George Yancopoulos
Board Co-Chair, Co-Founder, President and Chief Scientific Officer at Regeneron Pharmaceuticals
Thank you, Len. Starting with DUPIXENT. Regarding COPD, data from our second confirmatory trial, NOTUS was featured as a late-breaking presentation at the American Thoracic Society Conference and simultaneously published in the New England Journal of Medicine. In NOTUS, DUPIXENT reduced exacerbations by 34%, while significantly improving lung function confirming the unprecedented results from the previously reported Phase III BOREAS trial. Based on data from NOTUS and BOREAS, DUPIXENT was recently approved by the European regulatory authorities for eosinophilic COPD patients uncontrolled on maximum standard of care and health therapy. Additional submissions are under review with other regulatory authorities around the world, including in the U.S., China and Japan.
Beyond COPD later this year, we are looking forward to data readouts from Phase III studies of DUPIXENT in chronic spontaneous urticaria and bullous pemphigoid. seven years after its initial FDA approval and with approval in seven different indications around the world DUPIXENT continues to deliver potential new approvals for additional important disease indications. Regarding our small pilot study to potentially eliminate severe food allergies using our innovative approach that combines DUPIXENT and linvoseltamab our BCMA by CD3 bispecific, we continue to expect to see initial data by the end of this year. On itepekimab, our IL-33 antibody in development for certain COPD patients, our two Phase III studies are now fully enrolled, study readouts and regulatory submissions for our second therapeutic candidate for this devastating disease are expected in the second half of next year.
Moving to oncology. Starting with Fianlimab, our LAG-3 antibody in combination with LIBTAYO, at the upcoming ESMO meeting in September, we look forward to presenting longer-term follow-up on the metastatic melanoma cohorts from our first-in-human study. Responses have continued to deepen with the proportion of complete responders and median progression-free survival continuing to improve. These results strengthen our view that fianlimab and LIBTAYO may be the most promising immunotherapy combination in clinical development. As we recently announced, we are looking forward to the Phase III readout in this melanoma setting next year, which could position fianlimab and LIBTAYO as a new standard of care in melanoma and eventually potentially other cancer settings.
Additionally, we hope to gain insights into the antitumor activity of this combination in non-small cell lung cancer later this year. We are also advancing fianlimab development to earlier lines of therapy with proof of concepts in perioperative non-small cell lung cancer and perioperative melanoma now underway with additional indications likely to follow. On to bispecifics for solid tumors. Our costimulatory bispecific antibodies are being tested in numerous studies, including as monotherapies as well as in combination with CD3 bispecifics and with LIBTAYO. At the ASCO Conference, we presented results for our EGFR by CD28 bispecific in combination with LIBTAYO. In microsatellite stable colorectal cancer tumor historically unresponsive to immunotherapy EGFR by CD28 in combination with LIBTAYO demonstrated encouraging antitumor activity with an overall response rate of 20% in patients without liver metastases.
Regarding safety, to date, we have not observed severe immune-related adverse events with this agent at our recommended Phase II dose. Dose expansion cohorts testing EGFR by CD28 plus LIBTAYO continue to enroll in various solid tumors, including non-small cell lung cancer with or without EGFR mutations, microsatellite stable colorectal cancer, head and neck, squamous cell carcinoma and others. On to our PSMA by CD28 costimulatory bispecific, which has already demonstrated promising activity in late-line prostate cancer when combined with LIBTAYO. We have now initiated combination treatment of our PSMA by CD28 costim bispecific with our PSMA by CD3 bispecific, which based on preclinical studies may maintain the efficacy of served with the LIBTAYO combination that may improve the safety and tolerability profile. We are also testing PSMA by CD28 in other cancers.
Next, to our bispecifics for hematology oncology, the linvoseltamab, or BCMA by CD3 bispecific, an oral presentation at the European Hematologic Association Conference we presented updated pivotal data, which continue to demonstrate a potentially best-in-class profile in late-line myeloma in terms of efficacy, safety, dosing as well as hospitalization burden. As we expected, responses continue to deepen with longer follow-up. At 14-month median follow-up of 117 patients, 50% achieved a complete response or better with an objective overall response rate of 71%. Additional studies of linvoseltamab are now also underway in earlier stages of myeloma and in precursor conditions such as smoldering myeloma and monoclonal hemopathy of unknown significance or MGUS. Developing linvoseltamab in earlier-line myeloma settings presents an important opportunity for us to help patients and their physicians in these diseases, which currently have complex treatment paradigms.
Touching on our nononcology hematology pipeline, as highlighted previously, later this year, we are anticipating proof-of-concept results for our two Factor XI antibodies in the setting of prevention of venous thromboembolism after knee replacement surgery. The study for the antibody targeting the Factor XI A2 domain is now fully enrolled, and we expect to present results at a medical meeting in the second half of this year. Interim Phase II results for our second Factor XI antibody which targets the catalytic domain are expected by the end of this year for internal analysis. We have also started an additional proof-of-concept study to further evaluate the two antibodies profile for thrombosis prevention in patients, who have a peripherally inserted catheter. Results of these studies will inform whether to proceed to registrational studies with one or both of these antibodies by next year.
Moving to obesity. Our most advanced approach is designed to address the potential negative consequences of widespread use of GLP and GIP receptor agonists. As has been widely reported, the profound weight loss caused by these agents unfortunately, it can also result in substantial loss of muscle, which is particularly concerning older, obese patients. Our myostatin antibody when combined with semaglutide with or without our active antibody, may protect against this muscle loss as previously demonstrated in nonhuman primates. Part A of our Phase II study testing a higher dose of trevogrumab or myostatin antibody in healthy subjects has now been successfully completed with no new safety signals identified. Part B of the study, which evaluates our muscle preservation antibodies in combination with semaglutide and obese participants has started enrolling patients assuming a reasonable pace of enrollment, we continue to expect to report top line results, including changes in body weight, fat mass and muscle mass by the second half of 2025.
I will conclude with our genetics medicines efforts. At the ASGCT Conference, we presented updated data from our DBO gene therapy program for genetic hearing loss due to mutations of the atoferolin gene. The first child treated with this therapy, an 11-month old girl, who is profoundly deaf at baseline had hearing in the normal range by 24 weeks after treatment. We also initial hearing improvements were observed in a second child dose at four years of age at a 6-week assessment with additional follow-up plan. As of July, we have dosed five patients in our study, and we are on track to enroll several more patients this year. We also look forward to bringing additional atoferolin gene therapy programs to the clinic in the coming years with the potential to address more common forms of monogenic hearing loss.
Regarding our Intellia collaboration, transthyretin amyloidosis with cardiomyopathy, the world's first Phase III program for in vivo CRISPR-based therapy is enrolling at a rapid pace indicating considerable interest from investigators and patients. In addition, we are also on track to be the first to use CRISPR technology to insert a corrective gene in vivo for a deficiency disease, hemophilia B. As noted previously, we have enrolled initial patients in the leading portion of this trial and first patient should be dosed soon. Our siRNA collaboration with Alnylam has not only demonstrated successful silencing of genes in the liver, but also for the first time for siRNA in the brain. This opens up opportunities for us to go after other disease-causing genes in the brain.
A study of ALN SOD in ALS patients with SOD-1 mutations recently initiated. Other CNS-directed siRNA drugs are expected to enter the clinic shortly, including targeting HTT for Huntington's disease, synuclein for Parkinson's and tau for Alzheimer's and other neurodegenerative diseases. Additionally, with regard to our C5 program, our innovative approach involving the first combination of an antibody together with an siRNA both targeting the same molecule is progressing well, and we are expecting to present updated data for initial potential indication, paroxysmal nocturnal hemoglobinuria by the end of this year. We're also looking forward to starting our Phase III program in geographic atrophy in the second half of this year. In summary, we continue to drive forward our innovative development pipeline and anticipate reading out several pivotal and proof-of-concept data sets over the next 12 to 18 months. Our early research efforts continue to be productive with multiple novel programs potentially advancing to the clinic over that same time frame.
And with that, I will turn the call over to Marion.
