BASEL, Switzerland—Placing their rivalry in drug developmentaside, Swiss pharmaceutical giant Roche and Seaside Therapeutics, a privatelyheld, 30-employee company headquartered in Cambridge, Mass., have forged a landmarkalliance aimed at finding new treatments for fragile X syndrome (FXS), autismspectrum disorders (ASD) and mental retardation.
The deal will establish the biggest effort to date indiscovering new autism drugs, said Luca Santarelli, global head of RocheNeuroscience.
"Recent discoveries in genetics have shed light on thebiological underpinnings of these conditions, thus providing a basis formechanistic drug discovery," Santarelli stated in a June 19 news release. "Toestablish a leadership position in this field, we sought to build a solidpartnership with Seaside Therapeutics, a company that has successfullypioneered the research and development in this novel and uncharted area."
ASD refers to a group of enigmatic cognitive disorders,including autism and Asperger's syndrome, which impair social interaction andcommunication, whereas FXS is a rare genetic disease, whose symptoms closelyresemble those of ASD, and whose underlying mechanism may be similar.
Drug companies are hopeful that new drugs will be able torelieve some of the behavioral problems associated with ASD and FXS, includingpoor impulse control, speech delays and socialization problems.
The newly formed alliance aims to speed up research anddevelopment in this field and lead a fundamental change in the treatmentparadigm for FXS and ASD by developing therapeutics that target the molecularbasis, and in turn, core symptoms of these neurodevelopmental disorders.
The most commonly inherited form of autism involves the geneencoding FXS mental retardation protein (FMRP). Loss of FMRP function disruptssignaling between neurons, leading to widespread brain abnormalities and mentalretardation. Normally, FMRP is balanced by mGluR5, an important receptor in thebrain that is involved in learning and memory. Without normal FMRP, thisbalance is lost, leaving mGluR5 function unopposed. Early results from aclinical trial suggest that children with FXS can be helped by drugs thatinhibit mGluR5 activity.
Under the terms of the agreement, Seaside will licensepatents covering the use of mGluR5 antagonists for the treatment ofneurodevelopmental disorders exclusively to Roche, while Roche subsequentlyleads the development and commercialization of these compounds for thetreatment of ASD and FXS. Its mGluR5 drug candidate, RG7090, is currentlyenrolling patients in a Phase II clinical trial in FXS.
The agreement also calls for Seaside to develop its GABA-Bagonist program and retain exclusive rights to issue any pending patentscovering the use of GABA-B agonists for the treatment of FXS and ASD. Seaside'slead GABA-B candidate, STX209, is currently enrolling patients in Phase IIItrials in FXS and recently completed enrollment in a Phase IIb trial in ASD.
Roche may exercise options to commercialize STX209 uponcompletion of certain clinical development phases in FXS and ASD, but Seasidewill continue to lead the clinical development of these programs. Additionalterms of the transaction were not disclosed.
Roche will get exclusive rights to those patents fromSeaside, as well as the option to license commercial rights to Seaside'sarbaclofen. That drug, which works somewhat differently, is in late-stagetesting for FXS and in mid-stage testing for ASD.
Roche will provide an undisclosed sum to help Seasidecomplete its clinical trials of arbaclofen, according to the agreement. Seasidewill halt development of its own mGluR5 antagonist, which it licensed fromMerck, and will instead receive royalties on sales of Roche's drug.
Darien E. Wilson, director of public affairs at Roche, tellsddn, "Roche has a strong research focusin neuroscience and has been conducting research in autism-related disorders(ASD) for some time. Combining our respective expertise in fragile X and autismwill hopefully produce valuable insights for our drug development program.There is still much we don't know about the biology of autism."
Randall L. Carpenter, CEO of Seaside, said Roche is theideal partner for this venture.
"There is a long-history of scientific leadership andintellectual collaboration between Seaside and Roche to further the developmentof disease-modifying therapeutics for neurodevelopmental disorders," Carpentersays. "We believe our missions are aligned—which was a driving force in selectingRoche as a partner for Seaside. Roche has made a strong commitment toneurodevelopmental disorders, and specifically to serious conditions that haveno approved, effective or safe treatment. One of the major advantages of thisalliance is that our combined efforts will yield multiple shots on goal, withindustry-leading pipelines of programs specifically aimed at treating the coresymptoms of neurodevelopmental disorders."
Members of the Seaside team know firsthand the challengesindividuals with neurodevelopmental disorders and their caregivers face,Carpenter says. Seaside was founded specifically to develop disease-modifyingtherapeutics for these disorders.
"Neurodevelopmental disorders have complex and varyingetiologies, and the barrier to finding effective treatments has been a lack ofbasic understanding of the molecular mechanisms underlying these disorders," headds.