Great. Thank you, everybody, for joining us on the second day here of this track of the Oppenheimer Healthcare Conference of 2024. Got David Snow, the SVP and the Global Head of Dupixent franchise, and Ryan Crowe, the SVP of IR, joining us here, giving us a presentation, which I'm really looking forward to. Regeneron has been always a constant supporter of ours at our healthcare conferences. We really appreciate having them back. David will give us an update on Dupixent, and then from there we can jump into our fireside chat or just an overall update on the franchise, and we can jump into the fireside chat after that. So please take it away. Okay. Thank you, Hartaj, and always great to be a part of the Oppenheimer Healthcare Conference. Happy Valentine's Day to everybody out there. Just do a quick forward-looking statement, and then I'll hand it over to David for some opening remarks before we get to Hartaj's questions. So I would like to remind you that remarks made today may include forward-looking statements about Regeneron, and each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in such statements. A description of material risks and uncertainties can be found in Regeneron's SEC filings. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise. David, take it away. Thanks, Ryan. It's great to be a part of this today. Always excited to talk about Dupixent. It's a remarkable brand. It's transformed hundreds of thousands of lives, since our first launch in 2017 in atopic dermatitis in the U.S. It's continued to grow quite quickly as we add new age groups, new indications. I think it's a multi-dimensional growth opportunity still. I've been in the industry for 30 years, and I've never seen anything like it. And it's been a lot of fun to be a part of this over the last five years. So just to give you a quick snapshot in 2023, if we look back with our collaboration partners at Sanofi, we had a very good year. We almost got to $12 billion, $11.6 billion, in net sales. That's a 33% growth rate. We also continue to improve our profitability. We added, like, as I said, we added new indications and age groups. We had AD in Europe and Japan, EoE adults in Europe, prurigo nodularis in Japan. Not to just talk about 2023 and 2024 in the US, we've already improved the label in hand and foot atopic dermatitis and in EoE pediatrics, which is an incredible indication. We're really glad to have that. As you know, last year we announced some groundbreaking data in COPD with both the BOREAS and the NOTUS studies. Could not be more excited about what that means for us. We subsequently filed both in the US and Europe. We have five very distinct type 2 inflammatory disease indications. We are number one in each of those in the US and NBRx and new prescriptions. We are number one in total prescriptions in four out of five, and I expect we'll get to the fifth one before too long. AD continues to be our largest overall opportunity, and we continue to have very strong growth overall. The AD biologic penetration rate is in the teens. Glad to see it approach the teens, get there. And certainly the younger age groups are contributing to that overall growth rate. Second to AD is the asthma business. Despite the fact when we launched, we had five competitors, biologic competitors in the market, and there are six now. We are driving to achieve the number one position overall. We already have that in NBRx, as we expect to surpass Xolair shortly and achieve that in TRxs. Nasal polyps is just another amazing story of growth. We are the first-line option there. We continue to have a very high overall market share. It is a blockbuster indication by itself, just an incredible opportunity. And the transformations for patients and what they're able to smell, with this group has just been really powerful. And, we certainly continue to see a great growth opportunity there. If you'll bear with me, there's more indications. eosinophilic esophagitis itself is, another amazing, indication. We're the first there, talk about transformations for patients and their families. We've got 25,000 patients on therapy right now. We just added, as I mentioned, the pediatric indication there, down to amazingly down to one year of age. We have some added benefits in terms of, of weight gain within the labeling, symptomatic improvement, really helpful. Very excited about, EoE. We have another dermatological, indication we launched recently, prurigo nodularis. It's off to a great start as well. We already have about 11,000 TRx there. Really impressive to see what's going on in that indication as well as kind of an additional opportunity for us in dermatology. Kind of an embarrassment of opportunities, I think, when I look at overall. And then we've got COPD that's coming around the corner. We look forward to having that and other indications like BP down the road. There's a few others that we're looking at. But overall, look, we've benefited hundreds of thousands of patients around the world. It's a mega blockbuster brand. We still think there's significant growth opportunities, as I mentioned, across markets and age ranges and just continuing to penetrate the markets. So we look forward to continuing that. David, that's fantastic. And by the way, when Ryan read that, you know, initial statement, whenever I hear that, you know, I'm like, if I was in your shoes, David, I'd be like, "I'm not saying anything after that." and it just sounds kind of scary. I'm just kidding. I don't want to scare anybody. Sorry about that. I know. I've been around Hartaj. I'm good with it. I understand. Yeah, it's good to be a little bit scared. You know, it's good. Keeps us honest. But David, you know, before we just talk a little bit about COPD, and we want to spend time really there, you know, you said something really interesting. You've got high teens penetration or somewhere teens penetration in atopic dermatitis. Biologics have, other than asthma, have not really had a lot of penetration, you know, into your indications. Can you just kind of give us what do you think is still the delta? Like, where you're at and where do you think biologic penetration could get into the various indications? I certainly think it has much more room to grow if we look at other biologic benchmarks in psoriasis and RA that have been out longer. But they also have a lot of players there. I think you could safely say that getting into the 25-30 range certainly should be something that we ultimately get to overall in these indications. There's certainly that need. There are lots and lots of patients out there that continue to need the benefits that we can provide with Dupixent. So I would expect that we should see that. And you're right. And I think in asthma it's probably 25% already. And you know, again, I think there's still a lot of room to grow in asthma alone. Yep. You know, it's interesting on that point. When we've spoken with a couple of KOLs about three or four years ago, they definitely mentioned that there were some folks that were forward-thinking, you know, allergists and treaters, you know, pulmonologists that would take biologics up very quickly. And others were a little bit more cautious and maybe need to get experience with that. Are you still experiencing that in the various indications? We have seen really robust growth among prescribers. Obviously in areas where we're newer, like in GIs where we just started with eosinophilic esophagitis, we're seeing month-over-month improvement in the number of physicians who are prescribing Dupixent. Then we're seeing an added depth of prescribing among those that have comfort with that. So again, in areas like allergy where we have multiple indications, we have lots of multiple indication writers. Depth of prescribing is very strong. It's probably the strongest in dermatology where we've been out the longest. So you know, we're seeing growth, great growth across the existing pool of physicians, and we're always looking to bring more in. Yeah. No, that's a great sign. You know, you're seeing, you know, patient penetration could increase, and then the physicians also seem to be kind of like jumping on board, over time. Now, maybe we can just go to, you know, COPD. You know, assuming you get approval, sometime in the next few months, the middle part of the year, or maybe, you know, somewhere around there, what could the COPD launch cadence look like, David? Yeah. So I think we announced, I think our Sanofi partners mentioned that we had filed in December. We expect to get some feedback shortly on breakthrough designation. Well, we got breakthrough designation on BOREAS. So we expect to find out if we're going to get accelerated review. If we do that, then, you know, we could be launching towards the end of June at the earliest, and I think even if we had a normal cycle on that, which I can't imagine what happened given the data results, that would be towards the end of October. The great thing is, Hartaj, we already have a very strong pulmonology team that's out there. So many of the prescribers are the HCPs that would be writing for COPD patients. We already reach on asthma. Certainly, there's a few more out there that might be more focused on COPD, but we'll have those within the mix. And we're really excited about that team being able to bring COPD forward should we get approved. You know, one of the things we had done, again, a call on COPD with physicians, and they said that, you know, there are some patients that exhibit, you know, even with these high eosinophilic patients, you know, some comorbidity with asthma. How are you thinking about that, David? Like, do you think the patient population is good, is fairly well prescribed, for the kind of patients you'll be looking for, assuming you get, you know, approval for launch? Yeah. So the work that we've done and, often, Hartaj, the case is, our epidemiology is probably on the low side. We've seen really nice growth in areas like EoE where it may not have been as quite as accurate. And PN is also another one where we're very pleased with the results we're getting. You know, COPD, we think there's at least 300,000 bioeligible patients out there who could benefit from the higher EOS group. But you're right with the asthma indication. We know that there's these ACOS patients out there. There are probably some other patients as well that could benefit from Dupixent, depending on how they get at that. Yep. And then, you know, what, what's the overlap in terms of the patients, the allergists, immunologists? I imagine with asthma, would you have to be going out there to additional doctors, you know, for COPD, or is it pretty much close to 100%? It, we have very strong overlap overall. There's a few that are COPD, more COPD specific that we'll pick up. We're in the process of making sure we have that coverage now, working to make sure we have that group covered. So, it's not a massive lift on our part. We also, as you know, a big focus for us is mitigating as much disruption as possible. So we're able to accomplish that and be prepared for the launch whenever it comes. Yep. Got it. And then, you know, can you just talk a little bit about, assuming you get approval, whether in June or October, David, what's sort of the next steps? I mean, is it, you know, I know with EYLEA, we've now gotten conditioned to that temporary versus permanent J code. Are there any kind of specialties to the reimbursement landscape here that we should be aware of, you know, going assuming launch again in COPD? Yeah. So because Dupixent has such a robust payer footprint right now across our various indications and out for years, we have a very good standing with the payers and access. And that includes both commercial and Medicare. So we have a very good position right now. So don't foresee that folding COPD into that is a huge lift for us. So we'll certainly are doing all the work now to make sure we're prepared for that. And you know, again, like I said, we've already got that footprint in place. So you know, our launch sequence is obviously to get our final label, to understand what that is, to get our promotional materials out there. Our payer group will be out there working ahead of us to try and make sure that we've got everything in place. That will build over time. And with Medicare, as you know, it's usually a one-year cycle that gets started towards the summer for the next year. So we're already in for the, you know, 2024-2025 framework, and then we'll have to build in the future. And they'll have to think about what the implications are of having COPD with a biologic. The last piece is, you know, we're a pharmacy benefit. We're not really a J code. It's a medical benefit. So again, the ease of, the safety profile, the ease of use, the autoinjector we've got should easily be able to accommodate the vast majority of patients with at-home administration. Yep. Got it. Which the payers also like. Yeah. No, no. Which I'm liking more and more as I'm listening to you. So, you know, just on that note, the other thought that I would have is, you know, what's the breakdown between allergists and immunologists? You know, is it similar to asthma, which I imagine would be all pulmonologists? Sorry, all pulmonologists. So in COPD, would you be basically just detailing to all pulmonologists, or would there be some allergist or other kind of physicians there? Yeah. There are some other specialists who kind of consider COPD, but it really is most of the patients end up with a pulmonologist seeing them. And again, remember, we're talking about, you know, GOLD 3-4 more serious patients that are having exacerbations that are already on triple therapy. Most of those are going to end up with a pulmonologist. And that's, again, you know, that's a great sweet spot for us. Primary care, you know, they do like to treat these patients, but obviously once they start to have some difficulty on a triple or they've had a breakthrough single exacerbation, they're probably going to get referred to the pulmonologist. And since we're already covering the vast majority of those, that's really going to help us in terms of being able to get the message out there. Yeah. It's kind of amazing that, you know, on this background therapy of, you know, the triple that you're getting such good reductions in exacerbations. You know, I used to cover COPD when the pharma companies were tackling it about, you know, five or 10 years ago when they were coming up with triple therapies. And this is, I think the exacerbation data is, you know, pretty in COPD is really something special. What, what do you think, you know, David? Is there anything with the COPD launch that, you know, for lack of a better term, keeps you up late at night? Like, are there things that you think are important to sort of focus on or think about? I get that question a fair amount, you can imagine. DUPIXENT is, like I said, it's been the most unique brand I've ever worked with. It's incredible. What gives me a lot of comfort, I really don't have that much that keeps me up at night. The comfort that I've got is that our biggest indications in terms of AD, asthma, and nasal polyps continue to grow quite quickly. They're there. COPD is an incredible opportunity for us. It's another, you know, blockbuster potential indication. There's a lot of patients out there. We're excited about that. But we have so many great indications that are still in the steep part of their growth curve that continue to grow at an amazing rate. It's just trying to make sure that we balance the overall opportunities we've got, that we don't over-index on one that we're actually trying to pull all of those through. That's probably the biggest challenge we've got, but there's not really much that keeps me up. I think from a competitive standpoint, we've been able to withstand, you know, a lot that's come at us, and we expect that there'll be more in the future. There's always going to be payer pressures. There were payer pressures 20 years ago. There'll be payer pressures in 10 years. But when you have a therapy like Dupixent with the efficacy, with the safety profile, with the comfort that physicians have and the transformations that you see with patients, I, you know, I, I can't. It's not really a lot that I'm, I'm concerned about. Yep. No, that's good to hear. And really nice. Thanks for all the color, David. I just want to mention, you know, online, somebody just asked again, who are the presenters? So I'll just mention that again. It's David Snow, the SVP and Global Head, Dupixent franchise, and Ryan Crowe, the SVP of Investor Relations. And again, Hartaj saying I'm one of the analysts here at Oppenheimer. So just as an FYI, I think in our own world, we get so caught up in the details sometimes, you know, it's nice to get these questions. David, you know, a question that we had sort of that was maybe a little bit more kind of like analyst-like question. You know, it's important for us, you know, how much more incremental sales and marketing expense would you, you know, want to need to have on your team? Would it be mostly all marketing expense? Would you need some sales and medical liaison type of people too? Now you're going to get me in trouble with Ryan. No, actually, I think we're probably not going to narrow share a lot with that. But I think the comfort is, again, we have a very strong pulmonology team. We're covering a large subset of the market out there. We know what that looks like. Look at the data we've got. That's incredibly encouraging. It is pretty much, you know, we and we've been launching heritage indications almost every year, one or two. So, you know, we really know the sequence here. The team is well experienced in how do we step through those paces. And again, I don't foresee this as a big lift from us for us in terms of the operational standpoint. Obviously, you're entering into a new category where you're first in market. We've done that a few times already. I think we've got a good track record of understanding how do we lay out the Type 2 story, how do we present, you know, the biologic option here where it hasn't really been before. We know how to do that. We've got a very good platform in terms of PSP, in terms of how we pull patients through when the prescription gets written. So all those are pretty familiar to us. And for those who don't know me, I'm the Regeneron partner to Sanofi. So we have a partner with Sanofi globally. I'm the commercial lead for Regeneron working with Sanofi. Been on the Dupixent brand for about five years, across many of these launches, not all of them. And so again, just, you know, trying to make sure we get right. Certainly a big focus in the U.S., as the first launch market and our largest market. And then, but we also have great penetration in many of the large markets around the world working with our Sanofi counterparts. Yep. You know, well said. I can see Ryan kind of visibly relaxed and smiling as you were giving that answer. He was like, "Dave, Dave's doing a good job. Don't give in to these to these Wall Street analysts, though." And then, you know, just maybe we can just switch a little bit to itepekimab, itepekimab, right? Sure. It was kind of interesting why I bring that up. Last year, we had two folks from Regeneron, right, Ryan? And I believe one was a lady who was, I believe, head of the IL-33 franchise. And she said, "Hartaj, don't sleep on itepekimab." I'm kind of paraphrasing what she was saying. So we got to spend some time there. Maybe if you can just give us a quick update, David, as to where that program is right now, and then how you think about it from a commercial perspective. Ryan, do you want to give the perspective on it? If you want to give an update on where we are in terms of the program and what the. Yeah, sure. That lady last year was Jamie Orengo. She's on the immunology and inflammation research function and has been integrally involved in the development of both Dupixent and itepekimab, as well as various other exciting INI targets that we have in our preclinical portfolio. On itepekimab, you know, Sanofi and Regeneron are conducting 2 pivotal studies, AERIFY-1 and AERIFY-2. There's not much difference between them. I guess AERIFY-2 has a small cohort of current smokers, but the primary analysis for both will be reduction in the annualized rate of COPD exacerbations among nonsmokers or former smokers. So those that have previously smoked greater than 10 pack-years of smoking. So we are looking specifically at former smokers in these studies. These studies passed futility assessment last year, and we expect to fully enroll both studies mid the second half of 2024 with pivotal data expected about a year later, so in 2025. So IL-33 is an interesting genetic marker. We've seen with pretty high correlation that loss of function in IL-33 is associated with a reduced risk of COPD. We published these genetic results along with the results of the phase 2 study for itepekimab in The Lancet Respiratory Medicine publication in last year, July. I'm sorry, 2021 in July, not last year. We're a couple of years beyond that. So this study looked at all comers. It looked at both current and former smokers, and did not hit its primary endpoint. It was not significant. But when we did an analysis of a pre-specified analysis of current and former smokers, we found there was no benefit in current smokers, but in former smokers, there was a highly statistically significant 42% reduction in annualized exacerbations, which obviously would be even better than the data that we saw with DUPIXENT, where we saw a 30% reduction in annualized exacerbation rate in BOREAS and a 34% reduction in the NOTUS study. So the populations are slightly different as well with DUPIXENT, which is a drug that we are now—this would be the sixth disease that has a Type 2 inflammation signature. We had, at baseline, measured eosinophil count, and it had to exceed 300 at baseline. Itepekimab looks at basically everyone, every former smoker that is, regardless of their eosinophil count. So I think the programs are pretty similar, but with some key differences. In terms of the similarities, they're both 52-week studies. They both have the same primary endpoint, annualized reduction, moderate to severe, COPD exacerbations, same key secondary endpoint, which is FEV1, which is a lung function measure. The timing is slightly different. I think we did the secondary endpoint for BOREAS and NOTUS was at 12 weeks. And in AERIFY program, it's at 24 weeks, but same endpoint. All patients in both programs were on background maximal inhaled triplet therapy, and it excludes patients with an asthma diagnosis, which is very important to note, for both Dupixent and for itepekimab. So like I mentioned, the key difference is that we're only enrolling former smokers in the IL-33 AERIFY program. You don't need to have a minimum count for eosinophils at baseline. And for itepekimab, we're looking at both a 2 every 2-week regimen and an every 4-week regimen. So some differences, but more alike than different, I would say, in terms of the programs and how we're looking at COPD. And once we get the data, like I said, sometime in probably the second half of 2025, we'll see what we have and how it might fit into David's commercial organization. This is a very large population, even larger than that, with which Dupixent can address nearly a million patients, we believe, are former smokers, and regardless of eosinophil count in the G7 markets versus about 500,000 current or former smokers with eosinophils above 300. So, an incremental opportunity, some of it overlaps. I think once we get the data, we'll be able to to figure out what works best for those patients with the higher eosinophils. But in general, this would broaden the respiratory franchise at Regeneron in a very meaningful way, assuming we get results similar to what we saw in Phase 2. Yep. No, Ryan, that helps a lot. You know, David, I mean, in terms of just from a competitive dynamic, I guess, you know, when I worked in the industry for a little while, not that long, you know, having more products in the bag always help, right? I mean, you get if you potentially get another product in the bag on top of Dupi, does that help you? Or you just think Dupixent, with all its indications, especially getting COPD approval, is just going to be so far ahead that it's going to be, you know, difficult for, for folks to catch on, to catch up? I don't see any challenge with that. And I've been, through my career, in several situations where we had multiple brands within the same therapeutic area. You know, in this case, what I found really interesting was when I was reading up on itepekimab last year, some of the basic biology around IL-33 was clear and more, well, elucidated than it was for IL-4 and IL-13. So we've, you know, now we've got this great BOREAS, and notice data. And now we're trying to bring itepekimab along. You heard, Ryan, its patient population could be twice that. HCPs are, you know, these target pulmonologists are not concerned about former smokers. They think that's an ideal target for us to go for. But you know, overall, we've already got a framework about how we would put both of these in the market. We certainly will leverage our own expertise that we're building in respiratory across the board. But I think these actually will fit very nicely together. And I'm excited about having both options out there. I mean, given that, you know, higher EOS, that's a select target. That's a big target. We're really happy to have that with Dupixent. But it's really nice to be able to think about, you know, those lower EOS patients and being able to maybe have something for them. Yeah. And, you know, that's a really good point. I mean, I never smoked in my life, but I have friends who have and family members who have. I think if you're a former smoker, there's always that sort of the sword of Damocles hanging over your head, right? Whether it's exacerbations, lung function, you know, some effect on lung function, or maybe something even further down the line. So I would imagine that the unmet need here, David, is, you know, it's not straightforward to see, but I imagine it's pretty high because these people do think about their future, right, or their current state of affairs with their lungs. Yeah. Again, it's been over 10 years. We've had a number of, of combination steroid therapies, triples, et cetera. You know, this is the advent of biologics. It's a really big opportunity for us in a disease category that, you know, kills many Americans, many people around the world, where we haven't had a lot of innovation. So it's really exciting to think about having two of the first ones, in the market, to begin with. Yep. And, you know, that's, so that's our COPD discussion. David, since you're the head of Dupixent, I guess what we're, you know, kind of we've got about 2, maybe 3 minutes left. What we'll kind of end with is just sort of, you know, what do you see in the future? I mean, is it all Dupi? Are you, you know, with, of course, itepekimab, if it's successful as like a global head, I imagine you think out 5 and 10 years out also. How are you thinking about Dupi and then sort of what's next? It has been an incredible experience working within Regeneron that looks at, looks at development and discovery much differently. You heard from Jamie Orengo last year. She's very impressive in what she's bringing forward for us. You know, having been a part of the organization when they brought forward REGEN-COV and how quickly they could bring that forward and put that in the market just gives you an idea of, you know, what Regeneron is capable of. So from an INI standpoint, we're going to be very busy with Dupixent. We have a lot more indications. We have a lot more growth. We have, we've just begun. We're kind of through the end of the beginning with Dupixent. And then, somewhere in the next two or three years, we're going to bring itepekimab forward, hopefully. That's going to keep us quite busy. But then I have no concerns around what Regeneron thinks in the future and how quickly they can bring things forward. Hopefully, we'll have a much more robust INI opportunity over the next 5-10 years. Yep. And then this would have to be kind of a Ryan question for basically the last minute left. Ryan, if you can just remind us, what are the key, kind of, you know, key catalysts and important things to watch out for with Dupixent, itepekimab, you know, over 2024? Obviously, we hope to get our BLA, sBLA accepted for Dupixent by the end of this month. So in a couple of weeks, we'll find out if we got priority review or not. We are optimistic on that and potentially launching, you know, in late June, early July of this year. So that's probably the next one. Obviously, the PDUFA date itself and the launch would be in the second half and something to watch. The CSU, which we got a CRL for last October, we have another study ongoing, study C, which is looking at a biologic naive population. That study should read out in the fourth quarter of this year. Assuming a success like we saw in study A in the same population, we'd expect to be able to file or resubmit, I should say, our sBLA for that indication either late this year or into the first quarter of 2025. And then bullous pemphigoid, I believe, also has a readout in the second half of this year, which is a smaller indication, but one that nonetheless we think has a decent probability of success and is certainly a market that is in need of novel therapies. So itepekimab, I mentioned enrollment complete sometime in the second half of this year. And then as it is a 52-week study, we'd expect to get results in the second half of next year, which would then hopefully support a filing by the end of 2025. That's, that's pretty much it across Dupixent and itepekimab over the next, call it, 18-24 months. Did I forget anything, David? No, that's great. I mean, CSU and BP are both exciting opportunities. And, you know, CSU is probably as big as the, COPD in terms of the number of patients that are out there that could benefit. Yep. No, I'm writing furiously here, David, because you were talking about EoE and PN, some of the changes you've made, updates you've made there over time. And I, I actually think we might have to put that in our model. So that's going to be a priority now for going forward when I talk to one of my associates. But, you know, thank you both so very much. This was really, I mean, I, we could have just kept on talking. Thank you for taking the time, David. I know these are not easy to interact with Wall Street people. And Ryan, thank you for making David available. We're always, really thankful to Regeneron for, for, you know, being part of our conference. Thank you. We're thankful to you, Hartaj. Thanks for having us. Look forward to speaking again soon. Same here. Give our best to the team. Thank you, David. Thank you. Thank you.