On December 29, 2016 Aptose Biosciences Inc. (NASDAQ:APTO) (TSX:APS), a clinical-stage company developing new therapeutics and molecular diagnostics that target the underlying mechanisms of cancer, reported an update on the development of APTO-253, its investigational compound for acute myeloid leukemia (AML) (Press release, Aptose Biosciences, DEC 29, 2016, View Source [SID1234539166]). The company has successfully manufactured multiple batches of a new drug product formulation for APTO-253, including a batch that has been stable and soluble for over six months. However, Aptose will have to repeat the production of the fourth batch, a 40L batch that was the intended clinical supply, because of a correctable engineering design incompatibility during the filling process. Aptose expects the batch records and release specifications from such a new batch, along with the stability and sterility data, to be provided to the FDA during the first quarter of 2017.
The need to strengthen the filling process is not a reflection on the drug substance or new formulation, both of which continue to perform favorably. Indeed, the new formulation demonstrates an increase of three times plasma drug exposure as compared to the prior formulation and may have the potential to create additional intellectual property for the company. Aptose also demonstrated that APTO-253 acts by inhibiting expression of the c-Myc oncogene without toxicity to normal bone marrow and blood cells, thereby potentially increasing the likelihood of application to additional cancer indications.
"We remain committed to the development of APTO-253, a small molecule agent that may provide benefit to an important patient population," said William G. Rice, Ph.D., Chairman, President and Chief Executive Officer. "While we have encountered delays in manufacturing activities, we also have continued mechanistic and pharmacokinetic testing of APTO-253 which heighten its viability. In parallel, we also continue to advance the development of CG’806, an exciting preclinical compound for patients with FLT3-driven AML and certain B-cell malignancies."
In November of last year, Aptose’s phase 1b trial of APTO-253 was temporarily suspended because of the report of an operational difficulty with an IV infusion pump at a clinical site. The company has spent the year identifying the root cause of the clogging issue and actively evaluating multiple formulation and production methodologies in order to improve solubility and stability characteristics and select the best approach to optimizing the delivery of the product to patients with the goal of re-entering the clinic. Aptose is currently working on submitting information requested by the FDA as a result of the development of a new drug product that does not cause filter clogging or pump stoppage during simulated infusion studies.