclonal antibody cocktail for COVID-19. In June, the REGEN-COV Emergency Use Authorization, or EUA, was updated to include the lower 1.2 gram REGEN-COV dose with both intravenous and subcutaneous administration for non-hospitalized patients. This EUA was supported by Phase III data showing that the 1.2-gram dose reduced the risk of hospitalization or death by 70%. Just last week, the EUA was further expanded to include utilization in post-exposure prophylaxis for COVID-19 in certain populations, and also allows for repeated monthly dosing of REGEN-COV for high-risk patients, such as the immunocompromised who are at high risk of ongoing exposure to infected individuals in the same institutional setting. This latest authorization makes REGEN-COV the only treatment available for both treating infected individuals and also preventing infection in certain settings. We would like to emphasize that REGEN-COV is not a substitute for vaccination. Still under review by the FDA are additional data, which we believe could broaden the prevention application to pre-exposure prophylaxis as well as extend the treatment paradigm to hospitalized patients. The details of Part A of our Phase III prophylaxis study, in which we assessed efficacy and safety of subcutaneous REGEN-COV in preventing infection among previously uninfected individuals, have just been published today in the New England Journal of Medicine. We believe there is an enormous unmet need to try to protect immunocompromised individuals who have not responded to the vaccine, and we hope that the FDA will agree that our data will support an authorization in this pre-exposure prophylaxis setting. For hospitalized patients, we recently reported that REGEN-COV tested as part of the Oxford University Phase III RECOVERY study met its primary outcome, reducing the risk of death by 20% in hospitalized COVID-19 patients lacking immune response to SARS-CoV-2. Data from our own smaller study in hospitalized COVID-19 patients showed similar conclusions with a 35% reduction in overall mortality in this study, which was limited to earlier-stage hospitalized patients with no oxygen or low oxygen support. These collective data from the RECOVERY study and from our study in hospitalized patients have been shared with regulators. In addition, we are on track to complete the REGEN-COV BLA submissions in the second half of 2021. Outside of the United States, our collaborator Roche obtained emergency or temporary pandemic use authorizations for our COVID-19 antibody cocktail, known as Ronapreve outside the United States, in more than 20 countries across the European Union, India, Switzerland, and Canada, with more authorizations expected soon. Japan was the first country to grant formal regulatory approval to our antibody cocktail for COVID-19. Finally, REGEN-COV retains potent activity against all known variants of interest, including the Delta variant. For patients at high risk of serious consequences, including many with an inadequate response to vaccines, REGEN-COV could be an important option for patients and their physicians for the foreseeable future. Moving on to ophthalmology. In the coming months, we expect data from the Phase II study of a high dose of libracept in wet AMD. This readout will consist of efficacy assessments and other anatomical measures as well as safety on the 8-milligram and the currently approved 2-milligram of libracept dose and an 8-week dosing interval. In the 106 patients dosed in the open-label Phase II to date, we have not seen any concerning safety signals. While the smaller study will not be definitive on durability measures, the Phase II data will help provide insights into the larger Phase III studies, which are testing high-dose aflibercept dosing intervals out to 12 and 16 weeks. I'm pleased to announce that the Phase III studies in DME and AMD have completed enrollment, allowing for Phase III data next year. Moving on to Dupixent in our immunology and inflammation portfolio. Just last week, we announced that a Phase III trial in chronic spontaneous urticaria, where CSU met primary and all key 24-week secondary endpoints, showing Dupixent reduced itch and hive activity scores by nearly half. This is the fifth disease in which Dupixent demonstrated positive pivotal trial results, and efficacy in this disease raises the possibility of IL-4 and IL-13 being critical drivers in diseases not traditionally sought to be driven by type 2 inflammation. We plan to report results from a second trial in CSU patients who are not benefiting from the approved standard of care biologic in early 2022. This positive readout in CSU is continuing to build on Dupixent's efficacy and safety demonstrated across other inflammatory diseases. In the upcoming months, we also expect results from our confirmatory Phase IIIb study in adult and adolescent patients with eosinophilic esophagitis as well as readout of a Phase III study in prurigo nodularis. Thus far, Dupixent is approved in patients as young as 6 years old in atopic dermatitis and 12 years old in asthma. Later this year, we will report data from a Phase III study in preschool children as young as 6 months up to 5 years of age suffering from atopic dermatitis. In asthma, we anticipate a regulatory decision in October for children aged 6 to 11 years old in the United States. Moving to our anti-interleukin-33 antibody Itupikumab. Results of the Phase II study in COPD patients were recently published in Lancet Respiratory Medicine. All the trial exhibited strong trends in its primary endpoint of exacerbation reduction in the overall population, which did not meet statistical significance. A pre-specified subgroup analysis of former smokers with COPD accounted for the overall benefit with no negative subset in the remaining population. In the pre-specified former smoker subgroup, Itupikumab demonstrated a 42% reduction in exacerbations and improvement in lung function of 0.09 liters compared to placebo, with both endpoints reaching nominal statistical significance. Moreover, the publication includes genetic analyses that support a protective role for interleukin-33 in COPD. Based on these results, we and Sanofi are assessing the potential of Itupikumab in two Phase III studies focused on the former smoker population with COPD. I should also remind you that we have two ongoing Phase III studies with Dupixent in a complementary COPD population. We are also progressing our novel approaches to treat allergies by using cocktails of monoclonal antibodies to directly bind and inactivate allergens, which have produced robust results in Phase II studies. Results of the initial Phase III study of our antibody cocktail against birch allergy caused by the Betv1 allergen are expected later this year. The first Phase III study of an antibody cocktail for cat allergy caused by the Feld1 allergen is now open for enrollment. We are enthusiastic about these innovative additions to our inflammation and immunology portfolio. In oncology, following its recent approvals in the United States for certain first-line non-small cell lung cancer and certain advanced basal cell carcinoma patients, Libtayo was subsequently approved in the EU for these settings. Furthermore, compelling overall survival data in second-line cervical cancer patients were presented at an ESMO virtual planar in May, with the regulatory submissions to the FDA and EMA planned for this year. For lung cancer, we are pleased to report today that in our Phase III trial comparing Libtayo plus standard chemotherapy versus chemotherapy alone, the independent data monitoring committee recommended halting the trial for efficacy at the second interim analysis. Libtayo plus chemotherapy significantly improved overall survival as well as progression-free survival compared to chemotherapy alone in first-line locally advanced or metastatic non-small cell lung cancer. With these data, Libtayo is now the second PD-1 targeting antibody that has been able to demonstrate significant overall survival benefit both as a monotherapy as well as in combination with chemotherapy for treating advanced lung cancer. With this validation, Libtayo provides an important foundation for a broad and multifaceted approach to address the great unmet need that patients with cancer in general and lung cancer, in particular, still face. In addition to our Libtayo monotherapy and chemo combination opportunities in lung cancer, we are developing several bispecifics. Our EGFR by CD28 costim and Libtayo combination is in dose escalation for lung and other advanced cancers. Our METxMET bispecific antibody is enrolling non-small cell lung cancer patients with a broad selection of patients, including MET exon 14 gene mutation, gene amplification, and/or elevated MET protein expression. As we introduced at our ASCO investor event, our first antibody-drug conjugate METxMET ADC is poised to enter the clinic in the coming months, with a focus on patients with MET overexpressing cancers, including lung cancer, where MET overexpression occurs in as many as 25% of patients. In terms of building on the potential of Libtayo with combinations in skin cancer, we recently announced new clinical data for the combination of Libtayo with Fianlimab, our LAG-3 inhibitor, in advanced melanoma at the ASCO annual meeting in June. The combination demonstrated a 67% response rate in PD-1 or PDL-1 naive patients with potential for a more favorable safety profile than with anti-CTLA-4 PD-1 combinations. We plan to initiate a Phase III study of Fianlimab and Libtayo as a first-line treatment for advanced melanoma in 2022. Ovarian cancer is the first tumor type for which we are clinically testing three powerful combinatorial approaches. First, our MUC16xCD3 bispecific with Libtayo, where we hope to share initial data next year. Next, our MUC16xCD28 costim bispecific with Libtayo. And third, our novel combination of the CD3 and costim bispecifics for which we have now dosed the first patient. This latter combination of two bispecifics of two different classes has the potential to be a novel and disruptive approach for the treatment of solid tumors. Rounding out my commentary in solid tumors, our PSMAxCD28 program in prostate cancer continues in dose escalation with Libtayo, and we hope to share initial data next year. As we mentioned previously, we are planning on introducing a PSMAxCD3 bispecific to the clinic later this year, providing another unique experimental combination for prostate cancer treatment. The tumor viewed as nonresponsive currently to available immunotherapies. Moving on to hematologic cancers, starting with lymphoma. Odronextamab, our CD23 bispecific, has demonstrated encouraging efficacy and durability of responses in hard-to-treat patient populations. We have resumed enrollment in our potentially pivotal Phase II program in follicular lymphoma and diffuse large B-cell lymphoma, with lifting of the partial clinical hold following protocol amendments for a modified step-up dosing protocol. Later this year, we plan to initiate testing of the subcutaneous formulation. Next year, we will initiate the Phase III program as well as combination trials with our lymphoma-specific costim bispecific. In multiple myeloma, our BCMAxCD3 bispecific is on track to complete enrollment for the potentially pivotal Phase II study next year. We will also initiate studies evaluating a subcutaneous formulation in combinations with standard of care. With our unique position to mix and match multiple modalities and targets with the goal of deepening the responses we are already observing with our BCMAxCD3 bispecific, we are on track to start a combination study with a costim bispecific for multiple myeloma next year. I would like to conclude with our Regeneron Genetic Medicines efforts. As you know, these efforts start with our Regeneron Genetics Center and its ability to genetically identify and validate new disease targets and are coupled with emerging gene-based therapeutic solutions to address these targets, including CRISPR-based technologies with our collaborator Intellia, siRNA technologies with Alnylam, as well as viral gene delivery technologies we are developing in-house. The Regeneron Genetics Center continues to emerge as a world leader in human sequencing and in defining genetic variants that can either be protective or causative for human disease. Most recently, identifying a major new gene target that protects against obesity as described in a high-profile publication in Science last month. For this newly discovered target, we are deploying several strategies to develop new classes of potential therapeutics to fight obesity and potentially type two diabetes. In terms of progress with our gene-based therapeutic approaches, together with Intellia, we recently announced positive clinical data for the first-ever systemically delivered CRISPR-based gene knockout in human patients. In the first 6 patients with transthyretin amyloidosis, a single systemic treatment led to dose-dependent reduction in the disease-causing protein with no serious adverse events observed through day 28. This proof-of-concept clinical data increases the probability of success for both our knockout as well as our insertion CRISPR-based programs, unlocking the potential of many future possibilities for Intellia and Regeneron. Currently, we're evaluating more than 20 preclinical programs under this collaboration, and Regeneron has the rights to develop up to 15 in vivo products with Intellia. Regarding our efforts with Alnylam, on an siRNA for a novel NASH target identified by the Regeneron Genetic Center, we are hoping to see initial healthy volunteer data by the end of this year. This two-part first-in-human study is now enrolling NASH patients. We are currently evaluating about 20 preclinical programs under this collaboration, and Regeneron has rights to develop up to 30 products with Alnylam. With that brief glimpse into the future of genetic medicines, I would like to turn the call over to Marion.

Thank you, George. Our business performance in the second quarter reflects robust momentum, competitive strength, and focused execution across our commercial portfolio. Our in-line medicines continue to thrive, and our ongoing launches are progressing to plan, providing a platform for diversified growth. First, I will highlight our efforts supporting REGEN-COV, our COVID-19 antibody cocktail, which is available under emergency use authorization by the FDA. In the second quarter, U.S. net sales were $2.6 billion as a result of fulfilling our second contract with the U.S. government. There is significant ongoing need for effective treatments against COVID-19. As Len said, REGEN-COV utilization has recently accelerated and is now trending well over 50,000 doses ordered weekly. Uptake is driven by growing recognition of the importance of antibody cocktail treatment, focused educational efforts and competitive dynamics favoring REGEN-COV. We continue to work closely with all key stakeholders to increase REGEN-COV utilization and support hospitals and administration sites to reduce bottlenecks. The REGEN-COV antibody cocktail is both FDA authorized and NIH recommended and retains potency against known variants. We've also expanded our efforts following the recent post-exposure prophylaxis authorization, the first for an antibody therapy in this setting. Beyond REGEN-COV, our core portfolio performed very well in the second quarter. Starting with EYLEA. Second quarter global net sales grew 33% year-over-year to over $2.3 billion. In the U.S., EYLEA net sales grew 28% year-over-year to $1.42 billion, driven by underlying demand, category share gains, and a favorable comparison versus the second quarter of 2020. EYLEA is the anti-VEGF category growth leader and preferred treatment option. As a reminder, EYLEA sets a high bar for efficacy and safety with more than 40 million injections administered worldwide in a therapeutic category where patient vision and well-being are paramount. EYLEA continues to capture market and competitive share securing nearly 50% of the overall category and 75% of the branded category. Overall demand is improving with increased patient flow and return to pre-pandemic levels of new patient visits. Patients who may have delayed seeing the retina specialists are now seeking treatment. With this backdrop, we are accelerating promotional efforts to address the significant unmet needs in diabetic eye disease. We are confident in Regeneron's ongoing leadership position in retinal diseases, based on EYLEA's competitive advantages and future opportunities, including our high-dose program. Turning to Libtayo, where second quarter global net sales grew to $117 million and the U.S. net sales grew 23% to $78 million. As expected, at this early stage of new indication launches, the vast majority of sales come from advanced cutaneous squamous cell carcinoma, where Libtayo is the number one systemic treatment despite new in-class competition. Our launches in both advanced non-small cell lung cancer and basal cell carcinoma or BCC are progressing to plan. In BCC, Libtayo brand awareness is high among treating oncologists. We are encouraged by meaningful patient starts in the second quarter as Libtayo becomes a standard of care. We're also making considerable progress in lung cancer where efforts are focused on establishing Libtayo in our monotherapy indication and will be an important foundation for our potential future chemotherapy combination launch, which will be based on the data announced today. Our expanded field force is now fully deployed and securing early successes with treating physicians. We're raising brand awareness, progressing formulary positioning and payer coverage. Lung cancer thought leaders recognize Libtayo's clinical differentiation, highlighting the rapid response rates and efficacy in patients with clinically stable brain metastases or high PD-L1 expression. In this highly competitive market, we remain focused on differentiating Libtayo and increasing physician experience. Today's exciting chemotherapy combination news has the potential to dramatically expand the patient opportunity for Libtayo in non-small cell lung cancer. Turning now to Evkeeza, which was launched earlier this year in ultra-rare homozygous familial hypercholesterolemia. Key thought leaders recognize the benefits of Evkeeza which delivers efficacy, safety, and tolerability in a market where many patients have struggled to stay on therapy in the face of life-threatening LDL-cholesterol levels. We're encouraged by early initiations across switch and new-to-category patients and can see a future where Evkeeza becomes the standard of care. Moving to Dupixent. Global net sales in the second quarter were $1.5 billion, growing 59% compared to the prior year. In the U.S., net sales grew 49% to $1.15 billion driven by broad-based growth across all approved indications. New patient starts are steadily growing and are above pre-COVID levels. In atopic dermatitis, prescribing trends are strong across a spectrum of moderate to severe disease including adolescent and pediatric patients. There is significant and sustained growth opportunity for Dupixent in a market where it is the #1 dermatologist-prescribed biologic. This is based on its well-established efficacy and safety profile, broad label for patients as young as 6 years old, and unmatched real-world physician and patient experience. In addition, as George outlined, we see exciting future opportunities in dermatology, starting with CSU. Dupixent is the leading biologic in respiratory disease poised to capture meaningful growth now and in the future. Our asthma results outpace recent competitive biologic launches. Launch preparations are underway in the pediatric asthma setting, with the first regulatory approval expected in the U.S. this October. In nasal polyps, there's high demand among ENTs and allergists with patients initiated regardless of prior surgery. In summary, we delivered strong performance across our brands with current and potential future launches on track to deliver sustained growth. Now I'll turn the call over to Bob.

Thanks, Marion, and good morning and afternoon to everyone listening to the call. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis where applicable. In the second quarter, our core business continued to deliver impressive year-over-year growth bolstered by strong execution across the company to deliver the full 1.25 million dose contract to the U.S. government for REGEN-COV. For the second quarter, total revenues grew 163% year-over-year to $5.1 billion. Excluding revenues related to the COVID-19 antibody cocktail, total revenue grew 22% versus the prior year. Total diluted net income per share grew 260% year-over-year to $25.80 on net income of $2.9 billion. In the second quarter, we recognized $2.6 billion of U.S. REGEN-COV sales, representing the vast majority of revenue related to the delivery of 1.25 million doses to the U.S. government. Due to revenue recognition rules, a residual $34 million of net product sales for doses delivered under this contract will be recorded in the third quarter. Given the delivery of these doses to the U.S. government and current utilization rates, we anticipate the current U.S. government supply will be exhausted by the end of the year. We do not expect to record substantial additional sales this year in the U.S. unless the number of cases and related utilization continues to increase exponentially. I will now move to collaboration revenues, which were $955 million in the second quarter of 2021 as compared to $513 million in the second quarter of 2020. Let me begin with the Roche collaboration. Ex U.S. sales of the COVID antibody cocktail known as Ronapreve, outside of the U.S. were $470 million as reported to us by Roche; we recorded $168 million in Roche collaboration revenue for our share of profits from Roche's sale of Ronapreve, which is now available or approved in more than 20 countries. With new COVID cases on the rise globally, we expect Ronapreve will continue to be a meaningful revenue contributor in 2021. With regard to our Bayer collaboration, Ex U.S. EYLEA net product sales reported to us by Bayer were $904 million for the second quarter of 2021, representing growth of 41% on a reported basis and 31% on a constant currency basis as a result of broad market recovery and a favorable comparison versus the prior year. Total Bayer collaboration revenue was $349 million, of which we recorded $335 million for our share of net profits from EYLEA sales outside the U.S. Finally, total Sanofi collaboration revenue was $438 million in the second quarter of 2021. Our share of the profits from the commercialization of Dupixent and Kevzara was $328 million, which nearly doubled when compared to profits of $172 million in the prior year. Other revenue was $46 million in the second quarter compared to $212 million in the prior year. The decrease is primarily related to nonrecurring revenue from BARDA in 2020 for the development of COVID-19 and Ebola treatments. We continue to expect 2021 other revenue to be less than half of what was recorded in 2020 on a full-year basis. Moving on to our operating expenses. R&D increased 11% year-over-year to $643 million, primarily due to continued clinical development costs for our REGEN-COV antibody cocktail and higher headcount to support our expanding pipeline. Next, SG&A expense increased 21% year-over-year to $365 million due to costs related to COVID-19 activities, launch investments for Libtayo, growth initiatives for EYLEA, and higher headcount. Cost of goods sold increased versus the prior year from $93 million to $514 million, primarily due to REGEN-COV manufacturing costs. Finally, the effective tax rate was 17% in the second quarter of 2021, reflecting the impact of REGEN-COV sales, which are taxed at the U.S. statutory rate. Shifting to cash flow and the balance sheet. In the second quarter of 2021, Regeneron generated $478 million in free cash flow and ended the quarter with cash and marketable securities less debt of $5.1 billion. We received the full $2.625 billion of cash associated with the completion of our second REGEN-COV contract with the U.S. government in July. As the business continues its strong performance, we are reiterating our capital allocation priorities of investing in internal R&D, funding strategic external R&D partnerships, and returning cash to shareholders. Accordingly, in July, we announced a new $1.8 billion expansion of our Tarrytown facilities, primarily directed toward additional internal R&D operations and capabilities. We also continue to advance our next-generation technology partnerships with companies like Intellia and Alnylam, which are beginning to bear fruit as targets get selected and programs move forward into development. Finally, in the second quarter, we repurchased $289 million of our shares, and we remain opportunistic buyers in the market. To conclude, I'd like to provide select updates to our 2021 guidance. A complete summary of our latest full-year guidance is available in our press release published earlier this morning. We are updating our full-year 2021 guidance for SG&A to be in the range of $1.54 billion to $1.62 billion. The change is related to increased efforts in the second half for REGEN-COV. We are also revising our full-year 2021 guidance for R&D to be in the range of $2.65 billion to $2.75 billion. The change is driven by lower-than-expected spend on REGEN-COV. Finally, we now expect our full-year 2021 non-GAAP effective tax rate guidance to be in the range of 14% to 16%, driven by higher sales of REGEN-COV, which, as I said, are taxed at the U.S. statutory rate. In conclusion, Regeneron performed exceptionally well in the second quarter, with the core business continuing on a strong growth trajectory as we invest in our diverse and differentiated pipeline for long-term sustainable growth. With that, I'd like to turn the call back to Justin.

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

Your first question comes from the line of Chris Raymond with Piper Sandler. Your line is open.

Just on the EMPOWER study guys, we're getting a few questions about the comparison to KEYTRUDA. I know it's hard to compare across trials, but it's a bit tricky because EMPOWER had both squamous and non-squamous. But your 22-month median OS is right on top of the non-squamous experience for KEYTRUDA. I'm sure you're going to want to save a lot of detail for the full presentation, but can you maybe give us a sense of the balance here between squamous and non-squamous patients?

As you said, it's very difficult to compare across studies conducted years apart, especially when we included patients that were not previously allowed in other studies and so forth. As you pointed out, the median survival numbers are very close to each other. But as you also noted, we had two different subtypes in this study. I can comment in our preliminary analysis, and these remain to be fully validated. One of the subtypes, our hazard ratio was better than what was observed with the KEYTRUDA study, and in the other one, it was worse. It's important to point out that these things vary in these cross-study comparisons. In other settings, when you do cross-study comparisons, for example, comparing our monotherapy results in the greater than 50% PDL population, it looks like our numbers are substantially better. The important thing to point out is that in this field in lung cancer, very few have succeeded in both the monotherapy greater than 50% and in chemo combination all comers. Right now, the only two PD-1 antibodies that have demonstrated overall survival benefit both in the monotherapy setting as well as now in the chemo combination setting. This well positions Libtayo, and across all the studies, I think it is clear that it is a very active molecule that looks at least as active as any other agents out there.

Your next question comes from the line of Cory Kasimov with JPMorgan. Your line is open.

This is Gavin on for Cory. Just a thought on the last question. In terms of the longer-term outlook for Libtayo in lung specifically, you talked about the IO combo as kind of the differentiating strategy. And I'm just wondering if you're maintaining that position? Or with the results in hand today, has that view changed?

We think that certainly, we should be competitive right now. The opportunity for this class, which is evidently dominated by KEYTRUDA right now, because up until now, it was the only agent that had this strong data across the spectrum of monotherapy and chemo combination. Now it looks like we can be legitimate competitors in the lung cancer space. We see our combination opportunities as future growth and differentiation opportunities. In the short term, we expect to be a viable competitor now with these data. And in the future, we hope to use the combinations to elevate results to another level.

Your next question comes from the line of Ronny Gal with Bernstein. Your line is open.

Question on the immunotherapy. Can you talk a little bit about the path to establish that antibody cocktail as a treatment for patients who are immunocompromised? You need to have full authorization to begin to pursue this. But if we think about the product longer-term beyond the current wave of the epidemic, what steps are you making towards establishing it as a long-term part of the treatment paradigm in various diseases?

As you said, we believe that the immunocompromised population, which represents about 3% to 4% of the U.S. population, a few million individuals, a variety of studies are showing that approximately 50% or more of these individuals do not respond after 2 or even after 3 attempts with the vaccine. These people are left without their own antibodies to protect them. So it's a huge unmet need setting where these individuals will not be protected. As we're seeing, it's very unlikely that we will be eliminating the spread of infections through breakthrough infections throughout the population. For these individuals to be able to live normal lives, they will need protection. We believe that the most powerful protection is essentially providing them with these surrogate antibodies that our antibody cocktail provides. We already have very strong data to support the notion that this agent can be used in chronic prevention settings, and we intend to continue to explore future study opportunities where we can further enhance on the already existing data showing that after the first week, we obtain upwards of 90% protection against infection in individuals who do not have their own antibodies and are being exposed to the SARS-CoV-2 virus. This is very strong data that bodes well for this being an important treatment, particularly for these immunocompromised individuals who do not have antibodies on their own.

Let me just add that implicit in what George said is we're working with the agency to try and convince them that our data is strong. The agency has a lot on its plate and is trying to sort through whether or not these individuals should try a third dose or not of a vaccine. That has to get sorted out, and the FDA has our data. We're looking at ways to enhance our data, but we believe that in a pre-exposure prophylaxis mode, we have strong data, but it has not been authorized by the agency and is under review.

Your next question comes from the line of Geoffrey Porges with SVB Leerink. Your line is open.

So many questions. Perhaps one for Marion on EYLEA, a really strong result. And by the way, congratulations on the spectacular quarter. On EYLEA, tremendous return to growth. Can you talk about whether there was any catch-up in the second quarter? Or is this a sustainable revenue run rate going forward? Because it's clearly significantly above where we were expecting. And then perhaps you could just give us a little bit more color on the proportion of AMD and DME.

Yes, delighted to comment. We did have a very strong quarter, and certainly, EYLEA performance was driven by the return of market growth and our own share gains versus competition in capturing that market growth. We saw a return of patient flow to offices consistent with the pre-pandemic period. There are also more patients who may have delayed treatment coming back in. It's a combination of factors but certainly a very strong performance for EYLEA. We continue to see diabetic eye disease as the indications that have the highest growth trajectory, balancing against our wet AMD business, which is still the majority, roughly 50% to 55% of overall use of EYLEA.

Your next question comes from the line of Yaron Werber with Cowen. Your line is open.

Great. Maybe a question for Marion and Bob relating to REGEN-COV 2. Are you waiting for approval to receive the next U.S. government order, or are they just planning to use up our current supply before placing a reorder?

The contract we have has been fulfilled. The government needs to decide whether to have another contract or switch over to a commercial model. A lot of this depends on the government's assessment of what is the most efficient way to get people to use the product. Our penetration in terms of estimating eligible patients has gone up dramatically to somewhere around 25% to 30% recently in terms of eligible patients getting monoclonals. If that trend continues along with the trend of increasing cases, we will have to go with the government's direction regarding a new contract or actual switch over. Capacity is always an issue, but we believe we're well positioned to continue supplying similar amounts.

Your next question comes from the line of Terence Flynn with Goldman Sachs. Your line is open.

Congrats on the Dupixent CSU data. I was just wondering if there's incremental SG&A that's going to be required to launch this indication, or if you'd be able to leverage your existing commercial footprint? And then the corollary is just how to think about the continued ramp of profitability of the JV here into 2022? Are there any other significant investments that we need to consider in our models?

Yes, we're really excited about adding potentially another indication for Dupixent. CSU is a large opportunity with about 300,000 potential patients with the disease and very limited treatment options today. We will look at the impact of our educational abilities and promotion by indication. To your question, we do have a leveraging opportunity here because we're already calling on the audiences that would be required to effectively promote CSU. It's premature to say what additional effort we might need, but we'll be able to leverage our current footprint in all areas.

And Terence, I'll punctuate what Marion said on that. Clearly, and you can see it in the MD&A that we disclosed, our margins are getting better. We've talked about a lot of ex-U.S. launches and prelaunch expenses related to that that held that back a little. I think you're now starting to see the fruits of that labor. The leverage we've been talking about for a while is apparent.

Your next question comes from the line of Kennen MacKay with RBC Capital Markets. Your line is open.

Huge congratulations on the quarter really across the board commercially and clinically with a couple of surprises this season. Maybe a question on EYLEA. There was commentary from another earlier this Q2 earnings season that included conversation around somewhat aggressive development plans of EYLEA biosimilar. Just wondering beyond the 2023 composition of matter patent, if you could talk to which intellectual property you're most confident in keeping this franchise going, especially as it relates to the U.S.? Congrats again.

It's a great question, but we're going to have to defer on that one because of ongoing patent issues and what have you. We really can't make a comment on that.

Your next question comes from the line of Carter Gould with Barclays. Your line is open.

We've seen some pretty transformational events across how the FDA is addressing Alzheimer's since your last quarterly call. You did announce an early-stage program in conjunction with Alnylam, but just wanted to see your gauge your appetite to jump into the antibody-directed amyloid beta-lowering game. There are a few companies that innovate antibodies, and so as you think about your Alzheimer's efforts going forward, if that is a point of focus, any broader color on that space would be helpful.

We have a very robust effort in neurodegenerative diseases here at Regeneron, but we're not overly excited about some of the antibody developments and necessarily getting into those approaches. However, we have a lot of things that we're actually very excited about in the neurodegenerative disease space. We think novel ways of addressing targets as well as brand new targets that haven't been discovered elsewhere will be discussed in further detail over the coming months.

Your next question comes from the line of Brian Skorney with Baird. Your line is open.

Unfortunately, this seems like it’s going to be an evergreen question as we see SARS to genetic shift. But it seems like just this week, there's been some emergence of data showing potential increased resistance of vaccinations. Just wondering if you guys have any data yet on the antibody combo and how much activity it might retain against the strain?

So far, every variant and every strain we've tested, we retained potency. We took advantage of the cocktail approach so that even if one antibody gets minimally affected, the other one can take its place. We expect to retain robust activity. Also, we've announced that we have second-generation antibodies entering the clinic to continue broad coverage.

Your next question comes from the line of Geoff Meacham with Bank of America. Your line is open.

I just wanted to ask about commercial Libtayo. What sort of success or metrics can you provide us commercially with the initial first-line lung monotherapy rollout as well as the derm indication? Just see how that's going early in the launch?

For Libtayo with our first lung indication in monotherapy, as expected, that is the smaller indication. We're excited about the chemotherapy combination data that was shared today. If I quantify it, that indication is about 4 times the size of the mono indication. Today, we're still the standard of care in cutaneous squamous cell carcinoma. We retain our leadership despite a new competitor in that indication. In basal cell carcinoma, the launch is also going well. Efficacy and tolerability of Libtayo are paramount for those patients. With specialists believing Libtayo is evolving to become the standard of care. Early days, but on track with where we expected to be, with a lot more potential and work to do.

Tamia, we will have time for maybe 2 or 3 more quick questions.

Your next question comes from the line of Alethia Young with Cantor Fitzgerald. Your line is open.

I wanted to talk about how you see the therapeutic goals for NASH and your leadership in genetics, as there have been many ups and downs in NASH.

There are a variety of goals, but our major question is whether we can halt or reverse the inflammatory response to the steatosis that is not being addressed by other approaches. If we can achieve that, it would be an entirely different and potentially complementary approach to what anyone else is doing right now. The genetics point strongly to this, showing protective mutations related to the process.

Your next question comes from the line of Mike King with H.C. Wainwright. Your line is open.

I'm trying to understand the real-world application of REGEN-COV better. Can you clarify the percentage of patients that are eligible, as I believe Len mentioned around 25%? Do you have any market data on actual usage compared to what has been shipped and paid for by the government?

What we examine are the shipments from our distributor to institutions, hospitals, med centers, clinics, emergencies, etc. We believe, based on some real-world data, that about 70% of the daily cases that occur are occurring in people who are eligible for treatment, because they are obese or have underlying conditions, or are elderly, etc. We believe that around or above 90% of the institutions ordering have repeat orders, meaning they're not just stocking the product, they are using it up. The feedback from some institutions suggests they are actually low on inventory, indicating they're not stocking it up.

That's the characterization. We are continuing to educate and help with some of the bottlenecks experienced in the early days, so we are seeing growing utilization. The patient criteria who are eligible for treatment is broad, with many being in need of treatment, and we're doing everything we can to help them have product availability.

During the last surge, we were only reaching about 1% of potentially eligible patients. We're now well into the double digits in terms of the percentage of the eligible patients that we're probably reaching. We've had feedback from institutions where they actually run low on inventory, suggesting they're using it up.

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

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

Just a question on the Intellia collaboration. Can you share your views on the gene-editing space and your vision or where do you see new indications, as well as the strategic goal of the broad collaboration with Intellia?

These first-in-human results are incredibly exciting, both in terms of the percent knockdown and the observed safety. Both areas of our collaboration with Intellia have greatly bolstered in terms of confidence based on these initial results. We have a series of programs involving systemic-based approaches to achieve gene knockdown, and those chances of success are greatly bolstered by what we've seen. We also have an exciting CRISPR-based gene insertion program we're very enthusiastic about. Our collaboration comprises more than 20 programs under evaluation, and Regeneron has the rights to develop up to 15 in vivo products with Intellia. We're thrilled about the potential to change the practice of medicine with CRISPR-based gene therapies.

Thank you, everyone. Thanks for hanging in there a little longer today. Bob Landry and the IR team are around today to answer any further questions. We wish you a good end of the week and enjoy the rest of the summer. Please stay safe out there. Thank you.

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