Epix Pharmaceuticals

From NI January 2009

A bad year turned lucky for Epix, with the late-year approval of its imaging agent 'Vasovist', which caused the stock price to skyrocket. Earlier, PRX-00023 had failed in its Phase IIb for depression. PRX-03140, a 5HT-4 agonist, went into Phase IIb in the wake of its less-than-they-originally-seemed PhIIa results. PRX-08066 also went into Phase IIb for COPD. But with the QTc problems shown by PRX-07034, Epix had faced a dearth of funding, and the stock was at risk of delisting. They only have money through 1Q:09, but with an approval in-hand, finding cash will be infinitely easier.

From NI July/August 2008

A very mixed bag of a first half for Epix. Their 5HT-1a agonist PRX-00023 failed in depression, as it had failed in anxiety. More promising has been PRX-03140, a 5HT-4 agonist and optionable by GSK, recently reported PhIIa results. The unbelievably (literally) positive results (5.7 ADAS-cog point change in two weeks) that were initially reported turned out to be due to an arithmetical error, which left them positive but not earthshaking. PRX-07034, their 5HT-6 modulator originally intended as a cognitive upregulator for schizophrenia or Alzheimer's, had a good news/bad news experience: In Phase I, it caused weight loss, adding obesity to its roster of possibilities. However, it also increased QTc intervals, which eliminated all of the possibilities for the parent molecule. Epix believes that they can achieve the same anti-obesity effects with an enantiomer. GSK made a couple more milestone payments during 1H:08, reflective of progress in their GPCR alliance.

From NI February 2008

Epix's Epic Embarrassment: "Michael G. Kauffman, M.D., Ph.D., chief executive officer of EPIX Pharmaceuticals stated, “We are very excited by the measurable impact on memory and cognition, achieved in such a short period of time, in a trial that was designed primarily to assess safety and tolerability."
--Press release from Epix Pharmaceuticals, 12/18/07

"When things seem to be too good to be true, they usually are (too good to be true): Epix's Alzheimer's trial for its 5HT-4 drug PRX-03140 showed an amazing 5.7 point ADAS-cog improvement in just two weeks...albeit in just one 10 patient dose cohort, with two 14 point responders, the mean change for the others was 3.3 points, and the other six cohorts did not show significant benefit. And there was no benefit if the patients also received Aricept--Epix states that these patients hadn't been washed out, and thus were already at the cholinergic ceiling (dubious trial design and execution). But other than that, these were revolutionary results. So revolutionary, in fact, that NI strongly doubts that they will be replicated. Because they are not only revolutionary, they make no sense."
--NeuroInvestment 1/06/08

"The updated results described below reflect the correction of previously undetected errors that were included in the trial results as provided to the company from a third party contract research organization (CRO) and as reported by the company in a recent press release, as well as newly available data on other measures of cognition.

As a result of errors made in the transcription of data and calculation of the Alzheimer’s Disease Assessment Scale cognitive subscale (ADAS-cog) score, an independent re-analysis of the data has been conducted. The corrected results show that patients receiving 150 mg of PRX-03140 orally once daily as monotherapy achieved a mean 3.6 point improvement on the ADAS-cog versus a 0.9 point worsening in patients on placebo, which continues to be statistically significant (p= 0.021).
--Press release from Epix Pharmaceuticals, 1/15/08

"Oh. That's very different. Never mind."

--Gilda Radner 1976
Perhaps in the future, if circumstances warrant, Epix will conduct the "independent re-analysis' of suspect data before broadcasting them.

From NI January 2008

Comment 1: When things seem to be too good to be true, they usually are (too good to be true): Epix's Alzheimer's trial for its 5HT-4 drug PRX-03140 showed an amazing 5.7 point ADAS-cog improvement in just two weeks...albeit in just one 10 patient dose cohort, with two 14 point responders, the mean change for the others was 3.3 points, and the other six cohorts did not show significant benefit. And there was no benefit if the patients also received Aricept--Epix states that these patients hadn't been washed out, and thus were already at the cholinergic ceiling (dubious trial design and execution). But other than that, these were revolutionary results. So revolutionary, in fact, that NI strongly doubts that they will be replicated. Because they are not only revolutionary, they make no sense.

Comment 2: PRX-00023, a 5HT-1a agonist, is in Phase IIb for depression, and data is expected this quarter. PRX-03140, a 5HT-4 agonist and optionable by GSK, recently reported PhIIa results. As noted on p.7, the fact that one 10pt cohort showed stunning improvement on the ADAS-cog after just 14 days, but not if Aricept was also given, makes us think it was a fluke, with huge variance, a small n, and poor trial design. PRX-07034, their 5HT-6 modulator originally intended as a cognitive upregulator for schizophrenia or Alzheimer's, had a good news/bad news experience: In Phase I it caused weight loss, adding obesity to its roster of possibilities. However, it also increased QTc intervals, which eliminated all of the possibilities for the parent molecule. Epix believes that they can achieve the same anti-obesity effects with an enantiomer. Positive data were also found in their COPD program, and GSK paid a milestone during 2007, reflective of progress in their GPCR alliance.