Date: 2012-06-19
Type of information: R&D agreement
Compound: mGluR5 antagonists including STX209
Company: Roche (Switzerland) Seaside Therapeutics (USA)
Therapeutic area: Genetic diseases - Rare diseases - CNS diseases - Neurodevelopmental diseases
Type agreement: R&D
development
Action mechanism: The compounds that Roche and Seaside Therapeutics are developing are targeting aberrant glutamate signaling and GABA, thereby restoring synaptic transmission in ASD and FXS patients. The most commonly inherited form of autism involves the gene encoding fragile X mental retardation protein (FMRP). Loss of FMRP function disrupts signaling between neurons, leading to widespread brain abnormalities and mental retardation. Normally, FMRP is balanced by mGluR5, an important receptor in the brain that is involved in learning and memory. Without normal FMRP, this balance is lost, leaving mGluR5 function unopposed. Early results from a clinical trial suggest that children with fragile X syndrome can be helped by drugs that inhibit mGluR5 activity. STX209 is an oral selective gamma-amino butyric acid type B (GABA-B) receptor agonist. Pathologies observed in certain neurodevelopmental disorders, including autism spectrum disorders and fragile X syndrome are believed to be caused by excessive activation of glutamate receptors and abnormally high ratios of excitatory to inhibitory neurotransmission in the brain. GABA-B receptors play an important role in modulating the release of glutamate and optimizing the ratio of excitatory to inhibitory neurotransmission. STX209 has demonstrated efficacy in preclinical models, suggesting that it may improve function in individuals with autism spectrum disorders and fragile X syndrome. With STX209, Seaside has successfully completed the largest, randomized, blinded, placebo-controlled trial (Phase 2) in patients with fragile X syndrome and an open-label Phase 2a exploratory trial in patients with autism spectrum disorders. Two Phase 3 studies, one in adolescents and adults (ages 12 to 50) and one in children (ages 5 to 11) with fragile X syndrome, are currently enrolling participants. A Phase 2b study in children, adolescents and adults (ages 5 to 21) with autism spectrum disorders recently completed enrollment.
Disease: fragile X syndrome (FXS), autism spectrum disorders (ASD)
Details: Roche and Seaside Therapeutics have entered into a collaboration to develop disease modifying treatments for fragile X syndrome (FXS) and autism spectrum disorders (ASD), both neurodevelopmental disorders for which there are currently no effective pharmacological treatments that address core symptoms.
The alliance aims to speed up research and development in this field and lead a fundamental change in the treatment paradigm for FXS and ASD by developing therapeutics that target the molecular basis and, in turn, core symptoms of these neurodevelopmental disorders.
Under the terms of the agreement, Seaside will license patents covering the use of mGluR5 antagonists for the treatment of neurodevelopmental disorders exclusively to Roche. Roche will subsequently lead the development and commercialization of these compounds for the treatment of FXS and ASD. Its mGluR5 drug candidate RG7090, is currently enrolling patients in a Phase 2 clinical trial in FXS. Seaside will develop its GABA-B agonist program and retains exclusive rights to issued and pending patents covering the use of GABA-B agonists for the treatment of FXS and ASD. Seaside’s lead GABA-B candidate STX209 is currently enrolling patients in Phase 3 trials in FXS and recently completed enrollment in a Phase 2b trial in ASD.
Roche may exercise options to commercialize STX209 upon completion of certain clinical development phases in FXS and ASD, but Seaside will continue to lead the clinical development of these programs. Additional terms of the transaction will not be disclosed.
Financial terms:
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