ChemGenex has teamed up with MolecularMD in a deal that focuses on a drug resistance mutation seen in chronic myeloid leukemia (CML) patients, which has seen these sufferers no longer respond to Gleevec, a popular cancer treatment.
The collaboration has isolated the T315I point mutation, which has attracted attention globally as T315I expressing cells are resistant to the tyrosine kinase inhibitor Gleevec (imatinib mesylate).
Preliminary data has suggesed that CML patients with the T315I point mutation also fail to respond to treatment with either of two-second generation tyrosine kinase inhibitors currently in clinical development.
Under the terms of the agreement, the two companies aim to identify CML patients with the T315I bcr-abl mutation who may be candidates for participation in ChemGenex's phase 2/3 study of Ceflatonin, in CML patients with this mutation.
Ceflatonin (homoharringtonine or HHT) is a small molecule with established clinical activity as a single agent in heamatological malignancies. It affects a number of cellular pathways, including the regulation of genes associated with apoptosis and angiogenesis.
The drug has shown in vitro activity in CML cell lines with the T315I mutation and has already demonstrated clinical activity in human clinical studies for patients failing Gleevec.
Demonstration of positive results in CML patients with the T315I mutation who have failed Gleevec therapy could potentially serve as the basis for filing a New Drug Application with the US Food and Drug Administration under an accelerated approval, based on a high level of unmet medical need.
While newly diagnosed early chronic phase CML patients initially respond well to drugs like Gleevec, all of them have underlying residual disease which, unfortunately, will likely lead to eventual resistance and recurrence.
New drugs, with novel and complementary mechanisms of action, such as HHT, are badly needed to combine with other agents to avoid resistance or for those patients who have developed resistance.
"We are delighted to partner with MolecularMD," said Greg Collier, Chief Executive Officer and managing director of ChemGenex.
"CML patients typically develop genetic mutations as their disease progresses, requiring accurate and reliable molecular diagnosis to determine if alternative therapies or a combination of drugs might be needed, as well as to fully assess the efficacy of their treatment."
Co-founder of MolecularMD Brian Druker said: "We are pleased that ChemGenex is offering a treatment option for patients with the T315I mutation and look forward to assisting in identifying candidates for this study."