On April 21, 2020 Forma Therapeutics, Inc. ("Forma"), a clinical-stage biopharmaceutical company focused on rare hematologic diseases and cancers, reported that it will be presenting an electronic poster at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) taking place virtually June 22-24, 2020 (Press release, Forma Therapeutics, APR 21, 2020, View Source [SID1234556451]). The poster will include preclinical data from a potent and selective inhibitor of CBP/p300, a known co-activator of the androgen receptor (AR) and a driver of metastatic castration-resistant prostate cancer (mCRPC). The data demonstrate antitumor activity of a novel CBP/p300 inhibitor, FT-6876, in AR-dependent breast cancer cell lines and highlight the possible role of CBP/p300 in proliferation and survival of AR-dependent tumors.

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Specific findings indicate that Forma’s investigational agent, FT-6876:

Inhibits the bromodomain of CBP/p300 and prevents binding to acetylated lysine on histone and non-histone proteins;
Reduces histone acetylation at position H3K27, a modification associated with increased gene transcription;
Reduces AR-dependent transcription and AR protein levels; and
Reduces cell proliferation, including levels of Ki-67 in vitro and in vivo in prostate and AR-positive breast cancer models.
"These important data support the rationale that targeting the CBP/p300 bromodomain may provide a differentiated approach to modulating AR pathway activation in malignancies that are dependent on AR," said Patrick Kelly, M.D., chief medical officer of Forma Therapeutics. "The most prominent potential indication for this investigational agent is mCRPC, since there is a dearth of effective treatment options for this advanced form of prostate cancer. We hope to change that."

Abstracts of presentations accepted by AACR (Free AACR Whitepaper) will be published online on May 15, 2020.

About Metastatic Castration-Resistant Prostate Cancer (mCRPC)

Prostate cancer is the second leading cause of cancer death for men in the U.S., and mCRPC is the most advanced form of this disease. Prostate cancer cell growth is driven by activity of the androgen receptor (AR). Primary treatments of mCRPC include therapies that reduce androgen synthesis or inhibit androgen binding and activation of the AR. Studies have shown that approximately 20% to 40% of mCRPC patients demonstrate primary resistance to enzalutamide and abiraterone acetate, two commonly used therapies, and virtually all patients who demonstrate initial clinical responses eventually acquire resistance. There are currently no approved therapies specifically aimed at mCRPC over-expressing AR variants, including AR-v7; therefore, a novel inhibitor of AR co-activator CBP/p300 may play a role in the suppression of mCRPC driven by AR aberrations.

About FT-7051

Clinical development candidate FT-7051, borne from research compound FT-6876, is a potent and selective in vitro inhibitor of CBP/p300, a co-activator of androgen receptor (AR) signaling and a driver of metastatic castration-resistant prostate cancer (mCRPC). In vitro, both FT-7051 and FT-6876 are antiproliferative in AR-positive prostate cancer cell lines, including resistance variant AR-v7 positive models. Forma Therapeutics is evaluating the investigational agent FT-7051 for potential clinical benefit in mCRPC.