Great! Good afternoon, everyone. You know, I was just joking with the Regeneron team. There's a biotech bear market. I don't see it in London. These are packed rooms. It's really great to see everyone. And, you know, I also think that we're gonna have an XBI rally, but that's my hot take for the day. That aside, I do have the pleasure of hosting the Regeneron team, Bob Landry, CFO, and then Ryan Crowe, Head of Investor Relations. I will hand it off to them to make some introductory remarks, and then we'll get started.
Thanks, Akash. Great to be here again, and, you know, this is a very crowded conference. I think it might be time for a bigger hotel.
No, no. The claustrophobia is a feature, not a bug.
Anyway, I'll do some FLS disclaimer, and then Bob will have a couple, a minute or two on opening remarks, and then we'll get to Akash's questions here. 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. Bob, take it away.
Yeah. Thanks, Ryan, and Akash, thanks for the invite. I think Regeneron's has been a regular for the last couple of years at this conference, and it draws an incredible investor base, so we're very happy to come here. So we're fortunate. We just had our third quarter earnings kinda less than two weeks, so I was gonna spend maybe two minutes on kinda refreshing everybody, giving everyone a quick deep dive into what we talked about, and then I'm assuming Akash will go deep on a couple of these things. So we were proud on the third quarter. We had top-line growth of 15% on revenue. We were 4% on the bottom line.
We did take a $100 million IPR&D charge relating to the milestone that we paid for to Alnylam for the ALN-APP drug, so we're more than happy to pay that. If you, you know, if you consider that not there, we actually grew 11% on the bottom line. EYLEA HD, which I'm sure we'll get into, we had a strong quarter. You know, we were very happy with the quarter. It was, it was true demand. It was $43 million. It was above consensus, certainly above what Vabysmo, our competitor, did. We were on the market for six weeks. I think it was the third week of August that we launched, so it, it was, it was proud.
In the third quarter, we talked also about our two-year data with regards to PULSAR, which again, is the EYLEA HD, and it. I think people are realizing that it is going to be the new kinda standard of care with regards to the 8 mg within the VEGF category, so we're, we're fine with that. And we came away with market share. We normally give category market share at 45%, so if people wanna know what the EYLEA franchise is within the anti-VEGF category, including Avastin, it's 45%, which was, I think, almost like a 50 basis point slip versus Q2, so we're, we're holding well there. Dupixent, again, we'll get into that, did $3.1 billion for the quarter, up 33%.
Again, this is a product, I think, that launched in 2017, and to grow 33% on the baseline that we have is really kind of fantastic. Our margins continue to improve on that. You know, for those that follow the Regeneron story, we talk a lot about our cell bank that we use to make drug substance, in which we're getting kind of a 3-time benefit, and people are seeing that. I think year-over-year, our margins on the Dupixent brand are up, like, 400 basis points. You know, where Ryan was reminding me, we pick up, like, a 100 basis point improvement every quarter, and there's still a lot of life left with regards to that. We made big news on COPD.
So going into the third quarter, the question was, you know, we are in discussions with our Sanofi colleagues on whether or not we can do an interim look. We knew that at the time of our announcement, it was a material event, so we did tell our shareholders that we have been in contact with the FDA, and they have agreed that for the NOTUS trial, which is the second of our COPD trials, we read out the BOREAS, BOREAS trial in the first quarter of 2023, that with the NOTUS trial, that we'll do an interim look in the fourth quarter. If it's positive, we're gonna be able to bring COPD and Sanofi, Regeneron and Sanofi will be able to bring COPD to market 6-9 months earlier.
And just to kinda size the prize on that, there's about 500,000 people of kind of TH2 disease for COPD in the G7, so it is a big, big category, and we'd love nothing more to certainly bring this to help these patients out sooner rather than later, and I think it's the third leading disease in the world, so it is certainly a health crisis there. Libtayo, our PD-1, continues to do well. You know, we're actually annualizing at $1 billion on that drug. We continue to make headway. CSCC is our main indication, but we are making inroads on non-small cell lung. That's all fine. Pipeline stuff, we do have odronextamab, which is our lymphoma drug. It has a March 31, 2024 PDUFA date. This is really our first entree into Heme/Onc.
We have a couple of Heme/Oncs coming into the market. Odro will be the first one. We know it's a crowded market. We will not be first, but we think it's a good drug, and you know, we're going in later lines, and the goal is obviously to go into earlier lines, where we anticipate we're gonna be that much more competitive. We also have filing for our BCMA x CD3. We're gonna do that in the fourth quarter. The data on that looks very, very strong. Again, with Dupixent, we have another kind of indication. This is pediatric EoE. EoE has proven to be a bigger category and a better category than we actually thought it was when we launched it.
We have a PDUFA date on January 31, 2024, and we actually closed our second acquisition, albeit very small, with regards to Decibel, in September, you know, it was basically cell gene auditory therapy, and we actually had our first patient, right before our earnings, basically get injected with this cell gene therapy. And although it's a rare disease, this DB-OTO, we had, again, early days, we had success with that, and we're actually gonna, you know, obviously continue to dose patients on that. So pretty exciting quarter, you know, whether it be the numbers or, or the pipeline or everything going on, and certainly COPD was a nice event. So, Akash, with that, I'll hand it over to you.
Awesome. Thanks so much.
Yeah.
So, I wanna start off with maybe a question on BD. And, you know, like, you know, I always joke with clients, I think there's been almost kind of a spec pharmification of M&A, and you can see this on the IPO side, you can see this in terms of what pharma actually acquires, right? And to a certain extent, you followed the winners, right? Like, you look at what Lilly's done. They didn't diversify into five different things. They honed in on, you know, obesity and Alzheimer's, and then they took a long time-
Yeah
... to kinda develop these products, and then they had follow-ons. When you think about your BD strategy, right, why not... Especially given you're gonna have $10 billion in terms of cash on hand, and you have really good visibility in terms of runway, why not start looking at, you know, more commercial stage assets, start paying up, you know, $5-$10+ billion in order to, you know, add something onto your DUPIXENT franchise, add something onto your EYLEA franchise that's synergistic? That hasn't really been your approach to BD over the last couple of years. It, it, it seems like it's more early stage. But what is your appetite to potentially move up and start looking at some of these later-stage deals?
Yeah, I. You know, a lot of people think that it's just, you know, it's outside our DNA. I mean, I wouldn't say that. I would say something transformative would be outside our DNA. You know, kind of buying a late-stage phase III kind of revenue filler would be outside our DNA 'cause I think our management teams thinks that there are a lot more desperate people out there that are willing to pay, you know, what the value, you know, so much more than what we would be willing to pay on that. So we've kinda had that as a no-fly zone. But, you know, we remain super interested in kinda technology plays. We love platforms, we love franchises. We like things that can kinda combine with antibodies.
We have an RGC, a Regeneron Genetics Center, where we've sequenced over two million exomes, I think almost half of what's been done in the world. So we have a treasure trove of what kinda what the targets are. All the targets are not always fit for antibodies, so we do need other technologies, whether... You know, I think we've shown that with Intellia, with regards to CRISPR, and certainly Silence's siRNA with Alnylam. We like that. We will continue to like that. But, Akash, it has to be additive to what we already do, in which-
... you know, 1 + 1 is 3. We do have a heightened interest in stuff than we probably had before. You know, I think for the first growth years of Regeneron, it was a "not invented here." We kinda stayed away from stuff like that. But I think with regards to how cool the technology is, we love gene cell therapy and things of that nature. I would expect us to be more and more involved in that area, and we have, you know, we certainly have one of the cleanest balance sheets within the pharma and biotech industry to be able to do that. We have a ton of optionality it provides.
Understood. Now, I mean, one thing that, you know, it's kinda notable you didn't talk about... You look at Sanofi's strategy to model, like, you know, ex-life after Dupixent, right? And they have TSLP, and they have OX40, and, you know, they are taking multiple bets in I&I and kind of leveraging that sales force that, you know, they've been able to build over time. You would almost call it a plan to win. Who knows? But, I guess the question is-
Right
... for Regeneron, right, life after Dupixent, how do you kind of leverage the commercial infrastructure that you guys are starting to build, the expertise in I&I that you've built? Are there any targets or any areas in that space that you find particularly compelling?
Yeah, I mean, you know, if the CEO was here, he would tell you that there's still a long runway for Dupixent. You know, I think, our-
Sure
... composition of matter patent is 2031, and I think it's 2032 ex US, and I think we still have a host of indications that are coming in that space. You know, Sanofi has taken an approach where, you know, they are going after lifecycle management through kind of their BD approach. You know, we have things brewing that are probably a little too early to let the public know, but, it's not lost on us with regards to, you know, life after Dupixent and, and what we need to do, obviously, because we're building a pretty big I&I infrastructure, Akash, out there, and obviously, we're gonna need life after Dupixent. We just haven't let the public know exactly what that, what that is yet.
Understood. Now, I think, like, one of the, you know, proverbial white whales for you guys has been obesity. I mean, this is not, you know, Your, your targets that you're gonna introduce over the next couple of years are not the first time that you've gone after this indication. It's something that I know is really important to your team. You know, the, you know, the question is: Do you view a GLP-1 like a PD-1, right? Where it's like you have one asset, then you start overlaying, you know, maybe an Activin A, maybe you start overlaying other ingredients in order to get an additive benefit, but you need kind of that base GLP-1 to really be your entry into that franchise. Do you think that...
You know, I'm guessing you probably have some internally in development right now, but in terms of externally looking at some of the GLP-1 assets that are there to maybe speed up that process, what is the appetite for that internally at Regeneron?
Yeah, great question, Akash, and obviously, obesity is a huge category that's continuing to grow, and the GLP-1s have really changed the game there. In terms of backbone, I don't know, maybe. There's a lot to learn about how this impacts metabolism and weight over time, and we certainly are exploring those modalities and others internally at this point. But I think for some of the add-on antibodies that we have in our portfolio, including a myostatin antibody that showed when in combination with semaglutide in non-human primates, that we had greater weight loss and double the fat loss than semaglutide alone. So very promising, and we're looking to explore that combination as well as some others in the early part of 2024.
That will serve as sort of a proof of concept. What we do with it from there, I think we'll have to figure out whether it's continuing to partner or potentially developing something in-house. Maybe it's a bispecific that combines a GLP with a myostatin antibody. Maybe it's a co-formulation, something, really a lot to learn still. That's not the only iron in the obesity fire that we have. There's also a leptin-
... receptor agonist that's shown some very promising data in generalized lipodystrophy and also in a patient with congenital leptin deficiency, which is a very rare disease, but it normalized an extremely obese child and made them sort of a normal weight very quickly. So, dramatic weight loss there due to this genetic abnormality in this patient. And then finally, the genetic discovery from the Regeneron Genetics Center, GPR75, which we continue to search for the right way to target. Right now, we're working with AstraZeneca on a small molecule approach, as well as internally on an antibody and with Alnylam with an siRNA approach. This is the, you know, termed the skinny gene, where we sequenced... You know, we didn't sequence.
We searched over 650,000 exomes, found around 2,000 patients that had this genetic abnormality in GPR75 gene, and they on average weighed about 12 or 13 pounds less and had a 55% lower risk of being obese. So, we think it's a very good genetic finding and serves as a good target. We're just trying to figure out the best way to hit that target at this point.
Understood.
Yeah, a lot-
Yeah-
... a lot to go for obesity with Regeneron.
Understood. And, maybe just lastly on obesity, I mean, I think the question I get most often for investors is: Okay, garetosmab, you know, there were safety concerns with that compound.
Yes.
You could even point to the, you know, the Versanis Novartis asset that's now in the hands of Lilly.
Right.
How do you think about the therapeutic window with Activin A? I mean, right, like, these are millions of patients who are theoretically gonna get, treated-
Yeah
... with these types of medications. So, you know, why go with these assets in these types of markets? What makes you feel comfortable from a safety perspective that they'll be clean?
Well, I think we have a lot to learn, but certainly with Activin A, there's some some quote-unquote, "hair on that mechanism," and particularly for women of reproductive age who intend to have children. So something that we'll need to look at very closely. But I think with the myostatin antibody, we actually had a very benign safety profile and perhaps could serve as a better alternative. But we're gonna-
... put all these things in man next year, and we're gonna find out what, what kind of works synergistically in terms of preserving or building muscle while also achieving, as good or better weight loss than the GLPs alone.
Okay, understood. Now, maybe stepping to high-dose EYLEA and, yeah, I mean, you guys are absolutely right. A very, very impressive launch. Can you kind of so let's start with just the clinical data, and you hit on the PULSAR data, but I don't think that's really well appreciated by investors, the fact that you were able to maintain BCVA, you were able to maintain these patients actually staying on these 16-week regimens. Internally, I'm actually convinced if Vabysmo ran your trial, I think it actually would have failed. But at the same time, you talked to all of these doctors, no one actually uses these regimens, right? No one uses the, you know, the, the regimen that's on that are on these clinical trials. They basically treat to complete dryness, and then they start to extend over time.
So, you know, what feedback have you heard in a real-world setting in terms of how these are actually used in practice of high-dose EYLEA versus, let's say, both low-dose EYLEA and then also Vabysmo and some of the other competitors? How quickly are they able to get patients to complete dryness, and what is the kind of real-world interval that these patients are actually able to get to so far? And I know it's early days.
Yeah. I'll preface with it's very early days. You know, we're, what, 12 or 13 weeks into the launch here, but the early feedback's been very positive. We've seen a broad spectrum of patients using EYLEA HD, including those that were recalcitrant on very short intervals of EYLEA and unable to get dry, as well as short intervals of Vabysmo and unable to get dry and have come back after one injection with EYLEA HD with much improved retina dryness and even some completely dry. So very promising early feedback. We're also seeing switches from EYLEA with patients that are, you know, well-controlled but on shorter intervals, six, seven-week intervals, that are moving to EYLEA HD in hopes of extending the time between injections.
We're also seeing Avastin switches, and then even some small proportion is in naive use, which is also very encouraging. So, how doctors are using it, I think most of the time, they are not using the loading regimen for anyone who is not a naive patient.
They are taking the patient who's on EYLEA every six weeks, having them come in, giving them an injection of EYLEA HD, and saying, "Come back in six weeks, and we'll take a look at your retina." They come back in six weeks, hopefully, the retina's dry, and then they give them another injection of EYLEA HD and say, "Come back in eight weeks." And this treat and extend paradigm has really been what retinal specialists have used, and that's what we're seeing with EYLEA HD in these early days of the launch.
Understood. Now, I know there's been also some label changes for Vabysmo. I think there was an added warning on retinal vasculitis. Honestly, from our diligence, the absolute rate we're seeing from Vabysmo seems fairly low. I don't think that's actually concerning, but you did still get the change from the FDA on the label. So, what have you seen from doc feedback about that added label warning, and how that may have shifted the view of Vabysmo versus high-dose EYLEA, competitively?
Yeah, this was an update that was made to the Vabysmo label earlier this month, I believe, and it included the additional indication of RVO, but in the warnings and precaution section, it added a warning for retinal vasculitis and retinal vascular occlusion. The only other product in this category with that same warning is Beovue, which was obviously a product that had a very strong launch, but safety issues really made it a very limited use, extremely limited use today. So obviously, the FDA felt that there was enough prevalence of these side effects to add it to their warnings and precautions section of the Vabysmo label. I think the ASRS has also kind of brought forward some cases that, you know, maybe the prevalence is a little higher than what was seen in the clinical trials.
But I don't think it's, you know, a something that's going to completely derail Vabysmo in the same way it did Beovue. We'll have to see, though. This is something that will play out over time, and it's only been a week or two since the label update and the Dear Doctor letter was distributed.
Understood. Well, I guess for my FOIA request, I now have to add Vabysmo on top of covering GA, so good for me. But, okay, so now maybe going to the commercial market, and this is stuff that I think really matters and isn't well understood, right? You talk about about half of the market is Medicare fee-for-service, then you also have Medicare Advantage, and then you have commercial, right? And these are. I think, for most people, you know, they've already checked out. What. Can you bifurcate. So, like, these three distinct sectors of the VEGF market, how like, how is the adoption for high-dose EYLEA going to differ for each one of those sectors, and what's the rate of adoption, right?
It seems like fee-for-service might have much more, much faster adoption than, let's say, Medicare Advantage or commercial. But if you could delineate between those three subsectors, it'd be very helpful for us.
Yeah, Akash, I won't get into specifics, but just so for the audience to know, I mean, Medicare fee-for-service, I mean, it's 45% of the EYLEA franchise, right? So that's a big number, and there, there's no formularies associated with that, right? You come in, and, and the doctor's gonna give you what the doctor's gonna give you. And as I mentioned before, I mean, we're the category leader in, in, in that, so... And we are finding that, you know, that is working out fine. There are, you know, the payments are going through on that, and there's no issue, and we have it across all the jurisdictions in the U.S. with regards to Medicaid fee-for-service. The next category would be Medicare Advantage.
That's about 25% of the category, and there, you know, I mean, if you looked at our charts, if Mary, our head of commercial, was here, I mean, we're running better than expected with regards to making sure that we get on the formularies, and we haven't found the step edits to be much different than what we're experiencing or had experienced with EYLEA 2 mg. So, you know, that is all going well. It's probably going ahead of plan, and then the remaining is the commercial, and again, you know, we're doing well on, on that front. So, you know, without getting into exact specifics on where the $43 million came from in the third quarter, we have all, like you said, the three categories are moving along just as well as they could be at this stage.
Understood. And I know, like, obviously, there's competitive dynamics here, so maybe, Bob, just generally speaking, and this is, you know, a question I get a lot from investors as Regeneron goes into the 800s, which is: Do I look at EYLEA, especially in the United States, as a growth market through the switch, let's say, like, over the next three to five years? Is U.S. EYLEA a top-line growth story? Is it flat, or is it down? What are kind of the internal expectations for Regeneron, and why could we actually see growth through this switch?
Yeah, Akash, I mean, we won't give long-term guidance here with regards to that, so-
Right. I mean, you don't have to give guide-
... on it.
Even a line-
I would just say I think the outlook that the analysts have is-
Yeah
... is pretty dismal with regards to, you know, how good the PULSAR and PHOTON data has been in the start that we have with regards to 8 mg.
Maybe I'll leave it at that.
Okay.
Okay, without getting into much more granularity.
No, that was great. I understood. Understood. Now, maybe, stepping back, and, you get this question, and I know you can't give any answer, so I'm gonna ask a slightly different one. I call that West Virginia court literally every day. I don't know what this guy's doing, but I think one thing I do get a question on, and I just wanna make it clear, you know, like, people thought you'd have a decision by August. We're sitting here later in the year, and we haven't gotten one. There are some people who ask me, "Well, Akash, does that mean that, you know, these parties are settling, and this is a bullish interpretation for Regeneron," right? The fact that we haven't actually gotten a settlement. You know, maybe for you guys right now, just to...
I'm sure you get that question too. Should we interpret the delay in a decision on low-dose EYLEA as something that is bullish for Regeneron or just neutral?
I mean, we ask ourselves that question every day. We come in and say, "Today's the day." We feel better on Fridays, right? We're gonna get a court decision on Friday, and, you know, the timelines that were originally put out there by the judge in West Virginia, which was kind of late August, early September, you know, has come and gone. And, you know, I'm sure he's doing the proper due diligence and will find the answer when he's ready to kind of reveal the answer. There's nothing to make of it. I mean, we do the same thing. We sit around, "Akash, is this good? Is this bad?" You know, I will say that we did put our best foot forward, and I think kind of coming out of the...
The trial, I think people are the odds on Regeneron are certainly higher than they were going in. I will tell everyone the base case is that, you know, you should assume that we're gonna have biosimilar penetration on the third week of May 2024. That should be the base case. If we're able to kind of prevail on this trial, well, then that will be pleasant upside.
Understood. Understood. So, maybe going into Dupie, and, you know, you talked about... This is something that I don't think a lot of people appreciate, like COPD is a top three killer of people in the United States. Having a benefit on FEV1 is actually a very clinically meaningful outcome for patients. When you think about—and, not to mention, you have your bet on IL-33, so there, there seems to be a kind of a two-horse approach here. I know this is obviously a year out, and it's, you know, it's maybe too soon to say, but when you think about how quick the atopic derm launch was, or maybe how, you know, quick maybe the Eylea launch was, should we draw that same analogy for Dupixent in COPD? It's the first biologic for a high, you know, very high unmet need.
What do you think the cadence of that uptake will actually be, and do you feel like maybe investors aren't appreciating that?
I'll take that one. I think for Dupixent and COPD, obviously we need to get the results of the second study, but let's use the assumption that they will resemble at least the results of BOREAS, which, where we showed a 30% reduction in exacerbations and an 83 mL improvement on FEV1, as well as an improvement in patients' quality of life. If we're able to replicate that with NOTUS, and we're gonna be doing an interim analysis before the end of this year, I think there's a lot of patients that can benefit from this drug. Bob mentioned 500,000 in the G7. There's around 300,000 in the US.
These, I'll remind you, are patients that were already on maximal inhaled triplet therapy, so they were sort of out of options. There's no approved biologic for COPD. Dupixent would be the first, and with those kinds of dramatic improvements in exacerbation rates and FEV1, I think it would. It stands to reason there's gonna be a bolus of patients that could benefit from it, and the launch could be robust.
Understood. Maybe last question, and this will be on oncology. Look, it won't be on CD28. Let's just see how the safety profile plays out. But, you know, I think a lot of people... I remember going on IQVIA. J&J's BCMA CD3 launch has actually been pretty good. It surprised some people, and we'll see how Pfizer's drug does and the ability to give outpatient. I'll put myself in this bucket. I don't know—when I go see ASH and I see, like, an 80% or 90% OR for the... I'm like, "Okay, they're about all the same." But there is this kind of evolving role of both CD20, CD3s, and then BCMA CD3s that are starting to get, you know, sharpened in the eyes of doctors. Why do you think investors should be paying attention to these drugs?
They're not differentiated targets. There's not a meaningful differentiation, I would argue, on the clinical data. Maybe you could say that on the BCMA. Let's see how that plays out. But why could these markets actually be bigger than what investors expect and meaningful for Regeneron?
So I think that both, Odronextamab, the CD20 by CD3 that we've developed and are waiting for an FDA decision on with the PDUFA in March of next year, as well as linvoseltamab, the BCMA by CD3, are each differentiated against their competing CD3 biospecifics from some other companies. Particularly for linvoseltamab, where we, after about six months of follow-up, linvoseltamab had similar ORRs to J&J and Pfizer's products. But we know that they had when they had longer follow-up, and we know that with longer follow-up, these ORRs and complete response rates tend to improve over time. So we're optimistic that when we read out the registration-enabling data set-
... which should be soon, that we can be at least competitive, if not positively differentiated there. The other piece is the safety story, where we have demonstrated the lowest rates of CRS, and beyond that, lowest burden of hospitalization in our trials. And then finally, the dosing regimen for BCMA by CD3 linvoseltamab would start as weekly, extend to Q2W weekly, but then after six months, potentially go to every four weeks-
... if a very good partial response is achieved at that time point or thereafter, which would be an improvement over J&J's weekly and Pfizer's every other week dosing regimens. So there's a lot of positive differentiators for linvoseltamab. I do think the bolus of the revenue opportunity is in earlier lines, and that's gonna require additional studies, and we are in the process of getting those underway. So look forward to those results down the line here and think that, yeah, they have a real shot of being important revenue generators for Regeneron in due time.
Understood. I think I am out of time. I really, really do appreciate it. Great conversation, as always.
Thanks.
Thanks so much.
Thank you.
Really appreciate it.
Thank you.
Thank you.