George D. Yancopoulos
Board co-Chair, President and Chief Scientific Officer at Regeneron Pharmaceuticals
Thank you, Len. At last month's Healthcare Conference, we showcased our robust R&D efforts and the promising opportunities within our pipeline that have the potential to revolutionize the practice of medicine across several different disease areas. This year holds the potential to be transformative for Regeneron as we hope to capitalize on several of our scientific and technological breakthroughs.
We anticipate reporting pivotal or proof-of-concept data from multiple programs across diverse therapeutic areas, including in oncology, COPD and obesity, while also rapidly advancing our Factor 11 antibodies to multiple Phase-3 trials. These programs represent significant opportunities for Regeneron to address substantial unmet needs across large commercial categories, positioning Regeneron for long-term growth. Let me highlight some of these opportunities and recent pipeline advancements.
Starting with EYLEA HD, in December, we and Bayer reported positive data from the Phase-3 Quasar study in retinal vein occlusion, where EYLEA HD demonstrated non-inferior vision gains within every eight-week dosing regimen compared to the standard-of-care 2 milligram EYLEA dosed every four weeks. Additionally, approximately 90% of ILEA HD patients were able to maintain eight-week dosing intervals throughout the 36 weeks. These data together with our recently presented long-term follow-up data from the and Photon studies in wet-AMD and DME, respectively, continue to support EYLEA HD's best-in-class clinical profile.
We remain on-track to submit a supplementary BLA for this indication later in the first-quarter. We also plan to seek approval from the FDA to potentially include every four-week dosing, maximizing EYLEA's HD's dosing flexibility for physicians. Along with the submission for a prefill syringe and the potential FDA approval in April to extend dosing intervals to up to 24 weeks, the longest intervals in the category, EYLEA HD is set to provide the greatest dosing flexibility across the broadest indication set of any anti-VEGF therapy, all-in a convenient prefilled syringe.
Next, immunology and starting with Dupixent. In November, Dupixent was approved in Europe to treat eosinophilic esophagitis in children as young as one year-old, making it the first and only medicine indicated for these young patients in the US and the European Union and further highlighting Dupixent's exceptional safety profile. The supplementary BLA resubmission for chronic spontaneous uricaria was recently accepted by the FDA with a target action date of April 18, potentially making it the first new target therapy for CSU in a decade.
Finally, our supplementary BLA was submitted for late last year, marking another first as Dupixent is the only biologic to achieve significant improvements in disease remission and symptoms for this indication. While Marion will discuss the ongoing launch of Dupixent in COPD, I want to remind you of another potentially significant opportunity in COPD with, our antibody discovered by Regeneron. We anticipate reporting pivotal results in former smokers from the ARIFY program in the second-half of this year, a partially overlooping and distinct population from that treated with Dupixent.
As part of our long-term commitment to improving the lives of patients with allergic conditions, I would also like to highlight the compelling initial data from our ongoing Dupixent plus trial for severe food allergy. These two agents have the potential to eliminate E or IgE, the key driver of allergic reactions and prevent IGE from returning, thereby reversing severe allergies. Last month, we shared initial clinical data from the first patient in our proof-of-concept study, which showed greater than 90% reductions in both total and food specific IgE levels following initial treatments at low doses. This trial is continuing to enroll patients and we plan to provide updates throughout 2025.
Turning now to oncology, where we continue to break new ground. Last month, we announced positive data for Libtayo in high-risk adjuvant CSCC, becoming the first immunotherapy to show a benefit in this high-risk population. At the first pre-specified interim analysis for disease-free survival, adjuvant Libtayo demonstrated a 68% reduction in the risk of disease recurrence or death compared to placebo with no new safety signals identified.
This is the same setting in which Merck reported last year that KEYTRUDA had failed, highlighting that antibodies even within the same class do not always produce the same treatment effect. We plan to submit these data to the FDA in the first-half of 2025 and present these results at a medical meeting later this year. This data-set reinforces our belief that Libtayo provides a best-in-class foundation for combinations with our other oncology assets.
Data from early clinical trials in melanoma suggests that, our LAG3 antibody when combined with Libtayo might be the first combination to demonstrate meaningful additive benefit compared to PD-1 monotherapy without exacerbating safety. This combination is being studied in an ongoing randomized Phase-3 trial versus KEYTRUDA monotherapy in first-line metastatic melanoma with results expected in the second-half of these of this year. If these data confirm best-in-class activity in melanoma, it will increase our confidence for this combination in other cancer settings.
Turning to our CD3 bispecifics. We are pleased to announce that we have recently resubmitted the BLA for linvoseltamab, our BCMA by CD3 bispecific for relapsed/refractory multiple myeloma, following the resolution of third-party manufacturing issues. Linvoseltamab has the potential to be the best-in-class BCMA by CD3 bispecific due to its differentiated clinical profile, dosing and administration with nearly double the reported complete response rates at similar duration of follow-up.
Given the strength of the data in late lines of therapy, including the observed level of efficacy and favorable safety profile of illevoseltamab, we are pursuing a differentiated approach in earlier lines of therapy, emphasizing monotherapy and novel limited combination approaches. For odronextamab, our CD20 by CD3 bispecific, we are pleased to announce that we have resubmitted the BLA for relapsed/refractory follicular lymphoma where odronextamab has also demonstrated potentially best-in-class efficacy and we expect an FDA decision in the second-half of 2025.
In December, at the American Society of Hematology Meeting, we presented initial results from the safety lead-in portion of the confirmatory Phase-3 Olympia trial. Monotherapy delivered complete responses in all 12 patients evaluable for efficacy with previously untreated follicular lymphoma. As a reminder, the standard-of-care regimen in this setting, rituximab plus chemotherapy has historically achieved complete responses in approximately 67% of patients.
Based on this impressive monotherapy efficacy for otroneximab in both late-line and first-line patients, we are once again exploring a differentiated program in early lines of therapy, highlighted by our head-to-head evaluation of monotherapy compared to rituxan plus chemotherapy in our Phase-3 OLYMPIA-1 trial, which has already achieved over 40% enrollment.
Our CD28 co-stimulatory bispecifics for solid tumors are are also progressing. We're working to mitigate safety concerns related to their combination with PD-1 blockade while prioritizing combination with CD3 bispecifics. The science suggests that this approach may enhance efficacy with fewer immune-mediated adverse events. We will provide updates on these innovative combinations later this year.
Moving now to a rapidly advancing Factor 11 program. We're employing a two-pronged approach to anticoagulation that offers the potential for improved blood clot, prevention and lower bleeding risk. Supported by genetic data from the Regeneron Genetic Center, our approach has delivered two antibodies with unique profiles to meet different market needs. Regeneron 708, which targets the catalytic domain of Factor 11, may provide improved efficacy compared to standard-of-care options, offering patients who need significant anti-coagulation activity, a potentially more effective option.
On the other hand, Regen 9933, which targets the A2 domain is expected to carry a lower-risk of bleeding, potentially making it a viable option for patients with the highest bleeding risk who would otherwise not be candidates for currently available anti-coagulants. Late this year, we reported positive proof-concept data for the prevention of venous thromboebbolism following total knee replacement with both antibodies demonstrating robust anti-thrombotic effects. Regeneron 7508 was superior to noxaparin and non-inferior ipixaband, while Regen 9933 was numerically better than. These data support the advancement of both antibodies into broad pivotal programs across multiple indications and patients types. With initial Phase-3 studies expected to begin enrolling this year.
Moving briefly to obesity, where we are progressing early clinical programs and an expansive pipeline of preclinical assets. Our muscle sparing Phase-2 study is investigating the addition of to semaglutide with and without to improve the quality of weight-loss and evaluate the maintenance of weight-loss after discontinuing semaglutide. This trial is fully enrolled with data expected in the second-half of the year.
Moving to our Regeneron genetics medicine pipeline, starting with our differentiated siRNA plus antibody approach, we have the potential to address multiple complement-mediated diseases. In December, at the ASH Annual Meeting, we presented compelling updated results from an exploratory cohort in our Phase-3 program for paraxysmal and nocturnal hemoglobinurea.
Our combination achieved greater disease control compared to the standard current of care revolizumab and only our combination lowered mean LDH levels to the normal range. When revoluzumab patients were -- were switched to our combination, their mean LDH levels, which remained higher-than-normal, also became normalized. We are also evaluating this combination in generalized mycenia gravis with pivotal results expected in the second-half of this year.
In addition, we recently initiated our Phase-3 program exploring this combination in geographic atrophy in dry age-related, where we believe our systemic approach has several advantages over currently approved intravitreal agents. For DBOTO, our autopheral and gene therapy program for genetic hearing loss, we announced data last month from the ongoing clinical program. DBOTO is an AAV-based dual vector gene therapy delivered to the inner ear to enable hearing in children suffering from profound genetic hearing deficit.
We reported that 10 out of 11 treated children with at least one post-treatment assessment showed a notable increase in hearing with some reaching the normal range. We look-forward to continue to share additional data later this year. Regarding our collaboration with Alnylam, we are advancing several new siRNA CNS programs, including for Parkinson's and TAU for Alzheimer's and other neurodegenerative diseases with trials initiating later this year.
And finally, I would like to highlight two recent advances that extend our leadership position in the field of structured big data that will be necessary to allow computational approaches to revolutionize the healthcare industry. Over the past decade, we have become the leader in high-throughput human DNA sequencing, enabling us to create the world's largest DNA sequence linked healthcare database encompassing nearly 3 million individuals, all with DNA sequence linked to de-identified healthcare records. We are now emerging also as the leaders in high-throughput proteomics as reflected by the selection of the Regeneron Genetics Center to generate the proteomics data for the UK Biobank Pharma Proteomics project, building on our previous selection to provide the sequence data for the UK biobank.
Importantly, our new strategic collaboration with is expected to dramatically expand our database to include up to an additional 10 million individuals from network of leading US health system with the opportunity to generate both DNA sequence and proteomics information. While our leadership position in this big data space has already proven invaluable for our drug discovery and development efforts, we believe it can ultimately help us contribute to revolutionizing the field of healthcare analytics and management.
In summary, I have never been more excited about the future of Regeneron and our potential to transform the practice of medicine and revolutionize the healthcare industry. Our pipeline is more innovative and exciting than ever, and we anticipate several pivotal or proof-of-concept data readouts throughout 2025, positioning Regeneron for long-term success.
Let me now turn the call over to Marion.
