West Coast Editor

Memory Pharmaceuticals Corp. said F. Hoffmann La-Roche Ltd. has decided to quit developing on its own a pair of phosphodiesterase-4 inhibitors that were part of an ongoing deal begun several years ago.

Falling $1.32 cents, Memory's stock (NASDAQ:MEMY) closed Friday at $2.72, down 32.7%.

"The important thing is that both companies are sitting down to determine the best way forward with those [compounds]," said Tony Scullion, president and CEO of Montvale, N.J.-based Memory. "Both parties are keen to evaluate the next steps."

The two compounds are MEM 1414 for Alzheimer's disease and MEM 1917 for depression, neither of which has gone past Phase I.

"In a big company, there are many different factors and reasons" to make such decisions as Roche made, said Scullion, previously head of global business development for Glaxo Wellcome plc, of London, now GlaxoSmithKline.

"I won't talk about the specific [licensing] deal," he told BioWorld Today, but noted that the willingness by Basel, Switzerland-based Roche to help figure out what to do with the compounds "reflects the good nature of the collaboration."

Roche and Memory are still working on PDE4 inhibitor backup compounds under the deal that began in 2002, Scullion noted. Roche got a worldwide, exclusive license to any product candidate from Memory's PDE4 inhibitor program. Under an extension of the agreement made last summer, Roche had committed to at least 18 months of funding for Memory's PDE4 research, in the amount of $5.3 million. (See BioWorld Today, July 31, 2002.)

In its 2004 annual report, Memory said that Roche had paid $45.4 million so far in two separate deals that included the two PDE4 compounds and certain nicotinic alpha-7 partial agonists, including MEM 3454 and MEM 63908.

The former compound is at the Phase I stage for schizophrenia and might be useful against Alzheimer's disease. Also for Alzheimer's is MEM 63908, still in preclinical study.

"The first deal we struck with Roche is the PDE4 deal, which is a full program," Scullion explained. "All of that continues, because we extended the initial two-year collaboration for a further two years in the third quarter of last year."

In the third quarter of 2003, the second target collaboration with Roche began - an option agreement involving "a full program of leads and backups based on chemistries against this nicotinic alpha-7 target. The big difference is that we lead development through Phase IIa. In the first deal we did, in 2002, Roche leads from Phase I onward."

In the second program, while Roche has an option for worldwide rights to further develop and commercialize products, Memory got co-promotion rights. (See BioWorld Today, Sept. 19, 2003.)

Also in development by Memory and unpartnered is MEM 1003, a neuronal L-type calcium channel modulator for Alzheimer's disease. The firm is conducting a safety and tolerability study under an investigational new drug application, with results to be used in the design of a Phase IIa trial, expected to start in the first half of this year.

Memory is exploring a collaboration for MEM 1003, which also might be tested against vascular dementia and mild cognitive impairment, and for its PDE10A inhibitor program.

The PDE10A enzyme, present at high levels in neurons in areas of the brain closely associated with disorders such as schizophrenia, Parkinson's disease and obsessive-compulsive disorder, degrades the intracellular signaling molecules cAMP and cGMP.

Memory has identified two chemical series of compounds that have proven effective in the selective inhibition of PDE10A, with activity in several animal models of schizophrenia. The search for drug candidates is under way.

Meanwhile, Memory said in the annual report that existing cash and cash equivalents, and marketable securities - about $41.1 million - together with payments for research and development services to be made by Roche under the 2002 and 2003 deals, should be sufficient to fund operations through the first quarter of next year.

"None of those financials has changed," Scullion said.