Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) today announced positive early data for two novel and investigational bispecific antibodies – ubamatamab (REGN4018; MUC16xCD3) in recurrent ovarian cancer and REGN5093 (METxMET) in MET-altered advanced non-small cell lung cancer (NSCLC). The initial safety and efficacy results are from the dose-escalation portions of two Phase 1/2 trials and are being presented at the European Society for Medical Oncology (ESMO) Congress 2022 in Paris.

"Bispecific antibodies are an important component of our oncology pipeline because of their flexibility to potentially address a variety of cancers," said Israel Lowy, M.D., Ph.D., Senior Vice President, Translational and Clinical Sciences, Oncology at Regeneron. "At ESMO, we're showcasing this flexibility with ubamatamab and REGN5093, two novel bispecific antibodies that are initially being investigated as monotherapies for recurrent ovarian cancer and MET-altered advanced lung cancer, respectively. They were among the first in our pipeline to progress into clinical trials for solid tumors, and we're encouraged to see both showing anti-tumor activity in dose escalation. These first-in-class results give us confidence in our VelociBi^® bispecific development platform, and we look forward to investigating ubamatamab and REGN5093 further."

As shared in a mini-oral at ESMO, ubamatamab is a CD3-targeting bispecific under investigation for recurrent ovarian cancer and designed to bridge MUC16 on cancer cells with CD3-expressing T cells to facilitate local T-cell activation. Dose-escalation results were presented for 78 patients with recurrent ovarian cancer who had received a median of 4.5 prior treatments, including platinum-based chemotherapy and a median duration of exposure to ubamatamab was 12 weeks (range: <1 to 145 weeks).Within 42 patients who received ≥1 full doses of ≥20 mg ubamatamab, a 14% (6 of 42 patients) overall response rate (ORR) was achieved across dose levels. The ORR increased to 21% (6 of 29 patients) in those without visceral metastases (exploratory subset) and 31% (4 of 13 patients) in those with high MUC16-expressing tumors (preliminary exploratory subset). Across dose levels, the disease control rate was 57% (24 of 42 patients), and the median duration of response was 12 months per Kaplan-Meier estimates (range: 4 to ≥24 months).

Safety was assessed in 78 ubamatamab-treated patients, with the most common adverse events (AEs) in ≥15% being cytokine release syndrome (74%, all ≤grade 2), pain (87%) and anemia (51%). AEs that were ≥grade 3 occurred in 65% of patients with those in >5% including anemia (24%), pain (23%) and neutropenia (8%). There was one instance of a dose-limiting toxicity (neutropenia) and three deaths due to AEs, none of which were considered related to treatment by sponsor assessment. Based on these efficacy and safety data, the Phase 2 portion of the trial is enrolling patients with platinum-resistant ovarian cancer to further investigate ubamatamab as a monotherapy and in combination with Regeneron's PD-1 inhibitor Libtayo^® (cemiplimab).

Preliminary first-in-human results for REGN5093 were also published in an ESMO scientific abstract, with updated data and additional response rates to be detailed in a poster session on Monday, September 12. REGN5093 is a tumor-targeting bispecific designed to bind to the MET receptor in two places and trigger rapid internalization of this complex into cancer cells to degrade the MET receptor and block its ability to support cell proliferation. As highlighted in the abstract, among 36 patients with MET-altered advanced NSCLC who received the highest dose tested to date, 6 experienced a partial response with 5 of these responses occurring in patients who had received prior anti-PD-1 treatment. Total exposure to treatment was approximately 467 patient-weeks.

AEs that were ≥grade 3 occurred in 25% (n=11) of REGN5093-treated patients, with pneumonia and pulmonary embolism each occurring in 2 patients. One patient discontinued treatment due to increased alanine aminotransferase and aspartate aminotransferase. No dose-limiting toxicities or treatment-related deaths have been observed as of data cutoff. These early efficacy and safety data support further dose expansions, and a separate Phase 1/2 trial is ongoing to investigate an antibody-drug conjugate format of REGN5093 (REGN5093-M114).

The potential uses of ubamatamab, Libtayo, REGN5093 and REGN5093-M114 described above are investigational, and their safety and efficacy have not been evaluated by any regulatory authority.