United States Regeneron Tender

Regeneron Pharmaceuticals Inc. presented new data for REGN1979 in patients with relapsed or refractory RR B-cell non-Hodgkin lymphoma B-NHL including promising clinical results in follicular lymphoma FL and diffuse large B-cell lymphoma DLBCL which are the two most common types of NHL. In this Phase 1 proof-of-concept trial REGN1979 demonstrated an acceptable safety and tolerability profile with no observed dose-limiting toxicities DLTs. There were no clinically-significant neurotoxicities including no occurence of seizures or encephalopathy. REGN1979 is a wholly-owned investigational full-length bispecific monoclonal antibody designed to trigger tumor killing by binding CD3 on immune system T-cells and CD20 on B-cell malignancies.In the data presented at the 2018 American Society of Hematology ASH Annual Meeting heavily pre-treated patients with RR FL grades 1 to 3a who received REGN1979 doses of 5 mg to 40 mg experienced a 100 overall response rate ORR 8 complete responses CR and 2 partial responses PR 90 of responders maintained a response during treatment. Based on these data Regeneron plans to initiate in 2019 a potentially registrational Phase 2 trial investigating REGN1979 in RR FL.REGN1979 also showed encouraging dose-dependent clinical activity in heavily pre-treated patients with RR DLBCL. Among patients receiving doses between 5 mg and 12 mg the ORR was 18 2 of 11 patients including 1 CR and 1 PR. At doses of 18 mg to 40 mg the ORR increased to 60 6 of 10 patients including 2 CR and 4 PR. Regeneron plans to continue dose-escalation in DLBCL.While a high response rate is frequently observed in the first-line treatment of follicular lymphoma it is remarkable to see a 100 response rate in heavily pre-treated relapsed or refractory follicular lymphoma patients said Israel Lowy M.D. Ph.D. Head of Clinical and Translational Sciences Oncology at Regeneron. We plan to initiate a potentially registrational Phase 2 trial in 2019 investigating REGN1979 in relapsed or refractory follicular lymphoma and are also considering its potential as a first-line treatment for this disease. Furthermore we are continuing to dose-escalate in the more difficult-to-treat DLBCL setting to see if we can continue to further improve efficacy. Finally REGN1979 is being investigated in combination with Libtayo cemiplimab-rwlc in an ongoing Phase 1 study which we believe is the first to combine a CD20xCD3 bispecific antibody with a PD-1 or PD-L1 inhibitor. There have been tremendous recent advances in the field of immuno-oncology with new breakthrough therapies including checkpoint inhibitors and personalized cell-based therapies said George D. Yancopoulos M.D. Ph.D. President and Chief Scientific Officer at Regeneron. Regeneron has recently launched its first checkpoint inhibitor Libtayo for a serious skin cancer with no previously-approved therapies that were available. Regeneron is also advancing a broad and deep bispecific antibody platform which may offer off-the-shelf alternatives to cell-based therapies for both solid tumors and hematologic malignancies. Our bispecific antibody pipeline includes REGN1979 and a MUC16xCD3 antibody for ovarian cancer in clinical development and a BCMAxCD3 antibody for multiple myeloma expected to enter human studies before the end of this year. In 2019 we expect to start clinical trials of a new class of bispecific antibodies that engage cellular immunity in novel ways. We believe that cancer treatment in the future will require precision medicine-based combinations of these and other approaches and that Regeneron is well positioned to be a future leader in this exciting area.The objectives for this ongoing Phase 1 proof-of-concept trial are to assess safety tolerability and efficacy of REGN1979 monotherapy. The data presented at ASH included a total of 68 patients with RR B-NHL who were treated with REGN1979. These patients had received a median of three prior therapies including an anti-CD20 therapy. As of September 2018 14 patients had completed treatment 13 patients remained on treatment and 41 had discontinued treatment. The most common reason for treatment discontinuation was progressive disease 27 patients. Two patients discontinued treatment due to a treatment-emergent adverse event TEAE grade 3 hemolysis and grade 3 fatigue.In the trial the most common TEAEs occurring in at least 25 of patients were pyrexia chills cytokine release syndrome CRS fatigue increased C-reactive protein anemia hypotension infusion-related reaction IRR and nausea. IRR and CRS events were generally mild to moderate in severity and neither resulted in trial discontinuations. Three patients in the trial died due to adverse events. Of these one death in a patient with a tumor involving the gastric lining who experienced a gastric perforation was attributed to REGN1979.REGN1979 was invented by Regeneron using the companys proprietary VelocImmune technology that yields optimized fully-human antibodies and Regenerons proprietary Veloci-Bi bispecific platform. Veloci-Bi allows for the generation of full-length bispecific antibodies similar to native antibodies that are amenable to production by standard antibody manufacturing techniques and likely to have favorable antibody-like pharmaco-kinetic properties.