Tensha raises $15 million in Series A financing to advance bromodomains for cancer

Sep 12 2011

Tensha Therapeutics announced today that it has raised $15 million in a Series A financing to advance the development of small molecule bromodomain inhibitors for the treatment of cancer and other conditions by regulating the transcription of disease-associated genes. The company's lead program, presently in preclinical development, is a first-in-class small molecule aimed at the treatment of BRD4-NUT midline carcinoma (a rare, invariably fatal cancer), acute myeloid leukemias, multiple myeloma, and other malignancies. HealthCare Ventures is the sole investor in the financing.

“There is a compelling biological rationale for bromodomain inhibition in cancer”

Bromodomains represent a promising new set of epigenetic drug targets. Bromodomains are protein modules that play critical roles in 'reading' epigenetic marks on chromatin that serve as instructions for the transcription of specific genes. Research led by the company's scientific founder, James Bradner, MD, an Investigator at Dana-Farber Cancer Institute, was the first to identify and characterize potent, selective small molecule inhibitors of BET bromodomain proteins that are important for cancer cell growth. Tensha has an exclusive license to the technology from Dana-Farber.

In pioneering studies, first published in Nature (Sept. 24, 2010, online edition), Dr. Bradner and colleagues described a small molecule, JQ1, that blocks the activity of an aberrant bromodomain-containing protein, BRD4-NUT, which causes midline carcinoma. BRD4-NUT is a fusion protein containing the BRD4 bromodomain and the nuclear protein in testis (NUT) protein that results from a chromosomal translocation. In patient-derived cell lines and mouse xenograft models, the compound blocked the protein's proliferative activity and induced tumor cells to differentiate into normal-appearing, non-cancerous cells.

Subsequent studies from Dr. Bradner's laboratory, in collaboration with researchers at Cold Spring Harbor Laboratory, identified BRD4 as a therapeutic target in acute myeloid leukemia. These studies extended JQ1's antiproliferative and differentiating activity in multiple model systems of leukemia. The research also suggested that inhibiting BRD4 suppresses a notorious oncogene, MYC, that is linked to a wide range of tumors. The studies were published in the Aug. 3, 2011 online edition of Nature.

Most recently, as an Immediate Early Publication in the journal Cell (Sept. 1, 2011, online), the Bradner group demonstrated that JQ1 halted the growth of multiple myeloma cells in vitro and in vivo by selective inhibition of MYC expression, again via inhibition of BRD4. The research was conducted by Dr. Bradner and colleagues at Dana-Farber, with collaborative support from the Whitehead Institute for Biomedical Research, Cold Spring Harbor, and the Mayo Clinic.

"There is a compelling biological rationale for bromodomain inhibition in cancer," said Dr. Bradner. "Our collaborative studies to date have established the feasibility of targeting epigenetic reader proteins. Through Tensha, we have a foundation for developing and translating novel bromodomain inhibitors. This financing will allow Tensha to advance our first-in-class program through clinical proof-of-concept, lay the groundwork for clinical studies in other cancer indications, and advance the preclinical development of bromodomain inhibitors in areas outside of oncology." Dr. Bradner noted there is emerging data for bromodomain inhibition in a diverse number of conditions, including inflammatory and metabolic disorders.

Douglas E. Onsi, Managing Director of HealthCare Ventures, commented, "We are very pleased to be partnering with Dr. Bradner, who leads the premier laboratory in this important new area of research. Bromodomain inhibitors have great potential to lead to the discovery of new therapeutics for patients with serious unmet medical needs. Tensha highlights our strategy of making 'Focused Company' investments in highly innovative, pre-clinical or early clinical stage products with the potential to transform patient care. In line with our approach, we plan to develop Tensha compounds within a capital efficient organization to clinical proof-of-concept."