IGM Biosciences presents data from T cell engager portfolio

IGM Biosciences announced the presentation of data from IGM’s expanding portfolio of T cell engagers for hematologic malignancies, including IGM-2644, IGM-2537 and imvotamab, at the 2022 American Society of Hematology Annual Meeting and Exposition being held virtually and in-person in New Orleans, Louisiana, December 10-13, 2022. "As shown today, the preclinical profiles of IGM-2644, our CD38 x CD3 bispecific IgM antibody, and IGM-2537, our CD123 x CD3 bispecific IgM antibody, demonstrate the potential for encouraging antitumor activity coupled with favorable safety profiles," said Chris Takimoto, Chief Medical Officer of IGM Biosciences. "We are also presenting today biomarker data from the Phase 1 trial of imvotamab, our CD20 x CD3 bispecific IgM antibody, showing its encouraging activity in patients with low CD20 expressing tumors." The poster titled "IGM-2644, a Novel CD38 x CD3 Bispecific IgM T Cell Engager Demonstrates Potent Efficacy on Myeloma Cells with an Improved Preclinical Safety Profile" highlights IGM-2644’s greater complement dependent cytotoxicity activity as compared to conventional IgG anti-CD38 antibodies. Additionally, IGM-2644 achieved potent T cell dependent cellular cytotoxicity killing of daratumumab-resistant cell lines with minimal cytokine release as well as potent TDCC killing of myeloma patient samples. IGM-2644 was also shown to inhibit CD38+ tumor growth in humanized xenograft models, but it avoids killing immune effector cells as compared to an IgG bispecific T cell engager. IGM plans to initiate a Phase 1 trial of IGM-2644 in multiple myeloma in the first quarter of 2023, subject to Investigational New Drug application clearance. The poster titled "CD123 Directed IgM T-cell Engager, IGM-2537, Demonstrates Potent in vitro and in vivo Activity with Minimal Cytokine Release" highlights potent in vitro and in vivo activity with limited cytokine induction consistent with the potential for providing a favorable safety profile for a CD123-directed IgM-based T cell engager. IGM-2537 was shown to bind to human CD123 with high affinity, avidity, and specificity. IGM-2537 co-engaged with both CD123 and CD3 antigens, leading to T cell redirected killing of acute myeloid leukemia cell lines with concomitant T cell activation, and eliminated AML blast cells at physiologically relevant effector/target ratios in an ex vivo assay. IGM-2537 also showed significantly reduced cytokine release, exemplified by IFN-gamma, TNF-alpha and IL-6, as compared to an IgG T cell engager molecule. IGM expects to file an IND application for IGM-2537 in AML in 2023. The poster titled "Pharmacodynamics and Biomarker Correlates of Imvotamab (IGM-2323), the First-in-Class CD20xCD3 Bispecific IgM Antibody with Dual Mechanisms of Action, in Patients with Advanced B Cell Malignancies" features biomarker data from the Phase 1 trial evaluating imvotamab, the Company’s IgM T cell engaging bispecific antibody. The poster highlights that complete responses were observed even in patients with low CD20 expressing tumors. Biomarker data obtained from patients in dose escalation cohorts also demonstrated pharmacodynamic changes that support the TDCC and CDC mechanisms of action of imvotamab.