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Repligen Corp. presented at the Society for Neuroscience annual meeting in New Orleans results from preclinical studies of its Phase III product, secretin, as a therapy in two indications the company is pursuing.

A rat study showed that secretin and the secretin receptor are developmentally regulated in specific regions of the brain, including the amygdala, which is implicated in social interaction deficits found in autism and schizophrenia. The company also said the results suggest secretin might play a role in post-natal brain development and that exogenous secretin might act on those brain regions.

Secretin and the secretin receptor also were found to be more prevalent in the hippocampus and the cerebellum, both of which are implicated in autism and schizophrenia, the company said.

Separately, Waltham, Mass.-based Repligen presented data showing secretin is active in a model of schizophrenia known as prepulse inhibition. The results, the company said, provide more evidence that secretin is active in neural processes that involve the amygdala.

Secretin (RG1068) is the company's synthetic version of the neuroactive hormone secretin, which is produced by the duodenum. Repligen has it in two Phase III studies in autism and is planning a Phase II trial in schizophrenia. The data presented, Repligen said, support both those indications.

The first Phase III autism trial has completed its enrollment of 131 patients and is expected to report data early in 2004.

"We will be releasing the top-line data the week of Jan. 5," said Laura Whitehouse, senior director, market development, at Repligen, adding that the second trial "is under way and we would expect results mid-year 2004." The second trial is of an identical size, she said.

Secretin failed in a Phase II autism trial in 2001, but the company saw improvements in a subgroup, so it narrowed the focus of the Phase III. (See BioWorld Today, April 5, 2001.)

"What we found in the Phase II is that the youngest kids were the most responsive - the most robust results were in the 3- and 4-year olds," Whitehouse told BioWorld Today. "The Phase II involved 3-, 4-, 5-, and 6-year olds. The Phase III is in only 3- and 4-year olds."

The secretin Phase II trial in schizophrenia is expected to start this month and will include 45 hospitalized patients at five U.S. sites, testing four doses. In the first half of 2004, the company is expecting to start a second Phase II trial, that one in schizophrenia patients that are not hospitalized, instead living in community centers or someplace similar, Whitehouse said. Repligen also is expecting to start a secretin pilot study in an anxiety disorder in 2004.

The company has $27.7 million in cash and burns through about $2 million a quarter. The company "absolutely" has enough cash to power the Phase III trials to completion, Whitehouse said. For now, the drug is unpartnered, and if things play out the way Repligen plans, it won't be partnered for autism.

"We would, in terms of our strategy, look to outlicense adult indications, such as schizophrenia, but keep pediatric indications such as autism," she said.

In other news from the meeting:

• Titan Pharmaceuticals Inc., of South San Francisco, presented positive preclinical results demonstrating that continuous drug delivery using its ProNeura technology reduced the risk of motor symptoms in a validated primate model of Parkinson's disease. The company said Parkinson's patients sometimes develop side effects, called motor complications, while being treated. It suggested that the complications are not caused by the drug levodopa itself, but by the administration of the drug, which causes fluctuating dopamine levels. The ProNeura technology, it said, is a copolymer-based implant that incorporates a therapeutic drug, and is placed under the skin allowing the drug to be delivered at a consistent level over time.

• Myriad Genetics Inc., of Salt Lake City, said its drug, MPC-7869 (R-flurbiprofen), showed improved memory and spatial learning in a model of Alzheimer's disease. The study was designed to determine whether a reduction in the toxic Abeta42 peptide leads to improvement in memory and spatial learning in a mouse model. MPC-7869 is in Phase II trials in the UK and Canada. Myriad's stock (NASDAQ:MYGN) rose $1.68 Wednesday, or 15 percent, to close at $12.90.

• Pharmos Corp., of Iselin, N.J., said compounds from its CB2 receptor agonist program demonstrated efficacy in several preclinical pain models. The CB2-selective agonists are bicyclic cannabinoids, a family of compounds within Pharmos' non-psychotropic synthetic cannabinoid library. CB2-selective compounds have an affinity for the cannabinoid-2 (CB2) receptor, expressed primarily by inflammatory and immune cells, and lower affinity for the CB1 receptor, located mainly in the central nervous system. A lead compound with good oral bioavailability was chosen for further development, it said. Pharmos also is screening the compounds for activity in other animal models of inflammation-based and autoimmune diseases.

• Panacea Pharmaceuticals Inc., of Gaithersburg, Md., presented data from three abstracts on its drug candidates for acute and chronic neurodegeneration such as stroke and Alzheimer's disease, as well as disorders including Parkinson's Disease. It said it would "continue to explore and determine the application and action" of the compounds, then narrow down the candidates and enter preclinical studies.

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