BTM-3566 / Bantam Pharma - LARVOL DELTA

A phase 1 trial of BTM-3566 in relapsed/refractory mature B cell lymphomas. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT06792734 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

P1 data • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Selective pharmacological activation of the mitochondrial protease OMA1 inhibits tumor growth and induces regression in tumors expressing low levels of FAM210B (AACR 2025) - "Combinations of BTM-3566 with the BH3 mimetic navitoclax results in synergistic cell killing activity in select solid tumor lines in vitro. BTM-3566 targets an pathway important in mitochondrial quality control leading to tumor cell growth and regression. In vivo, drug activity correlated with low expression of RNA for the mitochondrial protein FAM210B. BTM-3566 demonstrated robust activity in vivo in solid tumors of diverse origin with low FAM210B RNA expression."

B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Esophageal Cancer • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Solid Tumor • Uterine Cancer • ATF4 • MCL1

Bantam Pharmaceutical Presents New Preclinical Data for BTM-3566 at the American Association for Cancer Research (AACR) Annual Meeting 2025 (PRNewswire) - "Bantam Pharmaceutical...announced solid tumor regression data from Bantam's lead product candidate, BTM-3566. These preclinical data will be shared in a poster presentation during the American Association for Cancer Research (AACR) Annual Meeting, being held from April 25-30, 2025 at the McCormick Place Convention Center in Chicago, Illinois...Key findings include: BTM-3566 exhibits in vitro and in vivo activity in a broad range of solid tumor models; BTM-3566 drives tumor regression in models with low FAM210B RNA expression, supporting the use of FAM210B as a potential biomarker for response; Ectopic expression of FAM210B blocks drug activity in multiple models, suggesting a mechanistic role for the protein in mediating response; BTM-3566 demonstrates additive and synergistic activity in combination with other agents from multiple classes in preclinical models, including BH3 mimetics, supporting future combination strategies."

Preclinical • Solid Tumor

Bantam Pharmaceutical Accelerates BTM-3566 Clinical Program Expanding Phase 1 Trial into Canada (PRNewswire) - "Bantam Pharmaceutical...today announced it is proceeding with a Phase 1 clinical trial evaluating BTM-3566 in relapsed/refractory mature B-cell lymphomas, based on a recent Clinical Trial Application (CTA) cleared by Health Canada. This regulatory milestone enables Bantam to expand its ongoing clinical program and to activate multiple clinical trial sites in Canada early in the second quarter of 2025....Initial clinical data from the trial are expected in the second half of 2025."

P1 data • Trial status • B Cell Lymphoma

Bantam Pharmaceutical Announces Activation of First Phase 1 Clinical Trial Site at MD Anderson Cancer Center (PRNewswire) - "Bantam Pharmaceutical...announced the activation of its first clinical trial site at The University of Texas MD Anderson Cancer Center for its Phase 1 study evaluating BTM-3566 in relapsed/refractory mature B-cell lymphomas. BTM-3566 is a first-in-class, small molecule cancer therapeutic which targets mitochondrial homeostasis via the ATF4-Integrated Stress Response (ISR) pathway to treat aggressive tumors....The Phase 1 clinical trial is a multicenter, open-label, dose-escalation and -expansion study. The study will evaluate the safety, tolerability, pharmacokinetics, anti-tumor, and pharmacodynamic effects of BTM-3566. Initial clinical data from the trial are expected in the second half of 2025."

P1 data • Trial status • B Cell Lymphoma

Phase 1 Trial of BTM-3566 in Relapsed/Refractory Mature B Cell Lymphomas (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Bantam Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Phase 1 Trial of BTM-3566 in Relapsed/Refractory Mature B Cell Lymphomas (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Bantam Pharmaceuticals

New P1 trial • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Pharmacological Targeting of Mitochondrial Quality Control Pathways Leads to Tumor Growth Inhibition in Solid Tumors (EORTC-NCI-AACR 2024) - "Treatment of cells with BTM-3566 in combination with the broad acting BH3 mimetic navitoclax resulted in additive activity in all cell lines except for A498 cells where synergy was observed. 1-Thiazol-2-yl-N—3-methyl-1H-pyrozole-5-carboxylic acids are novel pharmacophores that target pathways associated with mitochondrial quality control. These compounds have been previously shown to have robust activity in hematopoietic tumors. Our current work suggests that they will also induce growth arrest in select solid tumors of diverse origins."

Breast Cancer • Colorectal Cancer • Diffuse Large B Cell Lymphoma • Gastrointestinal Cancer • Hematological Malignancies • Melanoma • Oncology • Sarcoma • Solid Tumor • Uterine Cancer • ATF4

The integrated stress activator BTM-3566 overcomes therapeutic resistance in mantle cell lymphoma (AACR 2024) - "BTM-3566 inhibited cell proliferation across a panel of MCL cell lines, irrespective of resistance status to ibrutinib and venetoclax (IC50s of 142.5-687.6 nM)...Four PDX models encompassing naive, rituximab-resistant, BTKi-CAR T dual-resistant and BTKi-VEN-CAR T triple-resistant models were evaluated...Notably, no toxicity was observed during the treatment period. In summary, BTM-3566 is effective in treating MCL in vitro and in vivo in preclinical studies."

Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ATF4 • CASP3 • MCL1 • MYC

Targeting aggressive B-cell lymphomas through pharmacological activation of the mitochondrial protease OMA1. (PubMed, Mol Cancer Ther) - "Once-daily oral dosing of BTM-3566 resulted in complete regression of xenografted human DLBCL SU-DHL-10 cells and complete regression in 6 of 9 DLBCL patient-derived xenografts. BTM-3566 represents a first- of-its kind approach of selectively hyperactivating the mitochondrial ISR for treating DLBCL."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ATF4

BTM 3566, a Novel Activator of the Mitochondrial Stress Response Induces Robust Therapeutic Responses in Diffuse Large B-cell Lymphoma in vitro and in vivo (ICML 2023) - "BTM-3566 is an oral small molecule based on a pyrazolothiazol-backbone, developed for treatment of diffuse large B-cell lymphoma (DLBCL). Here we describe a novel, highly potent activator of the mitochondrial ISR, which is well tolerated in mice and dogs, has favorable pharmacokinetics and induces robust DLBCL regression in-vivo. An IND application in mature B-cells malignancies has been cleared by the FDA and Phase 1 study is ready to enroll in the second half of 2023."

IO biomarker • Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6 • MYC • MYD88

Pharmacokinetics and pharmacodynamics of the novel OMA1 activator BTM 3566 in a mouse model of diffuse large B-cell lymphoma (AACR 2023) - "The data support the use of both ATF4 transcripts and OPA1 cleavage as robust PD markers of target engagement and pathway effect in human clinical trials. An Investigational New Drug application for BTM3566 in B-cell malignancies has been approved with initiation of first in human clinical trials planned for spring 2023."

PK/PD data • Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ATF4 • CDKN1A • DDIT3 • MCL1 • TRIB3

Pharmacological activation of the mitochondrial stress protease OMA1 reveals a therapeutic liability in Diffuse Large B-Cell Lymphoma (AACR-NCI-EORTC 2022) - "We describe a novel antitumor mechanism in DLBCL, where BTM-3566 induces mitochondrial stress, activating the OMA1-DELE1-HRI-eIF2a-ATF4 pathway leading to apoptosis and tumor regression. An IND application in B-cell malignancies has been completed with initiation of first in human clinical trials planned in 2022."

IO biomarker • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ATF4 • EIF2A • EIF2S1

Bantam Pharmaceutical and Collaborators to Present New Data in Support of its Clinical Candidate BTM-3566 at Third AACR International Meeting - Advances in Malignant Lymphoma (PRNewswire) - "Bantam Pharmaceutical...announced that new data on the mechanism of action of its lead clinical candidate BTM-3566 will be presented at the Third AACR International Meeting - Advances in Malignant Lymphoma taking place on the 23-26 June in Boston....'Our data demonstrate exceptional single-agent activity in patient derived xenograft models of difficult-to-treat lymphomas. We are excited to bring this novel mechanism of action to the clinic in the coming months and explore its value as a treatment for relapsed and refractory DLBCL.'"

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

BTM-3566, A NOVEL ACTIVATOR OF THE MITOCHONDRIAL STRESS RESPONSE ERADICATES DIFFUSE LARGE B-CELL LYMPHOMA IN MICE (EHA 2022) - "Conclusion We describe a novel antitumor mechanism in DLBCL, where BTM-3566 induces mitochondrial stress, activating the OMA1-DELE1-HRI-eIF2a-ATF4 pathway leading to apoptosis and tumor regression. An IND application in DLBCL has been completed with initiation of first in human clinical trials planned in 2022."

IO biomarker • Preclinical • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Metabolic Disorders • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • ATF4 • EIF2A • EIF2S1

BTM-3655 co-opts mitochondrial quality control pathways to induce apoptosis, and complete tumor regression in DLBCL cell lines, xenografts and PDX models (AACR 2022) - "Taken together, these data support a novel antitumor mechanism in DLBCL, where BTM3566 induces mitochondrial stress, activating the OMA1-DELE1-HRI-eIF2a-ATF4 pathway leading to apoptosis and tumor regression. An Investigational New Drug application for BTM3566 in B-cell malignancies will be submitted by early Q1 2022 with initiation of first in human clinical trials the first half of 2022."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ATF4 • EIF2A • EIF2S1

Bantam Pharmaceutical and Collaborators to Present New Data in Support of its lead drug BTM-3566 at AACR Annual Meeting 2022 (PRNewswire) - "Bantam Pharmaceutical...will present new data on its lead drug candidate BTM-3566 at AACR 2022 taking place the 8th-13th of April in New Orleans. The data demonstrate that BTM-3566 co-opts a specific mitochondrial quality control pathway to induce apoptosis in cell lines, xenografts and patient-derived xenograft (PDX) models of Diffuse Large B-cell Lymphoma (DLBCL). The poster presentation on Wednesday, April 13th highlights the robust in vivo activity of BTM-3566, including complete and durable regressions in 6 out of 9 PDX models with a 100% response rate across a range of difficult to treat DLBCL tumors."

Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Btm-3566, a Novel Activator of the Mitochondrial Stress Response Promotes Robust Therapeutic Responses in Vitro and In Vivo in Diffuse Large B-Cell Lymphoma (ASH 2021) - "In summary, we describe here a novel, highly potent activator of the mitochondrial ISR, which is well tolerated in mice and dogs, has favorable pharmacokinetics and induces robust DLBCL regression in-vivo. An IND application in B-cell malignancies will be completed by early Q1 2022 with initiation of first in human clinical trials the first half of 2022."

IO biomarker • Preclinical • Bone Marrow Transplantation • Burkitt Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation • ATF4 • BCL2 • MYD88

605 Molecular Pharmacology and Drug Resistance: Lymphoid Neoplasms: Targeting Mitochondrial Survival Pathways (ASH 2021) - "Janani Ravikrishnan will discuss findings using a novel dual inhibitor of Bcl2 and Bcl-Xl in Chronic Lymphocytic Leukemia cells that relapse or are refractoray to Venetoclax treatment. Dr. Adrian Schwarzer will discuss the antileukemic effects in relapsed or refractory Diffuse Large B-Cell Lymphomas of BTM-3566, a novel activator of the mitochondrial integrated stress response."

Acute Lymphocytic Leukemia • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Mantle Cell Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Acute Lymphoblastic Leukemia • BCL2 • BCL2L1 • NAMPT • PRMT5

Data on Bantam Pharmaceutical's Lead Drug, BTM-3566 Highlighted During Oral Session on Targeting Mitochondria Pathways in Lymphoid Cancers at the 63rd Annual Meeting of the American Society of Hematology (PRNewswire) - "BTM-3566 induces rapid cell death in lymphoma cell lines, particularly those from DLBCL patients. In vivo, BTM-3566 was highly active in all patient-derived xenograft (PDX) models of DLBCL, and induced complete tumor regression in six out of eight models including those harboring genomic alterations usually associated with poor prognosis. Regressions were observed in multiple models of double-hit DLBCL....'These findings support our IND application in early 2022 and initiating first-in-human clinical trials in the first half of 2022'."

IND • New trial • Preclinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology

Bantam Pharmaceutical Announces Data on its lead drug, BTM-3566 to be Presented at the 63rd Annual Meeting of the American Society of Hematology (PRNewswire) - "Bantam Pharmaceutical...announced that data on BTM-3566, in development for the treatment of hematological malignancies including Diffuse Large B-cell Lymphoma, was selected for an oral presentation at the 63rd Annual Meeting of the American Society of Hematology (ASH), being held from December 11- 14, 2021, virtually and in-person in Atlanta."

Clinical data • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Non-Hodgkin’s Lymphoma • Oncology