On November 9, 2016 Curis, Inc. (Nasdaq:CRIS), a biotechnology company focused on the development and commercialization of innovative and effective drug candidates for the treatment of cancer, reported preliminary clinical pharmacokinetic (PK) and early biomarker data from the ongoing dose escalation stage of CA-170’s Phase 1 trial at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 31st Annual Meeting & Associated Programs in National Harbor, MD. CA-170 is a potent and selective, orally available small molecule antagonist of the programmed death ligand-1 (PDL1) and V-domain Ig suppressor of T cell activation (VISTA) immune checkpoints (Press release, Curis, NOV 9, 2016, View Source [SID1234516455]).

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CA-170 is the first orally available small molecule immune checkpoint antagonist to be investigated in cancer patients. Preclinical data presented previously demonstrated dose-dependent oral exposure in multiple non-clinical models, as well as immune modulation and anti-tumor activity with CA-170 in multiple syngeneic mouse tumor models. Clinical data from a limited number of patients in the Phase 1 trial presented at the SITC (Free SITC Whitepaper) conference, demonstrate that similar to the preclinical findings, CA-170 has a dose proportional and predictable PK profile in patients treated orally at various doses in the ongoing dose escalation stage of the study. Further, evaluation of patient blood samples demonstrate that CA-170 appears to be biologically active in modulating the immune system, with a several-fold increase in percentage of circulating CD8+ T cells expressing activation markers within 24 hours of oral dosing.

The clinical findings were presented in an oral session at SITC (Free SITC Whitepaper) by David Tuck, MD, Chief Medical Officer of Curis. Additional details will be presented during the conference at a poster session on Friday, November 11 at 12:15pm. In addition to the CA-170 data, Curis’s collaborator, Aurigene will also present pre-clinical data from the PDL1/ T-cell immunoglobulin and mucin domain containing protein-3 (TIM-3) program at a poster session on Saturday, November 12 at 11:45am.

"We are pleased with these early PK and biomarker data demonstrating that CA-170 performs in a predictable manner in patients, and very similar to what we observed in the preclinical setting. It is encouraging to observe significant drug exposure at the starting clinical dose, as well as increasing drug exposure with ascending doses. Based on the increase in the proportion of activated CD8+ T cells in blood samples of treated patients, we believe that CA-170 is biologically active in immune modulation by functioning as a checkpoint antagonist at these exposure levels using once daily oral dosing," said Ali Fattaey, Ph.D., Curis’s President and CEO. "These initial patient data also affirm our belief in this innovative small molecule checkpoint targeting strategy invented by our partner Aurigene, and we plan to continue to advance and expand this technology. We look forward to CA-170’s continued clinical development, as well as bringing our second small molecule, oral checkpoint inhibitor in this collaboration, CA-327, which targets PDL1 and TIM3 into clinical studies next year."

Figure 1: Preliminary Patient PK data from CA-170 Phase 1 trial


Patient Plasma
Cycle 1 Day 1
Dose (mg) 50 100 200 400
T1/2 (hours) 8.7 9.6 5.3 12.9
Cmax (ng/mL) 412 1107 1998 4100
AUClast (hr*ng/mL) 5197 11019 27488 66664
T1/2: half life; Cmax: maximum concentration; AUC: Area under the curve

Figure 2: Preliminary Biomarker Data (Activated CD8+ T cells)

A graphic accompanying this release is available at View Source

About CA-170
CA-170 is a first-in-class, orally available, small molecule that was rationally designed to target and inhibit the immune checkpoints, Programmed Death Ligand-1 (PDL1) and V-domain Immunoglobulin Suppressor of T-cell Activation (VISTA). CA-170 is currently being evaluated in a Phase 1 study to assess safety, tolerability and pharmacokinetics of ascending doses of CA-170 in patients with advanced solid tumors or lymphoma (clinicaltrials.gov identifier: NCT02812875).

About CA-327
CA-327 is an orally available, small molecule that was rationally designed to target and inhibit the immune checkpoints, Programmed Death Ligand-1 (PDL1) and T-cell immunoglobulin and mucin domain containing protein-3 (TIM3). CA-327 is currently undergoing IND-enabling studies.