ME-401

INDICATION / COMBINATION

CLL & Follicular Lymphoma

Relapsed/refractory
Single Agent
Pre-Clinical
Clinical Proof-Of-Concept
Pivotal
INDICATION / COMBINATION

Indolent Lymphoma & DLBCL

Relapsed/refractory
Rituxan® (rituximab)
Pre-Clinical
Clinical Proof-Of-Concept
Pivotal

The PI3K/AKT/mTOR pathway is an important signaling pathway for many cellular functions such as cell survival, cell cycle progression and cellular growth. PI3Ks are a family of enzymes within this pathway that have been shown to play a critical role in the proliferation and survival of certain cancer cells. There are several isoforms of PI3K that are expressed in different types of cells. The delta isoform is believed to be important for survival of certain B-cell leukemias and lymphomas.

We acquired exclusive worldwide rights to ME-401 (formerly PWT143) in September 2013. Data from pre-clinical studies show ME-401 to be a potent and selective oral inhibitor of PI3K delta, a molecular target that plays a critical role in the proliferation and survival of certain hematologic cancer cells. PI3K delta is a class of drugs that has shown promise in the treatment of B-cell malignancies, but with particular toxicities. We believe this provides an opportunity for development of a next-generation oral drug that can produce therapeutic responses at a safe, effective dose. ME-401 has a distinct chemical structure from certain other PI3K delta inhibitors, including idelalisib (marketed as Zydelig®). Data presented at the American Society of Hematology (ASH) Annual Meeting in December 2012 demonstrated that ME-401 has superior pre-clinical activity compared to idelalisib.

Data from a first-in-human, single ascending dose clinical study of ME-401 in healthy volunteers demonstrated on-target activity at very low plasma concentrations. In addition, the results suggest that ME-401 has the potential for a superior pharmacokinetic and pharmacodynamic profile and an improved therapeutic window compared to idelalisib, with a half-life that supports once-daily dosing. These results were presented at the American Association for Cancer Research (AACR) Annual Meeting in April 2016.

In May 2017, an independent safety review committee completed its pre-specified review of the first cohort of six evaluable patients in a Phase Ib, open-label, dose-escalation study of ME-401 in relapsed/refractory chronic lymphocytic leukemia (CLL) and follicular lymphoma. Based on its review of the safety and efficacy data, the safety review committee declared a minimum biologically effective dose (mBED) for ME-401 at the starting dose of 60 mg and recommended escalation to a 120 mg dose cohort. According to the study protocol, the mBED is defined as a dose that is safe and achieves a response in at least three of six patients. There were no reports of ALT/AST elevations, colitis or pneumonitis, events commonly reported with other drugs in this class. One patient in the study experienced grade 3 neutropenia that was considered related to the study drug; all other adverse events reported were grades 1 or 2. No patients have discontinued due to adverse events or disease progression. We plan to submit full data for presentation at an upcoming scientific meeting.

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