雷傑納榮製藥 (REGN) 2021 Q2 法說會逐字稿

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.

(Operator Instructions) 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 and business, 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 performed 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 readout.

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, or 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 of Dupixent as a pipeline in a product to address numerous inflammatory diseases.

In oncology, Libtayo 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, investigational 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 concern 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 rapidly at currently more than 50,000 doses ordered per week.

We also announced that the U.K. RECOVERY study showed a 20% reduction in risk of death in hospitalized patients who had not mounted 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 to be 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 all possible because of our Regeneron colleagues who have been working nonstop throughout this pandemic.

And unfortunately, the world is still in the throes of this global COVID-19 pandemic as the numbers of infected individuals in the United States are climbing again with nearly 100,000 Americans becoming infected every day.

Therefore, I will start with 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 nonhospitalized patients.

This EUA was supported by Phase III data showing that the 1.2-gram dose reduced risk of hospitalization or death by 70%.

Just last week, the EUA was further expanded to include utilization in post-exposure prophylaxis for COVID-19 in certain populations, and also allows for repeated monthly dosing of 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 that is 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, our additional data, which we believe could broaden the prevention application to pre-exposure prophylaxis as well as to extend the treatment paradigm to hospitalized patients.

The details of Part A of our Phase III prophylaxis study in which we assessed efficacy and safety of subcutaneous REGEN-COV in preventing infection among previously uninfected individuals has just been published today in the New England Journal of Medicine.

We believe there is enormous unmet need to try to protect immunocompromised individuals who have not responded to the vaccine and we hope that the FDA will agree that our data will support 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 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 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 RECOVERY 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 to 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 high dose aflibercept in wet AMD.

This readout will consist of efficacy assessments on drawing in other anatomical measures as well as safety on the 8-milligram and the currently approved 2-milligram aflibercept dose at 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 this 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, or 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 that IL-4 and IL-13 are critical drivers in diseases not traditionally thought 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, itepekimab.

Results of the Phase II study in COPD patients were recently published in Lancet Respiratory Medicine.

While 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 is what accounted for the overall benefit with no negative subset in the remaining population.

In the pre-specified former smoker subgroup, itepekimab 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 itepekimab in 2 Phase III studies focused on the former smoker population with COPD.

I should also remind you that we have 2 ongoing studies with phase -- 2 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 Bet v 1 allergen are expected later this year.

The first Phase III study of an antibody cocktail for cat allergy caused by Fel d 1 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 in 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 Plenary 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 EGFRxCD28 co-stim and Libtayo combination is in dose escalation for lung and other advanced cancers.

Our MET X MET 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.

And as we introduced at our ASCO investor event, our first antibody drug conjugate, MET X MET 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 PD-L1 naive patients with potential for a more favorable safety profile than with the 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 3 powerful combination approaches.

First, our MUC16xCD3 bispecific with Libtayo, where we hope to share initial data next year.

Next, our MUC16xCD28 co-stim bispecific with Libtayo.

And third, our novel combination of the CD3 and co-stim bispecifics for which we have now dosed the first patient.

This latter combination of 2 bispecifics of 2 different classes has 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, and starting with lymphoma.

Odronextamab, our CD20xCD3 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 odronextamab subcutaneous formulation.

And next year, we plan to initiate the Phase III program as well as combination trials with our lymphoma-specific co-stim bispecific.

In multiple myeloma, our BCMAxCD3 bispecific is on track to complete enrollment in a 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 co-stim bispecific for multiple myeloma next year.

I would like to conclude with our Regeneron Genetics Medicines efforts.

As you know, these efforts start with our Regeneron Genetics Center and its ability to genetically identify and validate new disease targets and is coupled with emerging gene-based therapeutic solutions to address these targets, including CRISPR-based technologies with 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 2 diabetes.

In terms of progress with our gene-based therapeutics approaches, together with the 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, or TTR 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 Genetics Center, we are hoping to see initial healthy volunteer data by the end of this year.

This 2-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 Genetics 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 #1 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 important foundation for our potential future chemotherapy combination launch, which will be based on the data announced today.

Our expanded field force is now fully deployed and securing early successes with treating physicians.

We're raising brand awareness, progressing formulary positioning and payer coverage.

Lung cancer thought leaders recognized 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 recognized the benefits of Evkeeza, which delivers on efficacy, safety and tolerability in a market where many patients have struggled to stay on therapy in the face of life-threatening LDL cholesterol levels.

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 an 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 outpaced 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's 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 continue 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 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 the 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 reimbursements from BARDA in 2020 for 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 related 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 were 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 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 the 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.

(Operator Instructions)

Please go ahead, Tamia.

(Operator Instructions) Your first question comes from the line of Chris Raymond with Piper Sandler.

Just on the EMPOWER study, guys, we're getting a few questions the comp to Keytruda.

I know it's hard to compare across trials, but it's a little 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, and 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, I mean, we're going to provide the details in future publication and/or conferences.

I think it's important to note, as you said, it's very difficult to compare cross studies done years apart and especially when we allowed classes of patients that were not previously allowed in other studies and so forth.

As you pointed out, the median survival numbers are right on top of each other.

But as you also point out, we had 2 different subtypes in this study.

I can comment in our preliminary analyses, and these remain to be fully validated and so forth.

In one of the subtypes, our hazard ratio was better than what was observed with the Keytruda study and the other one, it was worse.

It's important to point out that these things bounce around in these cross-study comparisons.

As you know, in other settings, if try to do cross country -- cross-study comparisons, for example, when you compare our monotherapy results in the greater than 50% PDL population, it looks like our numbers are substantially better in the skin and particularly with the CSCC comparisons they're better.

So these things bounce around.

It's always hard to do these things.

But I think the important thing to point out is that in this field in lung cancer, very few have hit in both monotherapy greater than 50% and in chemo combination all comers.

I remind you that Opdivo gained than most of the PD-L1s did.

So right now, there is only 2 PD-1 antibodies that standalone, having demonstrated overall survival benefit, both in the monotherapy setting as well as now in the chemo combination setting.

I think this really well positions Libtayo and across all the studies, I think it's -- the definitive conclusion is that it's a very active molecule that looks at least as active as any other agents out there.

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

This is Gavin on for Cory.

Just a follow-up on the last question.

In terms of longer-term outlook for Libtayo in lung specifically, you talked about the IO/IO combo as kind of the differentiating strategy.

I'm just wondering if you're maintaining that position?

Or with the results in hand today, that view has changed?

Yes.

Well, we think that certainly we should be competitive right now.

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

We think that now we can be legitimate competitors here in the lung cancer space.

We see our combination opportunities as future growth in differentiator opportunities.

But in the short term, we expect to be a viable competitor now with these data.

And in the future, we hope to use the combinations to take the standard of care and elevate results to another level.

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

Question on the [immunco].

Can you talk a little bit about the path to establish that antibody cocktail as a treatment for patients who are immunocompromised before treatment -- before cancer treatment and so forth?

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?

Yes.

As you said, we think that the immunocompromised population which, as I'm sure you all know, represents 3% to 4% of the U.S. population, that several million individuals, a variety of studies are showing that somewhere around 50% or more of these individuals do not respond after 2 or even after 3 attempts with the vaccine.

And so these people are left without their own antibodies to protect them.

So it's a huge unmet need setting where these individuals will not be protected.

And as we're all seeing that it's very unlikely that we will be eliminating spread of infections through breakthrough infections, whether it was symptomatic or otherwise throughout the population and for these individuals to be able to live normal lives, they're going to need protection.

And we believe that the most powerful protection is essentially providing them with these surrogate antibodies that our antibody cocktail provides.

We already have very strong data, we believe, to support the notion that this agent can be used in chronic prevention settings, and we do intend to continue to explore future study opportunities where we can further enhance on the already existing data that shows that after the first week or so, we seem to obtain somewhere upwards of 90% protection against infection in individuals who do not have their own antibodies and are being exposed to the SARS-CoV-2 virus.

I think that is very strong data that bodes very well that this is in -- potential to be a very important treatment, particularly for these immunocompromised individuals who do not have antibodies of their own.

Yes.

Let me just add that what's implicit and what George said is we're working with the agency to try and convince them that our data is strong.

And -- the agency, obviously, has a lot on its plate, and it's trying, I think, to sort through whether or not these individuals should try a third dose or not of a vaccine.

That has to get sorted out, I think.

And the FDA has our data.

And as George said, we're looking at ways to enhance our data, but we already believe that in a pre-exposure prophylaxis mode we have strong data, but it's not been authorized yet by the agency and it's under review.

So am I to understand you're seeking a label for chronic treatment of immunocompromised population and that you think you have the data at hand to obtain such a label?

So just to be clear, the current authorization allows chronic treatment but allows chronic treatment for people, for example, who are immunocompromised, but are in a institutional setting, working or living in a congregate setting where they're exposed to infected individuals, we would like to expand that to pre-exposure prophylaxis for the community-acquired infections.

That is where immunocompromised people might be able to go out in the community and have some protection.

So we do have chronic dosing for the immunocompromised in our current authorization, but that's restricted to this post exposure or ongoing exposure in the known infected people setting, and we're trying to expand that to protect these people in the community setting.

It's -- we think the data are strong.

But obviously, there's a lot going on and a lot of considerations, as I mentioned before, that need to get sorted out.

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

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.

Marion, could you talk about whether there was any catch-up in the second quarter?

Or is this a sustainable revenue run rate going forward?

Because it's clearly significantly above where we were expecting.

And then perhaps you could just give us a little bit more color on the proportion of AMD and DME.

Sure.

And thank you, Geoff.

Yes, delighted to comment.

We did have a very strong quarter.

And certainly, our EYLEA performance was driven by return of market growth and our own share gains versus competition in capturing that market growth.

In the quarter, we did see a return of patient flow to offices consistent with the pre-pandemic period.

And there also is the consideration of some patients who may have delayed treatment coming back in.

So it's a combination of factors but certainly a very strong performance for EYLEA.

As well, to your question related to future growth by indication, we do continue to see diabetic eye disease as the indications that have the highest growth trajectory.

So that's balancing out our wet AMD business, which is still the majority of roughly 50%, 52%, 55% of overall use of EYLEA.

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

Great.

Maybe a question for Marion and Bob relating to REGEN-COV2.

Are you -- in order to get the next U.S. government order, do you -- are you waiting for approval?

Or are they just waiting to exhaust their current supply and then reorder?

Maybe I'll take that question.

The contract we have has been fulfilled.

And so the government is going to need to decide whether or not they want to have another contract or they want us to switch over to a commercial model, which could occur before or after a regular approval as it did with Remdesivir.

I think a lot of that is going to depend upon the government's assessment of what they think is the most efficient way to get people to use that product.

There's been a tremendous acceleration in use.

Our penetration in terms of addressing what we would say, estimated eligible patients has gone up dramatically to somewhere in the low single digits to almost 25% to 30% more recently in terms of eligible patients getting monoclonals.

If that trend continues along with the trend of unfortunately, more cases, obviously, we're going to have to go with the direction that the government wants, another contract or a commericial switchover.

Capacity, of course, is always an issue, but we think we're sort of well positioned to continue to supply similar amounts that we've been able to supply and we'll have to look at -- and these demands continued pretty rapidly.

And of course, we do have our partner, Roche, who's got capacity that we can perhaps turn to.

So a lot of moving parts, Yaron.

And the most important of which is what is the shape of the current surge in the pandemic.

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

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 on profitability of the JV here into 2022?

Are there any other significant investments that we need to consider in our models?

So Terence, I'll start from the commercial perspective.

So yes, we're really excited about adding potentially another indication for Dupixent.

CSU is a large opportunity.

They're about 300,000 potential patients with disease adults and very limited treatment options for them today.

We will be able to always look at the impact of our educational abilities and promotion by indication.

But to your very clear point, we do have a leveraging opportunity here because we're already calling on the audiences that would be required to effectively promote CSU.

It's premature for us to say absolutely what sort of additional effort we might need.

But certainly, we will be able to leverage our current footprint in all areas.

Yes.

And Terence, I'll just kind of punctuate what Marion said on that.

Clearly, and you can see it in the MD&A that we disclosed, and you can do the calcs, right, our margins are getting better with this.

I mean this is something that we talked about.

Certainly, we've had a lot of ex U.S. launches, a lot of prelaunch expenses related to that, which kind of held that back a little bit.

I think you're now seeing certainly year-over-year, you're starting to see the fruits of the labor.

And the leverage that we've been talking about for a while, again, kudos to Sanofi, another strong ex U.S. quarter by them as we continue to see the indications really starting to kick in ex U.S.

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

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 call earlier this Q2 earnings season that included conversation around somewhat aggressive development plans of an EYLEA biosimilar.

Just wondering sort of beyond the 2023 composition of matter patent, if you could talk to which intellectual property you have the most confidence in, in keeping this franchise going, especially as it relates to the U.S.?

Congrats again.

Right.

It's a great question, but we're going to have to defer on that one because of ongoing patent issues and what have you.

We really can't make a comment.

Sorry.

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

Obviously -- I want to kind of change gears a bit.

Obviously, we've seen some pretty transformational events across how FDA is addressing Alzheimer's since your last quarterly call.

You did announce a early-stage program in conjunction with Alnylam, but just wanted to see if -- you gauge your appetite to jump in sort of the antibody-directed amyloid beta lowering game.

There's a few companies that innovate and iterate antibodies as well as Regeneron.

And so as you think about your Alzheimer's effort going forward, if that was a point of focus and any broader color on that space would be helpful?

Well, we should let the iterator and inventor answer that.

Sorry.

I'm sorry, I was just saying we should let the iterator and inventor answer that.

Go ahead, George.

Okay.

I was going to just -- sorry, I didn't hear you speaking here.

Yes, we have a very robust effort in neurodegenerative diseases here at Regeneron.

We are not overly excited about some of the antibody developments and necessarily getting into those type of approaches.

But 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.

We will be discussing these efforts going forward in more detail over the coming months and year.

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

Unfortunately, I kind of feel like this is going to be an evergreen question as we see SARS-CoV-2 to genetic shift.

But it seems like just this week, there's been some emergence of data for the lambda strain showing potentially increased resistance of vaccination.

Just wondering if you guys have any data yet on the antibody combo and how much activity might retain against the strain?

Yes.

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

But so far, every variant and every strain that we've tested, we retained potency.

And so far, there's hopefully no reason to think that's going to change because we prospectively took advantage of this cocktail approaches so that even if one antibody gets minimally affected the other one can take its place.

So we expect to retain robust activity.

That said, I think we've also announced that we have second-generation antibodies that are also entering in the clinic where we're going to continue to retain broad coverage.

But I believe that as far as it's been tested with lambda, we retain potency there as well.

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

I just wanted to ask on commercial Libtayo.

Just wanted to see what sort of success or what metrics you can give us commercially with the initial first-line lung monotherapy rollout as well as the derm indication as well to see how that's going early in the launch?

Sure, Geoff.

Happy to.

So for Libtayo with our first lung indication in mono, as expected, that is the smaller indication.

So we're really excited about the chemotherapy combination data that was shared today.

And in fact, if I quantify it, that indication in terms of patient potential is about 4x the size of the mono indication.

But what we're doing today in the market commercially is certainly foundational to Libtayo and our oncology portfolio more broadly.

I'll comment, we are still the standard of care in cutaneous squamous cell carcinoma.

That was a very effective launch.

We now have a competitor in that indication, but we retain our leadership.

The basal cell carcinoma launch is also going well.

And certainly, the efficacy and tolerability, safety of Libtayo is paramount for those patients, and we offer an alternative where the specialists in that area do believe Libtayo as evolving to become the standard of care.

It's early days in lung.

I think our team is doing a really good job.

And when we talk to the opinion leaders, they're most excited, as I mentioned, about our rapid action, our efficacy, even in those patients with stable brain metastases and with the high expression PD-L1 patients.

So early days, we are right on track with where we expected to be, but there's a lot more potential and a lot more work to do.

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

I just wanted to talk a little bit about how you guys see what the therapeutic goals are for -- in NASH for medicine since you're a leader in genetics and there's been a lot of ups and downs in NASH?

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

I think the genetics very strongly point to that.

That's what it actually shows that this genetic target affects and that's what the protective mutations are actually showing.

So we're excited about looking at this opportunity, whether we can halt or even reverse inflammatory signals, inflammatory processes and thus, actual progression of the disease irregardless of steatosis.

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

I'm not sure how long -- how quickly this question could be answered, but I'm just trying to get a better appreciation of what I would call the real-world use of REGEN-COV.

Can you point to -- I think Len said something about 25% of patients, but I think that was eligible.

I don't know if you have any market data from real-world use versus what's been shipped and paid for -- shipped to and paid for by the government?

Can we understand how that rubber band flexes a little bit more?

Sure.

So look, what we look at are the shipments from our distributor to institutions, hospitals, med centers and clinics, emergency rooms, et cetera, et cetera.

And we believe, based on some real-world data, that about 70% of the daily cases that occur are occurring in people who would be eligible for treatment, either because they're obese or they've got underlying conditions or they're elderly more -- we're seeing more younger and obese, frankly, than we -- than elderly that was seen earlier in the pandemic.

So if you take, for example, that maybe it was 100,000 new cases, maybe 70,000 of them would be eligible.

So that gives you an idea.

I was just looking, Mike, at this to see what our repeat orders were.

And the vast, vast majority, I think it's around or above 90% of the institutions ordering have -- are repeat orders, meaning that they're not people just stocking the stuff to have it around.

They're using it up.

And that's what our field people seem to tell us.

I don't know if Marion wants to maybe add anymore on that or not, but I hope that helps you.

That would be the characterization.

I think the other thing that's important is, we are continuing to educate and to help with some of the bottlenecks that have been experienced early days.

So we are seeing growing utilization.

And certainly, as Len mentioned, the patient criteria who are eligible for treatment is broad, to Len's point, age-related obesity, hypertension, diabetes, respiratory immune issues.

So there are a lot of patients who are very much in need of treatment, and we're doing everything we can to help them have availability of product.

Yes.

I'll just add a couple of thoughts or points to that is during the last sort of surge, as Len said, we were probably only reaching somewhere near 1% of the potentially eligible patients.

We're now well into the double digits in terms of the percentage of the eligible patients that we're probably reaching.

And we've had some feedback from some of these institutions where we distribute to where they're actually low on inventory, suggesting that they're not stocking it up.

Yes.

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

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

Just a question on the Intellia collaboration.

Can you just share your views on the gene editing space.

Your vision or where do you see the new indication and obviously, the strategic goal of the broad collaboration that you have with Intellia?

Yes.

Obviously, these first-in-human results are incredibly exciting, both in terms of the percent knockdown and also in terms of thus far in these early days, the observed safety.

And as we said, we have 2 types of broad collaborative program areas with Intellia, both of which we think are greatly bolstered in terms of confidence based on these initial results.

We have a series of programs which similarly involve systemic-based approaches to achieve gene knockdown.

So obviously, those are -- chances of success are greatly bolstered by what we've seen with these first-in-human results.

But we also have, I think, just as if not even more exciting, a CRISPR-based gene insertion program that we're very excited about.

And since it depends on essentially overlapping technologies, this program and its chance of success has greatly been increased based on the results we've seen to date.

So we think that with the fact that we have so many programs ongoing in our collaboration with Intellia, more than 20 programs under evaluation, and we have the ability to move forward quite a few of these, we're very excited that this could really change the practice of medicine and really bring CRISPR-based gene therapy to patients into the world.

So nothing to be more exciting from the gene medicines point of view.

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.