Portola Pharmaceuticals, Inc., a biopharmaceutical company focused on the development and commercialization of novel therapeutics in the areas of thrombosis, other hematologic disorders and inflammation, has initiated a phase 1/2 clinical study of PRT2070, a novel, oral, dual spleen tyrosine kinase (Syk) and janus kinase (JAK) inhibitor. The compound is being developed for patients with genetically-defined hematologic cancers, as well as for patients who have failed therapy due to relapse or acquired mutations. PRT2070's dual mechanism of action, which targets two validated pathways for tumor survival and proliferation, has strong scientific rationale in these settings, where other compounds have failed to demonstrate clinical benefit.

"We are pleased to advance our third wholly-owned program focused on addressing an unmet medical need into the clinic. Our goal with PRT2070 is to develop an effective and well- tolerated oral drug for the thousands of lymphoma and leukemia patients who are impacted by difficult- to-treat genetic subtypes or who become unresponsive to available therapies," said John T. Curnutte,  executive vice president of research and development for Portola. "With PRT2070, we have seen promising in vitro activity in cell lines with specific mutations and in tumor cells that have lost sensitivity to other compounds due to acquired mutations. We
look forward to seeing initial clinical data for this agent in 2014."

The open-label, multicenter, phase 1/2 proof-of-concept study will assess the safety, pharmacokinetics, pharmacodynamics and clinical activity of oral PRT2070. In the multi-dose, dose-escalation phase 1 part of the study, PRT2070 will be administered to sequential dose cohorts at increasing dose levels until the maximum tolerated dose is identified. The phase 1 portion of the study can include patients with relapsed or refractory chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma and non-Hodgkin lymphoma (NHL) (including diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma). The phase 2 part of the study is a cohort expansion that will evaluate measures of safety and efficacy in cancer types identified based on the responses seen in the dose-escalation phase. Portola has engaged the Sarah Cannon Research Institute, a global strategic research organization based in Nashville, Tenn., to conduct the study.  

PRT2070 is an oral, potent inhibitor of both the B-cell receptor (BCR) pathway (via Syk) and important cytokine signaling (via JAK) that promote survival and proliferation of hematologic cancers, such as chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphoma (NHL), and are also implicated in autoimmune diseases. PRT2070 is unique in that it simultaneously targets these two validated pathways in one therapy, which may particularly distinguish it in difficult-to-treat patient populations with certain genetic subtypes, such as diffuse large B-cell lymphoma (including patients with identified mutations) and in patients who have failed therapy due to relapse or acquired mutations.   
Portola is currently evaluating PRT2070 in a phase 1/2 clinical study and has worldwide rights to develop and commercialize the agent for hematologic cancers and other systemic indications. Rights for certain nonsystemic indications are shared 50/50 with Aciex Therapeutics.