Aptose expands oncology pipeline through partnerships

Canadian company links up with Moffitt and Laxai Avanti Life Sciences

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TORONTO—Aptose Biosciences has struck two deals intended to expand the clinical-stage company’s portfolio of epigenetic oncology drug candidates, which targets the underlying mechanisms of cancer. The first agreement establishes a collaboration between Aptose and Tampa, Fla.-based Moffitt Cancer Center that grants Aptose exclusive global rights to develop multi-targeting, single-agent inhibitors to treat hematologic and solid tumor cancers. The second agreement creates a drug discovery partnership with Laxai Avanti Life Sciences (LALS) geared toward developing potential epigenetic drug candidates, including those that arise from the Moffitt-Aptose partnership.
Aptose predicts that the partnerships will lead to the discovery of a lead drug candidate by late 2016, though it will take longer for the candidate to enter clinical trials.
“We’ve built an oncology drug development organization with valuable ties to leading clinical centers and thought leaders, and we are exceptionally pleased to partner with Moffitt on advancing new epigenetic inhibitors, specifically bromodomain inhibitors that simultaneously inhibit specific kinases in key regulatory pathways,” said Aptose Chairman and CEO William Rice in a statement.
APTO-253, the company’s lead drug candidate, has been undergoing a Phase 1b clinical study in patients with relapsed or refractory hematologic malignancies. Aptose is developing the small molecule, which has been shown to have potent anti-tumor activity in cancer cells, as a potential treatment for acute myeloid leukemia.
Development of APTO-253 faced a setback last November when the U.S. Food and Drug Administration (FDA) placed Phase 1b clinical trials in patients with hematological cancers on hold. The FDA described its action as an effort to ensure patient safety and consistent manufacturing and dosing procedures. The cause of concern arose following a review by Aptose that was triggered by reports of operational difficulties with an IV infusion pump at a clinical site. The review led to a voluntary suspension of dosing by Aptose, which was followed by the FDA’s hold. Further review by Aptose has revealed concerns about the documentation records of the manufacturing procedures of the drug product associated with APTO-253.
Aptose has launched an independent third-party review to investigate the situation. Chief Business Officer Avanish Vellanki confirmed to DDNews on Dec. 18 that the FDA’s hold was still in place. Rice noted in a press release that the FDA’s hold does not contradict or undermine APTO-253’s positive safety profile.
“While we expect some delay in the clinical trial, we are committed to ensuring that upon re-initiation of clinical dosing, the drug product is of the highest standards,” said Rice. “We plan to provide updated timeline guidance as soon as practical.”
The collaboration with Moffitt will give Aptose exclusive global rights to small-molecule agents that are highly differentiated inhibitors of the Bromodomain and Extra-Terminal motif protein family members, which simultaneously target specific kinase enzymes. The terms of the agreement grant Aptose access to the drug candidates developed by Moffitt and the underlying intellectual property covering the chemical modifications enabling potent bromodomain inhibition on the chemical backbone of a kinase inhibitor.
“Aptose views a multitargeting approach, which incorporates bromodomain inhibition, as an exciting means to enhance efficacy and diminish therapeutic resistance relative to the current landscape in cancer treatment,” said Rice. “This is even more beneficial when inhibition of the pathways is highly synergistic.”
Two principal investigators in Moffitt’s drug discovery program, Ernst Schonbrunn and Nicholas Lawrence, released a statement noting that epigenetic multi-inhibitors offer a highly promising strategy for developing new and more effective treatment for cancer. They said that “targeting broad-acting epigenetic regulators of transcription like bromodomain proteins is needed to suppress the induction of gene expression that results when cancer cells respond to kinase inhibitors.”
Aptose’s partnership with LALS is expected to generate multiple drug candidates. The agreement gives responsibility for developing those candidates to LALS, which specializes in accelerating drug discovery campaigns. This process will involve optimizing candidates that emerge from Aptose’s relationship with the Moffitt. The terms of the agreement grant Aptose global rights to all newly discovered candidates characterized and optimized under the collaboration, including all intellectual property.
“We have identified LALS as an organization with high-caliber medicinal chemistry and with robust and highly efficient drug discovery capabilities that complement our capabilities at Aptose,” Rice commented. “These collaborations are designed to build upon insights into the epigenetic field that were informed by the mechanism of APTO-253.”

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