A Q&A With Epizyme

The following is extra content related to the blog "3 Companies To Watch."

Excerpts from an interview with Jason Rhodes, EVP and chief business officer, Epizyme

WHAT ARE THE CENTRAL ELEMENTS OF YOUR DEVELOPMENT STRATEGY?
We’ll use a companion diagnostic to identify the relevant patients. And we’ll actually orient our clinical development plans and strategy around those patient populations from the very first trial. But rather than going to the broad general populations and hoping that we’ve powered trials well enough to pick out effects that are probably only occurring in certain patients, we have a very specific hypothesis around the target, an HMT with a translocation or point mutation or other genetic lesion. We determine whether the given HMT is actually disease causing — not just associated with the disease, but truly the driver of the disease in those patient populations. That begins very early in clinical development to give us Go and No-Go information at that stage. Assuming that our target hypotheses are correct and are borne out, the compound will also have a very short path to registration.

WHY DID YOU CHOOSE TO DEVELOP THE SPECIFIC CANCER AND OTHER APPLICATIONS FOR THE HMT INHIBITORS?
Many of the specific HMTs are involved in regulating developmental pathways and that’s why they’re involved in cancer. There are pathways or sub-pathways of cancers that are necessary for normal development. But at some point in a mature differentiated cell, for example, there is a translocation in a certain HMT enzyme and it changes its function to, for example, turning on a leukemogenic set of genes that cause a very specific subtype of leukemia in the case of our DOT1L program.

ARE YOU ALSO DEVELOPING THE COMPANION DIAGNOSTICS?
The diagnostics are already there to use clinically and commercially for DOT1L, which is our lead program. All of the MLL (mixed lineage leukemia) patients are currently identified by these tests, and they’re treated very aggressively, but they’re largely unresponsive to standard of care. So it’s about as strong a case for an unmet medical need as you could make.

IN WHAT WAYS HAVE YOU MADE THE CASE FOR HMT INHIBITORS?
Our strategy has been to establish a platform to pursue the HMT target class. People knew HMTs have a biological function but they never had any methodical or systematic way to describe the entire class. So we published a paper in Chemical Biology & Drug Design last year defining the whole class. We had to identify all the enzymes (all the genes) involved with HMTs and verify that they actually had the correct biochemical function. Then we prioritized roughly 20 of them based on their genetic disease associations in cancer, then created biochemical assays to evaluate their function, and then a chemical library. So our platform includes deep biology, biochemistry, and medicinal chemistry, along with IP, and we put together a very experienced leadership team and organization to pursue it. We make a product profile, including a companion diagnostic profile, as soon as we pick a target and say we’re beginning research on it — before any wet work is even begun. The second year was about building a platform, not just pursuing a program directed at one target. And the third year we used that platform to create our product programs. We have novel patents and very selective composition of matter that’s all proprietary for many of those top 20 enzymes that we identified, and DOT1L is our lead program, now partnered with Celgene ex-US with Epizyme retaining all US rights.