On April 5, 2017 Cascadian Therapeutics, Inc. (NASDAQ:CASC), a clinical-stage biopharmaceutical company, reported data highlights from presentations of preclinical data for the Company’s investigational orally bioavailable, potent and selective checkpoint kinase 1 (Chk1) inhibitor known as CASC-578 (Press release, Cascadian Therapeutics, APR 5, 2017, View Source [SID1234518480]). An additional abstract highlights data from the first public presentation on the Company’s preclinical antibody program targeting the immune checkpoint receptor TIGIT. These data were presented at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2017 in Washington, DC from April 1-5, 2017.

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"The research presented at AACR (Free AACR Whitepaper) illustrates why we believe CASC-578 is well positioned for IND-enabling studies," said Scott Peterson, Ph.D., Chief Scientific Officer of Cascadian Therapeutics. "CASC-578 has demonstrated anti-tumor activity as a single agent or in combination with a Wee1 inhibitor in preclinical models of acute leukemia, mantle cell lymphoma and non-small cell lung cancer. Furthermore, a recent GLP safety pharmacology study indicated CASC-578 has an acceptable safety profile with no apparent effects on QTc interval or cardiac contractility."

Dr. Peterson added, "Our TIGIT antibody program presentation profiles the discovery of highly potent, fully human TIGIT antibodies, which are active as a single agent in a mouse tumor model that is resistant to PD-1 antibody blockade."

A summary of data highlights presented at AACR (Free AACR Whitepaper) follows. To access these poster presentations, please visit www.cascadianrx.com.

CASC-578, a novel Chk1 inhibitor, is active as a single agent in solid tumors and displays synergistic anti-tumor activity in combination with Wee1 inhibition (Abstract #295)

CASC-578 is a highly selective, picomolar inhibitor of Chk1 that is active as a single agent and in combination with chemotherapeutic agents in a variety of solid tumor and hematological tumor derived cell lines. Chk1 is a protein kinase that regulates cell cycle progression in response to DNA damage response (DDR) signaling.

CASC-578 is active as a single agent in non-small cell lung cancer (NSCLC) tumor models and has shown enhanced activity with Wee1 inhibitor in vitro and in NSCLC tumor xenograft.
The novel orally available sub-nanomolar potent and selective checkpoint kinase 1 inhibitor CASC-578 is highly active in mantle cell lymphoma as a single agent and in combination with Wee1 inhibition (Abstract #297)

Targeting the DNA Damage Response (DDR) axis with CASC-578, alone or in combination with Wee-1 inhibition, presents a promising therapeutic approach to treating mantle cell lymphoma and other hematological cancers.
CASC-478 showed compelling single agent activity on mantle cell lymphoma cell lines — both in vitro and in vivo, including complete tumor regression in a Jeko-1 xenograft model.
Preclinical pharmacokinetics of CASC-578, a novel selective potent and orally bioavailable small molecule checkpoint kinase 1 inhibitor (Abstract #4090)

CASC-578 has desirable drug-like properties, including good oral availability and ADME/PK properties, sub-nanomolar Chk1 inhibition, limited off-target kinase activity (>1000x selective vs. Chk2) and balanced pharmacokinetics, potency and in vivo efficacy.
Discovery and characterization of novel antagonistic antibodies that bind with high affinity to human, cynomolgus and murine TIGIT, an immune checkpoint receptor (Abstract #578)

TIGIT is an emerging immune checkpoint target that regulates the induction of adaptive (T cell) and innate (natural killer or NK) cells. CASC-TIGIT antibodies represent a potentially attractive approach to immune checkpoint inhibition.

Novel, high-affinity, fully human antibodies have been identified that block TIGIT function.
Lead antibody binds with sub-nM affinity to human, cynomolgus monkey and mouse TIGIT and blocks ligand interactions and signaling in T cells
Potent single-agent activity in mouse model that is resistant to PD-1 antibody.