On December 6, 2020 Aptose Biosciences Inc. ("Aptose") (NASDAQ: APTO, TSX: APS) reported that highlights from a corporate update event held on Sunday, December 6th, in conjunction with participation at the 2020 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (Press release, Aptose Biosciences, DEC 6, 2020, View Source [SID1234572343]). The Aptose management team reviewed the current clinical status of CG-806, Aptose’s oral, first-in-class FLT3 and BTK cluster selective kinase inhibitor currently in two Phase 1 a/b trials, one trial in patients with relapsed or refractory acute myeloid leukemia (AML), and the other trial in patients with relapsed or refractory B cell malignancies; and the team also reviewed the clinical status of APTO-253, a first-in-class small molecule MYC inhibitor in a Phase 1 a/b trial in patients with relapsed or refractory AML or high risk myelodysplastic syndrome (MDS).
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The webcast of the presentation is available on Aptose’s website here.
Aptose provided a recap on CG-806 and included the following key highlights:
B-cell malignancy trial
Increasing plasma exposure with increased dose levels, with sustained steady state concentration (trough level) above 2M in the latest cohort (750mg)
Progressive accrual of leading indicators of pharmacologic and clinical activity to date, including robust inhibition of multiple key oncogenic target pathways (including BTK) on target lymphocytosis in classic CLL patients, and modest tumor reductions in different tumor types
Latest cohort (750mg) currently under expansion following a possibly drug-related DLT, however subsequent data and analyses suggest this event is unlikely related to study drug
Generally well tolerated with no toxicity trends to date that would prevent dose escalation
Based on clinical observations to date, study enrollment now focused on certain types of CLL patients
AML trial
Initiated dosing with 450mg BID as potentially active dose based on target engagement analyses
Rapidly enrolled four patients on study drug, including both FLT3-ITD and FLT3-WT
Initial PK data consistent with exposures observed with 450mg dose level in CLL/NHL patients
Observed potential anti-leukemic activity in one heavily pretreated FLT3+ AML patient, including reduction in the percentage of peripheral blood blast count from 93% to 10% in cycle one
Generally well tolerated with no toxicity trends to date that would prevent dose escalation
Aptose also reviewed the current status of APTO-253:
Continued favorable safety and tolerability in heavily pretreated patients with relapsed or refractory AML and MDS
Continued dose-related exposure, with sustained active drug species in the 2-3µM range at the fourth dose level of 100mg/m2
Observed reductions in MYC expression in PBMCs in 24 hours following dosing in most patients
Continuing dosing of patients at the fifth dose level of 150mg/m2
"The on-target lymphocytosis and modest nodal reductions we have observed in CLL patients being treated with CG-806 may be leading indicators of potential eventual responses, similar to what has been observed in the development of other successful BTK inhibitors," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "We are encouraged by the continued increase in plasma exposure, and we hope the current and future dose levels will deliver formal responses to these deeply relapsed or refractory CLL patients. In AML, we are pleased by the observation of an anti-leukemic blast reduction from 93% to 10% in one of our first patients who was heavily pretreated with several consecutive FLT3 inhibitors. For APTO-253, we continue to escalate the dose and observe MYC repression, suggesting future potential for broad anti-cancer activity. We are pleased by such indicators of activity from both CG-806 and APTO-253, and we look forward to providing further updates in the first half of 2021 and at the Annual EHA (Free EHA Whitepaper) Meeting 2021."
In addition, early clinical data, along with certain preclinical data for CG-806 and APTO-253, were presented at the ASH (Free ASH Whitepaper) Annual Meeting and Exposition. The posters are now available on the presentations page of Aptose website here.