IGM-2644 / IGM Biosciences - LARVOL DELTA

Selinexor, mezigdomide, and dexamethasone in patients with Relapsed/Refractory multiple myeloma who relapsed or are ineligible for T-cell–redirecting therapy: Stomp Phase 1 results (ASH 2025) - P1/2 | "Both selinexor (S), an oral exportin 1 (XPO1)inhibitor (approved in combination with dexamethasone (d) in penta-refractory MM and with dand bortezomib in RRMM after ≥1 prior therapy), and mezigdomide (M), a novel and potentcereblon E3 ubiquitin ligase modulator (under investigation in RRMM), have shown T-cellpreservation/stimulatory activity...Three pts (23.1%) had relapsed after TCRT (3cilta-cel; 2 talquetamab; 1 IGM-2644), and 4 after belantamab mafodotin, with 30.8% beingrefractory to B-cell maturation antigen–targeted therapy.As of July 8, 2025, no dose-limiting toxicities (DLTs) were encountered in cohorts 1 and 2... For the all-oral combination of SMd, TEAEs were consistent with AE profiles for S andM, and no new safety signals were detected; DLT of G4 neutropenia was reported butmanageable with filgrastim support and dose reduction. Across all dose levels, SMd showedefficacy in pts with heavily pre-treated RRMM in whom TCRT had failed or who otherwise..."

Clinical • IO biomarker • P1 data • Cardiovascular • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Leukopenia • Multiple Myeloma • Neutropenia • Targeted Protein Degradation • Thrombocytopenia • CCR7 • CRBN • TIGIT • XPO1

IGM Biosciences Provides Strategic Update on Autoimmunity Pipeline Programs (GlobeNewswire) - 'IGM Biosciences...today announced a strategic update to halt further development of imvotamab, an IgM-based CD20 X CD3 bispecific antibody T cell engager, and IGM-2644, an IgM-based CD38 X CD3 bispecific antibody T cell engager, for autoimmune diseases....'Interim data from the Phase 1b studies of imvotamab in rheumatoid arthritis and systemic lupus erythematosus show that the depth and consistency of B cell depletion is insufficient to meet our high bar for success,'...'Due to these findings, we have decided to discontinue further development of imvotamab...Concurrent with discontinuation of the imvotamab program, IGM-2644 is also being terminated due to strategic considerations.'"

Discontinued • Immunology • Rheumatoid Arthritis • Systemic Lupus Erythematosus

IGM Biosciences Announces Third Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Imvotamab (CD20 x CD3) trials in rheumatoid arthritis, systemic lupus erythematosus and myositis ongoing; initial clinical data expected by mid-2025....IGM-2644 (CD38 x CD3 T cell engager)....The Company expects to enter IGM-2644 into a single arm, open-label clinical study for generalized myasthenia gravis (gMG) by the end of 2024."

New trial • P1 data • Myasthenia Gravis • Myositis • Rheumatoid Arthritis • Systemic Lupus Erythematosus

Evaluation of IGM-2644 in Adults With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=4 | Terminated | Sponsor: IGM Biosciences, Inc. | N=100 ➔ 4 | Trial completion date: Aug 2026 ➔ Feb 2024 | Recruiting ➔ Terminated | Trial primary completion date: Mar 2026 ➔ Feb 2024; Company Decision

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Hematological Malignancies • Multiple Myeloma • Oncology

IGM-2644, a CD38xCD3 bispecific IgM T cell engager, shows enhanced anti-tumor activity compared to daratumumab in preclinical models of multiple myeloma (AACR 2024) - "The safety and efficacy of IGM-2644 has been initially studied in a phase 1 clinical trial for relapsed/refractory (r/r) MM. Applicability of IGM-2644 for the treatment of other plasma cell disorders is currently being explored, including autoimmune diseases."

IO biomarker • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

TRIAL IN PROGRESS: AN OPEN-LABEL, MULTICENTER, PHASE 1 STUDY OF IGM-2644 IN PARTICIPANTS WITH RELAPSED AND/OR REFRACTORY MULTIPLE MYELOMA (RRMM) (IMW 2023) - "IGM-2644 is a novel bispecific IgM T cell engager with both CDC and TDCC mechanisms of cytotoxicity and the potential to be active in daratumumab-resistant tumors. This Phase 1 trial is underway, and results will be presented at a future meeting."

Clinical • IO biomarker • P1 data • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma

IGM Biosciences Announces Second Quarter 2023 Financial Results (GlobeNewswire) - "IGM-2644 (CD38 x CD3):...The Company has initiated a clinical trial exploring the safety and efficacy of IGM-2644, a CD38 x CD3 IgM T cell engaging antibody, in patients with recurrent or refractory multiple myeloma."

Trial status • Hematological Malignancies • Multiple Myeloma • Oncology

Evaluation of IGM-2644 in Adults With Relapsed and/or Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: IGM Biosciences, Inc.

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

HIGH VALENCY OF IGM-2644, A CD38XCD3 IGM BISPECIFIC T CELL ENGAGER, DISPLACES DARATUMUMAB BINDING AND INDUCES POTENT MULTIPLE MYELOMA CELL KILLING (EHA 2023) - "Our preclinical data indicate that IGM-2644 maintains activity in the presence ofdaratumumab. A Phase 1 clinical trial in r/r MM is being planned to evaluate the safety and pharmacokinetics of IGM-2644. The clinical study will evaluate these preclinical findings, including the treatment of patients with circulating serum levels of daratumumab."

IO biomarker • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma

Novel CD38xCD3 bispecific IgM T cell engager, IGM-2644, potently kills multiple myeloma cells though complement and T cell dependent mechanisms (AACR 2023) - "Although therapeutic regimens, including anti-CD38 monospecific IgG antibodies such as daratumumab and isatuximab in combination with chemotherapies, demonstrate clinical efficacy, most patients eventually develop resistance. In summary, IGM-2644 is a novel, potent, bispecific IgM TCE that has both CDC and TDCC mechanisms of cytotoxicity with the potential to be active in daratumumab resistant tumors. The balance of potent TDCC and CDC cytotoxic activity, along with an improved preclinical safety profile compared to other CD38xCD3 bispecific IgG TCEs, supports the clinical development of IGM-2644 in MM."

IO biomarker • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology

IGM Biosciences Announces Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "IGM-2644 (CD38 x CD3): The Company announced today that the U.S. Food and Drug Administration has cleared its IND application for a Phase 1 dose escalation trial of IGM-2644, a CD38 x CD3 IgM T cell engaging antibody, in patients with recurrent or refractory multiple myeloma."

IND • Hematological Malignancies • Multiple Myeloma • Oncology

IGM Biosciences Announces Six Presentations at the American Society for Cancer Research Annual Meeting 2023 (GlobeNewswire) - "IGM Biosciences...announced the presentation of six posters at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2023....'We are proud to show the breadth and depth of our oncology pipeline at this year’s AACR meeting, as the emerging data from our clinical and pre-clinical efforts on IGM-8444, IGM-7354, IGM-2644, IGM-2537 and imvotamab continue to demonstrate the potential for encouraging anticancer activity coupled with favorable safety profiles'..."

Preclinical • Trial status • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor

IGM Biosciences Presents Data from T cell Engager Portfolio for Hematologic Malignancies at 2022 American Society of Hematology Annual Meeting (GlobeNewswire) - "IGM Biosciences, Inc....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 (ASH) Annual Meeting and Exposition being held virtually and in-person in New Orleans, Louisiana, December 10-13, 2022....Additionally, IGM-2644 achieved potent T cell dependent cellular cytotoxicity (TDCC) 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 (IND) application clearance."

New P1 trial • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

IGM Biosciences Announces Third Quarter 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "Pipeline Updates - IGM-2644 (CD38 x CD3): (i) Preclinical data for IGM-2644, the Company’s CD38 x CD3 bispecific IgM antibody, selected for poster presentation at 2022 ASH Annual Meeting and Exposition: The results will be presented on Sunday, December 11, 2022....Preclinical data will be presented that highlights the potency of IGM-2644 with potential activity in daratumumab resistant tumors and a preclinical safety profile with lower cytokine release and reduced T cell fratricide compared to other CD38 x CD3 bispecific T cell engagers; (ii) Phase 1 trial expected to initiate in first quarter of 2023: IGM expects to initiate a Phase 1 trial of IGM-2644 in multiple myeloma in the first quarter of 2023, subject to IND clearance."

New P1 trial • Preclinical • Hematological Malignancies • Multiple Myeloma • Oncology

IGM Biosciences Announces First Quarter 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "IGM expects to file an IND for IGM-2644, the Company’s CD38 x CD3 bispecific IgM antibody, in multiple myeloma this year."

IND • Hematological Malignancies • Multiple Myeloma • Oncology