imvotamab (IGM-2323) / IGM Biosciences - LARVOL DELTA

IGM-2323-102: A Phase 1b Study of Imvotamab in Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1 | N=33 | Terminated | Sponsor: IGM Biosciences, Inc. | Trial completion date: May 2026 ➔ Feb 2025 | Recruiting ➔ Terminated; Interim data from the Phase 1b studies of imvotamab in rheumatoid arthritis demonstrated that the depth and consistency in B Cell depletion required to measure success was insufficient.

Trial completion date • Trial termination • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

IGM-2323-103: A Study of Imvotamab in Active, Refractory Idiopathic Inflammatory Myopathies (clinicaltrials.gov) - P1 | N=2 | Terminated | Sponsor: IGM Biosciences, Inc. | N=10 ➔ 2 | Trial completion date: Nov 2026 ➔ Jan 2025 | Recruiting ➔ Terminated | Trial primary completion date: Aug 2025 ➔ Jan 2025; Program Discontinuation

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Myositis

IGM-2323-101: A Study of Imvotamab in Severe Systemic Lupus Erythematosus (clinicaltrials.gov) - P1 | N=17 | Terminated | Sponsor: IGM Biosciences, Inc. | Trial completion date: May 2026 ➔ Jan 2025 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2025 ➔ Jan 2025; Company Decision.

Trial completion date • Trial primary completion date • Trial termination • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

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

Imvotamab, a CD20-Targeted Bispecific IgM T Cell Engager, Effectively Depletes Low-Expressing CD20+ B Cells in Preclinical Models of Autoimmune Disease (ACR Convergence 2024) - P1 | "Imvotamab was substantially more effective than rituximab in killing low expressing CD20+ B cells, including switched memory and activated memory B cells from patients with autoimmune disease. Results using a low expressing CD20+ cell line further substantiate this finding, supporting the potential for improved killing of key pathogenic B cell subsets by imvotamab over rituximab. Imvotamab is currently being evaluated in phase 1b clinical trials with severe SLE (NCT# NCT06041568) and moderate to severe RA (NCT# NCT06087406)."

Preclinical • Immunology • Inflammatory Arthritis

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

IGM-2323-102: A Phase 1b Study of Imvotamab in Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: IGM Biosciences, Inc. | N=24 ➔ 40 | Trial completion date: Jul 2025 ➔ May 2026 | Trial primary completion date: Feb 2025 ➔ May 2025

Enrollment change • Trial completion date • Trial primary completion date • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

Cutting-edge approaches to B-cell depletion in autoimmune diseases. (PubMed, Front Immunol) - "In this review, we discuss the various BCDTs that are being developed in autoimmune diseases, describing the molecule designs, depletion mechanisms, and potential advantages and disadvantages of each approach as they pertain to safety, efficacy, and patient experience. Additionally, recent advances and strategies with TCEs are presented to help broaden understanding of the potential for bispecific antibodies to safely and effectively engage T cells for deep B-cell depletion in autoimmune diseases."

Journal • Review • Hematological Disorders • Hematological Malignancies • Immunology • Oncology

IGM Biosciences Announces Second Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "The Company announced that it has cleared both the first and second dose cohorts of its placebo-controlled clinical study testing imvotamab in severe rheumatoid arthritis and is currently enrolling the third cohort....The Company announced that it has cleared the first dose cohort of its open-label clinical study testing imvotamab in severe systemic lupus erythematosus (SLE), with each dose cohort designed to recruit six patients, all of whom are to be treated with imvotamab....Enrollment initiated in myositis.....The Company currently expects to begin enrolling patients in a single arm, open-label clinical study testing IGM-2644 in generalized myasthenia gravis (gMG) by the end of 2024."

Enrollment status • Myasthenia Gravis • Myositis • Rheumatoid Arthritis • Systemic Lupus Erythematosus

IGM-2323-001: A Study of Imvotamab Monotherapy and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=97 | Terminated | Sponsor: IGM Biosciences, Inc. | Trial completion date: Oct 2024 ➔ Feb 2024 | Active, not recruiting ➔ Terminated | Trial primary completion date: Oct 2024 ➔ Feb 2024; Strategic Pipeline Prioritization: Clinical development of imvotamab in autoimmune diseases prioritized.

Monotherapy • Trial completion date • Trial primary completion date • Trial termination • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Study of Imvotamab in Active, Refractory Idiopathic Inflammatory Myopathies (clinicaltrials.gov) - P1 | N=10 | Recruiting | Sponsor: IGM Biosciences, Inc.

New P1 trial • Myositis

Therapeutic Potential of Imvotamab, a CD20-Targeted Bispecific IgM T Cell Engager, for the Treatment of Refractory Autoimmune Disease Patients (FOCIS 2024) - "Given the promising durable response and safety profile in NHL, we evaluated imvotamab for depletion of peripheral and tissue-resident B cells in preclinical models of AI disease.Ex vivo cytotoxicity assays using human peripheral blood mononuclear cells (PBMCs) or serum from healthy donors and AI patients showed imvotamab induced potent killing of B cells from both AI patients and healthy donor PBMCs, and greater complement-dependent cytotoxicity compared to rituximab. Moreover, a CD20xCD3 IgM TCE can penetrate tissues to kill target cells in vivo. Clinical trials with imvotamab in AI patients are ongoing to evaluate the therapeutic benefit of this mechanism."

Clinical • Immunology

THERAPEUTIC POTENTIAL OF IMVOTAMAB, A CD20-TARGETED BISPECIFIC IGM T CELL ENGAGER, FOR THE TREATMENT OF REFRACTORY AUTOIMMUNE DISEASE PATIENTS (EULAR 2024) - "Background: B cell depletion therapy (BCDT) with conventional IgG antibodies (e.g. rituximab) has been used to treat autoimmune (AI) disease for several decades. Our preclinical data show imvotamab effectively kills peripheral B cells isolated from AI patients. Moreover, in a non-human primate model, a CD20xCD3 IgM TCE can penetrate tissues to kill target cells in vivo . Clinical trials with imvotamab in AI patients are ongoing to evaluate the therapeutic benefit of this mechanism."

Clinical • CNS Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lupus • Lymphoma • Multiple Sclerosis • Non-Hodgkin’s Lymphoma • Oncology • Rheumatoid Arthritis • Rheumatology • Systemic Lupus Erythematosus

IGM Biosciences Announces First Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "The Company has completed enrollment in the first dose cohort of its placebo-controlled clinical study testing imvotamab in severe rheumatoid arthritis....Enrollment continues in first dose cohort of imvotamab in severe systemic lupus erythematosus."

Enrollment status • Rheumatoid Arthritis • Systemic Lupus Erythematosus

Expanded Access of Imvotamab (IGM-2323) in Patients With R/R NHL (clinicaltrials.gov) - P=N/A | N=0 | No Longer Available | Sponsor: IGM Biosciences, Inc.

New trial • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

IGM Biosciences Announces Fourth Quarter and Full Year 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - “We also initiated two Phase 1b clinical trials of imvotamab in severe systemic lupus erythematosus and in severe rheumatoid arthritis...and we are optimistic that we will be able to generate meaningful initial clinical data by the end of 2024.”

P1 data • Trial status • Rheumatoid Arthritis • Systemic Lupus Erythematosus

A Study of Imvotamab in Severe Systemic Lupus Erythematosus (clinicaltrials.gov) - P1 | N=18 | Recruiting | Sponsor: IGM Biosciences, Inc. | Phase classification: P1b ➔ P1

Phase classification • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

A Phase 1b Study of Imvotamab in Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: IGM Biosciences, Inc. | Phase classification: P1b ➔ P1

Phase classification • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

A Study of Imvotamab Monotherapy and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=97 | Active, not recruiting | Sponsor: IGM Biosciences, Inc.

Monotherapy • Trial completion date • Trial primary completion date • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

MODULE 5: Future Role of Bispecific Antibodies in DLBCL (ASH 2023) - "Supported by educational grants from ADC Therapeutics, Genentech, a member of the Roche Group, Incyte Corporation, Kite, A Gilead Company, and Regeneron Pharmaceuticals Inc. Mechanistic similarities and differences among the various bispecific antibodies targeting CD20 and CD3 in DLBCL; implications for efficacy, tolerability and ease of use Key outcomes from the pivotal Phase II NP30179 expansion study leading to the FDA approval of glofitamab for R/R DLBCL Published findings with epcoritamab among patients with R/R DLBCL in the Phase II EPCORE NHL-1 trial; recent FDA approval of epcoritamab and its ongoing Phase III evaluation in EPCORE DLBCL-1 Recently presented data from the Phase I ELM-1 and pivotal Phase II ELM-2 studies of odronextamab for R/R DLBCL Early results with other bispecific antibodies for DLBCL, such as mosunetuzumab and imvotamab Tolerability profile of bispecific antibodies among patients with DLBCL; rates and severity of CRS, neurotoxicity and other..."

Diffuse Large B Cell Lymphoma • Oncology

Therapeutic Potential of Imvotamab, a CD20-Targeted Bispecific IgM T Cell Engager, for the Treatment of Refractory Autoimmune Disease Patients (ACR Convergence 2023) - "Background/Purpose: B cell depletion therapy (BCDT) with conventional IgG antibodies (e.g.rituximab) has been used to treat autoimmune (AI) disease for several decades. Our preclinical data suggests that imvotamab can effectively target and kill peripheral B cells from AI patients. Moreover, a CD20xCD3 IgM bispecific TCE can penetrate tissues and mediate direct killing of CD20-expressing target cells in vivo. Clinical studies with imvotamab in patients with autoimmune diseases, including RA and SLE, are planned to evaluate the therapeutic benefit of this mechanism."

Clinical • CNS Disorders • Hematological Malignancies • Immunology • Inflammatory Arthritis • Lymphoma • Multiple Sclerosis • Non-Hodgkin’s Lymphoma • Oncology

A Study of Imvotamab Monotherapy and in Combination in Subjects With Relapsed/Refractory Non-Hodgkin Lymphoma (clinicaltrials.gov) - P1/2 | N=97 | Active, not recruiting | Sponsor: IGM Biosciences, Inc. | Recruiting ➔ Active, not recruiting | N=260 ➔ 97 | Trial primary completion date: Sep 2024 ➔ Oct 2023

Enrollment change • Enrollment closed • Monotherapy • Trial primary completion date • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Phase 1b Study of Imvotamab in Moderate to Severe Rheumatoid Arthritis (clinicaltrials.gov) - P1b | N=24 | Recruiting | Sponsor: IGM Biosciences, Inc.

New P1 trial • Immunology • Inflammatory Arthritis • Rheumatoid Arthritis • Rheumatology • CRP

A Study of Imvotamab in Severe Systemic Lupus Erythematosus (clinicaltrials.gov) - P1b | N=18 | Recruiting | Sponsor: IGM Biosciences, Inc.

New P1 trial • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus

MODULE 3: Role of CD20 x CD3 Bispecific Antibodies in the Management of DLBCL (SOHO 2023) - "and AbbVie Inc., and Regeneron Pharmaceuticals Inc. Biological rationale for the evaluation of bispecific antibodies targeting CD20 and CD3 for DLBCL; mechanistic similarities and differences among the various agents, Key findings with epcoritamab in patients with R/R DLBCL from the expansion cohort of the Phase II EPCORE NHL-1 trial; recent FDA approval and ongoing Phase III evaluation, Recently presented outcomes from the pivotal Phase II NP30179 expansion study of fixed-duration glofitamab in R/R DLBCL; recent FDA approval and incorporation into clinical practice, Available data from Phase I and pivotal Phase II trials (ELM-1 and ELM-2) evaluating odronextamab for patients with R/R DLBCL; potential implications for management, Published findings with other bispecific antibodies (eg, mosunetuzumab, imvotamab) for DLBCL, Spectrum, frequency and severity of adverse events, including cytokine release syndrome and neurotoxicity, associated with bispecific antibodies in..."

Diffuse Large B Cell Lymphoma • Oncology • CD20