On December 9, 2019 Aptose Biosciences Inc. (NASDAQ: APTO, TSX: APS) reported that highlights from a corporate event and clinical update held at the 61st American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, FL (Press release, Aptose Biosciences, DEC 9, 2019, View Source [SID1234552103]). The event was hosted by the Aptose management team and included Stephen B. Howell, MD, Acting Chief Medical Officer, Distinguished Professor of Medicine, Moores Cancer Center, University of California, San Diego (UCSD); with analysis by Rafael Bejar, MD, PhD, Aptose’s incoming Senior Vice President and Chief Medical Officer and currently the Director, MDS Center of Excellence, Moores Cancer Center, UCSD; and participation remotely by Brian J. Druker, MD, Chair of the Aptose Scientific Advisory Board, Professor of Medicine, Division of Hematology/Medical Oncology, Director, Knight Cancer Institute, Oregon Health & Science University.
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The slides are available and the recording of the presentation will be archived on Aptose’s website here shortly after the conclusion of the event.
As the first clinical data from CG-806 in patients with chronic lymphocytic leukemia (CLL) have begun to emerge, Drs. Howell, Bejar, and Druker highlighted the consistency between the drug’s robust preclinical profile and the early clinical observations on safety, tolerability, pharmacokinetics, and activity. William G. Rice, Ph.D., Chairman, President and Chief Executive Officer of Aptose also provided a corporate update on the clinical activities of CG-806, Aptose’s highly potent pan-FLT3/pan-BTK inhibitor.
CG-806, an oral, first-in-class mutation-agnostic FLT3/BTK kinase inhibitor, is in a Phase 1 trial in patients with B cell malignancies, including CLL and non-Hodgkin lymphomas (NHL), who have failed or are intolerant to standard therapies. The first two dose levels, which required only one patient at each level, are complete. The first two patients, both of whom were CLL patients that had previously failed a host of other agents, completed multiple dose cycles at 150 mg BID and 300 mg BID, respectively. Screening is ongoing for the third dose level, which is planned to enroll three patients.
Key findings from dose levels 1 and 2 of CG-806 in heavily pretreated R/R CLL patients:
CG-806’s safety profile remains clean; no unexpected toxicities have been observed to date
Notably, no myelosuppression, no drug-related adverse events or dose-limiting toxicity
Early evidence of clinical response has already been observed in a R/R CLL patient at dose level 2
Robust increase in peripheral blood lymphocytes (lymphocytosis)
Evidence of Bruton’s tyrosine kinase (BTK) target engagement
Lymphocytosis, which is known as an indicator of BTK inhibition
Inhibition of Phospho-BTK, Phospho-SYK and Phospho-ERK have been observed with a plasma inhibitory assay (PIA) using plasma from the CLL patient on dose level 2
Meaningful oral absorption and predictable pharmacokinetic (PK) profile
Exposures are likely therapeutic for acute myeloid leukemia (AML) patients
A separate trial with CG-806 in relapsed/refractory AML patients is in the planning stage
APTO-253, the only clinical stage agent that directly targets the MYC oncogene, is demonstrating safety and MYC target engagement in a Phase 1b clinical trial for the treatment of patients with relapsed or refractory AML or high-risk myelodysplastic syndrome (MDS).
Key highlights:
Aptose has completed dosing of the first three cohorts (up to a dose of 66 mg/m2) of the Phase 1b trial with MYC inhibitor APTO-253 in patients with AML and MDS.
In the patients on the first three dose cohorts, no drug-related adverse events have been observed, including no myelosuppression, and dosing is planned to continue to ascend until a maximum tolerated dose is reached. The next expected dosing level is 100 mg/m2.
MYC biomarker data from AML and MDS patients in the first three cohorts continue to demonstrate reductions of MYC gene expression in their peripheral blood cells. The dose escalation portion of the study is designed to transition, as appropriate, to single-agent expansion cohorts in AML and MDS, followed by combination studies.
The Company continues to escalate dosing with both assets, as all current dose cohorts to date have exhibited favorable safety profiles and evidence of target engagement.