Regeneron Pharmaceuticals Inc (REGN) — Q3 2020 Transcript

Thank you, Justin, and thanks to everyone joining today's call. In the third quarter, Regeneron delivered another strong financial performance of double-digit top and bottom line growth while achieving numerous milestones in our research and development pipeline and making remarkable progress against COVID-19 with our novel antibody cocktail. Importantly, our growth and financial strength is being fueled by an increasingly diversified set of revenue and earnings streams while we invest in R&D for the long term. Furthermore, our results show the importance of products that meaningfully address serious medical needs and have the power to transform lives even during a pandemic. EYLEA is a great example. EYLEA Global net sales were $2.1 billion in the quarter and grew 9% compared to the same period last year. In the U.S., sales rebounded from second quarter COVID lows to $1.3 billion and grew 11% versus prior year. The efficacy, safety and convenience that EYLEA offers in protecting eyesight has proven to be highly valued by treating physicians and their patients as the product again outperformed the anti-VEGF market for retinal diseases. Next, we continue to build momentum with Dupixent as we in Sanofi recorded our first ever quarter of more than $1 billion in sales. This milestone speaks to the power of Dupixent across a broad array of type 2 inflammatory diseases and to our team's ability to execute despite COVID-19. Adding to this momentum, we've recently announced results from another successful Phase III trial, this time in pediatric asthma. We are eager to submit these data for regulatory review and expect that Dupixent will remain a robust and durable growth driver for years to come. In oncology, we are solidifying our leadership position in cutaneous squamous cell carcinoma. Additionally, the FDA has granted priority review for our regulatory filings in lung cancer and basal cell carcinoma as we prepare for potential launches in these indications early next year. Regeneron is also making critical advancements in the treatment of infectious diseases. Last month, the FDA approved Inmazeb, the first-ever treatment for Ebola virus infection. Building upon our work in Ebola, our team and rapid response technologies have developed our novel REGN-COV2 antibody cocktail in the fight against COVID-19. Last week, we announced another major data set from our outpatient study that showed our antibody cocktail significantly reduced viral loads as well as medically attended visits, such as emergency room visits and hospitalizations. We have submitted these data to regulators and eagerly await guidance on next steps. In closing, we could not be prouder of our teams and everything they have been able to achieve across the organization in the third quarter and in 2020 to date. Our momentum is accelerating with an impressive growth profile. In 2021, we look forward to building upon that momentum with several important launches for Libtayo, Dupixent and other programs, further enhancing our diverse growth platform. We are excited by the progress we are making against COVID-19, and we are confident that our investments in R&D to broaden and advance our pipeline across all stages will position Regeneron well for sustained growth. Now I'll turn the call over to George.

Thanks, Len. As Len mentioned, we are making progress on programs throughout all stages of our diverse and expanding portfolio. With the pandemic still ongoing and worsening, there is significant attention on COVID-19, so we will start with our REGN-COV2 program. Our efforts against the coronavirus attracted a lot of interest from the outset, particularly because of our success using a similar approach with Ebola. Len shared that we received FDA approval for our Ebola cocktail, which validates our approach for treating not only Ebola but also other lethal infectious diseases, especially COVID-19. We are currently investigating REGN-COV2, our antibody cocktail for COVID-19, in both infected patients and for prevention in several clinical trials. Earlier this year, we published a descriptive analysis of the first 275 patients in the REGN-COV2 seamless Phase II/III trial involving ambulatory patients. This early data provided important insights into the natural history of COVID-19. Many patients develop their own antibodies against the virus quickly, leading to a strong immune response that helps clear the virus rapidly and reduces the need for medical intervention. That's why most patients recover well. However, some patients take longer to develop an immune response, making them more likely to seek medical care. Our initial analysis indicated that administering our exogenous antibody cocktail was less beneficial for the rapid responders but helped those who struggled to mount an immune response efficiently, enabling REGN-COV2 to eliminate the virus faster and reduce future medical needs for these slower responders. Last week, we presented significant updates from this ongoing study in patients with COVID-19. Through a formal statistical analysis, we confirmed earlier findings with additional data from over 500 patients. The results indicated notable viral load reductions in patients treated with REGN-COV2 compared to placebo. Consistent with prior data, these findings were primarily seen in patients who had not created their own effective immune response at treatment initiation or had high viral loads at baseline. Notably, results from the combined analysis of the first 799 enrolled patients revealed a statistically significant reduction in medically attended visits, which includes hospitalizations and emergency room visits. This effect was particularly evident in patients with high-risk factors, high viral loads, and those who had not yet formed their own immune response. We shared these findings with the FDA as an update to our Emergency Use Authorization submission and are awaiting regulatory feedback. We’re also exploring the potential benefits of the REGN-COV2 cocktail in various stages of the disease through additional studies, including our household contact study, which is assessing the cocktail as a preventive treatment and has enrolled around 1,000 patients thus far. For hospitalized patients, we are conducting two ongoing studies, including our own study and the U.K. RECOVERY Protocol. All Regeneron-sponsored COVID-19 trials are overseen by the same independent data monitoring committee, which recently advised pausing enrollment in two cohorts representing severely hospitalized patients, while recommending that all our other trials proceed as initially planned, including the two less severe patient cohorts in our hospitalized study. Since the lower dose of REGN-COV2 showed comparable efficacy to the higher dose, we plan to explore even lower doses in future research. If successful, this could allow us to reach even more patients with our cocktail. As we await further regulatory developments, we are ramping up production of REGN-COV2. Under our U.S. government agreement, we now anticipate having treatment doses ready for approximately 80,000 patients by the end of this month, 200,000 total doses by the first week of January, and about 300,000 total doses by the end of January. We are also increasing our in-house production capabilities for additional doses of REGN-COV2 and are excited to partner with Roche to significantly boost global production capacity for REGN-COV2 as their facilities become operational early next year. Moving on to Dupixent, we recently announced promising Phase III data in asthma for children aged 6 to 11. In this study, Dupixent reduced severe asthma attacks by as much as 65% versus placebo over one year and also quickly and sustainably improved lung function in these children. We plan to submit these findings to regulators early next year. Additionally, in Europe, we received a positive recommendation from the CHMP committee for Dupixent in atopic dermatitis for children aged 6 to 11. The Dupixent clinical program continues to advance and expand across various type 2 inflammatory conditions. In September, the FDA granted breakthrough therapy designation for Dupixent in eosinophilic esophagitis based on early Phase III results, which we recently presented at medical gatherings. By the end of the year, we expect to share Phase II data of Dupixent used in combination with oral immunotherapy for peanut allergy. Moreover, ongoing Phase III studies for several dermatology and pulmonary indications will yield results in 2022 and 2023, and we plan to initiate more Phase III pivotal trials before the year's end. Overall, Dupixent is about to enter pivotal trials for eight type 2 diseases not currently included in its label, potentially addressing nearly 1 million additional patients in the United States alone. Dupixent is also crucial to our strategy against chronic obstructive pulmonary disease, or COPD, alongside etokimab, our anti-interleukin-33 antibody. After achieving a predefined efficacy milestone in an interim analysis of our first Phase III study in type 2 COPD, we launched a second Phase III study for Dupixent. We anticipate data readouts in 2023. We believe that our anti-IL-33 antibody could assist another group of COPD patients beyond those with type 2 disease. Based on proof-of-concept data awaiting publication, we think that inhibiting IL-33 may prove especially beneficial for COPD patients who are former smokers. The pivotal etokimab program involves two parallel Phase III studies, which will commence by year-end. We hope that Dupixent and etokimab can provide meaningful help to patients suffering from COPD. Turning to oncology, we first discussed Libtayo. At the European Society for Clinical Oncology meeting in September, we presented results from our first-line non-small cell lung cancer study, as well as our study for locally advanced basal cell carcinoma. These results have been submitted as supplemental label applications to regulators, with the FDA granting priority review for Libtayo as a standalone treatment for lung cancer, with an action date of February 28, 2021. We also announced the completion of patient enrollment in the Libtayo chemotherapy combination trial for first-line lung cancer, with results expected as early as next year. Additionally, the BCC results presented at ESMO suggest that Libtayo could be the first approved treatment demonstrating clinical benefit in advanced BCC cases after the failure of a hedgehog inhibitor. The FDA has also awarded priority review for our BCC filing, with an action date of March 3, 2021. We are making notable progress with Libtayo as a key component of our oncology strategy. Regarding our oncology bispecific initiatives, we have a pivotal program underway for non-Hodgkin's lymphomas with our CD20xCD3 bispecific, also known as REGN1979. We are also set to initiate a pivotal program for REGN5458, our BCMAxCD3 bispecific, targeting relapsed or refractory multiple myeloma. In solid tumors, we are continuing dose escalation for REGN4018, our MUC16xCD3 bispecific, in the first-in-human study for ovarian cancer, where we are seeing preliminary signs of activity. We are enthusiastic about the promising data from our CD3 bispecific studies. We believe that our primary advantage over other methods lies in our capability to combine these CD3 bispecifics not just with our anti-PD-1 treatments but also with our next generation of bispecifics, the novel CD28 or costimulatory bispecifics. Our CD3 bispecifics currently in clinical trials are designed to pair with corresponding costim bispecifics targeting various cancers, aiming to synergistically enhance the effectiveness of immuno-oncology beyond what is currently approved. Our first costim bispecific, PSMAxCD28, is progressing through dose escalation cohorts in combination with Libtayo for prostate cancer, and so far, the treatment has been well tolerated. We will soon initiate trials using two new costims, MUC16xCD28 in conjunction with either our MUC16xCD3 bispecific or with Libtayo for ovarian cancer, and our EGFRxCD28 alongside Libtayo for solid tumors, including lung, head and neck, and colorectal cancers. The first of a third class of tumor-targeting bispecifics, our MET X MET bispecific, has recently wrapped up dose escalation and is now entering the dose expansion phase of the first-in-human trial. This bispecific targets two distinct epitopes on the MET oncogene, leading to rapid internalization of the receptor and the removal of its signaling. MET mutations occur in approximately 3% to 4% of cases with MET gene amplifications and about another 3% of non-small cell lung cancers. As we move forward, we are pleased with the progress across all stages of our robust oncology portfolio, as we aim to enhance and extend the power of immuno-oncology to more patients dealing with a variety of cancers. In addition to oncology, our pipeline is expanding. In our C5 program, we will soon begin dosing healthy volunteers along with Alnylam's C5 RNAi inhibitor, cemdisiran. This combination aims for convenient self-administration with a subcutaneous dosage form, as well as more complete and lasting suppression of complement activation in patients affected by paroxysmal nocturnal hematuria and other complement-mediated diseases. This will be a pioneering combination of an antibody with RNAi targeting the same objective, and we believe it could represent the start of a trend towards innovative antibody-RNA combinations that might transform treatment paradigms across various diseases. We are also excited about ongoing collaborative efforts with Alnylam, utilizing their siRNA mechanism against targets identified through our Regeneron Genetic Center. Alnylam recently announced the initiation of dosing for siRNA targeting one identified target, HSD17B13, aimed at treating NASH. Additionally, I want to highlight a significant milestone in our innovative collaboration with Intellia. Soon, the first patient will receive dosing for a groundbreaking systemically delivered CRISPR/Cas9 gene editing therapy, which may represent a potential one-time treatment for transthyretin amyloidosis. As the initial systemically administered gene editing intervention, we anticipate that this will serve as proof-of-concept for future systemic gene editing initiatives. Our collaborations with Alnylam and Intellia symbolize a fresh strategic approach towards genetic therapies at Regeneron, as we seek to leverage our capabilities and expertise while also enhancing those of our partners to shift medical practices and make new forms of gene therapy a reality. By the year's end, we and our collaborators will have introduced eight new investigational therapies into clinical trials—an achievement we take pride in during a challenging year. In closing, we look forward to several upcoming catalysts over the next few months. We expect timely updates and additional data from our REGN-COV2 therapy, the first regulatory approval for evinacumab by February of next year, approvals for first-line lung cancer and basal cell carcinoma indications for Libtayo, the filing for Dupixent in pediatric asthma, and much more on the horizon. It truly is an exciting time at Regeneron. Now, I will turn the call over to Marion.

Thank you, George. Our third quarter commercial results reflect a solid execution across our core brands, EYLEA, Dupixent and Libtayo. We remain confident that the competitive strengths of our growing and diversified commercial portfolio will carry us through and beyond the COVID-19 environment. I'm going to begin with EYLEA, which grew 9% year-over-year to approximately $2.1 billion in global net sales. In the U.S., EYLEA grew 11% year-over-year with net sales of more than $1.3 billion as the anti-VEGF demand recovered. In the U.S., EYLEA outperformed the category with shared gains from both branded and unbranded competition. In fact, EYLEA's share of the branded U.S. category grew to more than 70% for the quarter based on volume, and EYLEA remains the #1 prescribed anti-VEGF therapy in wet AMD and diabetic eye disease. Patient volume increased as those who delayed treatment earlier this year have returned to retina offices. EYLEA's market-leading clinical profile offering dosing flexibility, real-world experience and established safety led to a quicker recovery and stronger growth across all indications than the competition. EYLEA's flexible 12-week dosing regimen in wet AMD and the newly launched prefilled syringe also support EYLEA's market-leading value proposition. We are monitoring the recent spike in coronavirus cases across the country. In some hotspots, retina offices are beginning to see some modest reductions in patient volume, which may impact future EYLEA demand. That said, retina offices have become highly effective in managing their patients in this environment compared to the early days of the pandemic. In summary, EYLEA had an impressive quarter. Turning next to Libtayo. Third quarter global net sales grew to $96 million. In the U.S., net sales were $72 million with consistent and steady volume growth aided by the gradual reopening of infusion centers and an increase in breadth of prescribing. Libtayo continues to drive overall market growth in advanced cutaneous squamous cell carcinoma and remains the most prescribed systemic treatment for CSCC. EYLEA remains the anti-PD-1 of choice with nearly 90% market share of the class. The overall profile of high response rate with many complete and durable responses positions Libtayo for continued growth. To fuel additional growth, we anticipate 2 new potential indication launches in non-small cell lung cancer and basal cell carcinoma in the first quarter of 2021. For basal cell carcinoma, we aim to build upon our success in CSCC and establish Libtayo as the standard of care for non-melanoma skin cancers. We expect Libtayo to be first-in-class and will work to establish it as the standard of care in second line BCC. Non-small cell lung cancer is the largest opportunity within the PD-1 space with more than 200,000 new diagnoses of lung cancer in the U.S. each year. We plan to leverage our oncology presence as the majority of treatment centers and oncologists are familiar with Libtayo in CSCC. We believe that patients, providers and payers prefer choice in determining the most appropriate treatment. Libtayo demonstrated an overall survival benefit in a real-world, higher-risk population of patients, including patients with stable brain metastases, infections and progressive disease. These data, along with additional product attributes, support Libtayo as a potential new option for anti-PD-1 monotherapy in the treatment paradigm. Finally, moving to Dupixent. Global net sales in the second quarter were $1.1 billion, representing 69% growth compared to the prior year. In the U.S., broad-based growth across all indications contributed net sales of $851 million. Among all specialties, patient visits improved throughout the quarter as the healthcare field has adapted to treating patients in the COVID environment. Current weekly new patient starts have recovered and are nearing pre-pandemic levels. The 300-milligram pre-filled pen was launched this quarter, providing additional patient convenience and choice. Atopic dermatitis remains Dupixent's largest indication and is a significant growth driver based on its rapid onset, proven efficacy and well-established safety profile. We continue to expand prescribing across both moderate and severe disease. Despite the impressive growth trajectory since launch, a low percentage of biologic eligible patients have been treated, leaving substantial opportunity for more patients to benefit. Our ongoing launches for both adolescents and pediatric patients are progressing very well. Since the May launch of the pediatric indication, we are seeing encouraging trends, comparable to the adolescent launch where initiations grew rapidly and HCPs were quick to prescribe. Significant runway is evident with approximately 400,000 adolescents and 90,000 children in this country that could benefit from Dupixent therapy. Moving to asthma, Dupixent continues to perform well in the competitive asthma space based on its clinical efficacy and safety profile. Our national DTC campaign is well underway, and we are seeing an uptick in new initiations. We look forward to submitting our pediatric clinical data to regulators, which could lead to further label expansion and benefit as many as 75,000 eligible children. Additionally, we see strong uptick in chronic rhinosinusitis with nasal polyps. Since approval last year, patients have been initiated on Dupixent regardless of prior surgery, while the availability of elective surgeries has improved as healthcare facilities have reopened. Demand for Dupixent remained strong among ENTs and allergists. Dupixent is making an important contribution to our business, and we're excited about the significant opportunity for future growth from our in-line business and from new potential indications, age groups and geographies. In closing, our commercial teams delivered strong performance across our diversified portfolio. We have a set of meaningfully differentiated products that are growing despite COVID-19. Additionally, we will enter a new phase of launches in 2021, including evinacumab for HOFH, pediatric asthma for Dupixent and lung and BCC for Libtayo. These launches will add to our momentum and the significant growth of our business. These are very exciting times at Regeneron.

Thank you, Marion. For the third quarter of 2020, Regeneron delivered strong growth on both the top and bottom lines, resulting from continued execution across all aspects of our business. Improving Dupixent profitability and contributions from additional revenue sources highlight the continued diversification of our business. For the third quarter, total revenues grew 32% year-over-year to $2.29 billion, driven by strong U.S. EYLEA growth and higher Sanofi collaboration revenues as a result of increased Dupixent sales and achievement of a $50 million sales milestone. Non-GAAP diluted net income per share grew 25% year-over-year to $8.36 on non-GAAP net income of $961 million. Since Marion discussed our U.S. EYLEA results, I will start with our Bayer and Sanofi collaborations. Starting with the Bayer collaboration. Ex-U.S. EYLEA net product sales reported to us by Bayer were $780 million, representing a growth of 7% on a reported basis, compared to the prior year and a 22% improvement from second quarter 2020 lows. Total Bayer collaboration revenue was $300 million, of which we recorded $288 million for our share of net profits from EYLEA sales outside the U.S. Total Sanofi collaboration revenue was $353 million in the third quarter. Our share of the profits from the commercialization of non-IO antibodies was $213 million. This compares favorably to profits of $94 million in the prior year, which was primarily driven by higher Dupixent profits. We also recognized a $50 million milestone payment from Sanofi as a result of Dupixent, Praluent and Kevzara ex-U.S. sales achieving $1 billion in the trailing 12-month period. Next, we announced in July a $450 million supply agreement with the U.S. government for batches of REGN-COV2. We record sales as batches are supplied to the government. In the third quarter of 2020, under this agreement, we recorded an initial $40 million of sales for REGN-COV2. We expect that in the fourth quarter of 2020, we will record sales approximating half of the value of this agreement. Sales for the remaining batches are expected to be recorded in the first quarter of 2021. In other revenue, we recorded $159 million versus $37 million in the prior year. The primary driver of this increase is the recognition of $70 million from the U.S. government associated with reimbursements of our Ebola and REGN-COV2 development recognition of $28 million in connection with the Regeneron Genetic Center sequencing a certain number of exomes as well as a reimbursement for ex-U.S. supply of Praluent to Sanofi. Looking ahead to fourth quarter in 2021, we expect the other revenue line to trend lower in the absence of an RGC milestone and reduced reimbursements from the U.S. government on Ebola. Moving to our expense base and starting with R&D. Non-GAAP R&D increased 35% year-over-year to $629 million, driven by significant clinical development costs for our REGN-COV2 antibody cocktail, higher headcount to support our expanding pipeline, increased clinical manufacturing activities and continued advancement of our partner programs with Alnylam, Intellia and other early-stage partners. Next, non-GAAP SG&A expense increased 10% year-over-year to $291 million. The year-over-year increase was largely driven by increased headcount as well as commercial costs for EYLEA and Praluent. Cost of collaboration and contract manufacturing was $143 million, compared to $110 million in the third quarter of 2019, primarily due to increased sales of Dupixent. Non-GAAP cost of goods increased 22% from the prior year related to higher sales of Libtayo and the inclusion of sales from Praluent and REGN-COV2. Turning now to taxes. The non-GAAP effective tax rate was 16.3% in the third quarter of 2020, compared to 13.6% in the third quarter of 2019, primarily due to discrete items to the quarters. Shifting now to cash flow and the balance sheet. Regeneron continues to maintain a strong balance sheet, ending the quarter with cash and marketable securities of $5.9 billion. Our third quarter free cash flow was negatively impacted by the extension of EYLEA payment terms to support physician offices during COVID. We expect this will reverse in 2021 as payment terms return to normal. Additionally, in the quarter, we issued $2 billion of long-term debt, leveraging historically low interest rates while decreasing our cost of capital. With the issuance of this debt, we expect to incur approximately $45 million of incremental interest expense on an annual basis. Finally, we repurchased $100 million of stock in the third quarter as part of our $1 billion Board-authorized share buyback program. Now I'd like to spend a few moments to provide updates to our full year 2020 guidance. We updated our guidance on several expense line items where, in many cases, we either lowered or narrowed guidance range. Please refer to our press release for our entire updated 2020 guidance. Specific to R&D. We are revising upward our forecasted 2020 non-GAAP R&D expense to be in the range of $2.42 billion to $2.47 billion. While we increased R&D guidance on our second call to reflect REGN-COV2 expenses, we have since substantially expanded the scope and enrollment targets across the REGN-COV2 clinical program, which will result in increased expenses in the fourth quarter and into the first half of 2021. Also, while we are not providing 2021 guidance today, we do expect that 2021 full year R&D expenses will increase to fund in advancing and expanding pipeline as well as early stage partnership assets. In conclusion, Regeneron's business remains healthy, and we continued to deliver strong year-over-year growth as we diversify our revenue and earnings and advance our robust pipeline. We remain well positioned for future growth with healthy core brands and multiple near-term launches while investing in our R&D engine to drive longer-term growth. With that, I'd like to turn the call back to Justin.

I guess for George and Len, clearly, a lot of enthusiasm around the potential for the costims as we look to some of those readouts. I guess when we look to 2021, are we going to have a clear signal if these are living up to their promise in 2021? I know moving through some of these dose escalations takes time, but do you guys have confidence we'll be in a position to have a clear read on if they're living up to their hype next year?

Well, it all depends on, as you said, these dose escalation studies, how they progress and proceed, we certainly hope that we will be getting signals of efficacy sooner rather than later, but it all depends on the clinical development and how that all goes. But we remain incredibly enthusiastic and excited about this class, and we're investing enormously. As I said, we have pairs of CD3 and CD28 bispecifics for numerous different cancers, not only the ones that are already in the clinic, but ones that will be entering into the pipeline over the next year or 2 or 3. So we're very excited about this class and the potential of combining them with the 2 sets of bispecifics as well as with the PD-1.

Just on REGN-COV2. Just wondering if you could walk through the biology behind why there would be a safety signal in these vented or high-flow oxygenated patients. I mean, I guess, especially given how clean it looked in mild-to-moderate cases, is there some threshold of viral load? Or is it underlying overactivation of the immune system that's driving this problem? And can you maybe describe the ADEs, please?

So first of all, we should point out that we remain blinded to what's going on in those 2 cohorts that were paused. They weren't halted, they were paused so that the IDMC could evaluate the ongoing patients and then decide what to do going forward. We do not know whether there really is any safety signal. And as you said, I think theoretically, there is not really a great deal of rationale why there might be a safety signal there. You could come up with all sorts of complicated scenarios to explain it. But until we're unblinded to the data, until we really get to look at it, at this point, it could simply be that there's lack of efficacy or maybe even early trends which will reverse. So as you said, theoretically, it does not make a great deal of sense. I think the whole concept of what they call ADE or antibody-dependent enhancement, is something that does not look like it's really playing a role in this disease. So we remain hopeful that there is not going to be a safety signal and eventually, at least in some subset of these patients, even the hospitalized patients that we may provide a benefit.

I'll limit it to one. So in the 10-Q, you listed the EUA for the AB cocktail during this quarter. Is this official guidance from the FDA? And any idea as to what patient population that this EUA would be granted for?

So it's Len. We are concentrating on the outpatient population that shows the best baseline characteristics suggesting they would gain the most benefit, including those with risk factors, high viral titer, or possibly low antibodies. There is currently no PDUFA timeline for the EUA. We anticipate some action in the near future, though there are no guarantees. The FDA is conducting a thorough analysis, as indicated by the types of questions we are receiving. We are hopeful for a successful conclusion, but we can't specify a timeline since none has been provided. We do know the FDA is working diligently, and we remain optimistic that we'll receive an answer soon.

Question is on EYLEA. Obviously, a very solid quarter. Can you maybe just give us some sense on the relative contribution from AMD versus other indication? How is the market share evolving in DME? What level of penetration have you achieved? And then obviously, COVID is spiking in the Q4...

Well, you have to ask one question. So far you're up to 3. Marion can handle the first one.

I will do my best. First, let me comment that during the pandemic, there was likely a greater impact on patients with diabetic eye disease who either did not receive a diagnosis or did not come in for treatment, but we are beginning to see a recovery in that area. I am pleased to report that the use of EYLEA for wet AMD is approaching 60%, which means over 40% of our business is coming from other indications, including diabetic eye disease. Overall, we continue to see diabetic eye disease as our largest future opportunity, but we remain the market-leading anti-VEGF therapy across all indications.

Just a quick follow-up on the REGN-COV2. The ongoing studies, George, are still across all patients, not just seronegatives. You clearly saw activity in seronegatives. Lilly sort of, obviously, both with their single and combo, really didn't see the same data. So any explanation to that? And why are you still sort of doing studies across all patients?

Yes. I'm not sure what you mean by Lilly didn't see the same thing. They didn't actually look for where their effect was. And right now, the way the program works is, we are not having any evidence of any untoward effect and maybe just a very small benefit in the seropositive patients who have their own antibodies. I think that if one could actually do point-of-care testing, which is unfortunately, at this moment, not immediately available in most cases. Once the drug might be available, let's say, under an EUA, you might want to limit it to patients based on those characteristics. However, because the benefit/risk does not have any evidence of negative untoward effects in those individuals, one could just treat the entire population, even though the benefit is mostly driven by those who, as we described, are seronegative, have higher viral loads and/or have high risk factors.

Yes, to expand on what George mentioned, it's important to note that we observed an effect in the overall population. This effect is primarily seen in individuals who needed the antibody because they had not developed their own immune response. Our team had predicted that those who had mounted their own immune response would not benefit significantly from additional antibody treatment, and this observation aligns perfectly with our findings. Conversely, those who had not mounted an immune response showed much greater benefits, which is consistent with our expectations. We also noticed this in placebo-treated patients; those without antibodies had a very high viral load, while those with antibodies started at a significantly lower level. The biological predictions made by George and the team were confirmed in an impactful way. Therefore, the focus should be on the source of the effect rather than the ability to treat the entire population.

Just a follow-up question on COV2. I'm just not sure how this is going to work. We can't even execute testing in this country reliably. So how are you going to screen the individuals who aren't mounting an immune response on an outpatient basis and then initiate treatment on an outpatient basis? It's just confusing. So help us understand that. And would it be sensible to treat everybody going to hospital for elective procedures of any kind or something else along those lines? It's just a little confusing how you're going to use this medicine.

I think what we've discussed, and as Len elaborated, is that the effect is observable in the broader population. It's primarily influenced by the specific individuals we've identified. Similar to the clinical studies, the treatment could be administered to all eligible outpatients since there is no risk to those who may not gain the maximum benefit. Thus, I believe the current strategy would be to limit the drug's availability without conducting advanced screenings, focusing instead on individuals at the highest risk of requiring medical intervention. This would apply regardless of whether point-of-care testing is available or their baseline viral load or antibody status. If testing becomes accessible in the future, it would then be sensible not to allocate the drug to those who are less likely to benefit. Initially, however, the priority would be to administer it to those at the greatest risk of complications in order to prevent those complications. As demonstrated in the study, administering the treatment to higher-risk individuals significantly decreases the need for additional medical attention. The reason to limit availability at this point is solely due to the constraints on the number of doses that can be provided for treatment.

Yes. Let me also add two points. First, as George pointed out in his presentation when we first disclosed this data, there is a very high correlation between the baseline viral load and the presence of antibodies. On average, individuals without antibodies have a viral load that is three logs higher. Therefore, viral load can be utilized. Everyone who is going to receive treatment undergoes a viral load test and a PCR test, which is reported as positive, but there is an actual cycle time involved. The testing process doesn’t necessarily need to change; however, the reporting may need to reflect the cycle time more accurately. A very low cycle time, indicating a high viral load, suggests low or no antibodies. As George mentioned, this information could be used to screen patients. The second point is regarding our partner, Roche, which is likely the leading company in testing. They have a platform for antibody testing that can accommodate hundreds of millions of individuals per quarter and is deployed at around 70,000 different healthcare locations. We are collaborating with them to determine if their test can be validated using our dataset. There are numerous approaches we can take; we can treat everyone while focusing on high-risk individuals, or we can narrow it down to those with high viral loads and low cycle times, or eventually rely on our partner's capabilities to identify individuals with no antibodies at the point of care. There is considerable flexibility in our approach. However, we do not have everything fully established in this emergency situation, and it is likely to evolve quite rapidly if we receive an EUA.

I have plenty more on COV2, but given the number we've already had there, I'll change the subject. I want to ask Bob about the R&D spend and really thinking about trends going forward. So in terms of the investment you're making on the antibody cocktail, how long do you expect this to kind of persist for? And just overall, wondering if you can give us any sneak peak into 2021?

Sure. Thanks, Cory. Let me see if I can give you a little bit of color. So as I said in our prepared remarks, we're not going to provide 2021 R&D guidance today. We do expect that next year's R&D expenses will be higher to support pretty much everything that George said with regards to the expanding pipeline, early stage assets, the partnerships with Alnylam and Intellia, which are really starting to blossom and certainly our ongoing COVID-19 efforts. If you look at 2020, where we sit right now, we anticipate spending approximately $400 million on our efforts against COVID-19 within the year of 2020. So if you back that spend out from our full year 2020 non-GAAP R&D guidance midpoint, our underlying growth rate in R&D spend, excluding the COVID program efforts, is trending about 15% higher than our 2019 as we move forward. So Cory, I would use that kind of as a stake in the ground in terms of where we're going to go. I mean, certainly, our COVID-19 spending is going to continue on. People can see on clinicaltrials.gov the extent of the programs that we have, trials that we have going, that will play a factor into 2021.

Another one on COV2. So just because it seems like this pandemic is just getting much worse in the United States and globally, can you talk about your efforts to expand manufacturing next year beyond the 300,000? And then I was just curious, given how profile it was that the President and others got a different combination therapies, can you biologically talk about your thoughts on should this drug be combined with Dex or other drugs immediately upfront biologically? And when would you just start like maybe a combo trial that would sort of evaluate that, sort of really make sure that this is a cure rather than just reducing the viral load and reducing time to recover in some patients?

Sure, George can handle that. I want to quickly address the manufacturing question. We are ramping up production and expect to significantly increase our output next year compared to this year. We will have a full year of manufacturing, which we didn't have when we delivered the 300,000 doses. Additionally, we anticipate having more operational facilities that are dedicated to this effort, and we expect to collaborate further with our partner, Roche, who has been an excellent partner so far. They are very experienced in the biologics field and are actively enhancing their manufacturing capabilities. Now I'll turn it over to George to address the question about combination therapy.

Yes. It's important to understand that our treatment acts as an antibody similar to the natural antibodies produced by many individuals. Essentially, we are providing this treatment to individuals who are either slow or unable to produce their own antibodies. There is no expectation or basis for any safety concerns regarding interactions with other medications. You should be able to combine this treatment with any drug that does not have significant side effects since we are simply supplementing the antibodies that the body usually produces. Therefore, in theory, you could combine our treatment with others without any evidence suggesting negative interactions. Currently, our data supports the use of our antibody in the outpatient setting, where other treatments like remdesivir or dexamethasone are not standard care at this time. Future studies will be needed to evaluate the efficacy of combination therapies in hospitalized patients to see if those receiving multiple treatments fare better than those receiving one type of treatment alone.

I would like you to discuss the potential growth opportunity you see. You've had an impressive launch so far, but you've also delved deeper into commercial marketing and direct-to-consumer strategies. I'm curious about how you plan to achieve deeper penetration into biologics, specifically in areas like ADN and asthma.

I'm happy to share that we reported strong results for Dupixent in both the U.S. and international markets. It's important to note that while we have made progress in assisting patients with atopic dermatitis and respiratory conditions like asthma and nasal polyps, there remains significant unmet need in all approved indications and potential future ones. In response to your question about strategies and promotional activities to enhance market presence, Dupixent has been positively affected by promotion. We've noticed an increase in new patients starting the therapy and a remarkable consistency in patients continuing their treatment due to the results they are experiencing, whether for skin or respiratory issues. We will continue our efforts, exploring various methods to enhance our promotional platform. Our field teams are highly effective, and we enjoy strong reimbursement across all indications and age groups. We will keep pushing forward with our current approved indications and ensure we are well-prepared for future ones as well.

Congratulations on a strong quarter. My question pertains to the relationship between EYLEA and Lucentis. You've noted a 10% increase in revenue, while they have experienced a 5% decrease year-over-year, indicating you're gaining market share. However, I'm curious about the new patient volume. Could you provide insight into how patient starts compare to last year? How much longer do we need to see improvement before returning to previous levels? Additionally, could you elaborate on pricing terms, as you briefly mentioned this in the press release?

In terms of EYLEA's performance in the anti-VEGF category, we are observing a rebound in patient treatment returning to offices. EYLEA's performance has improved compared to a year ago, and we are also experiencing an increase in market share from both branded and unbranded competitors. In the branded marketplace, EYLEA now accounts for over 70% of the market by volume this quarter. We attribute this strong performance to the overall value proposition of EYLEA for retina specialists when selecting anti-VEGF therapy, including its clinical and efficacy profile, dosing flexibility, and the convenience of the prefilled syringe, especially given the current focus on office efficiency. Additionally, we have established safety that supports this performance.

Can you discuss the competitive landscape in retina and share your thoughts on faricimab, especially with the Phase III data coming up soon?

Sure. I think we all learned a lot about this. I'm sorry, Len, please go ahead. I'll come back if you'd like.

No, no. I think you covered it. Let's go to the next question and the last question.

This is Dan on for Terence. Just for the Phase II trial of your BCMA bispecific antibody. Just wondering if you could share any more details on the trial and if you're working to develop a subcu formulation?

Yes. Right now, you'll receive updates on the BCMA program at ASH. We have announced that we will soon enter a pivotal program. It's reasonable to say that we will be developing a subcutaneous formulation.