aplitabart (IGM-8444) / IGM Biosciences - LARVOL DELTA

IGM-8444-001: Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants with Relapsed, Refractory, or Newly Diagnosed Cancers (clinicaltrials.gov) - P1 | N=272 | Terminated | Sponsor: IGM Biosciences, Inc. | Trial completion date: Aug 2027 ➔ Jan 2025 | Active, not recruiting ➔ Terminated | Trial primary completion date: Jun 2026 ➔ Jan 2025; Study terminated due strategic corporate pivot to focus on auto-immune indications

Trial completion date • Trial primary completion date • Trial termination • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Colorectal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Small Lymphocytic Lymphoma • Solid Tumor

Targeting Death Receptor 5 (DR5) for imaging and treatment of primary bone and soft tissue tumors: an update of the literature. (PubMed, Front Mol Biosci) - "The combination of DR5 agonists and commonly used chemotherapeutic agents, such as doxorubicin, can promote cell death...There are currently two ongoing clinical trials focusing on the activation of DR5, namely, IGM-8444 and INBRX-109, which have progressed to phase 2. Further modifications of TRAIL delivery with fusion to single-chain variable fragments (scFv-TRAIL), directed against tumor-associated antigens (TAAs), and in the use of stem cells focus on targeted TRAIL delivery to cancer cells using bi-functional strategies. In vitro, in vivo, and clinical trials, as well as advances in imaging and theranostics, indicate that targeting DR5 remains a valid strategy in the treatment of some relapsed and refractory cancers."

Journal • Review • Oncology • Osteosarcoma • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • TNFRSF10B

IGM-8444-001: Phase 1a/1b Study of Aplitabart (IGM-8444) Alone or in Combination in Participants With Relapsed, Refractory, or Newly Diagnosed Cancers (clinicaltrials.gov) - P1 | N=272 | Active, not recruiting | Sponsor: IGM Biosciences, Inc. | Recruiting ➔ Active, not recruiting | N=430 ➔ 272

Enrollment change • Enrollment closed • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Small Lymphocytic Lymphoma • Solid Tumor

IGM Biosciences Announces Second Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "Aplitabart: Enrollment completed in randomized colorectal cancer clinical trial....Based on its assumptions as to the timing of PFS events, the Company expects to be able to release top-line PFS results from this study by the end of the first quarter of 2025."

Enrollment status • Colorectal Cancer • Hematological Malignancies • Oncology

IGM Biosciences Announces First Quarter 2024 Financial Results and Provides Corporate Update (GlobeNewswire) - "(i) Enrollment target exceeded in ongoing randomized colorectal cancer clinical trial. The Company has exceeded its target of enrolling 110 patients in its randomized clinical trial of 3 mg/kg of aplitabart, a death receptor 5 agonist, plus FOLFIRI and bevacizumab in second-line metastatic colorectal cancer....Based on its assumptions as to the timing of PFS events, the Company expects to be able to release top-line PFS results from this study by the end of the first quarter of 2025; (ii) Enrollment target met in 10 mg/kg dose single arm colorectal cancer clinical trial. The Company has also met its target of enrolling 20 patients in its single arm clinical study of 10 mg/kg of aplitabart in combination with FOLFIRI and bevacizumab in the treatment of later line colorectal cancer patients."

Enrollment status • P1 data • Colorectal Cancer

Novel combinations of aplitabart, a DR5 agonist IgM antibody, with ADCs or chemotherapeutic agents lead to robust anti-tumor responses in solid tumor models (AACR 2024) - P1 | "Our findings demonstrate potent in vitro synergistic cytotoxicity and enhanced anti-tumor response in preclinical models in vivo by combining aplitabart with ADCs, or carboplatin and paclitaxel. These results support the combination of DR5 agonist IgM antibodies with agents known to upregulate DR5 expression on solid tumors. Aplitabart is currently under evaluation in a randomized clinical study in combination with FOLFIRI + bevacizumab in comparison with FOLFIRI + bevacizumab in patients with colorectal cancer (NCT04553692)."

Preclinical • Breast Cancer • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • TNFA • TNFRSF10B

IGM-8444 is an Agonist anti-DR5 IgM Engineered for Enhanced Potency and Safety (FOB-USA 2024) - No abstract available

Clinical

IGM Biosciences Announces Fourth Quarter and Full Year 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Evaluating 10 mg/kg dose in single arm colorectal cancer clinical trial. The Company also continues to evaluate a dose of 10 mg/kg of aplitabart in combination with FOLFIRI and bevacizumab in the treatment of later line colorectal cancer patients in its single arm combination clinical trial. The Company expects to complete enrollment of patients in this 10 mg/kg single arm combination dose cohort in the first half of 2024."

Trial status • Colorectal Cancer

IGM-8444-001: Phase 1a/1b Study of Aplitibart (IGM-8444) Alone or in Combination in Participants With Relapsed, Refractory, or Newly Diagnosed Cancers (clinicaltrials.gov) - P1 | N=430 | Recruiting | Sponsor: IGM Biosciences, Inc. | Trial completion date: Jan 2027 ➔ Aug 2027 | Trial primary completion date: Nov 2026 ➔ Jun 2026

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Small Lymphocytic Lymphoma • Solid Tumor

Medivir's partner IGM Biosciences announces strategic pipeline prioritization to extend its cash runway (PRNewswire) - "Medivir AB...announced today that its partner, IGM Biosciences, has communicated a strategic pipeline prioritization and reduction of workforce with the key aim of extending its cash runway in a challenging financial climate. In the announcement by IGM, a number of its programs are impacted by this pipeline prioritization, including the combination of IGM's DR-5 agonist, aplitabart and birinapant, which IGM licensed from Medivir in 2021....The announcement by IGM has no impact on Medivir's focus and development efforts with its lead program fostroxacitabine bralpamide (fostrox) for the treatment of primary liver cancer (HCC). Medivir continues to maximize the momentum of the fostrox development program as it accelerates a number of critical activities to enable initiation of a pivotal phase 2b study with accelerated approval intent by 2027."

Clinical • Gastrointestinal Cancer • Hepatocellular Cancer • Liver Cancer • Oncology • Solid Tumor

IGM-8444-001: Phase 1a/1b Study of IGM-8444 Alone and in Combination in Subjects With Relapsed, Refractory, or Newly Diagnosed Cancers (clinicaltrials.gov) - P1 | N=430 | Recruiting | Sponsor: IGM Biosciences, Inc.

Trial completion date • Trial primary completion date • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Small Lymphocytic Lymphoma • Solid Tumor

IGM-8444-001: Phase 1a/1b Study of IGM-8444 Alone and in Combination in Subjects With Relapsed, Refractory, or Newly Diagnosed Cancers (clinicaltrials.gov) - P1 | N=430 | Recruiting | Sponsor: IGM Biosciences, Inc. | Phase classification: P1a/1b ➔ P1

Phase classification • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Sarcoma • Small Lymphocytic Lymphoma • Solid Tumor

Pharmacokinetics and pharmacodynamics of IGM-8444, a first-in-class engineered pentameric DR5-targeting agonist IgM monoclonal antibody, in patients with R/R and newly diagnosed cancers. (AACR-NCI-EORTC 2023) - No abstract available

Clinical • PK/PD data • Oncology

A randomized Phase 1b study of IGM-8444 in combination with FOLFIRI + bevacizumab compared to FOLFIRI + bevacizumab alone in second line metastatic colorectal cancer. (AACR-NCI-EORTC 2023) - No abstract available

Clinical • Combination therapy • Metastases • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

A phase 1 study of IGM-8444, an IGM-based DR5 agonist, as a single agent (SA) in patients with relapsed/refractory (R/R) solid tumors. (AACR-NCI-EORTC 2023) - No abstract available

Clinical • P1 data • Oncology • Solid Tumor

IGM Biosciences Announces Second Quarter 2023 Financial Results (GlobeNewswire) - "Dosing ongoing in the randomized colorectal cancer clinical trial. The Company is currently enrolling patients in an open-label randomized clinical trial of aplitabart plus FOLFIRI and bevacizumab in second-line metastatic colorectal cancer. This randomized trial will assess the additional benefit of 3 mg/kg of aplitabart with a primary endpoint of progression-free survival (PFS) and secondary endpoints of overall response rate and overall survival as compared to the current standard of care treatment arm of FOLFIRI and bevacizumab. The Company’s goal is to have enrolled approximately 110 patients in the trial by the end of the first quarter of 2024 and to have median PFS data from these patients by the end of 2024."

P1 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

IGM Biosciences Announces Update on IGM-8444 Phase 1 Trial and Future Clinical Development (GlobeNewswire) - P1a/1b | N=430 | NCT04553692 | Sponsor: IGM Biosciences, Inc. | "Phase 1 data reported from a cohort of patients treated with IGM-8444 in combination with FOLFIRI, with and without bevacizumab, showed a very encouraging safety profile which was broadly comparable to that expected from chemotherapy alone in this setting. Specifically, in the 51 CRC patients treated with IGM-8444 plus FOLFIRI, with and without bevacizumab, no drug related clinically significant hepatotoxicity was observed and only grade 1 and grade 2 transient liver enzyme elevations were noted, through the data cut-off date of April 12, 2023....At the time of the data cut-off, multiple confirmed partial responses were observed among the patients treated with 3 mg/kg of IGM-8444 and FOLFIRI, with and without bevacizumab, including some patients who had previously progressed on FOLFIRI treatment."

P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology

IGM Biosciences to Host Conference Call and Webcast to Provide IGM-8444 Clinical Update (GlobeNewswire) - "IGM Biosciences, Inc...announced that it will host a conference call and live webcast to provide an update on its clinical development program for IGM-8444, a novel multivalent DR5 agonist, on Friday, June 2, 2023 at 7:00 p.m. ET. The Company will be providing a clinical data update on 3 mg/kg IGM-8444 + FOLFIRI (± bevacizumab) in median third line metastatic colorectal cancer patients from a non-randomized clinical trial cohort....In this presentation, the Company will not be providing a clinical data update from its recently initiated randomized study of IGM-8444 + FOLFIRI and bevacizumab in second line colorectal cancer patients."

P1 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor

IGM Biosciences Announces First Quarter 2023 Financial Results and Provides Corporate Update (GlobeNewswire) - "Dosing ongoing in the randomized colorectal cancer clinical trial. The Company is currently treating patients in a randomized clinical trial of IGM-8444 plus FOLFIRI and bevacizumab in second line metastatic colorectal cancer. The Company plans to assess both the 3 mg/kg and 10 mg/kg dose levels of IGM-8444 with a primary endpoint of progression free survival and secondary endpoints of overall response rate and overall survival as compared to the current standard of care treatment arm. Dosing ongoing in the venetoclax combination. The Company is currently treating patients with acute myeloid leukemia in its IGM-8444 plus venetoclax and azacytidine Phase 1 combination cohort....Additional clinical data expected in middle of 2023. The Company plans to present additional clinical data from the 3 mg/kg of IGM-8444 plus FOLFIRI cohort, with and without bevacizumab, of its non-randomized Phase 1 clinical trial in the middle of 2023."

P1 data • Trial status • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Leukemia • Oncology • Solid Tumor

Characterization of the synergistic tumor cytotoxicity of agonistic DR5 IgM antibody IGM-8444 with chemotherapeutic agents (AACR 2023) - P1a/1b | "In summary, IGM-8444 shows in vitro cytotoxicity and in vivo PD and anti-tumor efficacy responses in preclinical models, with enhanced activity in combination with several classes of chemotherapies reported to upregulate DR5 expression. IGM-8444 combination with FOLFIRI standard of care is currently under evaluation in a Phase 1 study in patients with metastatic colorectal cancer (NCT04553692)."

Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • CASP3 • TNFA • TNFRSF10B

IGM Biosciences Announces Fourth Quarter and Full Year 2022 Financial Results and Provides Corporate Update (GlobeNewswire) - "IGM-8444 (DR5): The Company announced today that it has treated the first patient in a randomized clinical trial of IGM-8444, an IgM agonist antibody targeting death receptor 5 (DR5), plus FOLFIRI and bevacizumab in second line metastatic colorectal cancer; The Company also announced today that it has dosed the first patient in its IGM-8444 plus venetoclax and azacytidine Phase 1 combination cohort in subjects with acute myeloid leukemia."

Trial status • Acute Myelogenous Leukemia • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Solid Tumor

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

[VIRTUAL] Mechanistic evaluation of anti-DR5 IgM antibody IGM-8444 with potent tumor cytotoxicity, without in vitro hepatotoxicity (AACR 2021) - P1 | "Indeed, we have demonstrated enhanced anti-tumor efficacy by combining IGM-8444 with chemotherapies such as 5-FU and irinotecan in colorectal cancer models, as well as combining with Bcl-2 inhibitor ABT-199 in hematological malignancy models. In summary, we have evaluated the mechanism by which IGM-8444 agonizes DR5, which potently kills tumor cells without accompanying hepatotoxicity. IGM-8444 is currently being evaluated in a Phase 1 study as a single agent and in combination with chemotherapy-based regimens in patients with solid cancers and NHL (NCT04553692)."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Hematological Malignancies • Oncology • Solid Tumor • TNFA • TNFRSF10B

Anti-DR5 agonist IgM antibody IGM-8444 combined with SMAC mimetic birinapant induces strong synergistic tumor cytotoxicity (AACR 2022) - P1 | "In summary, combined targeting of the extrinsic and intrinsic apoptotic pathways with IGM-8444 and birinapant respectively enhances tumor cytotoxicity in multiple preclinical models. The combination of IGM-8444 with birinapant is currently under evaluation in a Phase 1 study in patients with relapsed and/or refractory solid cancers (NCT04553692)."

Breast Cancer • Fibrosarcoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Sarcoma • Solid Tumor • Triple Negative Breast Cancer • KRT18 • TNFA • TNFRSF10B

IGM Biosciences Announces Update on IGM-8444 Phase 1 Trial and Future Clinical Development (GlobeNewswire) - P1a/1b | N=430 | NCT04553692 | Sponsor: IGM Biosciences, Inc. | " In 13 metastatic patients treated with doses of IGM-8444 from 1 to 10 mg/kg plus standard doses of FOLFIRI chemotherapy, there were four responses observed (three confirmed at 3mg/kg), and one additional patient had substantial tumor shrinkage allowing for subsequent complete surgical resection....Median progression free survival (PFS) among nine 3L+ patients was 5.5 months, with the longest observed PFS extending beyond 12 months....Based on these results, the Company is initiating a randomized trial in second line patients with metastatic colorectal cancer to assess the additional benefit of IGM-8444 combined with the current standard of care regimen of FOLFIRI and bevacizumab. This open label trial is planned to begin in Q1 2023."

P1 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Oncology