First, let me get through this forward-looking statement disclaimer. I'd 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 that are on our website. With that, Salveen, let's jump in.
Great. Chris, to start here, Regeneron has been challenged recently on both the earnings front, driven by headwinds facing the EYLEA franchise, and on the pipeline, most recently per fianlimab's phase III failure. In that context, how do you see the company positioned from here for second half of the year and into the end of the decade? Maybe touch on the key priorities for the company at this point.
Thanks, Salveen, I hope we have plenty of time for Andrés, because he's got a lot of exciting things to talk about. If you look at the Regeneron business, it's fundamentally strong, resilient, coupled with a balance sheet that provides us with a tremendous amount of flexibility to allocate capital in a way that we think will drive the most long-term value for our shareholders. If you look at the first quarter alone, we had strong double-digit growth both on the top and bottom line, driven by our core franchises, so continued strong performance from DUPIXENT. We basically saw LIBTAYO, which I have to say our commercial team has done a remarkable job of really driving and executing on LIBTAYO since we took that product back from Sanofi in the middle of 2022.
It really just goes to show you that when we as a management team sort of put the execution behind it and the focus, what you can do with a brand in our hands. Lastly, continued strength and momentum that we're seeing in the EYLEA HD franchise following the approval of the enhancements to the label at the end of last year in both retinal vein occlusion and every four-week dosing. A lot of reasons to be excited about the current core business as well as what the future holds. You mentioned fianlimab. fianlimab is one of basically 50 things in our pipeline. We historically, and will continue to be very focused on driving what we think is a world-class pipeline.
If you look at the perspective, it's always been multiple shots on goal, spreading those shots across multiple therapeutic areas, and having opportunities where we think in the short, medium, and long term have significant commercial opportunities. We're very excited about what the pipeline will be able to deliver over the next few cycles. If you look at the balance of the year, there's a few catalysts that we're also very focused on delivery. Some of them are regulatory catalysts. We've got the approval for the prefilled syringe, we've got an approval for cemdisiran in myasthenia gravis, and then we've got the approval for garetosmab in FOP. Looking at clinical catalysts, and I'm sure Andrés will talk about these, we've got data coming in our complement franchise in both PNH and geographic atrophy. A lot of catalysts coming in the second half of this year.
We're also at the same time laser-focused on commercial execution. I touched upon obviously our three growth drivers. We will continue in the remainder of the year to really stay focused on driving that commercial execution and doing it obviously in as efficient a way as possible and continuing to drive growth. One thing not to forget about as well is the repayment of the Sanofi development balance, which will be repaid by the end of the second quarter, which will allow an inflection in our share of collaboration profits basically in the second half of this year.
If you just think about other things that are there in the pipeline in terms of where we think we've got some exciting opportunities, I think Ryan and the IR team, coupled with members of management, have done, I think, a very good job using the Regeneron Roundtables as an opportunity to highlight where we have exciting near-term opportunities with large commercial potential in areas like multiple myeloma, anticoagulation, complement-mediated diseases, and obesity. Those are just some of the nearer-term opportunities. If you then turn and focus to a pipeline with 50 different sort of candidates in there are plenty of earlier stage opportunities that will eventually become mid and late-stage opportunities as we continue to drive those forward in exciting areas like inflammatory and immunology, ophthalmology, cardiovascular, metabolic, and even neuroscience. There's a lot going on at Regeneron and a lot to be excited about.
To touch on strategy here, it does seem like the company is increasingly open to larger M&A. Just speak to your view here regarding size of deal and modalities and therapeutic areas and stages of development. You've also spoken to valuations and cases being prohibitive in the context of return on investment and acknowledge competitive dynamics amongst acquirers. How do you think about all these factors when you put it together?
It's a very good question, Salveen. The way we view it, we're not limited by either the size of the transaction, as I said, we've got the balance sheet with an enormous amount of flexibility. We're not necessarily limited by therapeutic area. We really look at things and evaluate opportunities where we think the science really makes a lot of sense, and that can translate into commercial opportunities where there's unmet medical need. I think if you look historically, we've done more in the traditional collaboration side of things and not necessarily traditional M&A. Those historically have been opportunities where they are complementary technologies or things that augment some of our capabilities. As recently as in the past couple of months, we did a deal with Telix in radiopharmaceuticals.
We did a deal with Parabilis, using their Helicon technology coupled with our ability to conjugate them to antibodies to allow potentially targeting those Helicons in interesting ways. We will continue to do those sorts of things. We are also very active looking at larger scale M&A or even smaller types of transactions. You alluded to the fact that we've talked about being involved in some competitive processes as we've evaluated them and kicked the tires. What ends up happening in some of those situations are you have companies that probably don't have necessarily the discipline or don't evaluate the opportunities the way we look at them, that when you look at the value where those deals actually transacted relative to what we saw as the opportunity on a risk-adjusted basis, we just couldn't get there. That doesn't mean we won't get there in the future.
It really depends on the opportunities that present themselves. We have the ability to basically, in a disciplined fashion, execute if something made sense, and we'll continue to evaluate things going forward.
Great. Could we also touch on the Sanofi collaboration here from two standpoints, one from the IP, but also from the openness you've talked to about working with your partner to potentially add more assets into the collaboration? Where do these efforts stand, and to what extent are you looking externally for assets to bring in, and what characteristics are you looking for in terms of these assets? If I could just add, how long will this process take?
Maybe I could start with the DUPIXENT loss of exclusivity question. Clearly, that's of importance to investors given the impressive scale of the product and its continued very strong growth trajectory. DUPIXENT has a very broad and layered intellectual property estate that has expiries beginning in the early 2030s, including its composition of matter patent in March of 2031, but additional patents that go into the mid-2040s. These cover other facets of dupilumab, including its manufacturing, its formulation, as well as its methods of treatment for various diseases, which really underscores the clinical work that's gone into this antibody that's now approved in nine distinct diseases. There is no date certainty at this point. I think it's important to consider all of these different patents when trying to figure out when eventually biosimilars could launch.
The most important for us is continuing to drive the growth along with Sanofi and then put up a vigorous defense of the patents that we do have and feel very strongly can extend the runway meaningfully beyond the composition of matter patent in 2031. Updates will probably come as we approach that date and as the patent challenges and litigation processes get underway, but we're still a few years away from that really happening. Unfortunately, today, I can't tell you when biosimilars will launch, but I can assure you we are going to mount a very vigorous defense of all of the intellectual property that we have to extend DUPIXENT's marketing exclusivity for as long as we can.
Just on the maybe two aspects, one, the ability to expand upon the collaboration with Sanofi, but also on the life cycle front, the extended IL-13, when could we expect to see data from this agent or the other agent, and when could they enter the clinic?
I'll take the collaboration aspects of it, and I'll ask Ryan to speak to IL-13. I think if you look at what we and Sanofi have built with the DUPIXENT franchise, there's a tremendous amount of value that's been built there. If you just look at relationships with the provider community, relationships with the payer community, even just patients themselves in terms of the trust and confidence that they have in DUPIXENT, in terms of what it's been able to do for them, in a lot of instances, changing their lives in terms of the therapeutic efficacy there. Being able to leverage that is extremely valuable, and it makes a lot of sense if we can do that. With that being said, it's got to make, obviously, strategic and financial sense for both parties.
I will tell you, with Sanofi's new CEO joining, we've had some initial conversations along those lines, and we'll have to see where those conversations evolve. There are, I think you've alluded to it, a number of different opportunities that we basically have in the pipeline that we can bring, as well as whatever Sanofi might be able to bring, as well as external opportunities. We've got the long-acting IL-13, which Ryan will talk about, a long-acting IL-4, basically a super-duper, as we call it internally, as well as a bispecific. There's a lot of opportunities to really grow and develop what's there in terms of from an I&I perspective.
Chris, thanks for that, and I think the long-acting IL-13 antibody is the first in a wave of DUPIXENT, I call them next-generation opportunities for us. The long-acting IL-13 antibody went into its first patient earlier last month or earlier this month, the last couple of weeks. That will begin a phase I study in normal, healthy volunteers initially, but then move into patients with varying degrees of atopic dermatitis, where we hope to learn what the clinical activity looks like and what the durability profile is. We think that this fully human VelocImmune-derived antibody has an opportunity to meaningfully extend the dosing interval that DUPIXENT currently has without reducing its efficacy and maintain a similar safety profile. We're very excited to be in the clinic. We're moving it as quickly as we can.
We believe we have the expertise, the experience, the relationships, all the capabilities to run this program very efficiently start to finish. To Chris's earlier point on the collaboration, this is an opportunity that Regeneron wholly owns, and we intend to run this program to maximum effect and make sure we get it to the clinic or get it to patients commercially as quickly as possible and in a competitive timeframe.
Just switch before we go to the pipeline, just switching over to EYLEA HD. For the prefilled syringe, what are current expectations in the context of both sites?
We don't really have an update to provide. There's really no change from the information we provided on our Q1 earnings call. We have two pending applications with the FDA, one with Catalent and another with an alternative vial filler for the prefilled syringe. We continue to expect a decision on one or both of those applications before the end of the second quarter. Importantly, the momentum for the product continues to be very strong in its current presentation, and that we're not dependent on a prefilled syringe to continue to drive growth for this franchise. It's becoming increasingly recognized as the best-in-class product. The label enhancements that were added in November of last year only continue to add the bolus of patients on therapy. We're very excited about the revenue result in Q1 and hope for a very strong 2026.
What are the scenarios from here, just given the observations at Catalent, but also the PDUFA being passed for the other site?
I'm sure Catalent is working very hard to resolve the observations that were noted during their April inspection, and we would expect them to continue to dialogue with the FDA in order to tick all the boxes required to get that facility back to VAI status. Our alternate manufacturer, as you noted, the PDUFA date was in late April. The FDA opted not to act. There's been continued engagement between this manufacturer and the FDA, and hopefully progress is being made, and they can approve that file at some point in the future.
Just looking back at the first quarter sales for EYLEA HD, there was impact from pricing and inventory and seasonality. Maybe speak to which factors are specific to 1Q and how to think about that read-through to 2Q from them and beyond.
As you look at the performance in the first quarter, we talk about the underlying demand approaching basically 10% sequentially. As we talked about, obviously seeing continued momentum just based on the current product profile, as Ryan talked about. The biggest factor that we saw was definitely attributable to inventory. Wholesaler inventory is something that's totally at the discretion of the wholesalers. It was at an elevated level at the end of Q4. They drew down those levels in Q1, which impacted the net sales relative to the demand. There is pricing headwinds out there. It's a very competitive category, and we obviously have to operate in that environment and do what we feel is necessary to maintain our competitive position out there in the marketplace.
If you look at historical pricing and what you see in the class, we would expect similar competitive pricing pressure to continue going forward.
As we pivot over to the pipeline here, you do have a lot of programs that are reading out over the next 12 months and beyond. Where do you have the most conviction in terms of those programs translating to meaningful revenue?
I think a lot of them are actually being managed by Andrés, and I can't wait to get into some of his programs. Certainly C5, BCMA, and myeloma are three, and then obesity, which we can certainly talk about as not only about weight loss, but also about better managing cardiovascular risk. Those are three or four that I'm most excited about, and hopefully we can have Andrés dive into a few.
Perfect. Andrés, I'll turn it over to you for any comments here. Maybe we could start with the C5 pipeline here.
Great, Salveen. Thank you for having me and the opportunity to share what we are doing in hematology. Quite a lot going on, as Chris has said. C5. We are very excited with the prospects of our C5 assets and the approach that we are taking in exploring how different degrees of C5 inhibition may translate in defined and clinical outcomes for patients. We expand indications from, in hematology, PNH, paroxysmal nocturnal hemoglobinuria, to myasthenia gravis, and to geographic atrophy, diseases that are driven by complement dysregulation. From early on, we hypothesized that maximal C5 inhibition will be required, and tested that question, to benefit patients. We have learned a lot throughout these programs. I think the one that really, the readout taught us a lot about how the degree of complement inhibition may translate or not in clinical benefit has been in myasthenia gravis.
Maybe we can go a little bit into the results of our data in myasthenia gravis, which essentially is driving a launch at the end of the year in this disease. This is where we tested either driving full complement inhibition by combining an siRNA that inhibits the production of C5 with an antibody that inhibits the activation of whatever remaining C5 is in the circulation. What we learn in myasthenia is that you don't need full complement inhibition to actually benefit patients. Furthermore, the NIMBLE study demonstrated that single-agent siRNA benefits the vast majority of the patients in the trial. This was done with what we call a potentially sweet spot. We observe a 70% inhibition of complement, while in PNH, we know that we want to drive 100% inhibition of complement to decrease hemolysis.
Here we learned that in this disease, that was not necessary. We are very excited with the results of the clinical trial. We think that we have the potential for a best-in-class in terms of the C5 inhibition. We're looking across different studies, where we observed sustained benefit and improvement in symptomatology in patients. When I say sustained, why is this important? Because we observed the benefit throughout the dosing period, from beginning to the next dose, where patients sustained their symptomatic relief. Doing so with an administration that is very convenient to patients, every three months, given subcutaneously, which we think will drive a lot of the future market opportunity for cemdisiran in this disease. Importantly also, when we look at the study, the safety was very manageable. We had no serious adverse events in single-agent cemdisiran.
We had no discontinuations throughout the study period when we reported the 24 weeks outcomes, which we think is very favorable within the class. We think that there is a tremendous potential for cemdisiran there.
Where do you see it being positioned versus the FcRns or Amgen's UPLIZNA?
That's a great question. Let's start first with why it's different and what is the differentiation. One of the critical, I think differentiators, or let's start first, a very efficacious drug. We have comparable, if not better, to C5 inhibitors in terms of symptomatic improvement. When we look at the duration of that improvement vis-a-vis FcRns, it's sustained, it's not cyclical. Even in C5 inhibitions, it has been observed that you may see worsening of the symptoms as you get closer to the end of the dosing period. Sustained inhibition. Then convenience, of course. We are looking at subcutaneous administration, four doses a year, which I think, again, will be critical in terms of driving the success of this drug. I think that one aspect that sometimes goes unrecognized, and we should pay a lot of attention, is about safety.
We are hypothesizing, based on the data that we observe with minimal adverse events, or not minimal, but with no cases of meningitis, with no SAEs throughout the treatment, is the fact that potentially, this sweet spot that we found, where you don't necessarily need to drive full inhibition of complement, allows for some remaining complement activity that may potentially help in fighting infections. We have to generate more data to demonstrate this point, I think the data from the clinical trial already suggest, based on infections, SAEs, and so forth, that that may be an advantage of cemdisiran. When you look at where FcRns are depleting all immunoglobulins with other potential for infections, viral infections, and so forth, which you don't see with complement inhibition.
When you look at the CD19 inhibitor targeting plasma cells, again, we think that the complement inhibition may be associated with less infections and so forth. Lastly, I want to highlight the rapid onset of benefit that we observed. We looked at symptomatic relief. The first time we assessed this was at two weeks. In fact, the vast majority of patients already start experiencing symptomatic relief within 14 days of initiation of therapy. CD19s can take months. In fact, it takes half a year to get to that steady state of improvement. As we know, FcRns and other C5s potentially delay a little bit vis-à-vis what we observed here, but with the problem of this losing of benefit towards the end of dosing.
In geographic atrophy, you're going to disclose 26-week data. Could you just discuss the desired clinical profile here and the differentiation that you need to see to support further development and the likelihood of this given it's systemically delivered?
Absolutely. This is an excellent question. What are we going to learn from the first 225 patients, really? The first one is systemic C5 inhibition have an effect on the slope of progression of the growth of the lesions in the eye? That's the first thing that we're going to learn. Also, we're going to learn whether monotherapy or double inhibition with the antibody and the siRNA is necessary in this disease. We're learning myasthenia it's not. We know and we strongly believe that in PNH, that's necessary, but we don't know yet in the eye. Those are the first two things that we're going to learn, I think that the data that is going to emerge also is going to help us further refine the ongoing clinical program in GA. Moving to what is it that we are looking for.
We're looking at the slope of growth of the lesion, importantly in this study, prospectively, we are going to be looking at visual. As you know, that has not been done prospective in any of the clinical trials with injected C5 or C3 inhibitors. I want to point out, however, we are looking at 24 weeks. It's a bit early. As you know, most of the benefits are observed longer term, we're looking at the slope at 24 weeks, and we may get a hint on a potential benefit in terms of visual acuity. Those are the two important aspects that we're going to learn towards the end of the year, we're going to be sharing with all of you as the data becomes available.
We're going to learn about safety, which is always very important, but we think that we will learn more towards the end of the year.
Perfect. Ryan, you touched on obesity being a key focus for the team. We'll see some data by year-end. Maybe help us understand what proof of concept could play out with that data set, and then the overall strategy for the obesity portfolio.
I think for the strategy, it's really about more than just weight loss. I think that has largely been solved, right? I think we're going to focus on other elements, including improving tolerability, as well as addressing comorbid conditions, and starting with cardiovascular disease. Hansoh, the company that we in-licensed olatorepatide from, disclosed earlier this year top-line data in their Chinese patients with obesity, with weight loss on par with leading agents, but with a GI tolerability profile that was much more favorable than like run studies in China were. We're very encouraged by that, and we're in the process of enrolling a small phase II study in the U.S. to see if that GI tolerability profile can be replicated. Should it be replicated, I think we will have an impressive competing agent within a category that has room for many, many therapies.
Beyond just the monotherapy opportunity in obesity and type 2 diabetes, we're also in the process of co-formulating olatorepatide with our PCSK9 antibody Praluent. Of all the miracles that GLP, GIPs, and GLPs have produced, one that it has not is lowering LDLs. In the pivotal studies for those agents, something like a placebo-adjusted decline in LDLs was only in mid-single digit percentile, so not really having much of an effect on lipids. However, we think that about half of obese patients actually have elevated LDL levels and could benefit from being on a PCSK9 inhibitor like Praluent.
Our approach is going to combine these into the same weekly injection that many patients are already used to, and in addition to lowering their weight, we would also expect their LDLs to lower on par with what we saw in the Praluent monotherapy studies, which were in the range of 50%-60% at six months. This is a way for us to enter the market, a large and growing market, in a differentiated way. We have other potential combinations to address other comorbidities of obesity that we will talk about at a later time. Certainly, we feel this could be a differentiated opportunity and take a nice part of a large market.
You announced collaborations on radiopharmaceutical therapies with your agreement with Telix, and antibody Helicon conjugates via your agreement with Parabilis. Can you discuss your interest in these technologies and how you envision integrating them into your platform?
I think this is, as Chris was talking about, opportunities that really complement Regeneron's core strength, which is antibody development as well as genetics, but in this case, primarily focused on antibodies. We're going to use these antibodies that we make with our platform to better direct these radioligands and these Helicons that Parabilis makes in an effort to, in the case of Parabilis, address intercellular pathways that antibodies simply can't address. This is a way of kind of enhancing a core strength that Regeneron already has, but take us to places that we couldn't go with antibodies alone. We're very excited to get started with both. A lot of work to do, but this could be a very important expansion of our capability set to address some of these different types of opportunities.
Great. With that, thank you so much.
Thank you, Salveen.
Thank you, Salveen.
Thanks, Salveen.