On December 11, 2017 The OHSU Knight Cancer Institute and Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS) reported the presentation of preclinical data demonstrating that CG’806, a pan-FLT3/pan-BTK inhibitor, has broad and potent drug activity against acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL) and other hematologic disease subtypes (Press release, Aptose Biosciences, DEC 11, 2017, View Source [SID1234522544]). The data were highlighted in a poster presentation on Monday, December 11, 2017 at the American Society of Hematology (ASH) (Free ASH Whitepaper) 59th Annual Meeting & Exposition, being held December 9-12 in Atlanta, GA.
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The poster CG’806, a First-in-Class Pan-FLT3/BTK Inhibitor, Exhibits Potent Growth Inhibition as a Single Agent and in Combination with a BET Bromodomain Inhibitor and a Bcl2 Inhibitor Against AML and CLL Patient Samples, evaluated the activity of CG’806 on various hematologic malignancy cell lines and patient primary bone marrow specimens through the Beat AML Initiative. CG’806 exhibited broad and potent activity against primary patient samples over a diverse range of hematologic malignancy subtypes, including AML, CLL, myelodysplastic syndromes/myeloproliferative neoplasms (MDS/MPN), and acute lymphoblastic leukemia (ALL).
The poster presentation can be accessed on the Events & Presentations section of the Aptose website at the following link.
"In patient samples and cultured cell lines, CG’806 demonstrated potent and broad inhibitory activity against hematologic malignancies alone and in combination," said Stephen E. Kurtz, Ph.D., lead author and Research Assistant Professor at the OHSU Knight Cancer Institute. "Both AML and CLL are in urgent need of effective therapies that provide more durable clinical responses. CG’806 represents a potential new treatment approach that warrants further development."
OHSU researchers used an ex vivo drug sensitivity assay to determine the activity of CG’806 as a single agent and in combination with the BET bromodomain inhibitor OTX-015 or the Bcl2 inhibitor venetoclax on freshly isolated primary patient samples. Across the four general subtypes of hematologic malignancies in the dataset with patient samples, there was broad sensitivity to CG’806, with 55% (90/164) AML, 48% (46/96) CLL, 22% (6/27) ALL, and 53% (14/26) MDS/MPN cases exhibiting an IC50 < 100nM. CG’806 demonstrated median IC50 values of 70nM and 140nM against primary AML and CLL cells, respectively. CG’806 also exerted potent picomolar to low-nanomolar IC50 anti-proliferative activity against human AML, B-ALL, mantle-cell lymphoma, Burkitt’s lymphoma, and diffuse large B-cell lymphoma cell lines. CG’806 in combination with OTX-015 demonstrated median IC50 values of 20nM and 40nM against primary AML and CLL cells, respectively. CG’806 in combination with venetoclax demonstrated median IC50 values of 20nM and 10nM against primary AML and CLL cells, respectively.
"Collaborating with OHSU and the Beat AML initiative has provided us an exceptional opportunity to explore the activity of CG‘806 against a large and diverse set of freshly isolated patient bone marrow samples from patients with AML, CLL and other hematologic malignancies," commented William G. Rice, Ph.D., Chairman and Chief Executive Officer of Aptose. "CG’806 continues to reveal compelling preclinical results that are superior to other FLT3 or BTK inhibitors, and we are eagerly preparing CG’806 for clinical studies and look forward to an IND submission in 2018."
Separately, Aptose and The University of Texas MD Anderson Cancer Center researchers also presented new data on CG’806 at ASH (Free ASH Whitepaper) (see press release here).
In addition to the abstracts that were presented at ASH (Free ASH Whitepaper), two additional abstracts on CG’806 and two abstracts on APTO-253, Aptose’s small molecule c-Myc Inhibitor, have been published on the ASH (Free ASH Whitepaper) abstracts site. All abstracts will become part of the permanent ASH (Free ASH Whitepaper) and Blood abstracts archive.
For more information on Beat AML refer to View Source
About CG’806
CG‘806 is an oral, first-in-class pan-FLT3/pan-BTK inhibitor. This small molecule demonstrates potent inhibition of all wild type and mutant forms of FLT3 tested (including internal tandem duplication, or ITD, and mutations of the receptor tyrosine kinase domain and gatekeeper region), 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 wild type and Cys481Ser mutant forms of the BTK enzyme, as well as other oncogenic kinases operative in B cell malignancies, suggesting CG’806 may be developed for CLL and MCL patients that are resistant/refractory/intolerant to covalent BTK inhibitors.