Is Zafgen Kaput?

By Dr. KSS MD PhD, October 26, 2015

“It was like a teetering house of cards,

A contortionist strumming a ukulele,

A gorilla raging in someone’s attic,

A car graveyard frantic to get back

On the interstate highway in a tornado,

Tolstoy’s beard in his mad old age,

General Custer’s stuffed horse…

What was? I ask myself and have no idea,

But it’ll come to me one of these days.”

—-Charles Simic, in New York Review of Books, 5 November 2015 issue

An ugly corporate week for Zafgen ($ZFGN), one that seemingly intensified each day with new revelations from management, leaves us with ample reason to contemplate the future of this stock.

We introduced readers to Zafgen on 19 February 2015 in a column. We covered its tri-prong approach to obesity: that it was using relatively novel drug beloranib, an analog of a fungal compound fumagillin known to incur tremendous weight loss in laboratory animals. Zafgen was studying beloranib in Prader-Willi syndrome patients, in patients with severe head injuries that dysregulate appetite and energy disposition, and in the overnourished obese (including people with type II diabetes). Both beloranib and fumagillin are strong inhibitors of an enzyme called methionine aminopeptidase 2, an exopeptidase that normally completes post-transcriptional protein process by lopping an amino-terminal methionine residue off new-born proteins. By incompletely understood molecular mechanisms, this action happens to be highly anti-angiogenic; angio is a word base meaning blood vessel. In a column on Zafgen from 16 October 2015, Adam Feuerstein has raised the question of whether antiangiogenic compounds favor clotting; in support of this, he cites thrombotic episodes that occur in some recipients of Avastin (bevacizumab), an anti-vascular epithelial growth factor monoclonal used against many cancers. Here, I go on record as strenuously disagreeing with Feuerstein on this point. (N.B., I like Adam and have many friendly exchanges with him, and he means well.) Anti-angiogenic agents are not, as a class, prothrombotic (I can cite examples where they are anti-thrombotic). Unanticipated thrombosis in the patients he describes have to do with the fact that those patients have serious underlying malignancy, a state highly provocative of inappropriate clotting.

In plainsong, let’s lay out the events that vex us.

(1) on 18 September, Avi Goldberg, a Zafgen director with a babysitting seat on the board by virtue of his position with major Zafgen incubator funder Third Rock Ventures, sells 5000 shares for $225,000, leaving him with 53,734 shares.

(2) on 24 ...

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