The paragraph provides an introduction to Regeneron Pharmaceuticals' Fourth Quarter 2024 Earnings Conference Call. The operator, Tawanda, welcomes attendees and introduces Ryan Crowe, the Senior Vice President of Investor Relations. Ryan then acknowledges participants and outlines the availability of an archive and transcript of the call on the company's Investor Relations website. He introduces key executives present on the call, including Dr. Leonard Schleifer, Dr. George Yancopoulos, Marion McCourt, and Chris Fenimore. The paragraph explains that the call will include prepared remarks followed by a question-and-answer session, and warns that forward-looking statements will be made, which are subject to various risks and uncertainties.

The paragraph provides an overview of Regeneron's current financial and strategic status. It mentions the company's plan to file its Form 10-K with the SEC and highlights how it will discuss both GAAP and non-GAAP financial measures during their call. Dr. Leonard Schleifer, the President and CEO, reports that Regeneron experienced a strong fourth quarter in 2024 with a 10% revenue growth, driven by key products like Dupixent, Libtayo, and EYLEA. The company also made significant investments in its pipeline, leading to progress in several key programs. The call will include updates on the pipeline, commercial performance, and financial results, with contributions from George, Marion, and Chris, respectively. Dr. Schleifer plans to discuss performance drivers, pipeline opportunities, and capital allocation.

The paragraph highlights Regeneron's focus on science and innovation, resulting in significant product approvals and future potential. The company has developed a strong pipeline of approximately 40 product candidates and maintains a valuable DNA sequence linked healthcare database. At a recent conference, Regeneron discussed 10 promising pipeline opportunities with a market potential exceeding $220 billion. The company expresses strong confidence in its future, supported by robust early-stage assets and technology platforms. The quarterly results highlight Dupixent's success, with over 1 million patients treated globally across seven indications. In the U.S., Dupixent is a market leader and is well-positioned for growth, especially with its COPD launch and upcoming potential indications. Regeneron, along with partner Sanofi, has achieved significant progress in securing coverage and reimbursement for Dupixent in COPD.

The paragraph discusses the ongoing strategies and developments for EYLEA HD and other products by Regeneron. EYLEA HD is poised to strengthen its market position in the anti-VEGF category by introducing more convenient administration and expanded indications, promising increased uptake later in the year. The paragraph also notes that Libtayo became a blockbuster product in 2024, with plans to expand its applications in skin and lung cancers and seek regulatory approval for its use in high-risk adjuvant cutaneous squamous cell carcinoma. Additionally, the company anticipates regulatory approvals for linvoseltamab and odronextamab in treating various cancers, while also expecting significant data releases from other pipeline programs like the AERIFY studies for itepekimab in COPD.

The paragraph outlines Regeneron's plans and expectations for upcoming clinical data releases in 2024, including their fianlimab-libtayo combination for metastatic melanoma, a C5 antibody siRNA combination for generalized myasthenia gravis, and a potential weight loss enhancement strategy for obese patients on semaglutide. Additionally, the company announces a new quarterly cash dividend program and a $3 billion share repurchase authorization, bringing their buyback capacity to $4.5 billion. These moves, aimed at returning capital to shareholders, reflect confidence in future cash flows and seek to expand potential shareholder interest. Despite these shareholder returns, Regeneron emphasizes its ongoing commitment to investing in business development and innovation.

The paragraph discusses Regeneron's promising advancements in its research and development efforts, highlighted by presentations at the JPMorgan Healthcare Conference. The company is focusing on breakthroughs across various therapeutic areas such as oncology, COPD, and obesity, with plans to advance multiple programs, notably Factor XI antibodies, to Phase 3 trials. A key development is EYLEA HD, which in recent studies, demonstrated effective vision improvements in retinal vein occlusion with an eight-week dosing interval, maintaining its best-in-class clinical profile. Regeneron intends to submit a supplementary BLA for EYLEA HD and seek FDA approval for flexible dosing options. These initiatives aim to meet unmet needs and support long-term growth.

The paragraph discusses the recent advancements and upcoming developments in therapies by the company. EYLEA HD aims to offer flexible dosing with its prefilled syringe, potentially receiving FDA approval for extended dosing intervals. Dupixent has been approved in Europe for treating eosinophilic esophagitis in very young children, highlighting its safety profile. The FDA is reviewing a new application for Dupixent to treat chronic spontaneous urticaria, which could be a significant advancement in a decade, alongside a submission for bullous pemphigoid. The company is also exploring a new opportunity in COPD with itepekimab, an interleukin-33 antibody, with key results expected later in the year. Additionally, promising initial data from the Dupixent and linvoseltamab trial could lead to breakthroughs in treating severe food allergies by targeting IgE, the main cause of allergic reactions.

Last month, a proof-of-concept study showed promising results with over 90% reductions in IgE levels, and the trial continues to enroll patients with updates expected in 2025. Additionally, positive data for Libtayo in high-risk adjuvant CSCC demonstrated a 68% reduction in disease recurrence or death compared to placebo. This contrasts with KEYTRUDA's previous failure in a similar setting, emphasizing variability within the same class of antibodies. Data will be submitted to the FDA in 2025 and presented at a medical meeting this year. The combination of Libtayo with fianlimab in melanoma trials suggests additive benefits over PD-1 monotherapy without increased safety issues. Results from ongoing trials versus KEYTRUDA are expected later this year, potentially boosting confidence for this combination in other cancers. The paragraph concludes with a mention of CD3 bispecifics.

The paragraph discusses the resubmission of the Biologics License Applications (BLAs) for two bispecific antibodies, Linvoseltamab and odronextamab. Linvoseltamab, targeting BCMAxCD3, is highlighted for its potential best-in-class status in treating relapsed or refractory multiple myeloma due to its high efficacy and favorable safety profile. The strategy for Linvoseltamab includes exploring monotherapy and novel combinations in earlier therapy lines. Odronextamab, targeting CD20xCD3, has also shown promising efficacy in relapsed/refractory follicular lymphoma, with an FDA decision expected in 2025. Initial trial results showed a 100% complete response rate in previously untreated follicular lymphoma patients, compared to the standard regimen's 67%. The company is pursuing a comparative Phase 3 trial against standard care and has achieved significant enrollment. Additionally, progress is noted for their CD28 co-stimulatory bispecifics in solid tumors.

The paragraph discusses the development of innovative medical treatments, focusing on two main areas: combination therapies with PD-1 blockades and CD3 bispecifics, and a Factor XI program for anticoagulation. The Factor XI program employs two antibodies, REGN7508 and REGN9933, targeting different domains of Factor XI to offer improved blood clot prevention and reduced bleeding risk. REGN7508 shows enhanced efficacy compared to current treatments, while REGN9933 offers a lower bleeding risk, making it suitable for high-risk patients. Positive proof-of-concept data from trials supports further development into Phase 3 studies. Additionally, there's mention of ongoing work in obesity treatment involving both clinical and preclinical programs.

The paragraph outlines several key developments in medical research and clinical trials. The Phase 2 COURAGE study is examining the addition of trevogrumab to semaglutide for weight loss maintenance, with results expected later in the year. The Regeneron genetics medicine pipeline is focusing on a siRNA plus antibody approach for complement-mediated diseases, showing promising results in paroxysmal nocturnal hemoglobinuria and generalized myasthenia gravis, with further pivotal results anticipated. A Phase 3 program has started for geographic atrophy in age-related macular degeneration. Additionally, the DB-OTO gene therapy program for genetic hearing loss in children has shown positive outcomes, with continued data updates expected.

The paragraph discusses Regeneron's advancements in several areas. It highlights ongoing collaborations with Alnylam on new siRNA CNS programs targeting conditions like Parkinson's and Alzheimer's. The paragraph also emphasizes Regeneron's leadership in structured big data, specifically in high throughput human DNA sequencing, which has enabled the creation of a vast DNA-linked healthcare database. This leadership is further evidenced by their involvement with the UK Biobank Pharma Proteomics project and a new collaboration with Truveta, potentially expanding their database significantly. These efforts aim to revolutionize healthcare analytics and drug discovery. The paragraph concludes with optimism about Regeneron's future, citing an innovative pipeline and anticipated pivotal data readouts by 2025.

Regeneron's fourth quarter performance highlighted strong leadership in therapeutics, with a focus on optimizing growth opportunities for 2025. EYLEA HD and EYLEA had combined U.S. net sales of $1.5 billion in the fourth quarter, capturing 46% of the anti-VEGF market, with full year net sales increasing by 1.4% to $6 billion. Despite elevated inventory levels affecting EYLEA HD sales, the company is focused on increasing its adoption, with upcoming launches of a prefilled syringe and two-year label updates in the second quarter. Long-term data supports EYLEA HD's potential as a new standard for retinal diseases. Additional FDA approvals for new indications and dosing flexibility are anticipated later in the year.

In recent clinical trials, EYLEA HD demonstrated the ability to extend dosing to every 12 weeks, offering improved vision for RVO patients compared to the standard four-week dosing. There is anticipation for the FDA to approve a flexible four-week schedule for certain patients, potentially giving EYLEA HD the most adaptable dosing among anti-VEGF treatments. Despite the launch of an aflibercept biosimilar, EYLEA’s fourth-quarter net sales reached $1.2 billion, driven by strong physician demand, although increased inventory levels are expected to impact 2025's first-quarter sales negatively. Meanwhile, Libtayo achieved blockbuster status with global net sales of $1.2 billion in 2024, experiencing significant growth due to its success in treating non-melanoma skin cancers and lung cancer. Looking ahead, there's optimism for its approval in high-risk adjuvant CSCC in the U.S., which could benefit around 10,000 patients.

Dupixent continues to show strong performance in treating Type 2 inflammatory diseases, with more than 1 million patients benefiting across seven global indications. Atopic dermatitis, asthma, and nasal polyps have become blockbuster treatments, each generating over $1 billion annually. In the fourth quarter, worldwide net sales increased by 15% to $3.7 billion, with U.S. sales rising 10% to $2.7 billion, partly boosted by the COPD market launch. Despite new competitors, Dupixent remains a preferred choice for atopic dermatitis, due to its effectiveness in targeting IL-4 and IL-13 pathways. The recent U.S. approvals for eosinophilic esophagitis and prurigo nodularis are showing strong market uptake, and COPD approval in over 30 countries has begun promisingly. The medication has broad insurance coverage, with nearly 85% of commercial and 90% of Medicare patients in the U.S. having access. Dupixent is now included in the global gold treatment guidelines for COPD as the sole recommended biologic option.

The paragraph discusses Regeneron's strong financial performance at the end of 2024, highlighting a 10% year-over-year revenue growth to $3.8 billion, driven by increased Sanofi collaboration revenue, strong sales of Dupixent and Libtayo, and modest growth for EYLEA products. Fourth-quarter net income per share was $12.07, with a full-year total revenue of $14.2 billion, reflecting a 10% growth excluding Ronapreve revenues. Earnings per share for 2024 grew 4% to $45.62. Sanofi collaboration revenues for the fourth quarter were $1.2 billion, with Regeneron's share of collaboration profits increasing by 18%, mainly from Dupixent's volume growth and improved collaboration margins. The company is also preparing for a potential April launch of Dupixent for chronic spontaneous urticaria, pending FDA approval, which would be the first new targeted therapy in over a decade for U.S. CSU patients. Regeneron sees significant growth opportunities in 2025 and beyond.

In 2024, Regeneron reported strong financial performance, with its share of profits from a collaboration increasing to 20% of total antibody net sales. The Sanofi development balance decreased by $700 million from the previous year to $1.6 billion, with full reimbursement expected by 2026, which should boost future revenue and cash flow. Ex-U.S. net sales of EYLEA and EYLEA 8 mg with Bayer rose to $888 million, while total collaboration revenue was $377 million. Operating expenses also increased, with $1.2 billion in R&D supporting various clinical programs, and $681 million in SG&A attributed to new product launches and international growth. Regeneron achieved an 86% gross margin, $3.7 billion in free cash flow, and ended the year with $15.2 billion in cash and marketable securities net of debt. The company spent $2.6 billion on share repurchases, significantly increasing this activity in the fourth quarter.

The company is prioritizing its capital allocation by heavily investing in R&D to stimulate long-term growth, seeking business development opportunities, and returning capital to shareholders. They announced a $3 billion increase in share repurchase authorization, bringing the total to $4.5 billion. Additionally, they introduced a quarterly dividend of $0.88 per share, starting March 20. Confident in their growth prospects and cash flow durability, they anticipate increasing R&D spending to $5-$5.2 billion in 2025 to support an expanding pipeline, including late-stage programs. SG&A expenses in 2025 are expected to rise by 3% to $2.55-$2.7 billion, driven by oncology launches. Gross margin on net product sales is projected at 87%-88% due to a changing product mix and investments in manufacturing efficiencies.

The article discusses Regeneron's financial expectations for 2025, projecting collaboration manufacturing costs between $1 billion and $1.15 billion, driven by increased Dupixent volumes. These costs are generally neutral to net income due to reimbursement. Capital expenditures are expected to range from $850 million to $975 million, primarily for expanding R&D facilities and increasing manufacturing capacity in the U.S. and Ireland. The effective tax rate is anticipated to be between 11% and 13%. The article highlights Regeneron's strong financial performance in 2024 and its commitment to delivering long-term shareholder value. During a Q&A session, a caller inquires about expectations for sales erosion in the EYLEA franchise, seeking insight into whether current market expectations are reasonable amid competitive pressures and potential growth opportunities.

The paragraph discusses Marion McCourt's overview of the market outlook for EYLEA HD, emphasizing its strengths such as expected additional FDA approvals, new delivery systems, and strong clinical data that enhance its durability. Despite competitive pressures, including the presence of a biosimilar, the company maintains a strong market position with EYLEA HD achieving $1.2 billion in net sales and a 46% category share in the fourth quarter. Ryan Crowe invites the next question, leading to Tyler Van Buren from TD Cowen asking about the reasoning behind the company's early initiation of a dividend before settling the Sanofi development balance and whether there are plans to increase the dividend over time. Chris Fenimore responds, indicating confidence in their financial strategy and timing.

The paragraph discusses Regeneron's capital allocation strategy, highlighting a shift from focusing solely on share buybacks to also initiating dividends, thereby attracting a broader base of shareholders who prefer dividend-yielding investments. This change aims to provide more flexibility and appeal to funds with a dividend mandate. Additionally, in response to a question about the Libtayo adjuvant CSCC readout, the importance of achieving overall survival in addition to disease-free survival (DFS) is addressed. While there are few survival events in early-stage patients, confidence is expressed in the attractiveness of the data package. From a commercial standpoint, there is potential for about 10,000 U.S. patients to benefit from this indication.

In the paragraph, Salveen Richter asks about the impact of EYLEA HD inventory on the previous quarter and the market dynamics involving the biosimilar Pavblu. Marion McCourt explains that there was a build-up in EYLEA HD inventory, affecting the fourth-quarter inventory levels. The favorable impact on their net product sales was around $85 million, primarily benefiting EYLEA, due to higher wholesale inventory levels. George Yancopoulos finds it difficult to comment on Pavblu but mentions recent legal victories at the Federal Circuit Court of Appeals, which could limit competition to just one biosimilar competitor, influencing pricing dynamics. Ryan Crowe suggests seeking more insights from Amgen's call. The paragraph ends with the next question from Taylor Hanley, asking about future operating expenses.

The paragraph discusses Regeneron's approach to balancing investments across its pipeline programs. Leonard Schleifer emphasizes that the company's primary focus is on research and development. He notes that compared to other companies, Regeneron's R&D investments are highly productive. The company remains open-minded about partnering with financial or strategic partners if it benefits a program, focusing on flexible allocation of resources rather than fixed spending quotas. Schleifer believes this flexibility is beneficial given the breadth of programs in development. Following this, Ryan Crowe moves the discussion to the operator, who introduces a question from Sam Godshall regarding a modest price increase for EYLEA, noted as the first such increase.

The paragraph discusses a Q&A session about the pricing and market dynamics for EYLEA and EYLEA HD. Leonard Schleifer and Marion McCourt decline to provide detailed comments on the pricing strategy for EYLEA, although McCourt notes a modest price increase for EYLEA HD. Mohit Bansal from Wells Fargo inquires about the expected market dynamics for EYLEA HD, particularly with the potential adoption of a prefilled syringe format. McCourt points out the market composition, with patients switching primarily from EYLEA, aflibercept, and Avastin, but offers no further details on market dynamics. Leonard Schleifer suggests looking beyond EYLEA's focus, highlighting ongoing developments with Dupixent, itepekimab, and other products in the pipeline.

The paragraph involves a discussion during a conference call where participants address various questions. A trial in geographic atrophy is highlighted with an emphasis on the importance of a diverse research pipeline rather than dependence on a single program. Alice Nettleton from Bank of America attempts to ask another question about EYLEA, but Leonard Schleifer suggests returning to it later to allow for other topics. Akash Tewari from Jefferies inquires about Factor XI and recent studies comparing it to Eliquis in knee replacement surgeries. George Yancopoulos explains their strategy of developing two complementary antibodies that provide flexibility for physicians and patients in selecting the best treatment approach.

The paragraph discusses two antibody treatments, 7508 and 9933, designed for anti-coagulation therapy. Antibody 7508 targets the catalytic domain and is highly effective for patients requiring significant anti-coagulant control, performing well in initial studies. On the other hand, 9933 targets the A2 domain and is milder, posing minimal bleeding risk while offering slightly less anti-coagulation activity. These treatments provide flexibility for patients and physicians to balance anti-coagulation and bleeding risks. The need for such options is significant, as many patients with conditions involving thrombi and clots remain untreated or not optimally treated. The aim is to address this unmet need by gathering data on these two approaches.

The paragraph discusses the potential of an antibody and siRNA combination therapy in the treatment of myasthenia gravis (MG) and geographical atrophy (GA), highlighting its high efficacy in achieving complement inhibition in a larger percentage of patients compared to current drugs. While some Grade 5 adverse events (AEs) have been observed, these are consistent with the safety profiles of similar therapies. The combination therapy aims to offer a solution for approximately 30% of patients inadequately treated by standard-of-care. However, safety concerns remain, particularly for older AMD patients. The Phase 3 trial includes measures to minimize risks, such as enrolling lower-risk patients and ensuring vaccinations against risky organisms.

The paragraph discusses the challenges and strategies in treating vision-threatening conditions and obesity. For vision issues, there's a dilemma of using intravitreal approaches that could lead to immediate vision loss as a side effect. The focus is on finding safer alternatives. In addressing obesity, George Yancopoulos talks about the potential of combining myostatin with an Activin blocker to optimize body composition. He acknowledges concerns over the safety profile of Activin A blockade, though the GDFA blockade appears safer based on early data. They are testing both individual and combined approaches to balance efficacy and safety.

In the paragraph, the discussion begins with a mention of Lilly's receptor blocker targeting multiple growth factors, raising concerns about side effects, and contrasting it with their own program focusing on the two most important factors for muscle preservation to balance efficacy and safety. The conversation then shifts to a final question, where Chris, on behalf of Terence Flynn from Morgan Stanley, inquires about the efficacy benchmarks for advancing their LAG-3 plus PD-1 combo in non-small cell lung cancer to a pivotal program. George Yancopoulos responds by indicating that due to the small datasets available from their collaboration with Bristol, it's challenging to draw solid conclusions, so they are focusing more on their melanoma data.

The paragraph discusses the potential impact of upcoming Phase 3 melanoma study data, suggesting that it could greatly excite the medical community if the results align with earlier positive proof-of-concept studies. This data may not only benefit first-line melanoma patients but could also influence treatment approaches in other cancers, such as lung cancer. The expectation is that these Phase 3 results will be more definitive and insightful than smaller studies. Additionally, there's a brief exchange about Regeneron's pricing strategy for EYLEA in response to competition, with no specific details disclosed. The conversation concludes without further comments on pricing, and the call is wrapped up.

The paragraph concludes a conference call by thanking participants and apologizing to those still in the Q&A queue for not addressing their questions. The hosts express willingness to follow up on any remaining queries and wish everyone a great day before the operator officially ends the call.

This summary was generated with AI and may contain some inaccuracies.