(EPZM - Get Report) reported the first clinical data on its blood cancer pipeline candidate EPZ-6438 at the ASH Lymphoma Biology Conference last week. The drug is designed to block a specific enzyme, EZH2, which when mutated, is involved in development of certain cancers, including forms of non-Hodgkins lymphoma (NHL). Epizyme's technology platform focuses on developing drugs to regulate a class of cancer-causing enzymes known as histone methyltransferases (HMTs), of which EZH2 is just one.
The first look at EPZ-6438 came from an early-stage (phase I) study, but was encouraging. Two of the four NHL patients reported a partial tumor response, a third patient had stable disease. The responses came from relatively low doses of EPZ-6438 and the safety profile was clean enough to allow Epizyme to continue the study using higher doses of the drug. Ideally, higher doses of EPZ-6438 should lead to more enzyme inhibition and stronger and higher frequency tumor responses. Epizyme should have results from the higher-dose cohorts of the EPZ-6438 ready to report later in the year.
The one potential hiccup in the EPZ-6438 data presented last week was that the partial tumor responses reported came in NHL patients with "wild type" EZH2 enzyme. The stable disease patient had mutated EZH2. Ideally, the responses would have been reversed because it's mutated EZH2 thought to largely drive tumor growth. Epizyme says EPZ-6438 is capable of blocking wild-type and mutant EZH2, and there is some research suggesting both forms of the enzyme play a role in cancer growth. If this is true, seeing responses in NHL patients with wild-type EZH2 isn't surprising or concerning. However, as Epizyme enrolls more patients in EPZ-6438 studies, it will be important to see more robust responses correlating with mutated EZH2 status. This is something for investors to think about and watch going forward.
On the other hand, if EPZ-6438 is found to be effective in patients with wild-type EZH2 tumors as well -- perhaps as part of a combination regimen with existing NHL drugs -- the commercial market opportunity might expand significantly.
Sobek is long Epizmye and Celgene.