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spk04: Welcome to the Regeneron Pharmaceuticals First Quarter 2023 Ernst Conference Call. My name is Josh 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 Crowe, Vice President, Invest Relations. You may begin.
spk05: Thank you, Josh. Good morning, good afternoon, and good evening to all of you who are listening around the world. Thank you for your interest in Regeneron and welcome to our first quarter 2023 earnings conference call. An archive of this webcast will be available on our Invest Relations website shortly after the call ends. Joining me today are Dr. Leonard Schleifer, Co-Founder, President, and Chief Executive Officer, Dr. George Onkopoulos, 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 call is looking to save in the 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 10Q for the quarterly period ended March 31, 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, which can be accessed on our website. Once our call concludes, Bob Landry and the IR team will be available to answer further questions. With that, let me turn the call over to our President and Chief Executive Officer, Dr. Len Schleifer.
spk03: Len? Thank you, Ryan, and thank you to everyone joining today's call. Following our significant achievements in 2022, Regeneron is off to a good start in 2023. Highlighted by important regulatory and pipeline advances, commercial execution, and prudent capital allocation, all of which position better the company to deliver sustainable long-term growth and shareholder value over time. George, Marion, and Bob will cover details of our first quarter performance in a few moments. In the meantime, I would provide an update on our goal of continuing to grow our business while simultaneously diversifying our revenue and earnings streams, which is part of our long-term vision for Regeneron. We have made substantial progress toward achieving that goal. Over the past four years, while total revenues have nearly doubled, ILEA accounted for only 57% of total revenues in the first quarter of 2023 compared to 88% of total revenues for the year 2019. Driven primarily by the growth of Dupixent, our Sanity collaboration accounted for 25% of our total revenues in the first quarter of 2023 compared to only 6% of our total revenues in 2019. We expect this trend of revenue growth along with diversification to continue. For example, assuming the approval and successful launch of a Fliverset 8 milligrams, which has a June 27th, Purdue for date, ILEA 2 milligrams is expected to become a smaller share of our revenues, while the Fliverset 8 milligrams is expected to contribute to overall revenue growth. In addition, Dupixent remains in a high growth mode with global net product sales up 40% on a constant currency basis compared to the prior year quarter, driven by growth across all five approved indications. We believe the positive phase three results for Dupixent in a subpopulation of COPD patients with evidence of type 2 inflammation, as well as the promising results for our IL-33 antibody, Hittitechmab, and former smokers represent additional significant opportunities to accelerate revenue growth as well as diversification. Our oncology profile is also starting to make a meaningful contribution to our top line with last year's acquisition of full global rights to Lib-Tio and the recent launch of Lib-Tio in combination with chemotherapy in advanced non-small cell lung cancer. Moreover, we believe that Cianomab, our lag 3 antibody in combination with Lib-Tio has the potential to become an important therapy in both melanoma and non-small cell lung cancer where we have already advanced to pivotal studies. We are also quite excited about the emerging clinical profile for Limboseltamab, our BCMA by CB3 bispecific, updated data for which will be presented at the upcoming ASCO annual meeting. We remain on track to submit a VLA seeking accelerated approval in late stage myeloma later this year. We continue to invest in our research and development engine and expect it will deliver new differentiated medicines that will drive organic growth over time. Our broad development pipeline of nearly three dozen programs spans many different therapeutic areas and modalities, notably our co-stimulatory bispecifics in cancer, our early pipeline in cardiovascular metabolic diseases, as well as our collaborations with our Nylem, Intelia, Desipel and others are expected to drive medium and long-term revenue growth, profitability and diversification. Before handing over to George, I'd like to take a moment to recognize the contributions that Dr. Roy Vagelos has made to Regeneron over the nearly three decades that he has served as our board chair. Over the years, he has provided invaluable guidance and he continues to inspire us as we work to turn world-class science into medicines. Roy will retire from the board after his current term ends next month. At that time, in addition to our current roles at the company, George and I will be appointed by the board to serve as co-chairs and Christine Poon, a member of Regeneron's board since 2010, will be appointed as the board's lead independent director. With that, let me turn the call over to George. Thank you,
spk09: Ron. The first quarter of 2023 delivered multiple significant milestones for Regeneron and for our collaborations, from the positive Dupixin phase 3 COPD data, to progress in our oncologic pipeline, as well as exciting new landmarks from our genetic medicines programs. Starting with Dupixin, in March, together with our Sanity collaborators, we announced that Dupixin was the first new mechanism of action treatment to produce statistically significant and clinically meaningful results in a phase 3 trial for COPD in over a decade. Our Boreas trial enrolled COPD patients with moderate to severe disease and evidence of type 2 inflammation. Dupixin treated patients demonstrated a clinically meaningful 30% reduction in exacerbations, a significant improvement in lung function, as well as quality of life benefits, an impressive trifecta in a potential paradigm changing treatment for this deadly disease. We are looking forward to presenting the detailed Boreas results in a late breaking presentation at the upcoming American Thoracic Society meeting later this month. We also plan to discuss these exciting results with regulatory authorities and expect to report results mid-next year for the replicate phase 3 notice study. I would remind you that we are also trying to address an overlapping COPD population with our IL-33 antibody, which is in phase 3 studies based on positive phase 2 proof of concept data. This approach is further supported by genetic analyses from our Regeneron Genetics Center, which demonstrated association of loss of function in mutalucin-33 with reduced COPD risk. Similar genetic analyses supported the role for a Dupixin benefit in COPD. Borea COPD data indicate that Dupixin can help even more patients beyond the five current FDA approved indications and diseases caused or exacerbated by type 2 inflammation, including atopic dermatitis, asthma, chronic liner sinusitis with nasal polyps, eosinophilic esophagitis, and prurigo nangularis. We are also expecting an FDA decision for Dupixin for chronic spontaneous urticaria on October 22, 2023, and we are continuing to tailor Dupixin development to patients with other type 2 inflammatory diseases most likely to be responsive to this medicine. Moving to oncology. With the progress of our late and early stage pipeline, we are looking forward to several important milestones this year, starting with Leptile. In addition to expanded use in lung cancer, Leptile was recently added to the NCCN guidelines for neoadjuvant treatment of CFCC. The Leptile US label is also recently updated with more mature CFCC and BCC data, supporting its differentiated clinical profile in these tumor settings, and satisfying all post-marketing commitments that require full approval in these indications. Regarding our exciting new combinations with Leptile, starting with the Anomab, our lag 3 antibody, for which we are planning a broad pivotal program spanning several cancer medications. These efforts were triggered by our robust and confirmed data in first-line metastatic melanoma patients, which will be presented in further detail at ASCO, suggesting that the Theanomab-Leptile combination could produce about double the response rates, with longer progression-free survival than anti-PD monotherapy standards. Based on this, we have already initiated pivotal trials in metastatic and adjuvant melanoma, and we will start a study in perioperative melanoma in the second half of the year. In addition, based on promising data in small patient cohorts, we started a seamless phase 2-3 pivotal study for treatment of metastatic non-small cell lung cancer, and we will soon start a phase 2 study in the perioperative setting. Next, device specifics for solid tumors, which are being investigated in combination with Leptile. Earlier this year, ASCO's GU represented initial positive first in human data for a PSMA by C28 co-stimulatory bispecific in combination with Leptile in advanced prostate cancer, a tumor type considered immunologically cold and largely unresponsive to -PD-1 therapy alone. Over the next 12 months, we plan to present updated PSMA by C28 data in more patients, some of which will have been prophylactically treated with our anti-IL6 receptor antibody, SuriliMAP, to potentially reduce the severity of the new med-aid side effects while maintaining or improving anti-tumor activity. Also during this time frame, we plan to present data in advanced ovarian cancer for both our MUX-16 by CD3 bispecific and our MUX-16 by CD28 co-stimulatory bispecific, as well as data in several tumor types from our EGFR by CD28 co-stimulatory bispecific, all in combination with Leptile. Our hematology oncology pipeline continues to advance. In a new presentation at upcoming ASCO annual meeting, we will present updated data for Limbosalcomab, our BCMA by CD3 bispecific tested in late-line multiple myeloma. We believe these data will show that Limbosalcomab has the best in-class potential with differentiated efficacy, safety, and a favorable dosing schedule in the competitive environment of relapsed or frothy multiple myeloma treatment candidates. We remain on track for regulatory submission in the United States in the second half of this year for Limbosalcomab. For Odrinectomab, our CD20 by CD3 bispecific, we are on track to complete US and EU regulatory submissions for both relapse or refractory follicular lymphoma and diffuse large B-cell lymphoma in the second half of this year. Odrinectomab in late-line relapse or refractory follicular lymphoma has a potential best in-class efficacy profile, and our optimized step-up dosing regimen has improved Odrinectomab's safety profile without impacting efficacy. Also, we have initiated a first in-human study of our CD22 by CD28 costumatoid bispecific in combination with Odrinectomab in relapse or refractory DLBCL, which we hope could further improve upon the anti-cancer benefit for these patients. Now to genetics medicines, starting with our collaboration with L-myelin on siRNA therapeutics. Just last week, we in L-myelin announced an important update for our L-myelin APP program in early onset Alzheimer's disease. For the first time, an RNAi therapeutic demonstrates sustained silencing of a pathological gene in the central nervous system in a clinical trial. In the earnings call this morning, our L-myelin collaborators provided additional details on these results. Our siRNA approach aims to prevent production of amyloid precursor proteins as opposed to clearing existing amyloid plaques after they have already formed, providing a new way to potentially address Alzheimer's disease, which will still have a devastating impact on patients and their families even with the emergence of amyloid clearing antibodies. Patients treated with single doses of L-myelin APP experience dose-dependent, rapid, and sustained reduction of up to 90 percent in APP production as assessed by biomarkers in cerebrospinal fluid. The safety and tolerability profile with single dosing is encouraging so far. While the multi-dose Part B portion of the studies on partial clinical homes in the United States, due to findings observed in prior non-clinical chronic toxicology studies, Part B has already received regulatory approval to proceed in Canada, where the majority of the Part A clinical trial patients have been enrolled. Detailed results from the study will be presented in an upcoming medical meeting. We are looking forward to advancing additional development candidates for the many other neurodegenerative diseases that currently have few or no therapeutic options, such as other targets for Alzheimer's, as well as for ALS or Lou Gehrig's disease, Parkinson's, and Huntington's. In addition to these exciting developments in central nervous system diseases, we are continuing our progress in developing and developing treatments for ALS, including our broad and multi-pronged approach to develop treatments for NASH, or neonalcoholic steat cell hepatitis. We are enrolling a phase two study of ALN, HSD, and NASH patients with genetic risk factors, continuing clinical development of ALN PNP, and we are planning to progress additional more recently genetically validated NASH targets as well. Finally, I would like to highlight our recently announced collaboration with biotherapeutics, Discover, Develop, and Commercialize regulatory T cell therapies for autoimmune and inflammatory diseases. This collaboration will bring together our industry-leading technologies for the discovery and characterization of fully human antibodies and T cell receptors, as well as our additional biologic candidates with Sonoma's pioneering approach to developing and manufacturing gene-modified T-reg cell therapies. In conclusion, Regeneron's R&D engine truly continues its activity in both late and early stage pipelines. Before turning the call over to Marion, I would also like to thank Roy Fajals for serving as a role model for all of us as Regeneron, as well as for so many others across the industry. I hope that we can continue to live up to the high standards that Roy has set over his distinguished career. With that, I will turn the call over to Marion.
spk15: Thank you, George. Our first quarter performance demonstrates ongoing leadership across multiple therapeutic categories. Taken together, our in-market brands anticipated near-term launches, an extensive development pipeline uniquely positioned Regeneron to expand our leadership across multiple disease areas. First quarter ILEA U.S. net product sales declined 6% -over-year to $1.43 billion. On a sequential quarter basis, ILEA U.S. net product sales decreased 4%, reflecting the favorable impact of higher demand volume offset by lower sequential wholesaler inventory levels, higher sales-related deductions, and increasing competitive pressure. ILEA captured approximately 70% brand share in the first quarter. Based on presentations at scientific meetings, the retina community has expressed increasing enthusiasm about Regeneron's portfolio, with the Aflibrisab -milligram-piducidate now seven weeks away. ILEA is the well-established gold standard anti-veget treatment, and Aflibrisab 8-milligram has the potential to be as paradigm changing as ILEA when it was introduced more than a decade ago. In clinical trials, Aflibrisab 8-milligram demonstrated improvements in visual acuity with less frequent injections, and a safety profile comparable to ILEA, exactly what retina specialists have told us they need in the next generation medicine. Lunch preparations are well underway, and we look forward to bringing this important treatment option to patients following FDA approval. On to Leptile, which is foundational to Regeneron's oncology portfolio, first quarter global net product sales grew 49% on a constant currency basis, reaching 183 million, which includes 6 million from Sanofi transition sales in international markets. In the U.S., net sales grew 39% to 110 million. Leptile continues to lead the market in both advanced CSCC and advanced BCC as demand volume increases. Following last November's FDA approval of Leptile in combination with chemotherapy for first-line advanced non-small cell lung cancer, new patients starts have accelerated as physicians adopt Leptile as an important new treatment option, initiatives to raise brand awareness and improve access of driven share gains in both the academic and community settings. Outside the U.S., Leptile net sales grew 67% on a constant currency basis to 73 million, driven by steadily increasing demand and additional country launches. The European Commission recently approved Leptile in combination with chemotherapy for PD-L1 positive lung cancer, and we are in the process of securing access and reimbursement for this new indication. Turning to Depixin, first quarter global net sales grew 40% on a constant currency basis to 2.49 billion, and the U.S. net sales grew 43% to 1.9 billion, with notable volume growth across all approved indications. Driven by its outstanding efficacy and safety profile, Depixin is the number one prescribed biologic for new patients in all five of its approved indications. On the topic of dermatitis, Depixin is the leading systemic treatment based on its unique mechanism of action, clinical profile, and real world experience. Strong prescribing trends continue across moderate and severe disease and across approved age ranges. There's also significant opportunity to further increase market penetration as Depixin is uniquely positioned to provide an effective, safe, and convenient treatment for patients six months and older. In Crogonogelaris, Depixin is the only FDA-approved systemic treatment. Launch uptake is progressing well, and we anticipate ongoing growth as we leverage our dermatology commercialization capabilities for patients in need. Across the competitive asthma space, Depixin continues to gain market share as naive and biologic switch patients are initiated on treatment. Depixin also continues to capture the majority of market demand in nasal polyps with increased prescribing from allergists and ENTs. Our Stenocelic esophagitis launch is exceeding expectations. In the first year following US approval, more than 11,000 patients have initiated therapy, demonstrating extensive unmet patient need, and our strong launch execution and collaboration with Sanofi. Both gastroenterologists and allergists have embraced Depixin as the new standard of care, setting meaningful improvements in disease symptoms and quality of life for those now on therapy. A new patient campaign is underway to raise awareness of the scientific advancements in treating a Stenocelic esophagitis. Outside the US, Depixin's net sales were $587 million, growing 30% on a constant currency basis, driven by growth across approved indications and new geographies. Recent European approvals of the Stenocelic esophagitis, Paragonogularis, and atopic dermatitis in young children are expected to contribute to Depixin's ongoing growth. In summary, our commercial portfolio continues to diversify across many serious medical conditions and delivered solid results in the quarter. Moving forward, we are well positioned to serve even more patients, driven by the strength of our existing portfolio, coupled with anticipated launches that have the potential to advance standards of care. With that, I'll turn the call to Bob.
spk08: Thank you, Marion. My comment today on Regeneron's financial results and outlook will be on a non-GAP basis, unless otherwise noted. Regeneron performed well in the first quarter of 2023 with solid financial results. First quarter total revenues increased 7% year over year to $3.2 billion, as Depixin and Liptio contribute to increasingly diversified revenue and earnings streams. First quarter diluted net income per share was $10.09 on net income of $1.2 billion, which included a previously announced $0.42 impact of acquired IPR&D. Beginning with collaboration revenue and starting with Bayer, first quarter 2023 XUSI-LiA net product sales were $847 million, up 4% on a constant currency basis versus first quarter 2022. Total Bayer collaboration revenue was $357 million, of which $332 million related to our share of Iliya net profits outside the U.S. Total Sanofi collaboration revenue was $798 million in the first quarter and grew 26% versus last year's first quarter, which included a $50 million sales milestone that did not recur this year. Our share of profits from the commercialization of Depixin and Kevzar was $637 million, an increase of 53% versus the prior year. We continue to see increasing profitability from our antibody collaboration and expect further margin expansion as we begin to realize drug substance yield improvements from a new Regeneron developed manufacturing process for Depixin. Finally, we recorded gross collaboration revenue of $222 million in the first quarter for our share of gross profits from XUS sales or RonaPrieze related to a previously signed contract. We do not expect to record any additional revenue from RonaPrieze in 2023 absent a new contract. Moving now to operating expenses, first quarter 2023 R&D expense increased 28% year over year to $960 million as we continue to invest in our pipeline to drive organic growth. The increase in R&D was primarily driven by higher headcount and related costs and funding of the company's growing pipeline, which now encompasses approximately 35 programs in clinical development and more than 15 ongoing late stage studies with additional study starts expected this year. These late stage programs include our expanding Fianna Lab development program, upcoming phase three studies and early reliance for our HEMONC assets, as well as ongoing development programs for Depixin and Iterpecumab for which we now record our full 50% share of development costs as a result of the Liptio transaction. SG&A expense increased 32% year over year to $515 million due to higher contributions to an independent -for-profit patient assistance organization, higher headcount and related costs in the impact of the Liptio transaction. First quarter 2023 COCM was $249 million, up 26% versus last year due to increases in shipments of ex-US commercial supplies of Priline to Sanofi in manufacturing costs for Depixin. Reimbursements of these production costs are recorded as part of other revenue and Sanofi collaboration revenue respectively. Shifting now to cash flow and the balance sheet. In the first quarter of 2023, Regeneron generated $1.2 billion in free cash flow. We ended the first quarter with cash and marketable securities, less debt of $12.3 billion. We have continued to strategically deploy our cash to deliver on our capital allocation priorities, which are focused on investing and innovation, both internal and external, as well as returning capital to shareholders. We purchased nearly $700 million of our shares in the first quarter, with $3.1 billion remaining under our existing authorizations as of March 31. Additionally, as George discussed, we announced the collaboration with Sonoma Biotherapeutics investing $75 million through an upfront payment and equity investment to add a new approach to our scientific capabilities. I'd like to conclude with some select updates to our financial guidance and outlook for 2023. We're updating 2023 COCM guidance to be in the range of $820 to $880 million, an increase of $90 million at the midpoint, reflecting increased shipments of ex-US commercial supplies for Prylin and Depixin to Sanofi. Importantly, these are anticipated incremental expenses will be reimbursed by Sanofi, generally resulting in a neutral impact to Regeneron's operating profit. Approximately half of the incremental $90 million of reimbursements from Sanofi are expected to be recorded as Sanofi collaboration revenue, with the balance recorded as other revenue. As a result, we now expect 2023 other revenue to be higher than 2022 other revenue. For modeling purposes, second quarter 2023 other revenue is expected to be the lowest of the 2023 quarters, with the vast majority of the remaining other revenue to be recorded in the second half of this year. We are also updating our 2023 gross margin to be between 89 to 91 percent. The change in expected gross margin is primarily driven by an unfavorable change in product mix, as well as an increase in the startup costs associated with our new fill-finish facility located in upstate New York. Finally, we are lowering our guidance for our effective tax rate to 10 to 12 percent, reflecting the benefit of higher than previously anticipated stock-based compensation deductions. In conclusion, Regeneron continues to deliver robust financial results in the first quarter of 2023, and the company remains well positioned to drive further growth in the remainder of the year and beyond. With that, I will now pass the call back to Ryan.
spk05: Thank you, Bob. Josh, that concludes our prepared remarks. We'd now like to open the call for Q&A. To ensure we are able to address as many questions as possible, we will answer one question from each call before we make it to the next. Please go ahead, Josh.
spk04: Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone and wait for your name to be announced. To withdraw your question, please press star 1-1 again. Our first question comes from Mohit Bansal with Wells Fargo. You may proceed.
spk21: Great. Thank you very much for taking my question. Maybe, Marian, if you could elaborate a little bit on the ILEA Webismo dynamic at this point a little bit. Given the weakness in the quarter, you did mention that Webismo is taking some shares. So if you could elaborate on where this share is coming from, is it more of a switch, or do you think it is also some new patient start, and your confidence level in terms of flipping the situation once high-dose ILEA comes along? Thank you.
spk15: Sure. Very happy to comment. As I noted, as we're reporting on the quarter performance on a sequential basis, we did see with ILEA, if I look at a sequential quarterly basis, we did see with ILEA a net product sales decrease of 4%. As I mentioned, it was driven by a number of factors. Certainly, competitive pressure is one, but we also reflected on while we had slightly higher demand volume, it was offset by lower sequential wholesaler inventory levels and overall higher sales-related deductions. Specifically, as it relates to competitive pressure, I would say that this is overall competitive dynamic in the anti-vegetive category, not something that we would necessarily identify with a particular product, more the totality of competition. I will comment that in the quarter, we certainly maintained a 70% branded share and over at approximately, I believe it was a 46% share in the overall anti-vegetive category. So certainly, standard of the cure with ILEA, and very importantly, we look forward to launching a FlirberSepp® 8-milligram, as I mentioned, now is about seven weeks away.
spk05: Thanks, Mary. And Josh, next question, please.
spk04: Thank you. Our next question comes from Robin Karnoskas with Truist. You may proceed.
spk16: Great. Thanks for taking my question. So just some questions on lag three, and thinking about the first line melanoma market, I think you're going to be having data relatively soon. So what, I guess it's a multi-part question. What is the bar for success, do you think, for the combination to be competitive? And when you think about penetrating into the checkpoint monotherapy buckets for first line melanoma, can you help us to understand how big these buckets are so we can actually model this opportunity better? Thanks.
spk09: Well, as we've already reported based on our two confirmatory cohorts, we are seeing remarkable overall response rate increases over the PD-1 standard alone, almost doubling with much longer PFS. If we get anywhere near, anywhere near these numbers, along with a satisfactory safety profile, which we have seen a favorable safety profile in the small studies, but if we reproduce or come anywhere close to reproducing these results, we believe that this will establish an entirely new standard of care for this disease. And as we all know, the first line melanoma opportunity is very large, but we're also moving, you know, laterally and earlier and so forth into many additional applications within the melanoma opportunity itself. We're going, we're already now in adjuvant and entering neoadjuvant studies. We'll also be going to other cancer settings, including lung cancer and so forth. So we consider this a major opportunity and we can, you know, we can only hope to, if we approach the data that we've already seen in our earlier studies, it really has a chance to make a huge difference for these patients.
spk05: Thanks, George. Josh, please move to the next question.
spk04: Thank you. Our next question comes from Tyler Van Buren with TD Cowan. You may proceed.
spk13: Hey there. Good morning. Thanks for the question. For high dose Ilea, is there anything left to do on the regulatory front and have you guys started labeling discussions yet? And forgive me for the follow-up, but just briefly for housekeeping and related to your response to the first question and prepared remarks, Marion, can you quantify the impact of the lower Ilea inventory for the quarter?
spk03: So on the regulatory update, we don't comment on ongoing stuff. I like to say, yeah, we're looking forward hopefully to the action of the FDA on June 27th and along promptly thereafter. Marion, you can comment on the inventory.
spk15: Sure, Tyler. I can give you the detail there. So while still within the normal range of inventory related to your question on Ilea in the quarter, in the normal range is five to ten days, our inventory levels were approximately three days lower at the end of the first quarter of 2023 compared to the end of the fourth quarter of 2022. And when you do the calculation on that, as I'm sure you all will do, that's a negative impact in the first quarter net sales of approximately $70 million.
spk05: Thanks Marion and Tyler. Moving to the next question, please, Jeff.
spk04: Thank you. Our next question comes from Terrence Flynn with Morgan Stanley. He may proceed.
spk11: Thanks, Dennis, for taking the question. I was just wondering on the commercial footprint for Duke Picsant here, given the potential for another indication with COPD, if you could talk about any additional footprint or spend that's required there and again, maybe just how to think about leverage on the forward. Thank you so much.
spk15: Sure. Very happy to comment. And, you know, as we think of Duke Picsant and all the different therapeutic disease areas and specialists that we cover, you know, with some indications, there certainly is an amazing and wonderful synergy. And you give an example with COPD launch potentially. And obviously today we're in market with our asthma indication and with nasal polyps. As we look forward at COPD, it's a really important launch and indication, you know, to help patients in a way potentially that, you know, as George described, hasn't been achieved ever for this population. So we have the opportunity to use our existing footprint specifically in covering respiratory specialists, pulmonologists, but we'll also evaluate very closely with Sanity, as you've seen us done in dermatology indications, where we might need some additional coverage and where the synergy is adequate. And we'll be very disciplined and very thoughtful about that. But you can be assured that we'll make certain that we appropriately give commercialization effort to such an important indication as COPD.
spk03: It is interesting just to add a little bit to that, Marion, that the allergists seem to have really understood the concept of type 2 inflammation and the fact that type 2 inflammation is not a collection of individual unrelated diseases, it's a collection of related diseases. And I was speaking to an analysis the other day, he said that when you take an asthma patient, if you look carefully, many of them will have nasal polyps. And if you talk to dermatologists, they're beginning to understand that when they're treating atopic dermatitis, people who have concomitant asthma, for example, they get a benefit there. So I think the depiction really is kind of unique. And we are talking to the main doctors, including the allergists, the dermatologists, and the pulmonologists, with some of the ENT, as Marion said, we're covering them all and many of them are covering multiple diseases.
spk15: Yeah, you know, I'll add to the depiction as well. So this will be a very important future area for helping patients.
spk08: And with regards to your question on leverage, first off, welcome back, nice to have you back on the team. You know, you'll see with the issuance of our 10Q this morning, with regards to our share of the antibody alliance, you know, we're going to pick up quarter, you know, year over year for the quarter, roughly 300 basis points. And again, that's half the economics on the on the transaction. So we're beginning, you know, to see really great leverage into Marion's comment that should continue on with the COPD indication.
spk03: Obviously, we work very closely with Sanofi on all of these. And I believe it's fair to say they're equally excited about the potential for the future of depiction in all the current and hopefully future indications.
spk05: Thanks, everyone. Next question, please, Josh.
spk04: Thank you. Our next question comes from Christopher Raymond with Piper Sandler. You may proceed.
spk06: Thanks. Maybe another depiction question if you don't mind it. Len, I know you don't talk about regulatory interactions. But you know, I when you had the COPD data, I think, you know, the signal that I got from you guys that seemed to be pretty strong was that you were hoping to have some discussion with the agency on Boreas alone. Just kind of maybe can you map out how you anticipate communicating, you know, the results of that discussion with FDA once it happens? And then maybe a second part of that question is our KOL checks have been pretty consistent when we asked them about this data. They're very impressed. But one of the things we've heard consistently is that, you know, this cutoff for Sanofi is greater than 300 is sort of arbitrary and that this drug would see, you know, maybe add value to patients with the Sanofi council's lowest 200 to 250. Just maybe your thoughts on this and how you anticipate to sort of take advantage of that. Thanks.
spk03: Yeah, well, let me start with the regulatory aspect. The obviously what we're all staring at is an incredibly positive study in a phase three setting, where as we've mentioned, that we not only improve people's exacerbations, but we also improve their lung functions, and their lung function, and their quality of life, and all these other measures that were all part of the statistical hierarchy. So when you have a very robust study like that, and you have, I don't know how many patients we currently have, but it's a huge number, a very large patient commercial database, and so many indications, I think Sanofi and Regeneron concur that this is something that we should be discussing with the FDA to see how they feel about whether or not there's a potential filing. We don't have any update for you. If there's something once we have that meeting, if there's something definitive, I'm sure Sanofi and Regeneron will figure out a way to communicate that. In terms of cutoffs and what have you, I think it's a little premature to talk about that, other than to say you stick with what you brought to the trial, which is a cutoff of 300, and that's where you commercialize. Whether future work, one can look at in other studies, that's something obviously we'll think about, but I remind you, as George and both Mary mentioned, the IL-33 antibody gives a larger, although somewhat overlapping population potentially, so we really could cover many, many, many patients with great opportunity to help people with what has been really a very unfortunate progressive loss of lung function.
spk15: When to your comment, you were talking about numbers of patients. I can fill in there that as of March worldwide, we had over 600,000 patients on depiction in 57 countries.
spk03: Right. So that's a lot to be post-mortem experience of the product. Absolutely.
spk05: Next question, please.
spk04: Thank you. Our next question comes from Brian Abrahams with RBC Capital Markets. He may proceed.
spk20: Hey, good morning. Thanks for taking my question. Shifting gears, you recently reported with your partner, APP Data in Alzheimer's, and I'm curious what this proof of principle potentially opens up beyond this indication, how quickly you can expand into some of the other neurodegenerative diseases that you mentioned, and your level of confidence overall in the safety of the program. Thanks.
spk09: We think that the data were really game changing. This is the first time in human history that one has been able to use this very exciting sRNA technology within the brain and silence to a very high degree, higher than expected levels, an important pathological gene. Obviously, this could have important implications for Alzheimer's itself, but as you point out, the application goes way beyond that to every neurodegenerative disease, but also other types of CNS diseases as well. We have a number of programs that we're working with on that, and we have an exclusive relationship with them on all of these CNS targets, and we're trying to expedite a lot of them based on the work into the clinic, and we're also trying to expedite many of our programs that are behind as well. So we really think this opens up an entirely new way of addressing a whole assortment of brain diseases and neuropsychiatric diseases, not just neurodegenerative diseases. We're in exciting times. We have to go cautiously. We have to hope that the initial results in terms of the safety profile and so forth hold up. We're all in the early days, and we don't know for sure, but the low doses in which we saw this very marked reduction in the target give us a lot of hope that we can have a sufficient therapeutic window that will be applicable to these large variety of disease that could potentially be addressable by this modality.
spk03: So I just want to add to that two things. Streaming on a different channel, I think you might find some further data being discussed by our friends at Allen Island, which will speak to not only impressive result, but the durability of the effect. And one of the other things I want to come on is really to echo something George said. The recent amyloid plaque clearing antibody results by Lilly, previously by Biogen, are really quite important. As George said, even with the advent of them, there's still going to be a tremendous burden of Alzheimer's disease. But what the data seem to be speaking towards is that the process is ongoing, is that the pathologic role of amyloid is not over, and as George said, having another way, perhaps upstream, stopping the production of amyloid, maybe even a more advantageous way to deal with the ongoing process that amyloid seems to be generating, which is what the antibody data I think seems to be speaking towards.
spk05: Okay, thank you. Josh, next question, please.
spk04: Okay. Thank you. Our next question comes from Salveen Richter with Goldman Sachs. You may proceed.
spk18: Good morning. Thanks for taking my question. So with regard to ILIA high dose becoming the larger share of revenue on the Ford here, can you give us any color here on discussions with payers and how to think about formulary fit?
spk15: So Salveen, we are actively involved in all aspects of launch preparation, and certainly that includes all elements and levers associated with pre-market activities and then getting ready for the launch activities. We do have in place a very sophisticated market access payer and pricing team, and at the appropriate times, they most definitely will be involved with payers and other organized customers that will be important in our launch efforts. Additionally, this is a customer base that we know very well from our over-decade experience with ILIA. So we look forward to potential FDA approval and launch activities and working with all of our customer stakeholders. I'll also mention again the importance in the retinal space of the key opinion leaders and prescribers and the enthusiasm they have for a product that really can be a game changer for their patients in terms of visual acuity, duration, and the safety profile they've come to know with ILIA. So we're very enthusiastic and look forward to the launch opportunity and we'll be ready.
spk05: Okay, next question please.
spk04: Thank you. Our next question comes from Akash
spk19: Tewari with Jeff Rees. You may proceed. Hey, thanks so much. So just to clarify the moving parts on US ILIA, there was a 5% market share loss, a 70 million inventory impact, and then lower price. Any color on what the net price impact was on the quarter and how it should evolve in the back half of 23? And additionally, should we expect ILIA market share to hold at 70% going forward or potentially start to grow again as high-dose ILIA launches? Thank you.
spk15: So let me take some of the items and others may want to jump in here too. But first, I would say that some of the calculation related to market share shift is not exactly correct. There was some decline in the quarter but not to the height that you mentioned. When I look at market shares through the entirety of the first quarter period, then it's described it is a more competitive market, a variety of obviously competitors, very low cost, and others. And overall, ILIA performance is in a very strong situation as we look today to planning for our future portfolio and the Flibbersep 8-milligram launch. As to the specifics of pricing and calculation to the net, I can't give you specifics on that number, but I do think that we gave you some transparency on the overall item related to inventory, overall competitive pressures, and then our preparation for our next launch in the category coming up shortly, we hope, following FDA approval.
spk03: Obviously, as Marion mentioned, on a sequential basis, demand was modestly up. So obviously, we were upset by the factors that Marion referred to.
spk05: All right. Next question, please.
spk04: Thank you. Our next question comes from Chris Schott with J.B. Morgan. You may proceed.
spk10: Great. Thanks so much. I have a question on the IL 33 and COPD. I guess it's the success you've had with your kind of study design and results with DUPICS and increase all your confidence in that program and just, I guess, maybe just elaborate a little bit on how you see kind of those two interactions, kind of interacting as we think about the space overall. Thank you.
spk09: Yeah. We are more optimistic, obviously, that all of our decisions, all of the data that led us to do the particular study and the particular population of patients in COPD with DUPICS was made based on a lot of factors. And we also had, from our Regeneron Genetic Center, very strong human genetic evidence suggesting that it would have activity, particularly where we actually store activity. And so all of that gives us confidence, since we choose the same criteria, the same approaches, and so forth, to plan and design our IL 33 study, certainly the fact that everything that went into one and it all worked so remarkably well gives us confidence that the same approaches will lead to success with the IL 33. The results with DUPICS were really outstanding, as we've already mentioned. Not only a clinically meaningful reduction in exacerbations, but we hit all these other important endpoints, most importantly, improvement in lung function, as well as you rarely hit these quality of life improvements, unless you have a really active agent that the patient can really feel the difference for their function and for their quality of life. With IL 33, the genetics is very strong. We have a phase two study in the subgroup that we're doing the phase three study in. It was in that group we had demonstrated a 42% reduction in exacerbations in the phase two study. This will be an overlapping population with our DUPICS population. We think we already have a chance to really make a huge difference for this high unmet need population that really has had no new mechanism of action of drugs brought to help these patients for a very, very long time. We have one with DUPICS and we're hoping to hit another one with IL 33, and this could make such a huge difference for these patients who have been suffering for so long without much hope. It could really make a big difference for this population.
spk03: Dr. Robert R. Reilly I just wanted to repeat, maybe George said it probably two or three times, but maybe it's even worth saying a fourth time. In yesteryear, the way you did drug development is you identified a target based on some biology or what have you. You did your phase one and phase two and you hoped your phase two was an indicator for how your phase three was going to turn out. Obviously, that's how it is still done today. What George mentioned is that we can layer on top of it in a unique way our genetic insights and look and validate and say, is it reasonable to expect that if you block a certain target that you're going to have a beneficial effect? Is that target associated with the disease you're treating? I know George said it three times, I think it's worth saying a fourth time. That really gives you added confidence that's uniquely regenerated in many respects, how we can get this genetic information. People ask this a lot. If you think about the number of people that have been sequenced in the world, George can come and have done. I know we've sequenced a large part of them and coupled that with all this medical, anonymized medical information. We use that in so many ways, not only to identify targets, but to validate the work we're doing in specific targets, specific diseases. George, how much have we done?
spk09: We've seen about half of all the humans who have been sequenced.
spk03: That's a large database of millions and I think that that is what you're hearing is that that's why we had more confidence perhaps than others did with Diffixant and with now with anti-anial 33.
spk09: Since one expands it just let you know how it works. What we do is we identify genetic variations that mimic the blocking of a drug or exacerbation of this type 2 pathway. What we showed for Diffixant, for the genetic variations that mimic Diffixant, those people were protected from COPD, particularly the type 2 COPD patients. Whereas increased activity of the IL-413 pathway was associated with more disease. Obviously, that turned out to be the case. Human genetics is a very, very powerful predictor. We've done the same thing as Len said with IL-33 where we have genetic variation that mimics blocking the pathway or exacerbating the pathway. As Len said, this is one of the secrets to our ability to have high success rates in our studies is we use that as a criteria to make our decisions going forward.
spk05: Thank you. Next question, please, Josh.
spk04: Thank you. Our next question comes from Yaten Suneo with Guggenheim Securities. You may proceed.
spk12: Hi, this is Eddie Hickman for Yaten. Thanks for taking our question this morning. I was wondering if you could talk about the draft guidance from the FDA on the anti-VEGF trial designs and if that impacts your outlook on the high dose program at all. Thank you.
spk02: I don't think that has any impact on us on our program. Thank you, Len. Next question, please.
spk04: Thank you. Our next question comes from David Reisinger with SCV Securities. You may proceed.
spk14: Thank you. Yes, thanks very much. I guess I'll just go straight to the question. Len, you had mentioned in your opening remarks the ongoing diversification of the company's revenues away from ILIA. Could you please discuss your expectations for ILIA US sales growth in the year term, including the total ILIA franchise prospects after Regeneron launches the HD? Thank you. Let
spk03: me go right to the answer
spk14: since
spk03: you went right to the question. We don't give future guidance on specific quantitative measures of our sales. On a qualitative basis, Marion has said that we're anticipating that the combination of ILIA and 8 milligrams of Fliversep will be a growth franchise over time for the company.
spk05: Okay, thank you. Next question, please.
spk04: Thank you. Our next question comes from Art Austin with Oppenheimer. You may proceed.
spk17: Great, thank you. Just a quick question on Linmo Seltemab. Ash, you presented a phase one data, and these were your dose rating, I guess, data. Really interesting data you presented to Ash. Ask her what should we expect to see? Will it be dose expansion data and then any duration also on the patients from Ash? Then what would FDA like to see before you can go ahead and submit the application? Thank you.
spk09: Well, I think you're going to actually see an update on our pivotal phase two data, the actual data that with a little bit more maturing with the further update, we will be hoping to submit to the FDA for our BLA. So the data will be very close. We think that data will even get better as it matures because, as we all know, response rates and so get better with time as you follow these patients. But these data are going to show what we believe are the potential to have best in class efficacy as well as safety in a favorable dosing schedule based on the results that we'll show from our physical study at the upcoming ASCO.
spk05: All right, thank you, George. I think we have time for two more questions.
spk04: Thank you. Our next question comes from Carter Gold with Barclays. You may proceed.
spk01: Good morning. Thanks for taking the question. Sorry to belabor. Ilya, I guess just simply, was the pricing pressure that you guys highlighted in Q1, was that a seasonal dynamic or would you characterize it as that or something more permanent around that market landscape going forward? Thank you.
spk03: Before Mary answers that, I just want to come back to the BCMA story a little bit because it's one that I'm particularly excited about. The bi-specific field, which was initiated by Regeneron in terms of using bi-specifics, I think we were the first to put the bi-specific into patients, has obviously become a very clouded space and it's sometimes hard to differentiate what you've got compared to what the competition has and you look at somebody claiming one thing and then you're claiming another and so on and so forth. But if you take a dispassionate view, I think for the BCMA by CD3 program, you can really see a differentiated molecule and a potential to be best in class. Antibodies are not all created equal. Bi-specifics are not all created equally. You do see differences. Clinical trial programs are not all created equally. This is one I really encourage you to take a very careful look at and compare. Now there was some question on Ilea and Marin. You're going to answer
spk15: that. Sure. Carter, getting back to your question on the competitive dynamic and pricing pressure, I think if we look at the anti-vegeta category and look at it over time, go back multiple quarters, there has been increasing competitive pressure and that does then have a corollary to some extent on pricing dynamic and that would go forward. But I just want to share and remind all that in the category, in the vegeta category, what really is rewarded is product profile. And as we look at a product like Ilea that launched and was a game changer in the category, that was its profile not being the least costly. There's been a low cost alternative, very low cost alternative for a very, long time, but it was the product profile that made the difference for prescribers and patients. So that will always be a very dynamic to look at going forward and certainly has strong interest for prescribers as we bring a new product into the marketplace following FDA approval with a syllabus of 8 milligrams. But to your point, pricing pressure will continue in this category. But what's most important is product profile and the clinical attributes that the patient experiences.
spk05: Thanks. Last question, please.
spk04: Thank you. Our last question comes from Evan Ziegerman with BMO. You may proceed.
spk07: Hi guys. Thank you for squeezing me in. I'd love to have you expand on some of the feedback you've been hearing from physicians regarding the 8 milligram dose. Maybe some color to how they plan on using it, assuming approval come June. Thank you.
spk15: So of course the updates on actual prescribing will be even more important as the product comes into the marketplace and physicians have an opportunity to use it and select patients. We obviously have done a lot of work with our medical team, looked at the clinical data with a specialist and to give you an early answer to your question, I think there's opportunity for a variety of patients that are deemed to be appropriate candidates. And there's a range. Certainly when physicians are considering new patient starts, it's very attractive. We obviously have a strong portion of patients that are naive to ILEA today, but in the future the question becomes why wouldn't you start a new patient with a product that gives you all the visual acuity benefits and safety of ILEA, but it also gives you that durability and duration because you know obviously physicians know their patients are anxious and you know don't like to have more injections in the eye than they need to. Similarly you might have a patient that's very well controlled on another product. Maybe ILEA, maybe another product in the anti-degif category, but you'd like to give them that opportunity for duration and maybe in some cases if the product is in another area of the anti-degif category, improve visual acuity and duration. So I would say it's the combination of interest for patients who might be broadly anti-degif category switch patients or the potential for new patients as well. I hope that helps and look forward to the day when we can give you specifics from market experience.
spk05: Thank you Marion and thanks to everybody who dialed in and for your interest in Regeneron. We apologize to those remaining in the queue that we did not have a chance to get to. As always the IR team is available to answer any remaining questions that anyone may have. Thank you once again and have a great day everyone.
spk04: Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.
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