NOVEL MECHANISM OF ACTION
Potent effects on cancer cell metabolism that are distinct from known approaches.
Induce cell death in haematological tumors. No demonstrable effect on normal cells.
Demonstrated in vivo proof of concept in xenograft studies with B-Cell Lymphomas and KRAS mutant solid tumors
Therapeutic effect leads to the activation of the ATF4 mediated Integrated Stress Response (ISR) pathway, which is distinct from other therapeutics.
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
Using structure-based drug design, Bantam has identified novel compounds that reduce tumor cell growth and survival in a diverse set of cancer cell types. The mechanism of the action appears to be exclusive for tumor cell lines as the compounds don’t affect normal cells. The compounds display exceptional efficacy in xenograft studies including rapid tumor regression in lymphoid models, and potent activity against KRAS mutant solid tumors including colorectal and lung cancers. The lead compounds possess excellent ADMET properties and are well tolerated in vivo.
The mechanism of action is through the modulation the ATF4 mediated Integrated Stress Response (ISR) pathway. Activation of ISR is primed by dysregulation of essential metabolic pathways resulting in upregulation of the tumor suppressors ATF4 and p21 that ultimately lead to cell cycle arrest at G0/G1 and apoptosis. Based on biochemical, genomic, and cell line profiling, this mechanism of action is novel and distinct from other targeted therapeutics, including histone deacetylase, proteasome, and kinase inhibitors including the cyclin-dependent kinase inhibitors.
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 in the US, and the second application, a PCT application filed in November 2016 has entered national phase filings. These filings will support patent protection for Bantam’s pipeline and any derivative products through at least 2038.
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 cellcycle 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.