Astellas, CoMentis Sign $760M Alzheimer's Deal; Awaiting Wyeth's Results

Astellas Pharma, Inc. (ALPMF.PK) and CoMentis, Inc. announced Friday that the companies have entered into an agreement to develop products from CoMentis’ beta-secretase inhibitor program, including the recently initiated, phase 2, lead candidate compound CTS-21166, an oral beta-secretase inhibitor for the treatment of Alzheimer’s disease. The agreement also includes a research collaboration to develop additional beta-secretase inhibitors.

Upon closing, CoMentis will receive an upfront payment of $80 million and an equity investment of $20 million. CoMentis has the opportunity to receive up to $660 million in development milestones and may also receive performance-based commercialization milestones. In addition, CoMentis has the right to receive development milestones for next-generation beta-secretase inhibitors discovered under the terms of the research collaboration. Astellas will fund 100% of the pre-Phase III global development costs and CoMentis will share the Phase III development costs. Astellas has exclusive worldwide commercialization rights while CoMentis retains the right to co-promote in the U.S., where profit will be shared. CoMentis will receive royalties on sales outside the U.S.

Not a bad day for CoMentis; $100M upfront is a nice chunk of change for any program, let alone one that barely cleared phase I and showed no cognitive improvements (they weren’t measured, go figure). The mechanism of action of CTS-21166 centers around inhibiting one of the enzymes (beta-secretase) that clips off a part of a larger protein [APP] to form amyloid-beta, which comprises the plaques found in the brains of Alzheimer’s patients. It is thought by reducing the amount of amyloid, the disease course may be reversed or, at least slowed; a treatment outcome that is not currently possible. There is a sort of chicken and egg game over the origin of these plaques in Alzheimer’s. Some believe the formation of these plaques is the origin of Alzheimer’s and others take the opposite tack saying the disease itself creates the plaque.

There is controversy however, as Derek Lowe points out on his blog In The Pipeline. A one year old PNAS paper shows that mice which over express APP but lack beta-secretase, actually do worse on cognitive tests than mice that only over express APP. In the clinical realm, bapineuzumab, a mAb targeting amyloid-beta from Wyeth (WYE) and Elan (ELN), is currently in phase 2 and 3 and has yet to release any data including the all important ADAS-Cog score. If these therapies do not reverse the cognition score (as measured by ADAS-Cog) the FDA might not approve them regardless.

Alzheimer's is a tough disease and eventually, given enough shots on goal, one or two will go in. If bapineuzumab is successful, CTS-21166, would potentially have an advantage long term due to the oral (or so they say, the ph1 was IV) dosing and I’m sure the BD people at CoMentis delightfully highlighted that fact. This proof of concept for the mechanism of action will come mid to late ‘08 when Wyeth releases results of the extended phase 2 of bapineuzumab. I’ll be keeping my eyes peeled.

Disclosure: none

Comments

[BIOSTREET]

It's not about the plaques, which are endgame in this disease, it is about the toxic building blocks of plaques, Abeta oligomers, that impair neurotransmission. Beta-secretase inhibtors should lower Abeta oligomer levels. The caveat is that the beta-secretase enzyme also cleaves other substrates and one would not want to interfere with these normal and vital processes. Thus, the safety of this drug is not guaranteed, by a long shot. Agents that block Abeta from forming toxic oligomers, e.g. Prana Biotechnology's PBT2, are more attractive in this regard. Another viable alternative are gamma-secretase modulators, e.g. Eisai's E2012, that do not block normal enzyme function. Time will tell...