NOVEL MECHANISM OF ACTION

Selective activation of the ATF4 Integrated Stress Response suppresses tumor growth via metabolism, protein translation, and cell cycle.

CANDIDATE COMPOUNDS

Induce cell death in hematological cancers and growth suppression in broad range of solid tumor types.

EFFICACY

Regression and durable remission in xenograft models of Diffuse Large B-Cell Lymphoma. Growth suppression in KRAS mutated solid tumors.

MECHANISM

BTM-3566 modulates the ATF4 specific Integrated Stress Response (ISR) pathway via selective upregulation of eIF2α phosphorylation.

INTELLECTUAL PROPERTY

Bantam owns the intellectual property for the lead compounds and associated chemical space, including broad clinical applications. Patents ensure protection through 2038.

BANTAM SCIENCE AND PIPELINE

Bantam has developed novel compounds that reduce tumor cell growth and survival in a diverse set of hematological and solid tumor types.  These compounds display exceptional in-vivo efficacy in xenograft models:

  • Rapid tumor regression in lymphoid models (DLBCL)
  • Potent tumor growth inhibition in solid tumors including KRAS-mutated colorectal and lung cancers.

Bantam’s compounds have a unique mechanism of action (MoA), distinct from currently known targeted molecular therapeutics, including histone deacetylase, proteasome, and kinase inhibitors.  The MoA involves a series of actions that involve (1) activity of a novel mitochondrial membrane protein, (2) activation of the eIF2α mediated Integrated Stress Response (ISR), followed by (3) cell cycle arrest and upregulation of the ATF4 pathway, and (4) culminating in cancer cell apoptosis or suppression of tumor growth.

A critical component in this series of actions is a novel mitochondrial protein that is highly associated with cancer metastasis and poor clinical prognosis for certain hematopoietic and solid tumor cancers.

INTELLECTUAL PROPERTY

Bantam owns a rich intellectual property estate that covers the compounds, associated chemical space and broad clinical utility. Bantam also owns recently filed patent applications that feature additional claims related to the mechanism and all routes of administration. Claims in the first of the two more recently filed applications were published in December 2016, and the second application, a PCT application filed in November 2016 has entered national phase filings. These filings provide patent protection for Bantam’s pipeline and any derivative products through at least 2038.

MECHANISM OF ACTION

RECENT BANTAM PUBLICATIONS

“BTM compounds induce the integrated stress response and effectively inhibit growth of diffuse large B-cell lymphoma.” Matthew Kostura, Jedd Levine, Alan Cooper, Michael Luther. Inaugural AACR International Meeting Advances in Malignant Lymphoma: Maximizing the Basic-Translational Interface for Clinical Application.  June 22-26, 2018, Boston

“1-Thiazol-2-yl-N-3-methyl-1H-pyrozole-5-carboxylic acid derivatives as antitumor agents.” Cooper, Alan B. et.al. Bioorganic and Medicinal Chemistry Letters, 2017, 27, 4471-4477.

“BTM-3528 potently induces G1/G0 cell cycle arrest and is efficacious in pre-clinical models of diffuse large B-cell lymphoma.” Kostura M, Levine J, Oza V, et.al. Proceedings of 2nd AACR Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies. 2017, Abstract 45,63.