Aptose Biosciences Inc. and CrystalGenomics, Inc. announced an exclusive global option and license agreement focused on the development of CG026806 (CG’806), a first-in-class, highly potent, non-covalent small molecule inhibitor of the Bruton’s tyrosine kinase (BTK), FMS-like tyrosine kinase 3 (FLT3) and the Aurora kinases (AURK). Further to enacting the agreement, Aptose expects to undertake Investigational New Drug (IND) enabling studies immediately, and, if it exercises its option under the agreement, to initiate a phase 1 clinical trial by mid 2017.

The potential option exercise would occur prior to submission of an IND application in the US. Upon exercise of the option, Aptose will own global rights to develop and commercialize the programme outside of Korea and China – the Licensed Territory. Total deal value is up to $303 million USD, inclusive of development, regulatory and commercial-based milestones. CrystalGenomics will also receive a single-digit royalty on sales in the Licensed Territory.

CG‘806 has the potential to serve as a transformational agent for multiple forms of cancer, particularly those resistant to current BTK inhibitors or those that possess the FLT3-ITD alteration.  BTK plays a critical role in B-cell hematologic malignancies, such as chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), and certain autoimmune diseases. FLT3, including the Internal Tandem Duplication (ITD), a mutation of the FLT3 gene, occurs in approximately 30-35% of patients with acute myeloid leukemia (AML).  Aurora kinases participate in the epigenetic phosphorylation of histones and are key drivers in a series of hematologic malignancies and solid tumors.

"CG'806 offers a unique capacity through a non-covalent, reversible mechanism to inhibit wild type and mutant forms of the validated BTK, FLT3 and AURK targets, but with the discretion to offer a robust safety profile," commented Avanish Vellanki, Senior vice president and chief business officer of Aptose. "Indeed, we are impressed by the ability of once-daily oral dosing of CG'806 to demonstrate tumor eradication in the absence of toxicity in murine xenograft models of human hematologic malignancies," added William G. Rice, Ph.D., chairman, president and chief executive officer of Aptose.

"We are excited to work with the Aptose team, which is uniquely qualified to accelerate development of our BTK/FLT3/AURK inhibitors, including our lead compound CG’806,” said Joong Myung Cho, Ph.D., chairman and chief executive officer of CrystalGenomics. “With a demonstrated commitment to high scientific and development standards, Aptose and its clinical advisors recognize the potential of this class of anticancer compounds and will make clinical development a priority.”

“The in vivo potency of CG’806 shows unprecedented potential,” said Michael Andreeff, M.D., Ph.D., Professor of Medicine, Department of Leukemia, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center (MDACC), and a member of the Aptose Scientific Advisory Board. “The combination of this candidate’s potency with a stellar in vivo safety profile gives us enthusiasm for CG’806 as a therapeutic option for patients with AML, CLL and other malignancies.”