On November 8, 2015 Curis, Inc. (NASDAQ:CRIS), a biotechnology company focused on the development and commercialization of innovative drug candidates for the treatment of cancers, reported that its collaborator Aurigene presented preclinical data from two programs at the AACR (Free AACR Whitepaper)-NCI-EORTC AACR-NCI-EORTC (Free AACR-NCI-EORTC Whitepaper) International Conference on Molecular Targets and Cancer Therapeutics (EORTC-NCI-AACR) (Free ASGCT Whitepaper) (Free EORTC-NCI-AACR Whitepaper) including: (1) CA-170 (previously AUPM-170), a first-in-class oral, small molecule immune checkpoint antagonist targeting programmed death ligand-1 (PD-L1) and V-domain Ig suppressor of T cell activation (VISTA), and (2) the interleukin-1 receptor associated kinase 4 (IRAK4) inhibitor program. Curis recently exercised options to license both these programs under a collaboration agreement with Aurigene established earlier this year (Press release, Curis, NOV 8, 2015, View Source [SID:1234508105]).
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CA-170 (PD-L1/VISTA antagonist) presentation:
Aurigene presented a poster entitled "First-in-class orally available immune checkpoint antagonists for cancer therapy" on Friday, Nov. 6. The presentation included data from in vitro functional studies, which showed that CA-170 can rescue effector functions of T cells (such as cytokine secretion) that are inhibited specifically by interactions of PD-L1/L2 and VISTA checkpoint proteins but does not impact T cells functions that are modulated as a result of interactions of other checkpoint regulators such as TIM-3, CTLA4, LAG-3 and BTLA with their respective counterparts. Additionally, studies conducted with isolated human T cells demonstrate that short exposures to CA-170 (in the order of a few hours) are adequate to rescue and sustain activation of T cells functions. Daily oral administration of CA-170 resulted in anti-tumor activity in multiple syngeneic tumor models including melanoma and colon cancer but no activity was observed in immune deficient SCID-Beige mice, suggesting that the anti-cancer effects of CA-170 are mediated via activation of immune responses to these cancers.
"The collective in vitro and animal model data are very compelling and strongly support testing of CA-170 in human clinical trials in multiple cancers," said Ali Fattaey, Ph.D., Curis’ President and CEO. "We are working with Aurigene to complete the IND enabling studies for CA-170 and initiate clinical studies in the first half of 2016."
IRAK4 inhibitor presentation:
Aurigene poster entitled "Efficacy of novel IRAK4 inhibitors in ABC-DLBCL and AML models" was presented on Sunday, Nov. 8. This presentation included data from chemically distinct series of small molecule compounds with potent IRAK4 inhibitory activity in biochemical assays. Anti-tumor activity of lead compounds was confirmed in a MYD88 mutant DLBCL xenograft tumor model. Lead compounds also inhibited inflammatory responses in an in vivo model, suggesting that IRAK4 inhibitors have the potential for use in the treatment of inflammatory diseases. Preliminary in vivo safety studies demonstrate a favorable therapeutic index for further development of lead compounds for potential human testing.