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Operator
Welcome to the Regeneron Pharmaceuticals Third Quarter 2023 Earnings Conference Call. My name is Shannon, and I will be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. Please note that this conference is being recorded. I will now turn the call over to Ryan Crow, Vice President, Investor Relations. You may begin.
Ryan Crow
Thank you, Shannon. Good morning, good afternoon, and good evening to everyone listening around the world. Thank you for your interest in Regenron, and welcome to our third quarter 2023 earnings conference call. An archive and transcript of this webcast will be available on our 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 and head of commercial. and Bob Landry, Executive Vice President and Chief Financial Officer. After our prepared remarks, we will open the call 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 forecasting guidance, revenue diversification, development programs and related anticipated milestones, collaborations, finances, regulatory matters, payer coverage and reimbursement issues, 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 quarterly period ended September 30, 2023, 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 measures will be discussed in today's call. Information regarding our use of non-GAAP financial measures and a reconciliation of those measures to GAAP is available in our financial results press release and our corporate presentation, both of which can be accessed on our website. Once our call concludes, Bob Landry and the Investor Relations 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
Thanks, Ryan, and thanks to everyone joining today's call. Regeneron delivered another strong quarter marked by continued execution across the company, which drove double-digit top-line growth and notable progress across our innovative R&D pipeline. Total revenues increased by 15 percent on a reported basis compared to the prior year quarter, primarily driven by Sanofi collaboration revenues and the entire global net product sales, which grew by 50 percent and 62 percent, respectively. To PICS and global net product sales were 3.1 billion, up 33 percent, reflecting strong growth across all approved indications. Non-GAAP net income per share, diluted share, increased by 4 percent, including an unfavorable 77-cent impact from acquired IP R&D. Today I will briefly discuss the launch of ILEA-HD, the progress we continue to make across our pipeline, and our latest thinking on capital allocation. I will then hand the call over to George, Mary, and Bob, who will provide additional commentary on our pipeline developments, commercial execution, and our financial results for the quarter. Starting with ILEA-HD, which is off to a great start. We launched in late August, shortly following FDA approval, and recorded $43 million of net product sales in the final six weeks of the quarter, which compares favorably to recent launches in the retinal disease category. Importantly, revenues were driven by strong initial demand with multiple reorders by distributors before the end of the quarter. In addition, Samples for ILEA-HD were made available shortly after the launch, enabling prescribers and patients to trial the product. Early ILEA-HD utilization has come from across the spectrum of wet age-related macular degeneration and diabetic macular edema patients, and momentum continues to build as positive real-world clinical experiences accumulate. We have also made significant progress establishing access and reimbursement, and we will continue to work on positioning ILEA-HD, the highest dose anti-VEGF therapy approved by the FDA, as the new standard of care in these retinal diseases. Moving on to the recent progress we have made advancing our pipeline, within hematology oncology and our CD3 bispecific platform, the BLA for odronextamab, are CD20 by CD3 bispecific in certain lymphomas was accepted by the FDA and granted priority review with a March 31st PDUFA date assigned. We also remain on track to submit a BLA next month for limvoseltamab, a BCMA by CD3 bispecific for multiple myeloma, with pivotal trials now underway for both programs to support potential accelerated approvals We are preparing for two commercial launches next year. Last week, we reported a potential breakthrough for patients with profound congenital hearing loss. The first patient enrolled in the Phase I-II CORD clinical trial of DB-OTO, an investigational cell-selective adenovirus-associated viral gene therapy designed to provide durable physiological hearing to individuals with profound congenital hearing loss caused by mutations in the otofuralin gene, experienced hearing improvement six weeks after treatment compared to baseline. We are looking forward to continued follow-up with this patient as well as enrollment of additional patients to further validate this gene therapy approach. While otofuralin gene deficiency is an ultra-rare condition, We are hopeful that we can expand our approach to gene therapy in the year to more common genetic causes of profound hearing loss. Finally, regarding capital allocation. While we continue to prioritize internal R&D investment, given the strength of our balance sheet and anticipated future cash flows, we believe we have the flexibility to take additional actions to drive shareholder value. Beyond our ongoing share repurchase program, we continue to actively pursue emerging science and innovative platforms that complement our core R&D strengths. In addition to the decibel acquisition, we announced last month an expanded research collaboration with Intelia, combining our proprietary antibody-targeted viral vector delivery technologies with Intelia's CRISPR platform to jointly explore in vivo programs outside of the liver for neurological and muscular diseases. We have always managed Regeneron with a focus on generating long-term returns, and we will continue to think carefully about how to strategically deploy our capital with the goal of delivering breakthroughs to patients and value to shareholders. In closing, we had a strong third quarter. The ILEA HD launch is progressing well. Our pipeline is delivering important innovations, and we continue to look at ways to efficiently allocate capital. With that, let me turn the call over to George.
Ryan
Thanks, Len. I'd like to start with our recent data update for ILEA-HD. At the EU Retina Meeting last month, we presented the two-year results from the PULSAR study in wet AMD, which demonstrated that the vast majority of ILEA-HD patients randomized to 12- and 16-week dosing intervals continued to sustain vision and anatomic improvements through 96 weeks. 78% of all ILEA-HD patients were able to maintain at least every 12-week dosing intervals for the entire two-year period, with 88% assigned to at least every 12-week dosing by the end of the two-year period. Similarly, 70% of patients randomized to every 16-week dosing at baseline were able to maintain at least that interval through two years, with 78% assigned to at least every 16-week dosing at week 96. Moreover, during the second year, many patients met the criteria for extension to even longer dosing intervals, with 47% meeting the criteria for at least 20-week dosing intervals, including 28% who were eligible for 24-week dosing intervals. The safety profile of IVHD remained consistent with ILEA, sustaining vision and anatomic improvements while maintaining such extended dosing intervals over two years in both wet AMD and DME is a remarkable advancement for the patients and their physicians. We believe that these results give ILEA-HD the potential to become the new standard of care for these retinal diseases. Moving to our immunology and inflammation pipeline. On Dupixent and COPD, our first pivotal study, Boreas, met the primary and all two secondary endpoints in a previously unprecedented success for a biologic, in a phase three study in patients with uncontrolled COPD and evidence of type two inflammation. Based on recent feedback from the FDA, in addition to the positive results from the Boreas study, a positive interim analysis of the replicate phase three notice study would enable an SBLI submission. The Independent Data Monitoring Committee will conduct an interim analysis of the notice study later this year. For InterPICCAMAB, our anti-IL-33 antibody, Phase 3 ARIFI 1 and 2 studies remain on track for readout and potential regulatory submissions in 2025, both that apicumab and dupixin could transform the treatment paradigm for COPD by leveraging their distinct mechanisms of actions in reducing different types of inflammation that contribute to COPD disease progression, and we look forward to the results of these studies. Moving to oncology and combinations with Liptiae. We remain on target and are currently enrolling our pivotal study of Leptio combined with our LAG3 antibody, Theanilamab, in first-line metastatic melanoma. We believe this combination may provide a significant advance for patients in this setting based on our encouraging earlier stage studies. At the annual ESMO meeting, we presented data from a Phase II trial of neoadjuvant Leptio treatment for resectable cutaneous squamous cell carcinoma, or CSCC, which demonstrated event-free survival for the vast majority, 89% of patients at one year. It is also noteworthy that of the 51% of patients who had a pathological complete response, none have since experienced disease recurrence. These results add to the growing body of evidence that Leptile and other checkpoint inhibitors may have utility in earlier stages of CSCC and other malignancies. To further explore this, we are conducting a Liptio trial in adjuvant CSEC for patients at heightened risk. We're also evaluating the combination of Liptio and Pheanelmim in adjuvant melanoma and plan to initiate a study of this combination in the perioperative melanoma setting as well. On to bispecifics. First in hematology oncology. We are pleased that out your next demand are CD20 by CD3 bispecifics was recently accepted for review by both the FDA and European regulatory authorities in relapsed refractory follicular lymphoma and diffuse large B-cell lymphoma. Based on the pivotal Phase II data from the ELMS II study, we have initiated a robust Olympia Phase III development program investigating Otranexamab as monotherapy as well as in combination with current standards of care in earlier lines of follicular lymphoma and DLBCL. We are looking forward to the pivotal data presentations from L2 later this year. We are also on track to submit our regulatory application for oligosaltamab, or BCMA by CD3 antibody, for relapse refractory multiple myeloma by the end of the year. This bite-specific may potentially offer best-in-class efficacy and convenience. The Linker MM3 confirmatory phase 3 study evaluating oligosaltamab monotherapy compared to a standard of care regimen is enrolling and studies in earlier lines of multiple myeloma and other plasma cell diseases will be enrolling soon. Finally, in addition to the ongoing Phase I combination study of Otranextamab and our CD22 by CD28 co-stimulatory bispecific, we're also on track to initiate a study of limvoseltamab with the corresponding co-stimulatory bispecific next year. Next, on to bispecifics for solid tumors, which are being investigated in combination with Leptio and other modalities. At ESMO, we shared initial clinical data for the combination of Ubimatumab or MUX16 by C3 bispecific with Liptile in advanced ovarian cancer. In these early data, promising durable responses were observed with Ubimatumab monotherapy as well as encouraging combination activity with Liptile with evidence of turnaround responses after initial progression on monotherapy lead-in in multiple patients upon addition of the Liptile. A randomized Phase II expansion study is ongoing to evaluate two active monotherapy doses of Ubimatumab with the lower dose also tested in combination with Liptile in order to optimize dosing and evaluate the potential added activity of Liptile. In addition, we're exploring Ubimatumab in multiple rare cancers that are known to express high levels of MUX16. In terms of our co-stimulatory bispecifics for solitumins, We are currently exploring multiple different CD28 costimulatory bispecific antibodies in early clinical trials in a variety of tumor settings in combinations with TIA or with corresponding CD3 bispecifics. We are continuing development of our PSMA by CD28 costimulatory bispecific in advanced prostate cancer, focusing on identifying the window of opportunity for maintaining the remarkable antitumor activity observed with this treatment so far while minimizing serious toxicity. In order to explore this, we have expanded enrollment in the PSMA by CD28 monotherapy cohort, and we'll soon initiate cohorts in which investigators will have an option of adding a low dose of simipalimab to the PSMA by CD28 treatment in certain patients. Moreover, we plan to initiate a trial combining PSMA CD28 with PSMA CD3, since based on preclinical data, CD28 COSTIMS with appropriate CD3 bispecifics may yield anti-tumor activity without severe immune-mediated adverse events. We also hope to progress an additional prostate-specific CD3 bispecific toward the clinic in the next year, which we may also combine with our PSMA costumatory bispecific. In terms of our MUC16 by CD28 costum in combination with Leptia and ovarian cancer, we're planning on presenting initial data by the end of the year. Regarding our EGFR by CD28 costum in combination with Leptia, We're planning on presenting updated dose escalation data in 2024. We will soon commence enrollment across eight tumor-specific expansion cohorts in the study, including colorectal cancer with or without liver metastases, as well as EGFR mutant non-small cell lung cancer. Now to genetic medicines. We and INTELLiO recently announced expansion of our research collaboration to include Regeneron's proprietary antibody-targeted delivery technology with the goal of expanding the reach of in vivo gene editing to neurological and muscle diseases. The aim of this expanded collaboration is to address a current bottleneck in genetic medicine, the inability to deliver a genetic payload beyond the liver. Our proprietary pre-clinically validated antibody directed AV approach will initially test two in vivo non-liver targets. Additionally, we in INTELLiA announced FDA clearance to start a pivotal Phase 3 trial of NTLA-2001 for the treatment of ATTR amyloidosis with cardiomyopathy. The first time in investigational in vivo CRISPR-based gene therapy editing is clear to enter late-stage clinical development in the United States. The trial is expected to initiate by year-end 2023. Moving to our NILAM collaboration. NILAM recently presented updated interim ALN-APP data in early-onset Alzheimer's disease Updated data show that single doses of ALN-APP achieve sustained, robust reduction in APP-alpha and APP-beta measured in the CSF up to 10 months after administration, as well as reduction of amylogenic peptides implicated in Alzheimer's disease and in cerebral amyloid angiopathy. Alnylam has also announced that a first patient has been redosed with ALN-APP in the multidose portion of the study currently proceeding outside of the United States. We in L9M plan to initiate additional clinical programs for neurodegenerative diseases, including for amyotrophic lateral sclerosis next year. Finally, I would like to highlight DB-OTO, or Otoferulin Gene Therapy, Regeneron's first clinical program for genetic hearing loss, which we developed over the last few years in collaboration with Decibel Therapeutics, a company we recently acquired. Last week, we announced the first preliminary results from this trial. A child who received an intraocular injection of DbOtO in one year experienced improvements in hearing tests in that ear through week six compared to baseline, including both auditory brainstem responses as well as behavioral audiometry. We are looking forward to continuing evaluation of this innovative approach in the ongoing trial for the ultra-rare otofural and gene-related hearing loss, as well as in other planned clinical programs which include more common forms of genetic hearing loss. In conclusion, Regeneron's R&D engine continues to grow and deliver differentiated late and early stage opportunities, and we are looking forward to progress in the remainder of this year and looking ahead to 2024. With that, I will turn it over to Mary.
Len
Thank you, George. I'm delighted to share details of our commercial performance in the third quarter, including very encouraging early signals for ILEA HD, as well as ongoing results from our inline brands. Starting with our anti-VEGF retinol franchise, Regeneron achieved 1.49 billion in total net sales for the quarter in the U.S. We were excited to rapidly launch ILEA-HD in late August following its U.S. approval, and total net sales for the quarter were 43 million. Early launch indicators have been very positive. Physician enthusiasm was extremely high prior to ILEA-HD launch, and that interest has translated into early use in a broad range of patient types across wet AMD and diabetic eye disease. It is noteworthy that physicians are prescribing ILEA-HD in recalcitrant, switch, and naive patients. We are already hearing anecdotal case reports from physicians whose recalcitrant patients are returning. Many of these patients have now been able to achieve drying that they were unable to obtain with other products. To accelerate this early launch momentum, our highly experienced team is rapidly advancing reimbursement and market access. We have confirmed paid claims from 100% of Medicare jurisdictions, and many large payers have recently published coverage policies for ILEA HD. This includes both Medicare Advantage and commercial plans. While early, the speed of ILEA HD coverage is significantly outpacing recent competitive launches. In addition, we continue to be on track to have a permanent J code by April 1, 2024, which we anticipate will drive additional uptake. These early reimbursement successes and positive physician experiences are being shared by prescribers with our team and more broadly with the retina community. These initial results bode well for the future of ILEA-HD and substantiate our belief that ILEA-HD will rapidly become the new standard of care across its approved indications. ILEA-HD's unsurpassed safety and durability demonstrated in clinical trials, coupled with prescriber confidence in ILEA's efficacy and safety record, is expected to drive continued category leadership. In summary, while the launch is still in early days, we are pleased with our progress and look forward to providing future updates. ILEA remains the category leader with 45% anti-VEGF share for the quarter in an increasingly competitive market. With over 70 million injections worldwide since launch, ILEA continues to demonstrate a strong and consistent safety profile, a key differentiator given retinal vasculitis and intraocular inflammation events with certain new products introduced in the retinal category. With both ILEA HD and ILEA, our formidable retina franchise is poured for sustained leadership. Next to Depixent. Global med sales grew 33% year-over-year to $3.1 billion, and U.S. med sales grew 30% to $2.4 billion. This impressive third quarter performance demonstrates Dipixen's clinical and safety differentiation across all approved indications, as well as its continued growth potential. In the third quarter, more than 50,000 new patients are taking Dipixen in the U.S. alone, and there are now more than 750,000 patients on Dipixen worldwide. In atopic dermatitis, Dupixent's largest indication, we continue to see more than 20% growth six years post-launch. Physicians have great confidence from the combination of efficacy, safety, and ease of use across all age groups, including as young as six months. Not only is there remarkable adherence once patients begin therapy, we also see Dupixent as being the clear treatment of choice for new patients with moderate to severe disease with significant growth opportunity. In asthma, Depixin is differentiated from all other medicines in the category based on its rapid and sustained effect on lung function, reduced exacerbations, and reduced corticosteroid use. In the U.S., Depixin continues to lead new patient prescriptions, and we are quickly approaching our goal of being the number one prescribed medicine for asthma. Together with our partner Sanofi, Regeneron continues to advance recent launches in the synophilic esophagitis and progenit nodularis, which are already meaningfully contributing to Vixen's growth. Since FDA approval, approximately 20,000 new patients with acinophilic esophagitis have been initiated, and demand is also robust for priconodularis, where Depixen is rapidly becoming the standard of care within a year of approval. We also look forward to offering Depixen to even more patients in the future with anticipated regulatory approvals of pediatric acinophilic esophagitis, as well as multiple near-term Phase III data readouts on COPD, chronic spontaneous urticaria, and bolus pentagoid. In summary, Dipixen continues to be a key driver of our growth, and we look forward to seeing its transformational benefits extended to even more patients with Type II inflammatory diseases across indications, demographics, and geographies. And finally, to Libtyo. Third quarter global net sales grew 59% year-over-year on a constant currency basis, to 232 million, with U.S. net sales up 52% to 144 million. Global growth was driven by our non-melanoma skin indications coupled with increased utilization in both monotherapy and chemotherapy combination settings in lung cancer. We're working to expand access and use in many additional countries following recent regulatory approvals. We continue to see a growing number of prescribers choosing Leptio when treating their patients. In conclusion, Regeneron's performance in the third quarter continues to deliver growth and value for patients and shareholders with opportunity for sustained growth. We're encouraged by favorable early indicators from the ILEA HD launch and continue to deliver compelling performance from our inline brands, including ILEA, Dipixen, and Liptio. Now I'll turn the call over to Bob.
George
Thanks, Marion. My comments today on Regeneron's financial results and outlook will be on a non-GAAP basis. unless otherwise noted. Regeneron performed well in the third quarter with execution across the business continuing to drive strong top and bottom line growth. Third quarter 2023 total revenues increased 15% year-over-year to 3.4 billion, primarily driven by sales growth for Depixent coupled with improving margins within the Sanofi collaboration as well as continued growth from Liptayo. Third quarter diluted net income per share grew 4% to $11.59 on net income of $1.3 billion. This included a $100 million acquired IPR&D charge incurred in the third quarter of 2023, which decreased growth by approximately 7 percentage points. Moving to collaboration revenue and starting with Bayer. Third quarter 2023 XUS ILEA net product sales were $872 million, up 6% on a constant currency basis versus the prior year. Total Bayer collaboration revenue was $377 million, of which $350 million related to our share of ILEA net profits outside the U.S. Total Sanofi collaboration revenue was $1.1 billion in the third quarter, up 50% versus the prior year, which included the final $50 million sales-based milestones. Our share of profits from the commercialization of Depixon and Kevzar was $863 million, an increase of 57% versus the third quarter of 2022, driven by Depixon's continued volume growth and improving margins. As we guided last quarter, third quarter reimbursements for the manufacturing of commercial supplies from Sanofi, a component of Sanofi collaboration revenues, declined sequentially, primarily due to the ongoing phase-in of a new higher yielding manufacturing process. In the fourth quarter, we expect a continuation of this trend with reimbursements for manufacturing of commercial supplies expected to be sequentially lower by approximately $40 million. Other revenues were $138 million in the third quarter of 2023, up 62% versus the prior year, and inclusive of $34 million of reimbursements from BARDA for ongoing development of our next-gen COVID antibody, as per the agreement announced in August 2023. Moving now to our operating expenses. Third quarter 2023 R&D expense grew 17% year-over-year to $954 million, representing continued investment in our expanding pipeline. R&D growth was primarily driven by higher headcount and related costs in funding our advancing late-stage pipeline, as well as increased clinical manufacturing activity. SG&A grew 14% from the prior year to $534 million in the third quarter, reflecting higher headcount and related costs and higher contributions to an independent, not-for-profit patient assistance organization. In the third quarter, we recorded acquired IPR&D of $100 million, reflecting the payment of a development milestone to our collaborator, El Nilem, related to the Phase I ALN-APP program in early onset Alzheimer's disease. This impacted both GAAP and non-GAAP EPS by approximately 77 cents. Third quarter COCM was $212 million, up 20% versus the prior year, driven by manufacturing costs associated with higher sales volumes from collaboration products, partially offset by lower Depixent manufacturing costs. Fourth quarter COCM is expected to be the lowest quarter of the year as we continue to transition to the higher yielding manufacturing process for Depixen. Now to cash flow in the balance sheet. Through the third quarter of 2023, Regeneron generated approximately $3 billion in free cash flow and ended the third quarter with cash and marketable securities less debt of approximately $13 billion. We continue to deliver on our capital allocation priorities. buying back $507 million and $1.9 billion of our shares in the third quarter in the first nine months of 2023, respectively, with $1.8 billion remaining authorized under our existing share repurchase program. Additionally, in the third quarter, we also announced and completed the acquisition of Decibel Therapeutics for approximately $100 million to strengthen our genetics medicine portfolio. As Len mentioned, We continue to evaluate opportunities to utilize our strong financial position and build upon our core competencies with the goal of delivering long-term shareholder value. Finally, we've made some minor changes to our full year 2023 financial guidance based on our year-to-date results and our latest outlook. Updating the guidance ranges for SG&A, R&D, gross margin, COCM, and capital expenditures. A complete summary of our latest full-year 2023 guidance is available in our press release issued earlier this morning. As we approach the end of 2023, I'd like to provide some commentary on the preliminary outlook for 2024. We expect continued improvements in profitability from the Sanofi collaboration, which will continue to accelerate the paydown of the antibody development balance, which as of September 30, 2023, was approximately $2.5 billion. Once this balance is fully repaid in the next few years, we expect a meaningful step up in our share of Sanofi collaboration profits. Separately, for Prowland, we expect significant category and competitive pressures that negatively impact U.S. sales in 2024. Moving to our operating expenses, consistent with our capital allocation priorities, we continue to invest in our growing internal R&D pipeline to drive long-term growth. As you just heard from George, Our pipeline continues to broaden while our infrastructure to support that growth continues to expand. R&D investment in 2024 will be driven by advancing strategically important late-stage programs such as our pheanilamab and Liptio combination, confirmatory Hemonc studies, including an earlier lines of therapy, our expanding collaboration in genetic medicines, as well as higher clinical manufacturing costs and the continued expansion of our R&D organization. With this in mind, We expect year-on-year R&D growth in 2024 to be in the mid-teens compared to our anticipated 2023 spend. We also expect to make additional investments in our commercial business and G&A functions to support the launch of ILEA HD, our planned T-Monk launches, and our international expansion. In conclusion, Regeneron continues to deliver strong results, and our robust financial position allows us to make strategic investments to drive this growth over time. With that, I will now pass the call back to Ryan.
Marion
Thank you, Bob.
Ryan Crow
This concludes our prepared remarks. We will now open the call for Q&A. To ensure that we are able to address as many questions as possible, we will answer one question from each caller before moving to the next. Shannon, can we please go to the first question?
Operator
Thank you. To ask a question, please press star 11 on your telephone and wait for your name to be announced. To withdraw your question, please press star 11 again. Please stand by while we compile the Q&A roster. Our first question comes from the line of Evan Siegerman with BMO Capital Markets. Your line is now open.
Evan Siegerman
Hi, guys. Thank you for giving me the question, and congrats on all the progress. So you have over $15 billion of cash in marketable securities on your balance sheet. Maybe, Bob, you could talk about how you think about capital allocation. I know interest rates are high, but how else can you spend that money to derive even higher returns for Regeneron shareholders?
George
Yeah, thanks, Evan. I mean, I know having dealt with you and certainly many of our investors, this is certainly an issue that we've been tasked to solve. Now, you know, obviously interest rates are a lot higher. So obviously what we're returning on that is certainly much better than the kind of the days of 2020 and 2021. But, you know, we kind of stick to our knitting here with regards to our capital allocations. You know, I mean, George just went through a plethora of obviously pipeline progress that we're making. Again, first and foremost, we're going to make sure that that is fully funded to the extent possible on that. And then with regards to acquisitions, you know, you heard with Len's intro, I mean, we continue to look at a lot of opportunities. Certainly the market that is out there on the biotech space is, you know, not in the greatest shape. as you know. So again, we think there are opportunities out there, but just because we have the means doesn't mean that we're going to kind of push into something that, uh, you know, may not give us an optimal result. It may not be kind of, you know, we, we like franchises as you've heard me say that before. So we need to make sure that it's the right fit with, uh, George and the team with regards to that. So we'll continue to do that. And, you know, you've seen our, our, our share repurchases of which, you know, we're $1.9 billion through, uh, through nine months. We've done that at a very good price with regards to how we're buying that back. We're very kind of scientific in our approach on that. We do think that stock continues to be undervalued given all the, uh, the pipeline progress and the catalyst that we have. So we're going to continue to push that button going forward. So we're going to stick to our knitting, but again, you know, as Len kind of alluded to, we are looking at a lot of opportunities that are out there. And, uh, if the one, if the right one makes, makes the necessary fit, then, uh, you know, we'll move forward. And, again, you kind of saw that with Checkmate and Decibel. Albeit those were smaller, but, again, those were nice kind of franchise fits into the business.
Ryan Crow
Thanks, Bob. Next question, please, Shannon.
Operator
Our next question comes from the line of Mohit Bansal with Wells Fargo. Your line is now open.
Marion
Great. Thank you for taking my question, and congratulations on the progress. My question is regarding the ulcerative colitis trial you are doing with Defixent. Could you talk a little bit about the rationale behind that? And are you enriching this trial in any way on the basis of eosinophil counts or any other markers there? Thank you.
Ryan
Yeah. So as you sort of hinted at, what we have realized is that all of the diseases that we are treating with Dupixent really are interrelated diseases that reflect a systemic disorder, that is upregulation of so-called type 2 inflammation, and in some cases it manifests in the lungs, in some cases in the skin, in some cases in the gut, and so forth all over the body, and in many cases, in most patients actually, in more than one location. And so in every disease that we're going after, including now, as you mentioned, in ulcerative colitis, We believe that there are a subset of patients who may be marked with type 2 inflammation in their gut. We are, as you say, indicating, utilizing biomarkers that might select out these patients. And so we're going to see whether a subset of ulcerative colitis patients are driven by this type 2 inflammation that's driving all the other related manifestations of this systemic disorder.
Ryan Crow
Thanks, George. Let's move to the next question, please, Shannon.
Operator
Our next question comes from the line of Chris Raymond with Piper Sandler. Your line is now open.
Chris Raymond
Yeah, thank you. Just maybe on COPD, I think the last time we talked to you guys on this, you were talking about the risk-reward on taking an interim look on notice, just given the alpha hit. looks like you've decided to take that step here but can you give us a sense of the alpha hit you are taking by doing this interim look and I mean just looking at Boreas with the 30% reduction in exacerbations it would seem you'd have a decent amount of room here if notice is tracking similarly but you know if you can give us any more color on how you're thinking about this you know the risk reward of this decision and assume you're going to press release that result of that if it's going to be the end of the year thanks
Leonard Schleifer
Yeah, we're not going to get into the details of the statistical niceties on how you do this. An alpha sparing approach is what's typical for an interim analysis. We'll work closely with Sanofi on how to do this in the most efficient manner possible and get you the information as appropriate when it appears.
Ryan Crow
Thanks, Len. Next question, please, Shannon.
Operator
Our next question comes from the line of Colin Bristow of UBS. Your line is now open.
Colin Bristow
Good morning and congrats on the quarter. Not surprisingly, we've been getting an increasing number of questions on your obesity assets. And I was wondering if you could just talk to your strategy and level of enthusiasm here and maybe frame out some of the timelines. You've got the GLP-75, the leptin receptor antagonist. I think you shared some pretty provocative data at ADA on the myostatin blocker and the actamine A blocker. Maybe you could just tell us your liver enthusiasm. Is this something that you're going to go full force and plan to have a major presence in down the road? Just some color there would be helpful. Thank you.
Ryan
Yeah. As you said, we're very excited about, I guess, two of the approaches that we've been taking in obesity. One is our unique collection of targets that we've either been the first to discover, like the GPR75 genetically identified target that came from our Regeneron Genetic Center, which is a very exciting new target for obesity, as well as our new approaches such as our leptin receptor agonistic antibody. One thing we're doing is moving those programs forward and understanding exactly what their potential is in the field of obesity. But as you said, right now the field which is dominated by these GLP-1 agonists also is recognizing increasing problems with this type of weight loss, meaning that about 40% of the weight loss is due to muscle loss. That means if you lose 20 pounds, eight pounds of that approximately on average will be muscle. Most patients will never get that muscle back. This can, over time, especially if patients go off these drugs and regain the weight as fat, can create potentially a very large public health problem and dilemma. So we also have been, as you pointed out, very active in the field of muscle preservation and muscle growth agents. We've developed some of, I think, some of the most exciting candidates in the field that have the ability to do this. And we are certainly considering how to study these muscle preservation and muscle growth agents in combination with existing weight loss agents to see whether we can maintain or even grow muscle in the setting of weight loss, hopefully perhaps increasing the quality of the weight loss, maybe even resulting in greater weight loss, But most importantly, making sure that the patients, in terms of their muscle and so forth, do a lot better. And we will be talking about our clinical trials in this area, we hope, very shortly. Okay.
Ryan Crow
Thanks, George. Next question, please, Shannon.
Operator
Our next question comes from the line of Tyler Van Buren of TD Cowan. Your line is now open.
spk08
Great. Thanks, guys, and congrats on the tremendous quarterly results. It's great to see the early ILEA HD sales, of course. And you mentioned that Naive and Switch patients are being treated. But are you seeing switches from Vibismo specifically? And to what extent are you guys sending samples out as we think about assessing additional demand beyond sales?
Len
Thanks, Tyler. So let me just, the first part, and, you know, the positive anecdotal case reports we're getting back really carry across the theme of better vision, better drying than they've seen with other anti-VEGF products. They also comment on very frequently the tremendous confidence that they have in the safety of ILEA and the experience over many, many years. In terms of the switches, it's early days. We are seeing switches from ILEA, as you would expect, and, of course, are the category leaders, so there are more potential patients to consider as well. But we are also hearing switches from Foresmab. We're hearing also switches from Avastin and other products in the category. And the early reports have been quite encouraging. To your other part of your question related to sampling, we do have a sampling program for ILEA-HD. It's intended to give physicians experience with ILEA-HD in an appropriate way. The program is constructed on an on-demand basis. We don't disclose the number of samples or things of that sort, and certainly that's not what you were asking. But I can share with you that we have seen a high conversion rate from practices ordering ILEA-HD samples and then subsequently placing orders of commercial products through commercial channels.
Ryan Crow
Thank you, Marion. Next question, please.
Operator
Our next question comes from the line of Terence Flynn of Morgan Stanley. Your line is now open.
spk15
Great, thank you. This is Max Gore on for Terrance Flynn. Thank you for taking our question. Quick one from us. Could you provide an update on the timing or relative implications of the biosimilar ILEA litigation with Mylan? Thank you.
Leonard Schleifer
Yeah, so we had a trial in West Virginia, a bench trial, and we are waiting for a decision from the judge. It's out of our control, and As soon as it comes, it will come. It's been several months, so it could come soon or not. It's one of those things where it's really beyond our ability to predict and control.
Ryan Crow
Thanks, Glenn. Next question, Janet.
Operator
Our next question is from the line of Carter Gould with Barclays. Your line is now open.
Carter Gould
Great. Good morning, and congrats on all the progress. Maybe a follow-up for Marion. Thanks for all the color on the commercial dynamics. for a high-dose ilea. One thing you didn't touch on as much, though, is sort of how maybe some of the step edit language has evolved. Is that sort of tracking in line with what you were seeing with standard dose ilea, or any broader commentary on how that's tracking relative to your expectations? Thank you.
Len
Sure. So as a quick reminder, as we get into payer mix, I'll remind everybody that these are approximates based on typical patterns in the category. It's a little bit different when you look at a product that just launched. but about 45% of our overall business is in Medicare fee for service. And as I mentioned to you in the call today, we've made great progress there, not only in coverage, which is the first step to get coverage, but then taking the extra step to make sure that claims are being paid. So we're seeing now that 100% of Medicare fee for service jurisdictions have coverage and demonstrated paid claims. When we go over to... Medicare Advantage, which is roughly about 25% of anti-VEGF category business and commercial, which is about 20. What we're seeing so far, and we are making good progress with payers, we're seeing that ILEA-HC is being positioned consistently with ILEA and other brands in the category. And there are plans, as you know, that have a step edit or utilization management. The good news is that ILEA-HD is being positioned consistently with ILEA and other brands. We don't see a differentiation there.
Ryan Crow
Okay, Marion. Thank you. Next question, Shannon, please.
Operator
Our next question comes from the line of Robin Karnoskis with Truist Securities. Your line is now open.
Robin Karnoskis
Hi, guys. Thanks for the question. The question on CSU, I know it's a big opportunity. Many patients are not controlled well with antihistamines, and you have a CRL. Is study C sufficient? Anything in particular you think the FDA is looking for? Is there a disconnect? Are they changing what they view for the bar for approval? What's your thoughts there? Thanks.
Ryan
Yeah. Well, as you know, we had one very positive study. We had a second study that actually had a P of 0.049, but for various statistical purposes just missed, meaning it's a predetermined statistical hurdle, but it's certainly... All the indicators are going in the right direction. And what the FDA indicated that they wanted to see the results of our ongoing study C, as we call it, to make their decision. And so what we're hoping is that that study, which is in the same population of the very positive initial study, remember the second study was in these recalcitrant patients who had failed Zolair, among other therapies, But study C is in the same population as our very first study A, the very positive study. And we're hoping that if we get consistent data in that study, that the FDA will consider it and look favorably upon it.
Ryan Crow
Okay. Thanks, George. Next question, Shannon.
Operator
Our next question comes from the line of Salveen Richter with Goldman Sachs. Your line is now open.
spk12
Good morning. Thanks for taking my question. With regard to your cancer portfolio, as we look to additional data coming out at ASH and, you know, the proof of concept we've seen so far, but combination data that we're looking to with Liptio, can you just talk to us about the optimization still required here and how you're thinking about positioning it in the context of emerging targets and competitive dynamics? Thank you.
Ryan
Yeah, we have... a very large collection of combination opportunities that we're very excited about. The first one that we hope has a chance of really crossing the finish line in a very significant way, in a very significant population, is our combination of Liptio in combination with Theanlamab, putting together these two checkpoints, the anti-PD-1 and the anti-LAG-3. And I think in this case, we believe we have evidence that we have the best-in-class type of activity with both agents separately, and as you've hopefully seen in our earlier stage clinical trials, the data suggests that when we put them together, we really can make a remarkable advance for patients in terms of the number of patients who respond and the extent of their progression-free survival. And we're now, as we announced, in a pivotal trial where we hope that we will, within the next year, perhaps be able to provide the results from that trial, which might confirm this remarkable advance for patients. If it works in this first-line melanoma setting, it really opens up the door to a whole series of other opportunities, both in related melanoma settings, such as an even earlier stage melanoma setting, such as the adjuvant and perioperative settings, but we could be moving to other cancers as well with that proof of principle. So that's the nearest term LIPTIO checkpoint combination approach. As you know, with our BI specifics, the combination opportunities there are also very exciting, either with LIPTIO or with each other. And we have, in that space, shown that our individual agents, the important thing is we have now validated so many of our individual agents as having, once again, the potential for best-in-class type of activity, whether it's our agent for myeloma or our CD20 bispecific in, for example, follicular lymphoma and so forth and so on. But we're also excited about our COSTM bispecifics. We've released the data about the incredible efficacy at early stages that we see in combination with Liptio, but that one That one is countered by concerns with immune-mediated adverse events that we're seeing in these patients. It is hard to dramatically increase the extent of immunotherapy benefit without having it associated with increased autoimmune-type reactions. We're working very hard on that, and we think, based on preclinical data, that the trick may be combining our COSTIMs with our CD3 bispecifics where we don't see these dramatic potential increases in the mechanisms that may lead to immune adverse events. So in summary, our checkpoint combinations are very near term. Our bispecifics as single agents have been validated and hopefully will be being considered by the FDA for approval in the relatively near future. And the combinations are beginning to demonstrate exciting opportunity, and we're trying to tune that in order to try to present the best efficacy safety profile for patients.
Ryan Crow
All right. Thank you, George. Shannon, please, the next question.
Operator
Our next question comes from the line of Brian Abrams with RBC Capital Markets. Your line is now open.
Brian Abrams
Hey, guys. Congrats on the good launch so far, and thanks for taking my question. You mentioned in the press release some impact of price on ILEA. I'm wondering if you could elaborate a little bit more on this, when you think this might stabilize and the extent that this might affect high-dose ILEA as well. Thanks.
Len
Sure, Brian. So I would comment that in an increasingly competitive category, there, of course, has been some pressure on ILEA. I'd also reflect that in 12 years in the market, it's really modest rebating and discounting if you look at the history of the brand. And of course, that on a brand that has never taken a price increase. But we will continue to be very much watching uptake of ILEA-HD, taking very responsible and appropriate and thoughtful measures on pricing. And certainly, as I reported to you early days, we're making some very strong progress in the marketplace in terms of making sure that physicians gain confidence in reimbursement of ILEA-HD as they initiate patients
Ryan Crow
Okay, thanks, Marion. Please move to the next question, Shannon.
Operator
Our next question comes from the line of Yatin Suneha with Guggenheim. Your line is now open.
Yatin Suneha
Hey, guys. Thank you for taking my question. Question on depiction. Could you maybe share your views on the newer mechanism, example, Oxford or perhaps a longer-acting version of depiction on the franchise? Maybe if you can talk about your efforts in terms of lifecycle management of depiction. Thank you.
Ryan
Yeah, maybe getting back to some of the comments that I made before. The collection of so-called allergic or type 2 conditions, which depicts and addresses, are all characterized by a systemic inflammatory problem increase in the so-called type 2 inflammation, which if you look at the science and literature, is really a vestigial pathway that largely evolved and was one of the most active parts of the immune system to fight things like fecal parasites, which are really not an issue now in the developed world. This part of the immune system should essentially, in the modern world, be entirely quiescent. It serves almost no role. The problem is it becomes unleashed abnormally to do things that it shouldn't be doing, like fighting allergens or attacking the skin or the gut in atopic dermatitis or eosinophilic esophagitis. What Dupixen does uniquely is that it controls, and the data now demonstrate this, the incredible effect that it puts this useless angry tiger back in the cage where it belongs. And that is why it has this incredible profile of not only efficacy but safety because what it's shutting down is it's shutting down a pathway that should be vestigial in the modern world but becomes unleashed and attacks all different parts of the body. We believe that any of this current competition that's ongoing doesn't share these remarkable features that give Dupixent its incredible broad efficacy across the spectrum of diseases with its unique safety profile. Because all of these other approaches, including, for example, the OX40 approach and so forth, are addressing different fundamental immune pathways that are important in the immune system's function to do a lot of actually useful things in the modern world. like, for example, fighting viral infections and cancer and so forth. So Dupixent really has a very unique profile, which if we can help explain and if all physicians and patients can understand it, make it the perfect drug for this condition. It uniquely blocks this vestigial pathway that gets out of control inappropriately and causes disease all over the body, Dupixent, shuts down this, what should be a vestigial pathway, and it helps disease, whether in the same patients it could be manifesting in the skin, in the lungs, in the nose, in the gut, and so forth, it shuts it down without really untoward effects with regards to the ability of the body to actually fight infections and so forth. In fact, if you look at our clinical studies and some of the data that we published, in many if not most cases, you actually see unbelievably reduced infections in the setting of the Dupixent treatment. Because what you're doing is you're putting the bad part of the immune system back under control and you're allowing the rest of the immune system to do its function. All of these other approaches are trying to attack critical parts of the immune system that have important other functions and they don't address the widespread problem that occurs systemically and causes all of these diseases. So as you've seen already with various agents, they may work in one of Dupixent's indications, but they don't work. They failed in other indications. And if they work, they also often come with the concerns about safety because they're designed to be immunosuppressive, which Dupixent is not.
Leonard Schleifer
So just to add a small point to what George, the eloquent explanation of why Depixen is such a special drug and the prediction that it would be safe because it's attacking this vestigial part of the immune system, you're looking at somewhere in the neighborhood of three-quarters of a million people on the drug, many more than that, so that have demonstrated the safety that is predicted by the science.
Ryan
Including in children, as we know, as young as six months, it's approved. There where it's been demonstrating not only incredible safety but incredible efficacy Great points.
Ryan Crow
Thank you, Shannon.
spk03
I think we have time for two more questions, please Our next question comes from the line of Dane Leon with Raymond James your line is now open Thanks for taking the questions and congratulations on strong quarter This is actually really two quick ones for me. I First one being, can you just comment whether you saw any impact from increased utilization of biosimilar anabizumab during the quarter on ILEA sales? A number of high-volume clinics had highlighted favorable margin opportunities from using more biosimilar anabizumab, which seems to be potentially a transient impact in use of some of the brands, but would be interesting in your commentary there. And then, We've gotten just a lot of inbounds in terms of ongoing patent litigation of ILEA. Could you just maybe state for us what your current expectation is for ILEA patent life and just any thoughts you have on how the ruling that we're awaiting could actually impact your base case? Thank you.
Leonard Schleifer
Yeah, so I'll cover the patents, and then Maren can cover any additional insight into the marketplace. On the patents, we're involved in litigation. There's a couple of key patents that have been involved in this case. that both relate to formulation as well as dosing. The base case is that, for us, we're assuming that the exclusivity will expire in May, but we will see what happens in the litigation, which could be an upside, obviously, for the franchise.
Len
And on the RenabizVab impact, you know, it's relatively early in their launches, but there hasn't been a notable impact to the category. The Lucentis biosimilar share is in the low single-digit area in the third quarter, and certainly the impact has been seen more relative to Lucentis, which has declining share, but certainly this is not extended to ILEA or ILEA-HD.
Ryan Crow
Thanks, Marion. We'll just take our last question, please, Shannon.
Operator
Our last question is from the line of Brian Scorny with Baird. Your line is now open.
Brian Scorny
Hey, thanks for taking the question. It looks like J&J had a really good first quarter of their myeloma by specific, so it definitely seems like there's a good demand there, but also an element of them having control of a lot of offerings for myeloma. So obviously, head to head superiority always dominates use in oncology, but with the initial launch of myeloma, year-by-specific next year. I'm just wondering what your strategy is for competing in the initial late line as a third-to-market. Do you think that there's differentiated enough data here to kind of take share, or is the focus really on generating data in earlier line of combos to kind of move up market share? Thanks.
Ryan
Well, of course it's both. We do believe that data rules the best both efficacy safety profile, but also convenience profile. And we will be continuing to show our evolving and maturing data, which we believe could result in best in class in terms of efficacy, in terms of response rates and complete response rates, in terms of safety, in terms of the frequency of cytokine release syndrome and so forth. and in terms of differentiation, in terms of mandated hospitalizations. So we will be continuing to present our data. Of course, we'll see exactly ultimately what gets in the label and what the FDA supports, but there's the potential here for best-in-class differentiation in terms of efficacy, safety, and convenience and schedule. And of course, as you said, we're also moving with, we think, an exciting program in earlier lines of therapy. And all of this is also going to be combined with the opportunities for our future combinations. We have a variety of COSTM bispecifics that we're excited about combining specifically with this agent in the plasma cell dyscrasia setting. So we think it's a very exciting opportunity, as you said, Unfortunately, there's a large opportunity out there because there's a lot of patients that are still in need. I think that if you have the best agent for late-stage patients, a lot of people will want to use it. And then if we figure out the best program to demonstrate how it can be utilized in earlier-stage patients, that can certainly enhance that opportunity, let alone if we come up with one of our magic combos that really takes it to the whole next level.
Ryan Crow
Okay, thanks, George, and thanks to everyone who dialed in today and for your interest in Regeneron. We apologize to those remaining in the queue that we do not have a chance to hear from, but as always, the investor relations team here is available to answer any remaining questions you may have. Thank you once again, and have a great day.
Operator
This concludes today's conference call. Thank you for joining. You may now disconnect.
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