News_article_biocentury-2009-11-02_page6.pdf

BioCentury, THE BERNSTEIN REPORT ON BIOBUSINESS
Stabilizing fragile X
By Michael Flanagan
In mid-2005, Seaside took a license to the compounds.
Senior Writer
The single ascending-dose Phase I trial will evaluate the safety It has long been thought that excessive protein synthesis and pharmacokinetics of oral STX107 in healthy volunteers, with plays a role in neurological conditions like fragile X syndrome, results expected by the end of 1Q10.
though little progress has been made in identifying therapeutic “If all goes to plan we hope to be in patients with STX107 in targets. Seaside Therapeutics LLC thinks it has found one in
metabotropic glutamate receptor 5 and on Monday was to Seaside’s second program arose from discussions about the announce the start of a Phase I trial of an in-licensed small molecule antagonist.
“We found that the R isomer
of mental retardation and one of the fore- was much more active
generic baclofen for gastroesophageal re- in the fragile X mouse and
of Seaside. The condition is characterized actually rescued a number
by impaired neural and cognitive develop- of the abnormal symptoms
of the FMR1 gene, which encodes the similar to the way mGluR5
30 years as a racemic mixture. “We found fragile X mental retardation protein (FMRP).
that the R isomer was much more active in antagonism does.”
been suggested as a cause of a variety of neurological disorders, finding druggable Randall Carpenter,
lar to the way mGluR5 antagonism does,” targets has been easier said than done (see Seaside Therapeutics
SciBX: Science-Business eXchange, June 11, Seaside now thinks it might have hit on one that works.
established safety data for generic baclofen, this program has a According to Carpenter, FMRP normally would act as a head start,” he added. The lead candidate from the R-baclofen negative control on metabotropic glutamate receptor 5 (mGluR5).
program, STX209, began a double-blind, placebo-controlled, He said one theory on the pathophysiological underpinnings of crossover Phase II trial in adolescent and adult patients in fragile X syndrome is that FMRP is absent due to an FMR1 mutation. This leads to unchecked activation of mGluR5, which Results are expected in late March or early April 2010.
in turn causes excessive local protein synthesis and impaired Seaside’s primary source of funding for both programs is an synaptic plasticity, leading in turn to the neurologic and behav- undisclosed family investment fund that has so far provided $60 ioral symptoms characteristic of the disease. These include million, including a $30 million tranche closed in September (see cognitive impairment, delayed motor development, antisocial The company also has received translational research grants Much of the early research on which Seaside is based was from NIH as well as private groups like Autism Speaks and
conducted at the Howard Hughes Medical Institute at the FRAXA Research Foundation.
Massachusetts Institute of Technology by scientific founder
The family fund has committed additional capital that could Mark Bear, who first showed in FMR1 knockout mice that be sufficient to carry Seaside’s programs through to market in the mGluR5 and FMRP act functionally as an opponent pair. The U.S., though Carpenter said the company is in discussions about results were published in Neuron in December 2007.
Carpenter said Bear also was able to show that mGluR5 antagonism rescued abnormal phenotypic behaviors and symp- toms in the knockout mouse model of fragile X syndrome.
Autism Speaks, New York, N.Y.
“We set out looking for the most advanced set of compounds FRAXA Research Foundation, Newburyport, Mass.
against mGluR5 and ended up being at the right place at the right Massachusetts Institute of Technology (MIT), Cambridge, Mass.
time,” said Carpenter, when Merck & Co. Inc. decided to exit
Merck & Co. Inc. (NYSE:MRK), Whitehouse Station, N.J.
the psychiatry space and deprioritized a portfolio of small National Institutes of Health (NIH), Bethesda, Md.
Seaside Therapeutics LLC, Cambridge, Mass.
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