Aptose Prioritizes Development of First-in Class FLT3/BTK Inhibitor

Aptose Biosciences Inc. recently announced it will prioritize its resources toward the development of CG’806, an oral preclinical compound being developed for patients with FLT3-driven acute myeloid leukemia (AML) and certain BTK-driven B-cell malignancies. Aptose will temporarily delay clinical activities with APTO-253, a Phase I stage compound for AML, in order to elucidate the cause of recent manufacturing setbacks related to the intravenous formulation of APTO-253, with the intention of restoring the molecule to a state supporting clinical development and partnering.

Although Aptose has two compelling cancer drugs, current resources can support the full development activities of only one at this time. Recent advances with CG’806 have elevated this agent as having the best risk-reward profile to pursue with those resources. Such data established CG’806 as a well-differentiated pan-FLT3 inhibitor that demonstrates tumor eradication in the absence of toxicity in AML xenograft models, and it is on track for development as a therapy for certain AML patients. In addition, CG’806 is a potent non-covalent inhibitor of proliferation among certain BTK-driven B-cell derived cancer cells. The encouraging properties of CG’806, including its potency against well-established targets in diseases of severe medical need, warrant expeditious advancement and prioritization of resources toward this molecule.

“Concurrent evidence of a unique activity profile with CG’806 along with manufacturing delays for APTO-253 have led us to reprioritize our corporate strategy,” said William G. Rice, PhD, Chairman, President and Chief Executive Officer. “While we remain confident in the viability of APTO-253 as a potential treatment for AML, we believe the greater value proposition to shareholders and patients is to focus our available resources on CG’806.”

In November 2015, Aptose’s Phase Ib trial of APTO-253 in patients with AML was placed on clinical hold. Since that time, the company has actively evaluated multiple formulation and production methodologies with the goal of developing a superior IV formulation. After successfully manufacturing multiple non-cGMP batches of a new drug product formulation for APTO-253, including a batch that has been stable and soluble for over 6 months, the company recently encountered an additional manufacturing setback, which further delayed the return of APTO-253 to the clinic. While Aptose has made significant advances in understanding the novel c-Myc inhibitory mechanism of APTO-253, additional time will be required to define the cause of the cGMP manufacturing delay and to potentially restore APTO-253 to a state it can be developed clinically and partnered.

Based on information currently available, Aptose expects to report total cash and cash equivalents to be at a similar level as at September 30, 2016. As a result of activities to reprioritize its resources toward the development of CG’806, the cash on hand, which includes additional cash raised through its At-The-Market facility, is expected to provide sufficient resources to fund research and development and operations into Q4, 2017. Information reported above with respect to the financial year ended December 31, 2016 are preliminary and are subject to change and adjustment as the company’s 2016 financial results are finalized. Accordingly, investors are cautioned not to place undue reliance on the foregoing guidance. The company does not intend to continue to provide preliminary results in the future. Aptose expects to report its financial results for the financial year ended December 31, 2016, on or around March 14, 2016.

CG ‘806 is a once-daily, oral, first-in-class FLT3/BTK inhibitor. This small molecule demonstrates potent inhibition of mutant forms of FLT3 (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain), eliminates AML tumors in the absence of toxicity in murine xenograft models, and represents a potential best-in-class therapeutic for patients with FLT3-driven AML. Likewise, CG’806 demonstrates potent, non-covalent inhibition of the Cys481Ser mutant of the BTK enzyme, suggesting the agent may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.

Aptose Biosciences is a clinical-stage biotechnology company committed to discovering and developing personalized therapies addressing unmet medical needs in oncology. Aptose is advancing new therapeutics focused on novel cellular targets on the leading edge of cancer research coupled with companion diagnostics to identify the optimal patient population for our products. The company’s small molecule cancer therapeutics pipeline includes products designed to provide single agent efficacy and to enhance the efficacy of other anti-cancer therapies and regimens without overlapping toxicities. For more information, visit www.aptose.com.