Regeneron Pharmaceuticals, Inc. (REGN) Earnings Call Transcript & Summary

Welcome, and thank you for standing by. I would like to inform all participants that this conference is being recorded and will be available to clients of JP Morgan. Parts of this conference may also be reproduced in JPMorgan Research. If you have any objections, you may disconnect at this time. This call is not intended for EEA clients that only subscribe for written research, and members of the press are not permitted on this call. If you are with the press or subject of the MiFID II and do not have high-touch access, please disconnect now. [Operator Instructions] And would now like to turn over the call to your host, Mr. Cory Kasimov, you may begin.

Great. Thank you, operator. Good afternoon, everyone. My name is Cory Kasimov. I'm a Senior Biotechnology Analyst at JPMorgan, and I'm here with Matthew Holt from our team. Thanks for joining us for the latest installment of our 2020 Biotech Conference Call series. Today, it's our pleasure to be hosting Regeneron and representing the company, we have Marion McCourt, who heads the commercial organization as well as Justin Holko, Mark Hudson from IR. So thank you all very much for participating today. We really appreciate you taking the time. So one of our standard format for this call, given the amount of content to cover, we'll ask Marion to provide just some very brief opening remarks. And then jump into Q&A. We'll start with questions on EYLEA, not surprisingly, and then work our way through DUPIXENT, the emerging IO franchise as well as some bigger picture questions. As usual, feel free to e-mail me additional questions throughout the call, and we'll work in as many as we can, time permitting. So with that out of the way, let's get to it. And Marion, I'll turn things over to you and set the stage for our discussion.

Sure, Cory. And just before we jump in, just to make a brief forward-looking statement caveat here, we will be making forward-looking statements today. I encourage everyone to take a look at our 10-K to get a view of the risks associated with the business and recognize that not all we say may come to fruition. Marion?

Thank you. Thanks, Cory. Good afternoon to everybody. I'm very pleased to join you today. Really, these are important and exciting times at Regeneron as we advance our in-line portfolio and innovations in new medicines. We entered this year with strong business momentum as fourth quarter results showed double-digit growth on our 3 growth drivers, EYLEA, DUPIXENT and Libtayo, while we continue to make significant progress in our clinical programs. In fact, 2020 has a significant number of meaningful clinical catalysts for our key programs such as Libtayo as well as other specialized growth opportunities. We're making really important contributions to patients through our medicines and have every confidence in our strategy and our business. So thank you so much for the opportunity to speak today.

Okay, terrific. So let's kick things off with a discussion on EYLEA and start with some of the recent events we've seen in the market. So I guess, just to begin, curious to get your take on the safety issues observed with Beovu and the type of reaction you're hearing from the field on that front?

Sure. I mean, at the start, I mentioned that this really is not our news, obviously, as it relates to brolucizumab, as it is to Novartis. But certainly, we are aware of the recently issued statement updating members at ASRS on the adverse events issue for brolucizumab. I'll reflect upon EYLEA. And I think with a situation like this, a very serious situation like this, we need to reassure our prescribers and have that we have not seen any safety signal with EYLEA in relationship to IOI with vasculitis, including this occlusive retinal vasculitis. In the U.S. label for brolucizumab, in fact, the IOI rates are 4x higher for brolucizumab than for EYLEA's, 4% for brolucizumab, 1% for EYLEA. And certainly, at this point, it's important for us to note that EYLEA's safety is supported by clinical trials that have involved more than 3,000 patients and more than 30 million injections have been administered worldwide. In our clinical trials, there have been no cases of IOI with retinal artery occlusion or vasculitis reported. In our global post-marketing database, the incidence of IOI with either retinal occlusion or retinal vasculitis was reported at a rate of less than 1 out of every 6 million injections. And those cases appear to have been associated with infectious endophthalmitis. So in short, I think, EYLEA sets a really high bar in terms of efficacy and safety. Our market leadership has been based on a tremendous amount of experience in the retinal community with retinal specialists, and I hear an awful lot of comments about the importance of that profile, both clinically, from a safety standpoint, from multiple indications being a really important opportunity right now. And obviously, a reminder that safety can never be assumed with a new product.

Right. So obviously, this is creating a lot of noise amongst -- within the marketplace and amongst investors, what do you ultimately think this means for EYLEA's growth trajectory? Does it change how you think about the overall marketplace in the near to, say, medium term?

Well, as far as EYLEA's growth and the overall market in the near term, we've worked very carefully over the last years and certainly even more so in the 2019 window of time to create a dual strategy to build upon our wet AMD leadership and also to grow in diabetes indications. We restructured our sales force. We're very excited about the growth opportunities we see for EYLEA. As I look back at past year 2019, we were very happy with the performance of EYLEA, which grew at 14% year-over-year despite the launch of a new competitor in the fourth quarter. And certainly, that performance outpaces what we had seen in recent years. In part, this is because of the new strategy we have to really build opportunity within the wet AMD leadership and also separately to grow the diabetes indications with our now larger restructured sales force. We had the recent launch, of course, in diabetic retinopathy, and certainly, there's tremendous opportunity for both indications. But in particular, we're struck by the fact that the diabetes treatment is so low compared to the population of patients so based on the severity of their disease as related to diabetes or candidates for treatment, and we really do think that it is our responsibility to make sure that we're educating the market using technologies for screening, using consumer education and a variety of techniques to make sure that we build appropriate treatment for diabetic patients, so they avoid vision loss.

Okay. So you kind of alluded to this a little bit in some of your earlier comments. But when thinking about the longer term, an element, I'm curious to get your take on, is whether you think this experience that we've seen in the last couple of weeks will result in physicians, kind of, broadly becoming more cautious on newer treatments going forward, taking more of a wait-and-see approach? Or do you think they'll look at this as more of an isolated incident?

So I think, certainly, we view EYLEA as one of our key pillars of growth, and we see this as an enduring product with significant future opportunity. I think, absolutely, there's going to be a renewed scrutiny of safety with any products coming into the marketplace that don't have experience and real-world evidence. We remain very confident on EYLEA as the anti-VEGF of choice based on clinical and real-world performance, unsurpassed vision, our safety, dosing flexibility, broad range of FDA-approved indications. So I think we feel very confident about the future. As to the recent developments surrounding brolucizumab, safety should by no means be assumed for the class or for any potential new entrants. Inflammation remains a major concern for the retinal community and, specifically, the types of safety signals and concerns that have been seen recently, so we think that there will continue to be a demand for a very high bar on safety. And that the safety of new agents is going to be really analyzed and scrutinized more closely than ever before.

Okay. So taking that a step further, but looking beyond brolu, how are you thinking about the competitive landscape for EYLEA from other novel treatments, such as Roche's port delivery system, faricimab, potentially new modalities such as gene therapy, things along those lines?

Sure. So obviously, as leaders in retinal disease R&D, we are very interested in advancements that we might bring to the marketplace for the future. And we certainly will follow competitive efforts closely, while at the same time, investing in our own next-generation products and technologies. What we have learned over the years through our own efforts is that EYLEA sets a very high bar for both efficacy and safety. We've previously tested, for example, anti-ANG2 antibody with EYLEA, and did not see a significant benefit in the Phase II trials in wet AMD and DME. You mentioned specifically the Lucentis port delivery system requires a surgical operation, as all know. There are added risk with complications that I concur with that, instead of what might be a much simpler outpatient intravitreal injection. As it relates to biosimilars, there's always the potential issue of formulation challenges, manufacturing processes, safety signals. So obviously, we'll look to the future to advance as Regeneron can through our own R&D but also pay a very close eye to competitive efforts, recognizing there'll be a lot of scrutiny, not only on the efficacy, the vision impact, but also the safety of products.

Okay. So you mentioned biosimilars. How do you think about the potential impact that biosimilars for other products, not to EYLEA, but for other products like Avastin and Lucentis, what kind of impact that might have in the market?

Sure. So the first thing that I always comments on when this question comes up is that there is a low-cost alternative in the marketplace today with Avastin. And EYLEA, obviously, has performed very well in the competitive marketplace. Going forward, one would expect that a biosimilar is most likely -- if successful in coming to market with all the hurdles associated with that, is most likely to have an impact on the branded product, which it competes directly with. So we remain confident on EYLEA as the anti-VEGF of choice based on the aspects that I've mentioned of clinical, real-world performance and all the aspects that have been brought together in our FDA-approved indications. That really is important for us is to have flexibility of indications, dosing flexibility, safety and, perhaps as important as all of that comes together, to making a tremendous contribution to the vision improvement and maintaining vision for our patients who are in need. Lastly, I'll mention the prefilled syringe for EYLEA has been an important launch for us. We started at the end of last year. We're now moving towards full market supply of the EYLEA prefilled syringe, but that does create an additional convenience for treaters and serves as another positive differentiator versus potential biosimilars.

Okay. And so when you think about biosimilars specifically to EYLEA. I guess, first and foremost, can you remind us of EYLEA's LOE in the U.S. and outside of it? And your expectations -- or what your expectations might be in terms of time lines on the -- on -- as far as the biosimilar entrant is concerned because it's not always perfectly coinciding with LOE?

Sure. So I'm sure that, Cory, you and all on the call today can appreciate that with a brand as important as EYLEA, we're very focused on vigorously defending our intellectual property. The EYLEA composition of matter patents expire in the U.S. in June of 2023 and in the EU in May of 2025. In the U.S., we also have formulation at administration regimen patents that expire in 2027 and 2032, respectively. In the EU, the formulation patents expire in 2027. Also in the U.S., we have the 12-year regulatory exclusivity period. Since EYLEA was approved in November of 2011, our regulatory exclusivity currently extends to November 2023 in the U.S. We're planning on obtaining the pediatric-exclusivity extension, and that would extend the regulatory exclusivity by another 6 months to May of 2024. In Europe, May 23, 2025, is most likely the earliest date that an EYLEA biosimilar could enter the market in Europe. That's the patent's SPC expiration date. May 23, 2025, is the expiration of our patent exclusivity. November 22, 2022, is the expiration of our regulatory exclusivity. And then patent exclusivity and regulatory exclusivity are independent from one another and run in parallel. So we have, obviously, an enduring plan and are ensuring that we have appropriate protection for our IP high-dosed EYLEA as well.

Okay. That's very helpful. And then I guess, lastly, on EYLEA before we move over to DUPIXENT. Wanted to just go back to diabetes for a minute. You mentioned it briefly, earlier in this conversation. But can you talk a little bit more specifically about the opportunities that you see here and how you're viewing the commercial marketplace in diabetic retinopathy without DME, now that you've been in the market for about a year or so?

So this is relatively early in a launch where it's a market creation opportunity. We are gaining share in diabetic retinopathy, and we're also growing the market in terms of new patient starts here. Interestingly, as well, the attention and the work on the diabetic retinopathy launch is also providing a bit of a boost to our DME business, which is important, and we're pleased to see that because, holistically, we want to make an impact on treatment and saving vision for patients with diabetic eye disease. We're pleased with the feedback from retina specialists in the early interest and uptake among the major practices, but we do view that there's a lot of work to be done. We have a lot of opportunity here to really change the paradigm of treatment for patients with diabetic eye diseases. There's a lot of underdiagnoses, and there's a tremendous extensive under-treatment, so we are investing in targeted initiatives with physicians and consumers to not only increase diagnosis but also get appropriate patients to treatment. We're working, as I mentioned previously, to apply technologies to support screening and opportunity to reach larger groups of patients for appropriate diagnosis, so we will continue to work to not only build our strength in wet AMD leadership but also to grow in diabetes indications with not only our sales force but also through other opportunities to impact market, understanding, education and to make sure patients get the cure they need.

All right. Got it. All right. So let's switch gears now and turn to DUPIXENT. And I'll start off with just a very high-level question. In regards to the overall launch of the product, how would you characterize the stage you're currently at? And what do you see as the next key kind of leg of growth?

Sure. So DUPIXENT launch has performed well so far. We continue to see, as I mentioned, in the fourth quarter of last year in the U.S., very strong double-digit growth. It's continuing across all metrics, which we -- and I monitor very closely our new prescriptions, our total prescriptions, overall sales. Certainly, that performance is driven by the continued growth in atopic dermatitis. The asthma launch continues to perform better than many of our biologic competitors, specifically the IL-5 -- anti-IL-5 products have performed. And certainly, we're really excited about the launch we had in chronic rhinosinusitis with nasal polyps. More immediately, as we look to future growth drivers, we're really pleased and await the FDA decision on our application for the DUPIXENT auto-injector. We look forward as well to an upcoming FDA decision on DUPIXENT approval for the pediatric patient population, obviously, the 6- to 11-year-old age group. The PDUFA date, there is May 26 of this year. The disease burden for these young patients is particularly concerning and, obviously, impacts the entirety of the family when these young children have such a serious condition. Towards the middle of the year, we're also expecting reports from our Phase II and clinical study work being done in eosinophilic esophagitis, so we look forward to that. In the second half of the year, we'll also be hearing more about our Phase III study for asthma in pediatric patients, and we have opportunities, obviously, on the horizon for food and airborne allergies. Something that we're excited about, grass allergy. Some of this data we'll be presenting in 2020. And obviously, the peanut allergy combination is also something that we'll be reporting on further this year. Finally, we're also pursuing 4 new skin indications and 1 new respiratory indication, all of which have biology suggesting that Type 2 inflammation is important in disease pathology. So there's a tremendous opportunity for DUPIXENT, not only with the current indications, but we have to -- what we have coming.

Okay. So we're going to -- we'll touch on a number of these going forward here in the conversation. But I guess, maybe specifically, in atopic dermatitis. Can you remind us what level of penetration you have in the adult population? And when you think about growth from here, is it mostly just blocking and tackling at this stage? Or are there still other doctors and patients you need to get out and educate?

Well, it's a combination of efforts, and certainly, the importance of our execution for the commercial team is very significant within this. We've done a lot of good work so far, but there's a whole lot more to be done. For atopic dermatitis in adults, we've really only captured 20% of the population of moderate to severe patients that are in greatest need. The total population will be between 300,000 and 400,000 patients in need would be our estimate. So there's a tremendous opportunity there. The experience that we've had with adults and adolescents bodes well for our ability to be successful with the pediatrics indication. So we're very much looking forward to that approval. We'll look forward in the future to give you more insight and content on our strategy, but we feel positive about what's happened to date in atopic dermatitis and where we're going in the future. Certainly, DUPIXENT continues to have incredibly impressive data, efficacy, safety, and our activity across the Type 2 disease spectrum is very, very important as well as the convenience of self or home administration or caretaker administration of the product were required when a young child is being treated. Certainly, the profile of DUPIXENT sets a competitive barrier and a very high bar for any other potential products entering in the space of atopic dermatitis as it's really being established as the standard of care.

Okay. So thinking more about as you go younger and younger here with DUPI, and you mentioned the pediatric approval anticipated in May. You -- what's been the experience within the adolescent patient population relative to adults? And how do you maybe read through from that to what you might expect as you launch into the peds?

Sure. So certainly, with the adolescent launch, it's ongoing. And obviously, launches are ongoing for multiple indications in many countries. So atopic dermatitis will remain a significant growth driver for DUPIXENT. The brand DUPIXENT continues to outpace other biologics that launched in dermatology, and there's significant room for further penetration. We're expanding the market through increased prescribing, both for moderate and severe disease. The recent adolescent launch is contributing to growth. It's obviously aided by physicians' experience and their comfort with DUPIXENT, both from an efficacy and a safety profile, which is important for all patients, adults, adolescents, but obviously, even more important and has higher scrutiny as we go into the younger and pediatric age group. If approved in the pediatric population, it will be another opportunity for us to reinforce our competitive position in atopic dermatitis. And we do look forward in the future to giving more insight and more content on our strategy, size of population, our go-to-market profile for the pediatric patients. We certainly will be ready, and we feel very positive about what's happened to date in atopic dermatitis and where we'll be going in the future.

Okay. And then what's your view on the competitive outlook here for DUPI in AD from things like JAK inhibitors against both oral and topical as well as other biologics?

Well, we'll continue to always take potential competition very seriously and seek to understand clinical data and information on various products. Certainly, DUPIXENT's differentiation continues to be based on best data, including efficacy and safety, activity across the spectrum of Type 2 diseases as well as convenience of administration. Commenting specifically on the JAKs, DUPIXENT, in contrast, gives us the ability to selectively block -- based on the mechanism of action, selectively block just the IL-4 and IL-13 signaling. So this approach is incredibly important, and it's in contrast to the JAK inhibitors, which appear to be much less specific. So as a result, when we look at the result of using a more immunosuppressive approach with the JAK inhibitors, there are significant manifestation of differences in the safety profile, and specifically, the JAK class has black box warnings for serious infection, malignancy, thrombosis. The JAKs require routine laboratory monitoring for changes in lymphocytes, neutrophils, hemoglobin, liver enzymes, lipids, all of which do not apply, that type of monitoring simply doesn't apply to DUPIXENT. And then as we get into some of the other areas of consideration, it will always come down to a balance between efficacy and safety.

Okay. So when investors are particularly focused on how the efficacy of JAK inhibitors might stack up versus DUPIXENT. How important is efficacy in the framework of -- the broader framework of safety?

So with DUPIXENT, we certainly have incredibly high efficacy in terms of all aspects of scoring the impact of disease to the patient and relief for the many manifestations of atopic dermatitis. But in balance with that, we also show an incredibly strong safety profile, and it is that combination and not having to have a disproportionate balance in risk-benefit that we hear from our prescribing physicians is so important to them and why DUPIXENT has quickly become a standard of care in their practices.

Okay. All right. Great. So let's move on to asthma. And I guess, I mean, can you talk about this launch relative to your expectations? And where you're seeing the majority of the uptake in terms of patient severity and OCS dependents?

Sure. So very happy to talk about DUPIXENT in asthma and how we see the launch going, certainly quite favorable. We've seen asthma is a significant opportunity with about 900,000 patients who might be eligible for biologic treatment. And as of the fourth quarter, less than 15% of these patients were being treated with the biologic. We're seeing now that approximately 80% of new DUPIXENT patients are biologic-naive, indicating that we're growing the market. Similarly, we're making strong progress in terms of both allergists and now pulmonologists, who historically haven't used as many biologics, being interested in the profile and selecting DUPIXENT as the product to initiate therapy on for their asthma biologic candidate patients. We're being prescribed -- DUPIXENT is being prescribed to patients, both with high EOs and also systemic corticosteroid dependence due to our differentiated label and efficacy in both reducing exacerbations and also improving patient's lung function, all of that also associated with this very strong safety profile that we highlighted a few moments ago and spoke about with their atopic dermatitis patients.

Okay. And then what about nasal polyps and kind of the progress you're making here and your just latest thoughts on the commercial opportunity?

The nasal polyps or chronic rhinosinusitis with nasal polyps launch is off to a really strong start. DUPIXENT is the first and only biologic to be approved in this condition. We find in the U.S., patients are being initiated on DUPIXENT regardless of prior surgery. Prescribing is being driven both by ENTs and allergists. And we're seeing an increase in new prescribers because of this indication, which is another sign that the launch effort is going quite well. We have an opportunity for nasal polyp patients, the population in the U.S. is about 90,000 patients who do not have control disease despite using either systemic corticosteroids or having had a prior surgery, about -- for reference, about 55,000 patients have had prior surgery. And then in Europe, we're targeting the 45,000 chronic rhinosinusitis with nasal polyps patients who've had a -- post a surgery. And certainly, that population will be dependent on reimbursement decisions in various markets.

Okay. Yes, I figure it's easier just to say nasal polyps instead of the whole chronic rhinosinusitis with nasal polyps.

It, certainly, is for me. Just easier to say nasal polyps. That is true.

So last thing on Dupi for now is I want to go back to what you mentioned upfront and touch on what's next for DUPIXENT component of the story. And how would you characterize the ongoing development of this agent across the range of other indications you're evaluating? Maybe is there 1 or 2 you're particularly excited about, given perhaps some of the early data you've seen and/or because of the commercial opportunity?

Sure. I mean as we highlighted before, there are many, many future opportunities. But to your question about what I think are some of the most exciting, if I'm forced to choose, I really do think the data in eosinophilic esophagitis is going to be very, very important. This is a population of patients that have tremendous unmet need, and we've had little to offer them. But I do think the data that we start to see in mid-2020 is going to be important. And we look forward to, obviously, being able to progress this indication as appropriate. The other areas that I would point to is the opportunities in food and airborne allergies remains something that we're really excited about. We're looking at a proof-of-concept for the grass allergy data that will be presented in 2020 as will we see additional information for our combination work for peanut allergy, and that probably will be more towards the 2021 time frame. And then as I mentioned, these additional indications for various skin problems and skin disorders and the additional respiratory indication will also be another means of expanding the opportunity for DUPIXENT for patients that have this profound Type 2 inflammation.

Okay, great. Does Paul Hudson seek your input when he talks about EUR 10 billion as a peak number for -- at least EUR 10 billion for DUPI?

Well, we have a lot of discussion and a lot of alignment between the organizations. We don't give future guidance. But we certainly are aligned in terms of our excitement and our ambition and our investment in what DUPIXENT has to offer for patients on a global basis.

Okay. I'm going to turn things over now to Matthew to ask some questions on the immuno-oncology front. Matt?

Great. Thanks, Cory. And so let's move over to immuno-oncology. And for this, can you start by talking about why you think Regeneron is well positioned to effectively compete in this hyper competitive space when oncology hasn't exactly been a centerpiece for you in the past?

Sure. So certainly, oncology is becoming a centerpiece for us now and in the future, we certainly believe that Libtayo has the potential to be the leading anti-PD-1 treatment with the profile we currently see. In cutaneous squamous cell carcinoma, we have response rates at greater than 40%, which surpasses anything seen with other anti-PD-1s in this setting based on cross-trial comparison, and we're now the #1 systemic treatment in CSCC surpassing other anti-PD-1s and chemotherapy. With the ongoing development program in NSCLC, we strive to establish Libtayo as the treatment that can be competitive with other leading treatments in this large and rapidly evolving lung cancer space. Our recent ORR data certainly suggested that we have an active drug in NSCLC, and certainly, this is an incredibly important and large anti-PD-1 market. If approved, Libtayo would be competitive in this market. And certainly, we would look forward to that opportunity from a commercialization standpoint

And Matt, the other thing I'd just add to that is that this is a very data-driven market. And we've seen new leaders emerge in this space who historically were not oncology companies. So I would say that the data really speaks volumes as it pertains to how these drugs can ultimately do in these very competitive markets.

Got it. And then, so you have an upcoming readout for Libtayo on, basal cell carcinoma. Can you help set the stage on what you're hoping to see and what -- or how you view the ultimate market opportunity?

Sure. So for the basal cell carcinoma patients with locally advanced or metastatic disease, they currently have very few treatment options. We're expecting a readout of the potentially registrational Phase II study. And if data supported it, we're planning on filing for FDA approval for this indication later in 2020. The estimated size of patients that are diagnosed in the U.S. with locally advanced and metastatic BCC is about 28,000, and about 3,000 patients in the U.S. sadly die from basal cell carcinoma each year.

Great. And I guess, just for reference, can you remind us how this compares with your current CSCC indication?

So for the current CSCC indication, we would be looking at a patient population in the U.S. market of about 5,000 patients. We've stated in the past, 5,000 to 7,000.

Got it. And then maybe a question for Justin about Regeneron's efforts in NSCLC. Can you help us understand what the key similarities or differences are for your Phase III NSCLC trial in high PD-L1 expressors relative to Merck's KEYNOTE-024 study?

Sure, happy to. So our 1624 study is monotherapy, and it is in patients with high levels of PD-L1 expression, meaning greater than 50% of tumor cells staying positive for PD-L1. And this study was begun a couple of years ago, it was designed, again, to look a lot like the KEYNOTE-024 study. We had initially about 350 patients or so as estimated to be the full enrollment. At that time, not too far after when we started the study, we saw the results from the KEYNOTE-042 study, which, as you know, is another Merck study. And in that study, while it was successful, the data in the high expressors, while strong, was not as strong as what was seen in KEYNOTE-024. And so the team here wanted to ensure that if there's an efficacy signal that the study would be appropriately powered, particularly if the benefit looked more like 42. And so at this stage, we are fully enrolled. We have an interim analysis this year for overall survival. And as Marion mentioned, we looked at the -- some of the overall response rate last year, that data looks quite compelling, and it gives us confidence that Libtayo could have a meaningful benefit in lung cancer, but obviously, we have to see how the overall survival data ultimately pan out.

Great. And I appreciate you might not be able to answer this question, but do you guys have a base case expectation for your interim analysis? And the reason I ask is because if I'm remembering correctly, the KEYNOTE-024 study stopped at the second interim.

Yes. So I would first just say trying to pick when studies are going to start or stop based upon when other studies completed or completed early is probably not the way to look at it. These studies are running what could be different patient populations, given ultimately, that no 2 studies are ultimately identical. So I would first say that we just have to see how the drugs are going to perform in this study, and I don't know that we can necessarily predict that based upon what other studies have done.

Got it. That's helpful. And I guess, just to that point, given the differences in geographies, design and the timing of these studies, how comparable do you anticipate these trials to be? And I'm not asking about how you see the results playing out, but more so whether this will be an apples-to-apples comparison when we do see the data?

Yes, Matt, I think it just goes back to the fact that no 2 studies are alike and trying to do cross-study comparisons, that's what we all do because in the absence of the head-to-head, that's your next best. But again, we just have to see how the data ultimately play out. Again, the studies were designed to be fairly similar, but there's going to be variation, and we'll just have to see how that plays out. We hope and anticipate that, that all plays out in favor of Libtayo in this particular study, but we're anxiously awaiting the data as well as everybody else.

Got it. And then maybe just on how you're thinking about Libtayo and lung on the commercial side and maybe we can break this up into 2 different scenarios. Like should the data be more or less comparable to pembro, how does Regeneron compete in this marketplace? And then for the second scenario, if Libtayo is shown to be more efficacious than pembro, how does this change how you guys prepare for a launch?

Sure. So we believe that Libtayo has potential to be a leading anti-PD-1 treatment with the profile we currently see. The cross-trial comparisons for the first interim analysis data suggest ORR is similar to reported results of other studies in the anti-PD-1 class, the next interim analysis of overall survival from the monotherapy study in NSCLC will be likely in 2020. Recall, co-primary endpoints in the Libtayo monotherapy study are PFS and OS. Our next step is data readout, which if positive would be followed by appropriate regulatory action and obviously launch if approved. Our other lung Phase III study, the Libtayo plus chemotherapy combination, is more than halfway enrolled. In CSCC, we have response rates at greater than 40%, which surpasses anything we've seen with other anti-PD-1s in this setting based on cholesterol comparison. And we're now the #1 systemic treatment in CSCC, surpassing other anti-PD-1s in chemotherapy. With the ongoing development program in NSCLC, we strive to make sure and we'll establish Libtayo's as the treatment that can be competitive with other leading treatments in the lung cancer space. So we look forward to the additional data readouts. And certainly, as we see more on product profile, we will prepare for our commercialization, and we're certainly very excited about getting into this space.

Got it. And so I guess, before I hand it back over to Cory, I just have a couple of questions on your bispecifics program. So specifically on REGN1979, how do you think about the trade-offs between efficacy and safety relative to some of the other CD20, CD3 bispecific in that space and as well as CAR-T therapy?

We're currently conducting the potentially registrational Phase II study, which will test 1979 in relapsed/refractory FL, DLBCL and other NHL subtypes. Data from this study could support accelerated approval in these patients with greatest unmet need. We do believe our data compares favorably to CD20xCD3 bispecific competition, and our 1979 has competitive efficacy and superior safety and convenience versus approved CAR-Ts.

Got it. And then just in terms of your kind of co-stimulatory bispecifics. How are you at this stage, thinking about the time lines to where we could potentially see data?

Sure. And that's a great question, and it's a common one that we receive. We would share investor enthusiasm for this program. Certainly, it's quite innovative, and it's something that we believe could be quite differentiating should the data play out positively. That being said, it's very early. I'm sure most people know by now, the history with the CD28 target and the fact that it's can be very significant in terms of how it activates the immune system. We are now in humans. We are combining with Libtayo actually in the setting of prostate cancer. The challenge for us on getting too specific on a time line right now is that we are, as you can imagine, proceeding very cautiously, given the history of this target, but we do believe that our bispecific has the potential to activate the immune system only in the presence of a tumor. But that being said, we're at the very low end of the dose-range finding ladder. We don't know necessarily how many doses it will require for us to be able to see anything from an efficacy or safety signal. I think we'd all love to tell you that it would be right around the corner, but we just don't know as it's, literally, you enroll a few patients. You try the dose. You see what happens. You determine if you're able to move up to the next dose. And so at this stage, we're just beginning that process. Again, we are in combination with Libtayo in prostate cancer. And hopefully, we'll have some updates sooner rather than later. You can imagine that once we do see data we'll be interested and anxious to get it out there. But at this stage, it's just too difficult for us to be too precise or predictive on when we'll have data.

Great. So with that, I'll turn it back over to Cory.

All right. Thanks, Matt. So we didn't intend to ask many questions beyond IO with regard to the pipeline on this call, but just given the circumstances, everything that's happening in the world, I did want to ask you on COVID-19. And maybe if you could just remind us what Regeneron is doing on this front? And when we could potentially hear more about your efforts?

Sure. Thanks, Cory. We -- as you can imagine, we do have a lot that we are doing in this space. Just to rewind a little bit, we do have a proven track record as it pertains to responding to these outbreaks of infectious disease. Back in 2012, we responded to the call with MERS. We most recently spoke about the fact that we have what looks to be a potentially curative cocktail against Ebola that was found to be superior to other therapies and that readout in last August. And so you can imagine that the team here is very much focused on this as it pertains to the new -- the COVID-19, SARS-CoV-2 outbreak. We do have the capabilities to move on this very quickly. The technologies that we've been able to build up over the years allow us to really approach the problem from discovery of antibodies through scale-up and, ultimately, manufacturing. So I'd say, again, the team is moving very quickly on this. We hope to be in a position where we can have doses available for human use by late summer. It's a priority for the team. And I would just say that given our experience and expertise here, we're definitely doing everything we can to address this issue that, obviously, has a lot of attention for a lot of different reasons.

All right. And then...

Just one quick add for you, Cory. We had mentioned that we're currently obviously screening for the most potent antibody candidates, and we're aiming to have hundreds of thousands of prophylactic doses ready for human testing by the end of August.

Okay. Terrific. Good luck with that. So -- and the fact that we're not talking about the pipeline broadly, I guess, just to give you the opportunity, anything else that you would want to highlight on the clinical front? I mean you, obviously, have a ton that's going on, so any other maybe early assets, mid-stage assets that you're particularly excited about that you just want to quickly highlight here?

Yes, I guess, where Marion started the call, there's a growth story here, obviously, between EYLEA, DUPIXENT and Libtayo. And so that's always a good thing to be talking about. But on top of that, we actually do have some very interesting catalysts that are taking place this year. We mentioned earlier that atopic dermatitis indication for pediatrics for DUPIXENT, we expect regulatory action for that in May. Evinacumab, we'll be submitting the file in HoFH, again, a rare disease, but a bit of a specialized growth opportunity. And with that program, we saw 50% LDL reductions in patients who are on basically every lipid-lowering therapy you could think of, including PCSK9s. The Ebola filing is underway, as we mentioned that. Garetosmab, we -- I believe, Cory, at your conference top lines some of that data with respect to a devastating disease where patients' soft tissue forms into bone. So we're looking to have regulatory discussions around the filing of that program. And then as you think about some of the key data readouts, we've talked about the interim analysis in lung cancer for Libtayo. We talked earlier about basal cell carcinoma. Phase II data could be potentially pivotal. And you can imagine, we'd love to get that filed as soon as possible should the data play out. We have pediatric asthma data, Phase III, which will be coming later in the year as well as the Phase II portion of a Phase II/III study we have in eosinophilic esophagitis or EOE. One of the programs that we don't talk a whole lot about is -- and just given that, I think we're cautiously optimistic on it, but is fasinumab, our anti-NGF antibody. We're expecting data towards the middle of this year and the back half of this year. And again, these are Phase III studies, both in terms of efficacy and long-term safety follow-up. We've been watching the competitive developments in this space with respect to file acceptances and the expectation for an advisory board. So we expect to very much be in the mix of this. The DSMB, the Data Safety Monitoring Board continues to look at our data every several months. And the word we keep getting from them is the studies should continue. So again, cautiously optimistic there, and that we may have found a dose that could allow us to see some benefit with -- while mitigating any potential side effects that are known with this mechanism. Beyond that, we have a very high level of enthusiasm for our C5 program. We've shown some early data in PNH, but the team here has a very broad view of where our antibody could play in C5-mediated disease. Importantly, we have a collaboration with Alnylam, where we'll be looking to combine with their RNAi therapeutic. We'll start in PNH. But again, the ability to combine with their therapeutic and potentially even co-formulating for subcutaneous injection is something that why early stage has us quite excited. And then we hit upon a little bit earlier on, but we do have an emerging and broadening bispecifics platform. In addition to the PSMA and the CD20xCD3, we have a couple of BCMA antibodies in the clinic, and there will be more that come into the clinic this year. So it's really -- as you think about the commercial growth story, coupled with the catalysts in late-stage development, but also how the early-stage pipeline is moving along as well, there's a lot for us to be excited about.

Yes, there's definitely a lot going on. There's no doubt about that. All right. So in our last 5, 10 minutes we have here, I just want to work in a couple of bigger picture financial questions and a couple of e-mail questions we haven't touched on yet. I guess, first, on the financial front. With the recent Sanofi collaboration amendment, is the plan still to update us before the end of the quarter? And kind of how to think about that and the impact that has on the model going forward?

Sure. So we will obviously have future updates in December towards the end of the year. We did announce that we and Sanofi were going to change our antibody collaboration for KEVZARA and PRALUENT by restructuring the agreement. Certainly, there will be future updates and more discussion on the financial implications of that work with Sanofi.

And Marion, how much do you focus on PRALUENT in your day-to-day job now, just given the restructuring and what's happened with that asset?

PRALUENT is a very important product. We've talked today about the major growth drivers of the business, and there is a difference in terms of the level of opportunity with PRALUENT. So we always put appropriate commercial effort into our programs based on what the opportunity is. But I do think PRALUENT has an amazing profile, and there's tremendous cardiovascular need. We'll continue to work with PRALUENT and determine best commercial strategy and plan, so that we do the right thing, both from the standpoint of helping patients in need but also having a proper ROI for PRALUENT in the U.S. market. Obviously, Sanofi will be holding and maintaining responsibility in full for PRALUENT outside the United States.

Okay. And then speaking to Sanofi as we head into their lockup expiration. What kind of volatility do you expect around that? Maybe asked another way, how can Regeneron mitigate potential volatility should Sanofi decide to decrease their investment stake in the company?

Sure. Cory, it's a good question, and we've had several questions on that since their Capital Markets Day late last year. I think the first thing that is important is just to ground everyone as to what is permissible or, I guess, what some of the restrictions are around what they're able to do once the lockup expires. So that happens in December, December 20, this year, so coming up, obviously. Basically, in terms of if they were to want to sell their shares in the open market, there are limitations in that they can only sell 1 million shares every 3 months. So just doing the math, they have more than 20 million shares of Regeneron, that would take more than 5 years for that to unwind. So that, I think, has helped investors get some perspective on what limitations there are around just limiting volatility through what is -- what they're permitted to do. And obviously, we have our own share buyback program that is out there. We have been buying the $1 billion authorization that we announced last November. So we're in the market. But we could also be on the receiving end of some sort of registration that they may ultimately want to do. You have to have a seller as well as a buyer. But certainly, we have flexibility to do something along those lines. There's some additional registration rights that we could get more into detail on. I would encourage you to check out our website within the Investor Relations section. In December, we posted a couple of slides that just speak to in detail what some of those limitations may be with respect to the expiration of the lockup.

Okay. All right. That's helpful. And then, I guess, Marion, I wanted to get a kind of bigger picture, political question in for you and just your latest thinking on healthcare reform and specifically on that front as it relates to Medicare Part B and the proposal around IPI. At a high level, how does Regeneron prepare for something like this, given all the uncertainty, whether it happens or doesn't happen? And what if it does happen, what it ultimately even could look like?

Sure. So let me say first, we are firmly against the notion of an international pricing index and believe that implementation of that kind of a pricing system in the U.S. would have significant legal and implementation challenges as well as a negative impact on stifling innovation in the U.S. biopharmaceutical industry. We have no control over pricing, for example, for EYLEA outside the United States. We do believe making meaningful changes to the U.S. healthcare system requires compromise on the part of a lot of different parties. And we all want solutions that help make medicines more affordable for seniors but while still preserving innovation at Regeneron and across the industry. So for example, the bill that was drafted by the Senate Finance Committee last year is something that we can support. We feel like it caps costs for seniors. It saves the government some money. It encourages competition, deals with inflation of drug prices, doesn't import ex U.S. prices and doesn't penalize innovative companies like Regeneron. So we still think that, that is a good compromise in lieu of some other options, and certainly, we'll continue to closely monitor activity and, where appropriate, make our voices heard.

Okay, terrific. And then just to wrap up, I want to go and hit on a couple of e-mail questions we have. In fact, I just want to combine 2 questions into 1. And it's going back to EYLEA, and how we should be thinking about updates around the life cycle extension for EYLEA? And then on those lines, what have -- what should we think or expect for gross margins with the prefilled syringe. I guess, how it compares to EYLEA now?

So [Audio Gap] the marketplace in a responsible way, and we very much look forward to having both vial and prefilled syringe available in the future but certainly would guide towards similar gross margin.

Okay, terrific. And then I think we'll stop it there. So thank you guys very much for the time today. This is very helpful and insightful call. Really appreciate you speaking with us. So thanks, and have a great weekend.

You too. Thank you very much, everyone, for participating and joining the call today.

Thanks, guys.

That concludes today's conference. Thank you all for participating. You may now disconnect.