Oncology therapeutics on the move

Sunesis is advancing its BTK and PDK1 inhibitor programs to aid cancer patients

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SOUTH SAN FRANCISCO, Calif.—Sunesis Pharmaceuticals Inc., a biopharmaceutical company focused on the development and commercialization of new oncology therapeutics for the potential treatment of solid and hematologic cancers, closed 2015 with the presentation of two posters detailing preclinical data from its Bruton’s tyrosine kinase (BTK) and PDK1 inhibitor programs at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston.
Sunesis is committed to advancing products to improve the lives of people with cancer. The two poster presentations were titled “SNS-062 is a potent noncovalent BTK inhibitor with comparable activity against wild type BTK and BTK with an acquired resistance mutation” and “PDK1 inhibitors SNS-229 and SNS-510 cause pathway modulation, apoptosis and tumor regression in hematologic cancer models in addition to solid tumors.”
“These data represent the first peer-reviewed presentations by Sunesis of our two proprietary kinase inhibitor pipeline programs,” said Dan Swisher, CEO of Sunesis. “Each shows compelling, anticancer activity and a distinct product profile.”
SNS-062 is a non-covalently binding inhibitor of BTK. This target mediates signaling through the B-cell receptor, which is critical for adhesion, migration, proliferation and survival of normal and malignant B-lineage lymphoid cells. BTK has been well validated as a target for treatment of B-cell malignancies, with a BTK inhibitor approved for relapsed/refractory mantle cell lymphoma, relapsed/refractory chronic lymphocytic leukemia (CLL), CLL with 17p depletion and Waldenström’s macroglobulinemia. SNS-062 may provide differentiated opportunities for treatment of B-cell malignancies and other blood cancers. Sunesis plans to file a Clinical Trial Authorization application with the European Medicines Agency to support a Phase 1a study of SNS-062 in healthy volunteers. The rights to develop SNS-062 for oncology indications were in-licensed from Biogen Idec in December 2013.
In January 2014, Sunesis in-licensed a series of PDK1 inhibitors from Millennium that were discovered under a research collaboration agreement between Biogen Idec and Sunesis. PDK1 is a key kinase that is critical for activation of the PI3K/AKT signaling pathway, which is essential for regulating cell growth, differentiation, survival and migration and is frequently activated in cancer. Sunesis has taken a series of PDK1 inhibitors with confirmed antitumor activity in vitro and in vivo into preclinical development and selected two PDK1 inhibitors, SNS-229 and SNS-510, for possible absorption, distribution, metabolism and excretion and safety studies.
There are multiple PI3K pathway inhibitors in late-stage development for use in CLL and solid tumor indications, including breast cancer and pancreatic cancer. Inhibitors of PDK1 are expected to be able to provide similar clinical benefits to those observed with PI3K inhibitors and have the potential to provide additional benefits through inhibition of PI3K independent cancer signaling pathways, especially in cancer types in which PDK1 is overexpressed, such as breast cancer and acute myeloid leukemia (AML). Sunesis’ PDK1 inhibitor can be differentiated from PI3K and PDK1 inhibitors currently in research and development and that may provide novel opportunities for treatment of solid and hematological malignancies, according to the company.
“Because PDK1-dependent activation of AKT is critical for PI3K pathway activation, we believe that PDK1 represents a key oncology target within the PI3K pathway,” Swisher tells DDNews. “We believe Sunesis' PDK1 inhibitors are potential first-in-class compounds with demonstrated inhibition of AKT activity and a compelling in-vitro and in-vivo profile, that have potential for single agent and broad-spectrum combination activity, thus providing a novel therapeutic opportunity for targeting the PI3K signaling pathway in both solid and hematologic malignancies.”
Sunesis also announced the presentation of results from a Washington University-sponsored Phase 1 trial of its lead drug, vosaroxin, plus azacitidine in patients with myelodysplastic syndrome, and from an analysis of the company's Phase 3 VALOR trial of vosaroxin and cytarabine in relapsed/refractory acute myeloid leukemia (AML) at the 57th American Society of Hematology Annual Meeting in Orlando, Fla. 
QINPREZO (vosaroxin) is an anticancer quinolone derivative, a class of compounds not previously for the treatment of cancer. Preclinical data demonstrate that vosaroxin both intercalates DNA and inhibits topoisomerase II, resulting in replication-dependent, site-selective DNA damage, G2 arrest and apoptosis. Both the U.S. Food and Drug Administration (FDA) and European Commission have granted orphan drug designation to vosaroxin for the treatment of AML. Additionally, vosaroxin has been granted fast track designation by the FDA for the potential treatment of relapsed or refractory AML in combination with cytarabine.

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