Astellas Pharma has terminated its six-year collaboration with CoMentis to develop and commercialize beta-secretase inhibitors for Alzheimer’s disease, the companies said—a partnership that had been expected to generate up to $780 million for CoMentis.

Astellas said its decision came “based on the outcome of the research and development collaboration,” without elaborating. The pharma giant said it recognized impairment losses on other intangible asset of ¥8.1 billion (about $59.5 million) in the first three months of the company’s current fiscal year, which began April 1.

CoMentis’ website lists the status of the company’s lead product, identified only as “BACE inhibitor” as “confidential.”

That product, CTS-21166 (ASP1720), was reported to have shown promising results in two Phase I trials. In one such trial, for which findings were published in 2008, the oral small-molecule BACE inhibitor was reported to be safe when injected intravenously into Alzheimer’s patients with doses as high as 225 mg. Results showed a dose-dependent reduction of plasma beta-amyloid (Aβ) levels for an extended period of time, with significant inhibition of plasma Aβ persisted beyond 72 hours.

Similar results were obtained from a second phase I trial on subjects receiving an oral liquid solution of 200 mg CTS-21166, for which results were published in 2012. A six-week trial in 13-month-old transgenic mice with Alzheimer’s showed a one-third reduction in brain Aβ—though chronic dosing produced no detectable change on myelination in peripheral nerves.

CTS-21166 was designed to inhibit the accumulation of Aβ fragments into plaques within the brain. The fragments are made through the cutting of larger proteins called amyloid precursor protein (APP) by two enzymes, the enzyme BACE and γ-secretase. CoMentis reasoned that inhibition of BACE through compounds that could pass the blood-brain barrier could stop the progression of Alzheimer’s.

“CoMentis’s approach of BACE inhibition targets the underlying disease mechanism and has the possibility of being one of the first disease-modifying therapies for Alzheimer’s disease,” CoMentis states on its website.

However, the compound had not appeared on Astellas’ updated lists of pipeline drugs. In an updated listing of its R&D pipeline as of Aug. 1, Astellas lists only one Alzheimer’s compound—ASP3662, developed in-house.

Under their deal, announced in April 2008, Astellas agreed to pay CoMentis $80 million upfront, plus a $20 million equity investment; the pharma giant bought CoMentis’ Series D preferred stock. CoMentis was eligible for up to $660 million in payments tied to development milestones, plus commercialization milestone payments.

CoMentis also received the right to development milestone payments for next-generation beta-secretase inhibitors discovered under the research collaboration. Astellas also agreed to fund 100% of the pre-Phase III global development costs, with CoMentis sharing Phase III development costs.

In return, Astellas won exclusive worldwide commercialization rights to CTS-21166, while CoMentis retained the right to co-promote the drug in the U.S., where the companies agreed to share profits. The companies also agreed that CoMentis would receive royalties on sales outside the U.S.

The memory-robbing ailment has long eluded drug discovery efforts, with the failure rate for experimental treatments between 2002-2012 an astounding 99.6%, researchers at the Cleveland Clinic Lou Ruvo Center for Brain Health and Touro University Nevada College of Osteopathic Medicine reported in “Alzheimer's Disease Drug Development Pipeline: Few Candidates, Frequent Failures,” published online July 3 in the journal Alzheimer's Research & Therapy.

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