Shares of Memory Pharmaceuticals Corp. slid 35.8 percent Monday on news that MEM 1003, its calcium channel modulator, failed to demonstrate efficacy in treating acute mania in patients with bipolar disorder.

Results from an 84-patient Phase IIa study showed that the drug missed the primary endpoint, as measured by the percentage of patients treated with MEM 1003 who had at least a 50 percent improvement from baseline in the Young Mania Rating Scale (YMRS) at 21 days compared to placebo. MEM 1003 also fell short of the trial's secondary endpoints, defined as the mean change from baseline in the YMRS, the Modified Clinical Global Impression-Bipolar Scale and the Montgomery-Asberg Depression Rating Scale.

Shares of Memory (NASDAQ:MEMY) lost $1.12 Monday to close at $2.01.

"Obviously, we're disappointed" by the results, said Jzaneen Lalani, general counsel for the Montvale, N.J.-based company, adding that investigators will continue "a complete review of the data."

In the meantime, Memory is looking ahead to the results of two Phase II trials expected later this year, including a Phase IIa study of the same compound in Alzheimer's disease. Lalani said the company does not believe that the bipolar data are indicative of MEM 1003's effect in Alzheimer's.

The bipolar and AD trials are "differentiated by the target symptoms being treated," as well as the measurements of those symptoms, she told BioWorld Today. The bipolar study assessed "mood-stabilizing effects on mania," while the AD trial measures the effects on cognition.

Up until 2005, AD was the primary indication for MEM 1003, a neuronal L-type calcium channel modulator, and to date, Memory has compiled promising data from preclinical and Phase I studies.

The company added bipolar mania as a potential indication upon an agreement with Stanley Medical Research Institute, which pledged to commit up to $3.2 million for a Phase IIa trial in bipolar patients. Since calcium-signaling abnormalities are believed to be a cause of bipolar disorder, the idea was that MEM 1003 might be able to regulate those abnormalities, thereby controlling the manic aspect of the disorder.

But based on the results, "it's clear that MEM 1003, at the doses used in this study, does not have a significant impact on acute mania," Stephen Murray, Memory's vice president of clinical development, said during a conference call.

Murray said 84 subjects were evenly randomized to receive either MEM 1003 - administered at initial doses of 60 mg twice daily and, in most patients, escalated to 180 mg twice daily - or placebo for 21 days. Of those patients, a total of 48 completed the study (23 in the treatment group and 25 in the placebo group). The percentage of responders who showed at least a 50 percent improvement to baseline in the YMRS was 26 percent for the MEM 1003 group versus 38 percent in the placebo group.

No serious adverse events were reported in the treatment group, and the most common adverse events included headache and gastrointestinal effects, as expected, as well as four instances of pruritus, which the company expects to investigate further.

While Memory will continue to explore those data, "we have no plans to move forward [in the bipolar indication] at this time," Murray said.

In addition to the ongoing Phase IIa trial of MEM 1003 in AD, the company has started screening patients for a Phase IIa trial of MEM 3454, a partial agonist of the nicotinic alpha-7 receptor, also in AD. Top-line results from that trial are expected in the fourth quarter.

"We're also planning a Phase I trial of MEM 63908," Lalani said. That product is another nicotinic alpha-7 receptor partial agonist, which has shown improved learning and memory in animal studies.

Both MEM 3454 and MEM 63908 emerged from a collaboration with Basel, Switzerland-based F. Hoffmann-La Roche Ltd. Under the terms of that deal, Roche retains an option to license MEM 3454 after Phase IIa development and agreed to take over development of MEM 63908 upon successful completion of Phase I.

Memory also has an ongoing partnership with Thousand Oaks, Calif.-based Amgen Inc., focusing on PDE10 inhibitors. That program is in preclinical development.