George D. Yancopoulos
Scientific Founder, President and Chief Scientific Officer at Regeneron Pharmaceuticals
Thanks, Len. I'll start by briefly addressing our novel monoclonal antibodies for COVID-19. As Len mentioned, we are rapidly developing next-generation antibodies that retain potency against Omicron and other variants of concern.
Early in 2019, we anticipated that the virus would mutate and thus began generating large pools of virus-neutralizing antibody candidates from both human survivors and our VelociGene mice. We have continually evaluated and refreshed this pool and now have next-generation candidates that based on preclinical studies effectively neutralize Omicron and other variants of concern. We're on track to initiate clinical trials with the first of these in the coming months.
In addition, we are in discussions with the FDA regarding how to streamline the development program for monoclonal antibodies, considering the unwavering unmet need and demand for these medicines, especially with potential future virus variants in mind. As Len already highlighted, since we believe that monoclonal antibodies will continue to play an especially important role in the treatment and future protection of the several million immunocompromised people in the United States alone, we are committed to undertaking a development pathway that will make this possible in the near future.
Moving on to ophthalmology. At the upcoming Angiogenesis Meeting, we will present the final Phase 2 data from the Aflibercept 8 milligram CANDELA study in patients with wet AMD. In this study, Aflibercept 8 milligram, given at the same protocol specified dosing schedule as currently approved EYLEA 2 milligram, met its primary safety endpoint with measures of drawing numerically favoring the 8-milligram dose over the 2-milligram dose. These Phase 2 results give us more confidence that the upcoming Phase 3 readouts has the potential to show that the higher 8-milligram Aflibercept dose can at least match the efficacy and safety of EYLEA but with more convenient dosing.
Moving on to Dupixent. Building on the outstanding clinical success Dupixent has shown so far across a wide spectrum of allergic or Type 2 inflammatory diseases, the second Phase 3 study in Prurigo Nodularis recently met primary and key secondary endpoints, making Dupixent the first and only systemic medicine to demonstrate such success in this indication. These data confirm the results from the first Phase 3 trial where 60% of Dupixent patients met the primary endpoint of itch reduction compared to 18% of placebo patients at 24 weeks.
Nearly 3 times as many Dupixent patients experienced reduced skin lesions compared to placebo as well. Prurigo nodularis marks the sixth disease for which Dupixent has demonstrated profound benefit for patients, providing convincing evidence that the IL-4 and IL-13 pathways inhibited by Dupixent are the key drivers of the Type 2 inflammation underlying all of these diseases. We have to appreciate how remarkable the Dupixent story is in terms of the important benefit it provides for the many patients across this diverse set of clinical conditions, together with its well-established safety profile and highlights how Dupixent is delivering on its promise of providing a pipeline in the product.
At the upcoming AAAAI meeting, in addition to the other important Dupixent updates, we will present pivotal results for the recently top-line studies in eosinophilic esophagitis, or EoE, and for the first Chronic Spontaneous Urticaria, or CSU, study. EoE is a complex disease and we are excited to share these data with the scientific community and patients. Our first regulatory submission for EoE in adolescents and adults is underway with regulatory submissions for prurigo nodularis also starting in the first half of this year.
Anticipated flow of Dupixent-related clinical data updates continues. We're planning on reporting results in an additional Phase 3 study in CSU this time in omalizumab experienced patients and also for the chronic cold induced urticaria indication in the second half of this year. These represents more difficult-to-treat patients or conditions and present a higher bar for Dupixent. We're looking forward to results of these pivotal studies.
Moving on to oncology and, first, Libtayo. Progress in our oncology portfolio includes pivotal readouts and regulatory filings for Libtayo, presented an anticipated data readouts for our bispecifics as well as multiple upcoming milestones with novel diversified pipeline entrants. As Len mentioned, the Libtayo and chemotherapy combination for patients with non-small cell lung cancer is under review at the FDA with a PDUFA date of September 19, 2022, which could address a larger portion of the patients with lung cancer.
In hematology, at the American Society of Hematology Annual Meeting, we presented encouraging data for REGN5458, our BCMAxCD3 bispecific investigated for relapsed or refractory multiple myeloma. With safety data that has shown no Grade 3 or higher cytokine release syndrome to-date and strong efficacy data, we believe our investigational agent is promising and has the potential to be competitive in this indication. We are planning on investigating this product for earlier lines of myeloma therapy in combination with standard of care and are excited about the combination with an appropriate co-stimulatory bispecific, which could further enhance responses.
Odronextamab, our CD20xCD3 bispecific, has the potential for a best-in-class efficacy profile in both follicular lymphoma and diffuse large B-cell lymphoma, and our updated step-up dosing protocol may mitigate safety concerns and decrease the need for hospitalizations to manage cytokine-release syndrome.
In terms of progress of our bispecifics for solid tumors, as previously disclosed, we are observing early signs of activity for our MUC16xCD3 bispecific monotherapy developed for late-stage ovarian cancer and we are excited to be sharing these early data later this year. In addition to monotherapy, the MUC16xCD3 bispecific is being investigated in combination with Libtayo and, in a first of its kind, in a combination trial with a MUC16xCD28 bispecific. These combinations are in early stages that are advancing through dose escalations.
Later this year, we are hoping to share initial results for a unique biparatopic METxMET antibody studied in advanced non-small cell cancer patients with MET protein alterations. Early signs of clinical activity we have observed so far with the naked METxMET bispecific antibody, especially in patients with MET overexpression, bode well for our follow-on agent, the METxMET bispecific antibody drug conjugate, which is now enrolling patients in a Phase 1 study.
We are also excited about our early-stage EGFRxCD28 costimulatory bispecific program for lung and other cancers. For prostate cancer, we are expecting initial readouts from our first costimulatory bispecific PSMAxCD28 later this year as well. PSMAxCD28 is progressing through dose escalation in combination with Libtayo. We are excited about the potential of our broad oncology portfolio, which includes multiple Phase 1, 2 and 3 assets, as many are beginning to believe the future is going to involve the right combination of targeted immunotherapy agents.
Concluding with our Regeneron Genetics Medicines efforts. We and our collaborators have made significant strides in expanding the capabilities and scale of our groundbreaking work in genetics medicines. In terms of our siRNA collaboration with Alnylam, Alnylam HSD is progressing through healthy volunteers and initial data in NASH patients are anticipated by the middle of this year. For the C5 siRNA and antibody combination, another first of its kind, healthy volunteer data were presented at ASH, demonstrating PK and PD results supportive of the monthly subcutaneous dosing regimen selected for pivotal studies.
Phase 3 studies of the combination for paroxysmal nocturnal hemoglobinuria, or PNH, were also initiated. Recall in PNH we are planning to test our combination in both naive and switch patients tested against standard of care therapies, including rovelizumab and eculizumab. Also, Alnylam has recently announced submission the CTK application for Alnylam APP, the industry's first ever investigational RNAI therapeutic for CNS diseases. This agent will be evaluated in both the relatively rare disease driven by amyloid precursor protein known as cerebral amyloid angiopathy, or CAA, as well as in early Alzheimer's disease.
Finally, later this quarter, we and Intellia will provide an update on our joint TTR CRISPR-based knockout program for transthyretin amyloidosis. This will include additional ascending dose interim clinical data from the polyneuropathy arm of the ongoing Intellia 2001 Phase 1 study. We have also expanded this study to include patients with transthyretin amyloidosis with cardiomyopathy, which we believe will address an even broader patient population.
We are very excited by our large and diverse pipeline of siRNA candidates that we are advancing with Alnylam ranging from targeting the liver, the brain and the eye as well as our CRISPR-based approaches in collaboration with Intellia and our viral targeted gene delivery programs such as with Decibel. While still early, we think these groundbreaking approaches have the potential to change the practice of medicine.
And with that, I will turn the call over to Marion.
