Conatus Pharmaceuticals (CNAT) announced the failure of its lead candidate, emricasan, in two separate clinical trials in NASH cirrhosis. With unusual candor, the management team stated it was “game over” for Emricasan.[1] The company will fulfill its obligations to Novartis for the partnership to create combination therapy, but the prior hope for emricasan as a monotherapy is over.

If you’re interested in details, you should read the announcements.

The gamble came down to this: does interdicting caspase-directed inflammation enough to create a reasonable monotherapy for NASH?

The answer is “No”. It’s not enough for commercial application as a monotherapy.

Caspases are an extremely effective killer of cells. It has amazingly fast and potent cellular toxicity. We saw it used to kill dysfunctional and cancer cells in mice and primates.

…and emricasan is really good at halting the caspase cascade.

We talked to executives and scientists at other biotechs; they liked the team and the drug.

Here’s what we wrote in our recent update on Conatus:

“Emricasan is a strong anti-inflammation, anti-apoptotic drug. We’ve seen too much evidence to support it. NASH is a “dirty disease” and we’ve had our doubts that it is wholly amenable to one drug. That’s why even the successful drugs only target meaningful subsets.

The answer is likely yes.

The answer is: we don’t know. The animal work at Conatus and Novartis remains hidden. Unlike prior work, the combination work remains opaque.”[2]

In the meantime, very recent literature underscores the difficulty with treating NASH. It’s more complicated than previously thought and it was already complicated enough! We wonder whether it should be viewed as only one catch-all disease. Although the current view is to differentiate by stage of disease, we think that someday, there will be important markers. This is the case with cancer.

Although combination therapy is a different animal, the emricasan star is dimmed. We should not bank on something that is so opaque. We would not be surprised if emricasan is a good combo therapy component, but there’s no evidence to support it.

We wish the management team well. They believed in their drug and when it didn’t work, they pulled no punches. They are exploring alternatives and their future is unknown. It isn't going to be easy.

We may write one more post-mortem.