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 programme 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 III trials in FXS and recently completed enrollment in a phase II b 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.

“Roche is committed to finding new treatments in areas of high unmet medical need such as autism spectrum disorders,” comments Luca Santarelli, Global Head of Roche Neuroscience. “Recent discoveries in genetics have shed light on the biological underpinnings of these conditions thus providing a basis for mechanistic drug discovery. To establish a leadership position in this field we sought to build a solid partnership with Seaside Therapeutics, a company that has successfully pioneered the research and development in this novel and uncharted area.”

“This collaboration is a real win for patients and caregivers—aligning leading minds and organizations committed to rapidly advancing transformational drugs to treat autism and fragile X syndrome,” said Randy Carpenter, MD, president and CEO of Seaside Therapeutics. “Importantly, this collaboration also provides Seaside with additional resources to complete late-stage clinical development of STX209, which we believe has the potential to change the treatment paradigm for fragile X and autism and thereby help patients and their families achieve an improved quality of life.”

ASD refers to a group of enigmatic cognitive disorders, including autism and Asperger’s syndrome, which impair social interaction and communication, whereas FXS is a rare genetic disease, whose symptoms closely resemble ASD, and whose underlying mechanism may be similar. With no approved pharmacological therapies that address core symptoms for either condition, the unmet medical need remains high. The compounds that Roche and Seaside Therapeutics are developing hold the promise to become the best-in-class treatments by 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.

Seaside Therapeutics is working to correct or improve the course of autism, fragile X syndrome and other neurodevelopmental disorders by translating breakthrough discoveries in neurobiology into therapeutics that will improve the lives of patients and their families.

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 II) in patients with fragile X syndrome and an open-label phase II a exploratory trial in patients with autism spectrum disorders. Two phase III 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 II b study in children, adolescents and adults (ages 5 to 21) with autism spectrum disorders recently completed enrollment.

Roche has a strong commitment in the area of neurodevelopmental disorders, in particular in ASD with currently three compounds in clinical development. A Phase 2 trial is currently ongoing in adult and adolescent fragile X patients through a wide age range to investigate the safety and efficacy of Roche mGluR5 antagonist RG7090. In parallel Roche is exploring biomarkers to identify patients most likely to benefit from this treatment.

A recent study demonstrated that chronic treatment with Roche’s mGluR5 antagonist corrected fragile X symptoms in a mouse model, even if started after the disease onset. These new data suggest beneficial effects in a wide range of symptoms and a disease-modifying potential for mGluR5 antagonists in fragile X syndrome.

Roche is also committed to establishing connections with leading academic institutions and biotechnology companies. Recently, an international consortium of scientists, led by Roche and King’s College London, has launched the largest single grant for autism research in the world and the largest for the study of any mental health disorder in Europe. Read more about European Autism Interventions – A Multi-centre Study for Developing New Medications (EU-AIMS).

Roche also signed an agreement with the Harvard Stem Cell Institute, Harvard Medical School, Children’s Hospital Boston and Massachusetts General Hospital to develop cell models for autism spectrum disorders.

Key players in the field of ASD research across the industry, including Seaside Therapeutics, academia and patient advocacy groups recently gathered at the fourth edition of Roche - Nature Medicine Translational Neuroscience Symposium, to share the latest advances in the field of “Autism Spectrum Disorders: From Biological Understanding to Therapeutic Strategies”.

Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. It is the world’s largest biotech company with truly differentiated medicines in oncology, virology, inflammation, metabolism and CNS.