Regeneron Pharmaceuticals Inc

NASDAQ:REGN

Q1-2025 Earnings Call

[Operator]

Welcome to the Regeneron Pharmaceuticals First Quarter 2025 Earnings Conference Call. My name is Josh, and I will be your operator for today's call. Please note that this conference call is being recorded. I will now turn the call over to Ryan Crowe, Senior Vice President, Investor Relations. You may begin.

[Ryan Crowe, executive]

Thank you, Josh. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regeneron, and welcome to our first quarter 2025 earnings conference call. An archive and transcript of this call will be available on Regeneron's Investor Relations website shortly after the call ends. Joining me on today's call are Dr. Leonard Schleifer, Board Co-Chair, Co-Founder, President and Chief Executive Officer; Dr. George Yancopoulos, Board Co-Chair, Co-Founder, President and Chief Scientific Officer; Marion McCourt, Executive Vice President of Commercial; and Chris Fenimore, Executive Vice President and Chief Financial Officer. After our prepared remarks, the remaining time will be available for Q&A.

I would like to remind you that remarks made on today's call may include forward-looking statements about Regeneron. Such statements may include, but are not limited to, those related to Regeneron and its products and business, financial forecast and guidance, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement, intellectual property, pending litigation and other proceedings and competition. Each forward-looking statement is subject to risks and uncertainties that could cause actual results and events to differ materially from those projected in that statement.

A more complete description of these and other material risks can be found in Regeneron's filings with the United States Securities and Exchange Commission, including its Form 10-Q for the quarter ended March 31, 2025, which was filed with the SEC this morning. Regeneron does not undertake any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. In addition, please note that GAAP and non-GAAP financial measures will be discussed on today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our quarterly results press release and our corporate presentation, both of which can be found on the Regeneron Investor Relations website. Once our call concludes, the IR team will be available to answer any further questions. With that, let me turn the call over to our President and Chief Executive Officer, Dr. Leonard Schleifer. Len?

[Leonard Schleifer, executive]

Thanks, Ryan, and thanks to everyone joining today's call. For my remarks, I will review some of our key performance drivers, then briefly discuss some pipeline advances we have made this year. I will then hand the call over to George, who will provide additional insights on our pipeline.

From there, Marion will review our first quarter 2025 commercial performance. And finally, Chris will detail our financial results and provide an update on our 2025 financial outlook. Let's get to it. Regeneron's performance in the first quarter was mixed with some difficult news related to our retinal franchise, offset by encouraging news relating to the rest of our commercial portfolio as well as advances in our robust pipeline of differentiated clinical candidates, beginning with EYLEA and EYLEA HD. On a macro basis, in the first quarter of 2025 and the overall size of the branded anti-VEGF category contracted due to an increase in the usage of low-cost off-label repavastin, likely driven by patient affordability issues because of a funding gap at co-pay assistance foundations.

With respect to EYLEA, first quarter 2025 U.S. net sales were $736 million down 39% compared to the first quarter of last year and down 38% compared to the fourth quarter of 2024. However, physician unit demand decreased by 14% sequentially, with the balance of the decline primarily attributable to lower wholesale inventory levels, which ended the quarter in the normal range.

With respect to EYLEA HD in the United States, first quarter 2025 sales were $307 million, up 54% compared to the first quarter of last year, and were essentially flat on a sequential basis. Compared to the fourth quarter of 2024, EYLEA HD physician unit demand grew by 5% which was offset primarily by a modest wholesaler inventory jot down. On the regulatory front, last Wednesday, we were disappointed with the FDA's decision to issue a complete response letter for our submission seeking approval for the EYLEA HD prefilled syringe. Since receiving the CRO, we have held several teleconferences with the FDA to better understand the content of the CRO and believe the key outstanding issue relates to a question posed by the FDA to a third-party component supplier.

This component supplier has expeditiously responded to FDA requests for information. The CRL did not identify any issues with respect to the safety or efficacy of EYLEA HD the usability of the device proposed labeling or preapproval inspection findings. We also recently announced that the FDA had accepted for priority review and BLA for EYLEA HD to treat macular edema following retinal vein occlusion or RVO, and for monthly dosing in approved indications following the use of a priority review voucher. We believe these product enhancements will strengthen EYLEA HD's position in the competitive anti-VEGF category, if approved.

Moving to DUPIXENT. First quarter 2025 net product sales grew 20% globally on a constant currency basis versus the first quarter of 2024 reflecting strong growth across all approved indications in all groups -- in all age groups, I should say, and in all geographic regions. In the U.S., where net product sales grew 19%, DUPIXENT now leads in both new-to-brand prescription share and total prescription share across all of its approved indications with the only exception being chronic spontaneous Artcare or CSU, which was approved by the FDA only 11 days ago. The COPD launch in the U.S. continues to gain momentum with prescribers increasingly appreciating the role of type 2 inflammation in certain patients with COPD, coupled with greater urgency to identify and treat edible patients.

Payers are increasingly recognizing the value that DUPIXENT offers and have implemented broad and favorable coverage decisions for commercial and Medicare patients. With those pieces in place, we now look to drive patient awareness of DUPIXENT as a new treatment option for COPD through a recently launched direct-to-consumer campaign.

Libtayo in the U.S. grew 21% compared to the first quarter of last year and has established itself as a cornerstone therapy for advanced non-melanoma skin cancer while the share of the lung cancer market continues to increase. In the highly competitive first line advanced non-small cell lung cancer market, Libtayo is now second in new-to-brand prescription share despite launching years after other competing therapies, reflecting its differentiated clinical profile and our commercial strategy.

We expect Dupixent EYLEA HD and Libtayo to continue delivering significant growth for the foreseeable future to additional penetration in approved indications potential future indications, potential combinations with other pipeline candidates as well as other potential product enhancements.

Now briefly moving to our pipeline, which now includes approximately 45 product candidates in clinical development. We continue to make significant investments in R&D, which have yielded notable progress across 7 key programs so far this year including 4 regulatory approvals and 9 regulatory submissions. For the remainder of 2025, we anticipate U.S. regulatory approvals for limboseltimab and relapsed refractory multiple myeloma and odeneximab in late-line follicle lymphoma, Libtayo in adjuvant CSCC, Dupixent in PulasPimfogoid as well as differentiated enhancements to the EYLEA HD U.S. label.

We also now expect to read out pivotal or proof-of-concept data across programs in immunology, oncology, hematology, internal medicine and rare diseases, programs that George will discuss in a minute. In closing, Regeneron remains in a very strong position, scientifically, commercially and financially, enabling us to invest heavily in R&D and deliver scientific breakthroughs, maximize growth opportunities from our in-line brands, successfully launched new products and indications and return capital directly to shareholders through dividends and share repurchases. We look forward to providing updates on these efforts as we move through the remainder of 2025. With that, I'll turn the call over to George.

[George Yancopoulos, executive]

Thanks, Lynn. 2025 is shaping up to be an exciting year for advancing our broad and differentiated pipeline, and we look forward to reporting several pivotal or proof-of-concept data sets from multiple programs. I would like to briefly highlight the significant opportunities and discuss additional pipeline advancements, starting with DUPIXENT, which continues to set a high bar across multiple type 2 allergic diseases.

Earlier this month, DUPIXENT was approved for the treatment of adults and adolescents with chronic spontaneous urticaria who remain uncontrolled despite antihistamine treatment. This approval marks the seventh type 2 allergic disease for which DUPIXENT has been approved by the FDA and is the first new treatment option for CSU patients in over a decade. DUPIXENT was also accepted for priority review for the treatment of [indiscernible] with a PDUFA date of June 20, bullish pemphigoid represents yet another first-in-class opportunity for DUPIXENT, which is the only biologic to achieve significant improvements in disease remission and symptoms in this set.

And finally, DUPIXENT became the first ever biologic medicine to be approved for COPD in Japan, marking the 45th country in which the COPD indication has been approved. We are eagerly awaiting the pivotal readout for linvoseltamab, our interleukin-33 antibody for COPD and former smokers regardless of eosinophil levels with data expected in the middle of 2025.

In addition to COPD, we recently initiated a Phase III program for iriticumab in chronic rhinositis with nasal polyps, an indication of strong genetic validation as well as a Phase II study in chronic rhinositis without nasal polyps. In addition, next year, we are expecting proof concept data for inepicaman in noncysticfibrosis bronchiectasis.

Turning now to oncology efforts. We recently submitted U.S. and EU regulatory filings for Libtayo, [indiscernible] where Libtayo became the first immunotherapy to show a benefit in a high-risk population. In early June, these data will be presented in an oral presentation at the American City of Clinical Oncology or ASCO Annual Meeting, highlighting a 68% reduction in Arista disease recurrence or death compared to placebo with no new safety signals identified.

This data set underscores our belief that Libtayo provides a best-in-class foundation for combinations with our other oncology assets. And in this regard, Libtayo is being tested in combination with fianlimab, our LAG-3 antibody in several solid tumor settings. In melanoma, early clinical data have suggested that this combination can provide substantial additive benefit compared to PD-1 monotherapy without exacerbating safety.

An ongoing Phase III trial in first-line metastatic melanoma evaluating this combination compared to KEYTRUDA monotherapy is expected to read out in the second half of this year. We reiterate that these data confirm best-in-class activity in melanoma, we will increase our confidence for this combination in other cancer settings. In first-line advanced non-small cell lung cancer, a preplanned interim analysis was conducted this month on 2 ongoing Phase II studies evaluating this combination.

Due to limited follow-up, the Phase II portion of the studies will continue unchanged until additional data are available. The next analysis for these studies are expected in the first quarter of 2026 in which a decision whether to advance to Phase III will be made. No new safety signals were observed in either study.

Turning to our CD3 bispecifics. The European Commission recently granted conditional marketing authorization for LinoZific or limboceltaman, or BCMA by CD3 bispecific for the treatment of adult patients with relapsed/refractory multiple myeloma we have received at least 3 prior therapies, marking [indiscernible] first global regulatory approval in the U.S., our resubmission of the limboseltumab BLA for relapsed/refractory multiple myeloma was accepted by the FDA with a PDUFA date of July 10.

We believe limvosetimab has the potential to be the best-in-class BCMAxCD3 bispecific due to its differentiated clinical profile, dosing and administration. Our broad clinical program in earlier lines emphasizes monotherapy and limited combinations and continues to advance with a confirmatory Phase III linker MM3 study in relapsed/refractory multiple myeloma now fully enrolled.

At ASCO, also in oral presentations, we will present the initial results from the Phase I/II linker MM2 trial, the valuing limboceltumab in combinations with carfilzomab and with bortezumab in patients with relapsed/refractory multiple myeloma. Both combinations demonstrated a high rate of deep and durable responses with a safety profile consistent with the individual drugs, supporting further development.

For odronextamab, our CD20xCD3 bispecific, the FDA has accepted the BLA resubmission for relapsed/refractory follicular lymphoma with a PDUFA date of July 30. Ogenextumab has demonstrated potentially best-in-class efficacy in this late-line setting in our differentiated clinical development focuses on monotherapy and limited novel combinations in earlier line and continues to advance.

Turning to hematology. We are rapidly advancing our Factor XI program where we are investigating 2 different antibodies that target different Factor XI domains to create a tailored approach to anticoagulation offering the potential for improved blood clot prevention and lower bleeding risk. We remain on track to enroll patients in pivotal studies this year, both in settings with large patient populations and longer follow-up as well in settings with small populations and shorter follow-up that may provide a quicker path to market.

Moving to our obesity efforts. Regeneron has decades of experience in muscle biology, growth factor signaling pathways and genetics. We are capitalizing on this expertise to position ourselves as a key player in the rapidly expanding obesity market by investigating agents that enhance GLP-1 weight loss by maintaining muscle mass. Our muscle-sparing Phase II CAR study is investigating the addition of[indiscernible] , our GDF8 antibody to semaglutide with and without gartatimab are active in antibody with the goal of improving the quality of weight loss. We expect to report data for the 26-week primary endpoint including percentage of weight loss and percentage of fat loss compared to baseline in the second half of this year.

At the upcoming American Diabetes Association meeting in June, we anticipate that Lilly will present Phase II data from a very related program evaluating semaglutide combined with an antibody that binds to active and type 2 receptors, which blocks myostatin in active and signaling. The weight loss lean mass preservation overall metabolic profile along with safety and tolerability will help perform next steps for our programs as well.

And finally, moving to our Regeneron Genetic Medicines pipeline. Our novel C5 sRNA and anybody combination has demonstrated rapid, complete and uninterrupted inhibition of C5 as seen in our ongoing pivotal program in patients with paroxysmal maternal hemoglobin urea. These profound findings increase our confidence in seeing robust improvement in generalized myasthenia gravis, where pivotal results from an ongoing Phase III program are expected in the second half of this year.

Our unique mechanism of action provides more complete C5 inhibition than observed with other C5 approaches that are approved in this indication as well as the potential for more convenient subcutaneous regimens. In summary, Regeneron continues to deliver scientific firsts and drive innovation. Our unique R&D capabilities have allowed us to build with the most prolific pipelines in our industry, and we look forward to reporting multiple impactful readouts later this year. With that, let me turn it over to Marion.

[Marion McCourt, executive]

Thank you, George. Despite a challenging environment in the first quarter, our commercial teams are positioned to capitalize on multiple near-term opportunities across the portfolio including product enhancements and launches of both new medicines and new indications for previously approved medicines.

Looking to the future, as Stuart highlighted, our pipeline is poised to deliver the next wave of significant commercial opportunities that may provide innovate medicines to even more patients. Beginning with our first quarter results for EYLEA HD and EYLEA, combined U.S. net sales were $1.04 billion, down 30% sequentially, primarily reflecting lower wholesaler inventory levels for both products, which declined during the quarter to the normal range as well as continued competitive pressures in aggregate sequential physician unit demand for ELE HD and EYLEA declined by 11%.

We believe there was a significant negative impact in the branded anti-VEGF category due to an ongoing funding gap at nonprofit patient assistance foundations that provide copay support for eligible patients with retinal diseases. Consequently, low-cost off-label repackaged Avastin increased its anti-VEGF category share by approximately 6 percentage points to 32%.

Despite these challenges, EYLEA HD and EYLEA captured 41% of the anti-VEGF category, maintaining market leadership. For the first quarter, EYLEA U.S. net sales were $736 million primarily due to lower wholesaler inventory levels, lower physician demand as well as increased competition. While we expect competitive pressures for EYLEA to persist, our focus remains on promoting the ongoing adoption of EYLEA HD, which has the potential to become the new standard of care.

EYLEA HD was the only branded medicine in the anti-VEGF category to maintain U.S. net sales quarter-over-quarter, achieving $307 million and growing 54% year-over-year. In August, we anticipate potential FDA approvals of EYLEA HD in retinal vein occlusion and for every 4-week dosing across all approved indications. If approved in RVO, EYLEA HD would be the first and only treatment that can be dosed up to every 8 weeks, which is twice as long as any other product in the category.

In addition, with the potential approval of every 4-week dosing, EYLEA HD would offer physicians the most flexible dosing options in the category. With these label enhancements and anticipated approval of the prefilled syringe, we expect to see an acceleration in EYLEA HD demand. And now to DUPIXENT. In the first quarter, DUPIXENT achieved global net sales of $3.7 billion, representing a 20% year-over-year increase on a constant currency basis.

In the U.S., net sales grew 19% to $2.6 billion based on robust demand across all approved indications. In the first quarter, U.S. net price was unfavorably impacted by the annual reset of commercial insurance deductibles and the implementation of Medicare Part D redesign. DUPIXENT continues to live up to its potential to dramatically improve patients' lives with approvals in 7 indications, 4 of which have achieved blockbuster status globally.

DUPIXENT's unique mechanism of action makes it the only medicine that addresses the underlying drivers of disease and treats multiple comorbid type 2 conditions. Despite increasing competition in established indications, DUPIXENT remains the market leader. In atopic dermatitis, increased promotional spend from competitors and accelerated market growth with DUPIXENT continuing to capture the vast majority of new patients.

In asthma, DUPIXENT continues to lead all biologics new-to-brand share and is now the category leader in total prescriptions. Momentum in new indications continues to build and COPD uptake is accelerating. Most pulmonologists have extensive experience in prescribing DUPIXENT for asthma and are increasingly prescribing it for COPD. Many have remarked on DUPIXENT's ability to reduce exacerbations, rapidly and meaningfully improve lotion and reduce the need for oxygen therapy with physician and patient awareness building and strong reimbursement established.

The COPD launch has outperformed all other DUPIXENT indication launches in cumulative new-to-brand prescriptions with the exception of atopic dermatitis. Earlier this month, DUPIXENT was approved to treat patients with chronic spontaneous urticaria or CSU, where we estimate there are more than 300,000 patients in U.S. with the disease inadequately controlled by antihistamines.

DUPIXENT is the first new targeted treatment for CSU in over 10 years, providing a new treatment for patients that previously had limited options. The launch is underway and early feedback has been favorable. Our DUPIXENT team is also preparing for potential approval in bolus pemphigoid which would represent the fourth approval in a chronic and debilitating skin disease driven by type 2 inflammation.

Nearly 30,000 adults in the U.S. suffer from this difficult to treat condition where current care is limited to corticosteroids and immunosuppressants. These treatments have core clinical efficacy as well as safety concerns, particularly in older patients. Improved DUPIXENT will be the first and only targeted medicine to treat this disease.

In summary, DUPIXENT is now firmly established as the standard of care across a range of type 2 conditions and has substantial growth opportunities in both existing and new indications. Turning now to Libtayo. First quarter global net sales grew 8% year-over-year on a constant currency basis to $285 million, with U.S. net sales reaching $193 million, up 21%.

First quarter results reflect typical seasonality dynamics and the timing of shipments and lower inventory levels and the U.S. demand continues to increase across both non-melanoma skin cancer indications and lung cancer and we are seeing growth in approved indications internationally. We look forward to the potential FDA approval of Libtayo for adjuvant treatment of high-risk cutaneous squamous cell carcinoma where we estimate there are approximately 10,000 patients in the U.S. who may benefit from this treatment.

Our oncology teams are excited about the potential to launch 2 new hematology products later this year. linvoseltamab in relapsed/refractory multiple myeloma and odronextamab in relapsed/refractory follicular lymphoma, both have demonstrated best-in-class clinical profiles in these later-line settings. In summary, our commercial portfolio is well positioned to capitalize on many near-term growth opportunities enabling us to deliver more treatments to more patients. With that, I'll turn the call over to Chris.

[Christine Poon, executive]

Thank you, Mario. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis, unless otherwise noted. First quarter 2025 total revenues were $3 billion, inclusive of higher Sanofi collaboration revenue driven by DUPIXENT growth and higher U.S. net sales of EYLEA HD compared to the prior year.

First quarter diluted net income per share was $8.22 on net income of $928 million. Beginning with collaboration revenue, revenues from the Sanofi collaboration were approximately $1.2 billion, of which $1 billion related to our share of collaboration profits. Regeneron's share of profits grew 27% versus the prior year driven by volume growth for DUPIXENT and higher collaboration margins. The Sanofi development balance was approximately $1.5 billion at the end of the first quarter, reflecting a reduction of approximately $180 million from the end of 2024.

Moving to Bio. First quarter net sales of EYLEA and EYLEA 8 mg outside the U.S. were $858 million, up 5% versus the prior year on a constant currency basis and inclusive of $146 million of EYLEA 8 mg sales. Total buyer collaboration revenue was $344 million, of which $317 million related to our share of net profits outside the U.S.

Now our operating expenses. R&D expense was $1.2 billion in the first quarter. Modest growth versus the prior year was driven by continued investments to support Regeneron's innovative pipeline, including higher personnel expenses and clinical manufacturing costs. First quarter SG&A was $537 million down 8% from the prior year. The decline was driven by lower general and administrative expenses, while selling expenses were flat year-over-year.

Third quarter 2025 gross margin on net product sales was 85%. The lower gross margin versus the prior year reflects higher inventory write-offs in the first quarter of 2025 and a change in product mix. Our effective tax rate increased versus the prior year, primarily driven by a lower benefit from stock-based compensation deductions.

Regeneron generated $816 million in free cash flow in the first quarter and ended the quarter with cash and marketable securities of $17.6 billion and debt of approximately $2.7 billion. We continue to monitor developments regarding pharmaceutical sector tariffs. While we do not expect previously enacted tariffs to have a material impact on our business, any potential impact from sector-specific tariffs is not quantifiable at this time due to uncertainty around the details of implementation.

Regardless of any potential tariffs, Regeneron has always been committed to making significant investments in the United States to expand our manufacturing capabilities. We recently announced a new agreement with Fujifilm Diosynth Biotechnologies in North Carolina to invest over $3 billion to nearly double our U.S. large-scale manufacturing capacity.

This agreement, along with our $3.6 billion expansion of our Tarrytown, New York R&D and preclinical manufacturing facilities, our fill/finish facility in Rensselaer, New York and the acquisition of an additional property in Saratoga Springs, New York represent planned U.S. investments of over $7 billion. These investments will enable us to continue to grow in the U.S. and support our differentiated R&D engine while significantly increasing our ability to manufacture both clinical and commercial supply.

Beyond these investments, we continue to return capital to shareholders in the first quarter, both through share repurchases and the payment of our recently initiated quarterly dividend. We repurchased approximately $1.1 billion worth of our shares in the first quarter with approximately $3.9 million remaining available for share repurchases as of March 31. We continue to see share repurchases as an efficient use of capital and remain opportunistic buyers of our shares. In addition to share repurchases, our newly initiated dividend program allows us increased flexibility to return capital to shareholders.

We paid our first quarterly dividend last month, and the Board of Directors has declared the next dividend of $0.88 per share, which will be paid in June. Finally, we have updated our 2025 gross margin guidance to be in the range of 86% to 87%. This change is primarily driven by higher-than-expected inventory write-offs in the first quarter. A full summary of our latest guidance can be found in our press release issued earlier this morning. In conclusion, Regeneron's strong position will allow us to continue to invest in our differentiated R&D capabilities and pipeline to deliver new medicines to patients and long-term value to shareholders. With that, I'll pass the call back to Ryan.

[Matthew Holt, analyst]

Thank you, Chris. This concludes our prepared remarks. We will now open the call for Q&A. [Operator Instructions] Josh, can we go to the first question, please?

[Operator]

[Operator Instructions] Our first question comes from Tyler Van Buren with Cowen .

[Tyler Van Buren, analyst]

Regarding the EYLEA HD CRO for the prefilled range, can you elaborate further on the question posted by the FDA and perhaps more importantly, compare the situation to the original EYLEA HD CRL as that to resolution was very quick. About 2.5 months, if I'm not mistaken, which would still be ahead of the RVO and every 4-week dosing PDUFA in August.

[Leonard Schleifer, executive]

Right. Tyler, thanks for the call. Len speaking. I think you have to understand a little bit of detail on the processes and what happens in that. When you're reviewing -- when the FDA is reviewing your submission for an approval of a new device, we don't necessarily make all the components.

And in this case, we don't make all the components. You might be buying a stop from somebody, some glass from somebody else and needle to somebody else and so forth. And we have the design and then we have an assembly when the FDA has a question about one of the components, that's what's referred to as a drug master file. They go to the holder of that drug master file. Let's say it's somebody who makes one of the components, the FDA has a question, well, how do you guys do this? And then the hold of the master file responds to the FDA.

By rule, we are not partied to that up and back between the FDA and the third-party component supplier. The reason we're not partied is because most of the time, these questions relate to general practices where -- in which the supplier is not only supplying Regeneron, they might be supplying 20 other pharmaceutical companies, which is, in fact, the case in some of these DMFs we're dealing with here.

So that's the general tone of things. The questions get asked. In this particular case, based on our phone calls after we received the CRL last Wednesday, we realized that nobody had gotten these questions until the day of the CRL or a day before, literally after the CRL. In any case, based on our conversations with BBA, we believe that there's one key issue that is left to resolve. There are a few other minor ones, which I think just clarifications.

But the one key issue relates to a supplier, and the supplier has told us that the FDA asked for some data. They have all the data. They expeditiously supplied it. Now of course, we don't know the data because we can't be involved by rule in that process. We take it that word that they think that they have satisfied the agency, of course, the FDA has to review this. They could be up and back. You said this, well, we really wanted that, maybe have more of this and so forth. So that leads to a little bit of uncertainty on how fast this could all get resolved.

We do have commitments from the FDA that they will move expeditiously as well. That doesn't mean they'll approve it, but they will review quickly the data that's submitted and have up and back because they recognize, I think, the importance in advance of the prefilled syringe being a better way of administering the product than out of a vial for patients getting intravitreal injections. So boil all that down, how long can this take, it could go quickly. As you said, the last time this happened, it took a few months. It could go longer. We don't think there's a reinspection involved. It's not an issue related to that.

So we don't think there will be these in turn of a long time lines for that. But we'll know more in the coming weeks or months, and we will hopefully get it across the finish line in a short while, what we'll try and keep you posted once we know what the FDA is really up to. I'm sorry that that's a little indefinite, Tyler, but the nature of the process.

[Ryan Crowe, executive]

Thanks, the next question, please.

[Operator]

Our next question comes from Alexandra Haven with Wolf Research. .

[Alexandria Hammond, analyst]

I want to pivot a little bit, and I'm curious on the line. So your Factor XI antibody is how do you prioritize which indications to go after? And how should we think about the timing of launches? Can you provide any follow-up to on your discussions with regulatory authorities aligning trial design?

[Unknown Executive]

How do we or I couldn't...

[Ryan Crowe, executive]

indications.

[Unknown Executive]

Well, we're doing a combination of indications that are maybe to be expected and will take a little bit longer as well as some indications that we haven't disclosed that we think we might be able to get across the finish line sooner. In terms of our approaches, what we're trying to prioritize or indications and studies where we'll be able to show the benefit not only of the anticoagulation profile but of the differentiated bleeding risk profile, both of these and bodies.

And the hope is to actually show that one or both of these antibodies have very favorable anticoagulations as well as substantially lower bleeding risks than available options for patients. So we haven't disclosed all the indications. We haven't shown the timing of them, but there's a variety of them. And there -- some of them will be coming in sooner. Some of them will be taking a little bit longer. And we hope that they will be emphasizing, as I said, the potential for really addressing what's holding back a lot of patients in this field for receiving anticoagulation therapy, which is minimizing the bleeding risks that these people invariably suffer from. As we've announced, we are beginning to enroll Phase III studies this year.

[Ryan Crowe, executive]

Okay. Thanks, Georgette. Next question comes from Chris Shott with JPMorgan.

[Christopher Schott, analyst]

I just had one on EYLEA and the foundation funding. I appreciate the color on the call. But just any updated thoughts on when we could think about the foundation reopening. And how quickly, once it's reopened, we could think about some of these volumes moving from the generic Avastin back to branded agents.

[Leonard Schleifer, executive]

Chris, thanks for the question. Just for the benefit of everybody, let me just remind everybody how all this works. When you're under commercial insurance and you're younger than 65, if you have a co-pay in your insurance program, sponsors that people like Regeneron can directly to patients supply co-pay assistance in the form of a coupon, et cetera, et cetera.

When a patient turns 65 and if they go on Medicare, which most of our patients getting intravitreous injections are -- those patients that are responsible for a co-pay typically around 20%, if they're playing or Medicare, it varies somewhat if they're a Medicare Advantage. Some people, many people have insurance, supplemental GAAP insurance, AARP, or whatever you want to call it, which covers these co-pays.

But there are still others who don't have the insurance and can't afford the co-pay associated with an injection of an anti-VEGF agent, for example. The government has indicated that companies can be part of the safety net, if you will, to help patients who need financial assistance. And the way this works is that companies and others can support independent charitable foundations who then assist patients with retinal disease regardless of the drug they need.

The foundations taken financially eligible patients and give out the assistance that they can afford to give out on a first come first serve basis. And so there is no direct relationship. If we give money to a foundation, it could go to support for [indiscernible], it could go to support Patlu could go to support EYLEA, it could go to support. In fact, the refines as they're constructed today, it could go to support the drugs for geographic atrophy. There's no connection as there shouldn't be and what we give and then what the -- how the foundation go out to the resources.

We would like to help as many patients as we can. And it turns out we -- if not the sol, the vast supporter of these foundations in the recent history, we're talking about having given large sums of money in the neighborhood of over $400 million last year to do this charitable work. As our commercial outlook in the field has changed as our resources have changed.

We looked at this and said, we'd like to continue doing this, but we can't do it all ourselves. We'd like to help as many people possible. And so we're trying to come up with a way where others and Regeneron could make sure that people in need get the drug, co-pay support without regard to what drug they actually choose or the doctors choose.

And one of the things that we've come up with is sort of a standard thing that's done. We all have seen this in our charitable philothopic efforts. We're considering a matching program where Regeneron would put up and say, we'll put up X dollars to some amount and that people -- depending upon other people putting up, we would match their contributions. We would hope that this might stimulate others to be more philanthropic than they've been. We are working through the mechanics of this with the foundation. When this all can get launched, we hope in the not-too-distant future whether or not others will step up to the plate, I'm not sure, but we certainly hope because patients do need this.

I hope that answers your question, and since this is such an important issue, if you Chris, if I haven't answered it, we'll give you another question to drill down on this a little further.

[Ryan Crowe, executive]

Okay. We'll move on for now. [Operator Instructions] Josh, let's move onto the next question, please.

[Operator]

Our next question comes from Terence Flynn with Morgan Stanley.

[Terence Flynn, analyst]

Just wanted to ask an additional one on the prefilled syringe. Lynn, thanks for all the details. But can you confirm that this component is something used in your prefilled syringes that's already approved in Europe? Or is this a different component? Or is the component used in any other prefilled syringes? Just trying to understand the novelty here and why this might be a hangup.

[Leonard Schleifer, executive]

Yes. This is the same device, same design and the same components that was approved in Europe last year and has been safely used for months. So we don't think there's any issue whatsoever with the approvability of this, but the FDA has their own set of questions. They want to know how to do this, or weighs the data for that and that sort of thing, and they don't just automatically approve it just because Europe has improved. But yes, your question is a good one, Terence, it gives us all some confidence that these issues should be resolvable because they were resolved for European approval.

[Ryan Crowe, executive]

Let's move to the next question, please.

[Operator]

Our next question comes from Akash Tewari with Jefferies. You may proceed.

[Akash Tewari, analyst]

So you mentioned $400 million in patient assistance to good days. Can you comment on what percent of your U.S. patient base received funding in 2024? Is 25% a fair estimate? And just to kind of drill into the specifics from what you've seen in Q1, what percentage of those patients are dual covered or have supplemental insurance so they would be able to get back on to EYLEA without help from good days?

And then, Len, assuming that other Roche and some of these other players don't -- aren't receptive to this matching program, what is your team going to do, right? Is there a situation where funding to good days doesn't return at any point in 2025?

[Leonard Schleifer, executive]

Al right. A lot of questions embedded in there. But the first series of questions we can't answer. We don't do any correlations about our contributions and the implications for EYLEA usage. That's not permitted, it's not appropriate. And the people who make the decisions at Regeneron are not the commercial people. This is not a conduit of any shape, manner or form and that's not permissible under the rules. So we don't -- we can't answer any of those questions about EYLEA.

In terms of what our game plan is, well, I think you've heard it. we want to stimulate a community of givers. You mentioned one, it doesn't have to be. It could be somebody else, Elon Musk wants to give, that's good by us, too. We're not targeting anybody in particular. We're just saying that we would like to stimulate others. And I should just leave it at that.

[Ryan Crowe, executive]

Let's move onto the next question, please.

[Operator]

Our next question comes from Carter Gould with Cantor.

[Unknown Analyst]

Sorry to come back to the regulatory operations, and I appreciate all the color on nuance on the prefilled range. But Len, this is your fourth CRL and as well as a delay in the past sort of 12 months. Is there acknowledgment this performance is unsatisfactory across the regulatory group? And maybe you could highlight any steps you've taken to improve regulatory performance. I recognize there are various increases. And if I'm being unfair, please, correct me, but the rate of CRLs and delays really stands out versus peers?

[Leonard Schleifer, executive]

Well, that's a tough one. Well, if anybody is going to take responsibility, it's going to be me. I'm not putting this on a regulatory group whatsoever because I think they've done a spectacular job as a manufacturing group. We have a lot of activity on the FDA. I can't remember what we said in the 9 submissions and so we're going to have more than our share of regulatory interactions.

I think our team is first rate, the kinds of issues that have come up are reflecting, in my view, an increased scrutiny by the FDA post-COVID on contract manufacturers performing a variety of functions. All of our CRs I should say, not all, but for the vast majority of our CRLs, they relate to these issues at third-party suppliers, which the FDA recognized were woefully behind the times during COVID. There wasn't enough of them. They were flunking infections.

And so I think the FDA is trying to step up the game, if you will, of these contract manufacturers. And since we're so active, we see more. I don't think it's -- I'll acknowledge it for sure that we're unhappy about this. And if there's a blame, I'm happy to take it personally, but it's certainly not a reflection on a regulatory group or manufacturing people who are working really hard to get this right.

Now in some cases, the rules have changed to the mid game. We had a CRL where we hadn't quite enrolled enough people. And why did the FDA change that sort of approach? Well, it's because other manufacturers weren't bothering to enroll anybody over a 10-year period. And so they've said we're not going to do these accelerated approvals. So we got caught up in that, but we've rectified that, and we're expecting that approval to come.

There was another CRO related to a manufacturing thing with -- originally with EYLEA out of our control. We got that. I don't want this to sound like excuses. We own the issues because it's our product, but it is reflective, I think, more of what is going on at the level of the contract manufacturers.

[Ryan Crowe, executive]

The next question, please.

[Operator]

Our next question comes from Brian Abrahams with RBC.

[John Newman, analyst]

This is Joe on for Brian. So for itepekimab has there been any further evolution of our understanding in IL-33 as a therapeutic target since its Phase II COPD data and the mechanistic rationale behind iPeMS pronounced benefit in former smokers. And as you expand Pecuma development, how will the COPD results guide the further expansion.

[Leonard Schleifer, executive]

Well, A lot of our insights into IL-33 come from genetics in the pathway. As you know, from our Regeneron Genetics Center, we have a large number of human sequence. We can actually see variation in the IL-33 pathway.

And what we actually see is that patients who are genetically deficient in this pathway are protected from COPD and those who have excess IL-33 activity or more prone to COPD as well as a series of other diseases, some of which we've described we're investigating with additional clinical trials.

So that's where the whole rationale and the whole idea comes from which indications we go after. As we've already said, our Phase II study showed an overall reduction in exacerbations that was driven by this former smoker population. We think we might be understanding a little bit about that mechanism, but nothing definitive and new up until this point. And I do remind you that these Phase III studies did pass an interim analysis about halfway through the program, which gives us additional hope and confidence. So the genetics is strong here. The Phase II data was strong here and the fact that we passed an interim efficacy barrier give us confidence here. But obviously, we'll be getting the data in a short period of time, and that will be definitive.

[Unknown Analyst]

Any thoughts on future indications based on the COPD results?

[Leonard Schleifer, executive]

Well, we announced, as I just described in my comments a few ongoing studies and a few studies that we're initiating. We're also very excited about the opportunity in ASCO. The data is very strong there. And I think that depending on the COPD results, we might be considering moving into that space as well because the genetics there is also very, very strong. .

[Ryan Crowe, executive]

Let's move onto the next question, please.

[Operator]

Next question comes from William Pickering with Bernstein.

[William Pickering, analyst]

On the EYLEA HD monthly dosing submission, the ELARA safety trial just completed enrolling in March, and I believe that you submitted the filing before that. So what percent of the total enrollment was included in the submission? Did you have alignment with the FDA this would be sufficient? And what's your overall level of confidence in the submission at this point?

[Leonard Schleifer, executive]

I don't know if we're going to get into the details of all of that. Suffice it to say that they've accepted our submission and therefore, there's no deficiency, say, like we didn't have enough numbers or something like that. Now it's a review issue, and we'll see how that process goes, and we'll let you know when we know something. But in terms of whether or not we've satisfied the requirements for evaluation we did pass that hurdle because it was accepted for review. .

[Ryan Crowe, executive]

Let's move onto the next question.

[Operator]

Next question comes from Evan Siegerman with BMO Capital Markets.

[Evan Seigerman, analyst]

I want to pose one for you, Lynn. Hypothetically speaking, if you could redesign a way to provide patient assistance without the use of charities and current legislation aside, how would you structure that program for Medicare? Would it be direct kind of co-payments for patients who need it or other kind of mechanism? How do you think about that?

[Leonard Schleifer, executive]

Yes. That is a great question. And I addressed that, I think, recently on a CNBC interview that I gave, but let me revisit it. Just the level set everybody, remember, the point being is that we cannot do direct patient assistance to people who are having their drugs paid for by government funding.

I suggested with the stroke of a presidential pin that they could choose to allow sponsors to provide co-pay assistance directly the way we do for commercial patients. The notion that somebody is going to take an expensive drug that requires treatment for cancer, let's say, or an injection in the eye or something like that because they get co-pay assistance seems to me ill founded.

And maybe it might increase utilization, perhaps, but more importantly, is it means patients will get the best drug that they and their doctors choose for them. There is lots of evidence and we just had it this quarter that we -- most retinal specialists will tell you that Avastin is not the best drug to treat patients with a variety of retinal diseases, yet people who are poor who can't afford copays wind up getting that in a disproportionate number, as you saw when there was no co-pay assistance.

And that's really the wrong that needs to be righted. And while I'm designing this, I would allow copay assistance by directly from sponsors to patients. I think one could literally do this. If the President wanted to do this, he would get millions and millions of seniors would be greatly appreciative that they weren't fussing and worrying and figuring out, am I getting the best treatment that's going to make me not lose my vision? Or am I getting the right cancer treatment so that I can live to see the next year and so forth, I think that, that would be a great thing for the President to do.

[Ryan Crowe, executive]

Let's move to one more -- next question, please.

[Operator]

Our next question comes from Salveen Richter with Goldman Sachs.

[Salveen Richter, analyst]

You tightened your capital expenditure guidance for this year. Can you help us understand this in the context of your recent manufacturing announcements and cadence here for forward spend noting the current environment. .

[Leonard Schleifer, executive]

Yes. Thanks, Salveen, for the question. We lowered the top end of the range by $25 million. There's nothing really to look through that other than just some timing. And of the way we see the expenditures going out, but we're committed to our capital plans and nothing has changed accordingly.

[Ryan Crowe, executive]

Okay. Let's -- I think we have time for one more question.

[Operator]

Our next question comes from David Risinger with Leerink Partners.

[David Risinger, analyst]

Yes. Thanks very much. So Len, I'm hoping you can address a big picture question. The industry is facing 3 major U.S. government risks, specifically actions that are harming biopharma innovation including FDA disruption, questioning of proven medical science, evisceration of the NIH. In addition, tariff threats -- and then finally, the Trump administration's agenda to take down drug prices more than the Biden administration.

So considering what appears to be a lack of appreciation in Washington of the benefits that the biopharmaceutical industry brings to Americans, could you please comment on how you and your executive team and Board are engaging differently today with Washington leadership to change the political agenda for the better?

[Leonard Schleifer, executive]

Great question, David. Look, I think during this transition period, there is a lot of disruption in Washington. There is loss of personnel reduction in force, new people in charge, new focuses and so forth. I told the President that I thought that RFK junior, while he thinks outside the box needed some assistance on the science front.

I said that's straight out and offer to provide that. And I think that there are others who feel similar, as I do, that we can't lose the ability to do science. Does that mean that the way science has been done in this country, the way grants have been given out is done exactly right, no. There is for improvement across all of what we do. We saw that during COVID when one of our antibodies didn't get the kind of indication. It clearly should have based on the science, why that happened, somebody wasn't following the science.

So there's room for improvement. But of course, there's risk, David, as you point out. If we take a path where we just stopped following science and we give up on tried-and-true methodologies, I think we could be in trouble. If we take a fresh look at things, but still get guided by scientific principles, I think things could improve.

Obviously, experience does matter, and I really hope that we do not lose really good people at the FDA in the rank and file or even at the policy level. I think that would be deleterious. So I think we don't get to set the policy. We hopefully get to influence a little bit and we try and work through it. But the company spends a fair amount of effort trying to keep people on a path that will serve the health of our citizens as best it can.

[Ryan Crowe, executive]

Okay. Thank you, and thanks to everyone who dialed in today for your interest in Regeneron. We apologize for those remaining in the Q&A queue who we did not have a chance to hear from today. As always, the Investor Relations team is available to answer any or many questions you may have. Thank you once again, and have a great day.

[Operator]

Thank you. This concludes the conference. Thank you for your participation. You may now disconnect.