On April 20, 2016 Curis, Inc. (NASDAQ:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of human cancers, reported that Curis and its collaborator, Aurigene, presented data from the following programs at the Annual Meeting of American Association of Cancer Research (AACR) (Free AACR Whitepaper) in New Orleans, LA (Press release, Curis, APR 20, 2016, View Source [SID:1234511139]).

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Curis poster presentation on CUDC-907, an oral inhibitor of histone deacetylase (HDAC) and phosphoinositide 3-kinase (PI3K)

Aurigene presentation on 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), as well as data from the PD-L1/ T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) antagonist program

Aurigene presentation on CA-4948, the lead compound from the interleukin-1 receptor associated kinase 4 (IRAK4) inhibitor program
"Our data show significant effect of CUDC-907 on MYC levels and the compound’s antitumor activity in multiple preclinical models of MYC-altered malignancies, providing further support to the results of our Phase 1 trial where we observed objective responses in patients with DLBCL, and particularly those with MYC-altered disease," said Ali Fattaey, Ph.D., Curis’ President and CEO. "The presentations by our collaborator, Aurigene not only highlight our progress in immuno-oncology with CA-170, which we look to advance into the clinic in the first half of the year, but also Aurigene’s ability to extend the small molecule discovery capabilities to now target TIM3 in a separate program."

CUDC-907 presentation:

The Curis poster "Novel dual HDAC & PI3K inhibitor, CUDC-907, for MYC-driven malignancies" provided data on the activity of CUDC-907 in multiple MYC-altered disease models using both in vitro experiments and in vivo animal studies. Cell line and animal model studies using multiple MYC-altered DLBCL models showed that CUDC-907 had significant anti-tumor activity that correlated with the compound’s effect on downregulating MYC levels in a time and dose dependent manner. This effect was independent of disease subtypes classified using other molecular markers. CUDC-907 also showed potent anti-tumor activity in multiple cell lines of NUT midline carcinoma (NMC), a rare genetically defined tumor, which also demonstrates MYC dysregulation. CUDC-907 downregulated MYC levels in NMC cell lines and was more potent than BET inhibitors in in vitro assays of growth inhibition. The anti-tumor effects of CUDC-907 in NMC were further confirmed in a xenograft mouse model and in several MYC-amplified patient-derived xenograft models of solid tumors.

CA-170 (PD-L1/VISTA antagonist) and small molecule PD-L1/TIM-3 antagonist presentation:

The Aurigene presentation "Oral immune antagonist targeting PD-L1/VISTA or PD-L1/Tim3 for cancer therapy" provided data outlining the novel approach of identification and characterization of oral antagonists of immune checkpoint proteins. The lead IND-ready molecule, CA-170, targets PD-L1 and VISTA and has an optimized pharmacologic and safety profile required for human testing. Data from a second, independent program within the collaboration with compounds that target PD-L1 and TIM-3 immune checkpoints were also presented. In vitro studies showed that AUPM-327, a representative molecule from the PD-L1/TIM-3 program, can rescue T cell functions that are inhibited by addition of PD-L1 or TIM-3 checkpoint proteins, but does not affect other checkpoint regulators such as VISTA, CTLA4, and LAG-3, demonstrating its selectivity. Additionally, daily oral administration of the PD-L1/TIM-3 antagonist resulted in anti-tumor activity in multiple syngeneic tumor models including melanoma and colon cancer.

IRAK4 inhibitor presentation:

The Aurigene presentation "Efficacy and safety of highly selective novel IRAK4 inhibitors for treatment of ABC-DLBCL" provided a detailed profile of the pharmacologic and biologic properties of the lead molecule, CA-4948. This compound has favorable drug metabolism as well as pharmacokinetics properties and appears to have a clean in vitro toxicity profile. CA-4948 showed potent anti-tumor activity in vivo in two models of MYD88 mutant- DLBCL disease. CA-4948 also had potent anti-inflammatory effects in a rodent model of inflammation suggesting the potential use of an IRAK4 inhibitor in both cancer and inflammatory diseases.

Curis has exclusive licenses to CA-170 and CA-4948 under a collaboration agreement with Aurigene established in 2015.