Sosei Heptares Doses First Subject in Phase I Trial with HTL0048149, a First-in-Class GPR52 Agonist for Schizophrenia

• HTL’149 has been designed as a once-daily oral treatment to address positive and negative symptoms and cognitive impairment in schizophrenia patients without the adverse effects typically associated with existing antipsychotic drugs
  
  

Tokyo, Japan and Cambridge, UK, 3 July 2023 – Sosei Group Corporation (“the Company”; TSE: 4565), the world leader in G protein-coupled receptor (GPCR) focused structure-based drug design (SBDD) and development, announces it has dosed the first subject in a Phase I trial evaluating HTL0048149 (HTL’149), a first-in-class GPR52 agonist, which represents a novel mechanism of action for the treatment of schizophrenia and related neurological diseases.

HTL’149 was developed, leveraging insights generated from Sosei Heptares’ StaR technology and SBDD platform, as a once-daily, orally available small molecule drug with an antipsychotic and pro-cognitive profile and to avoid the adverse effects typically associated with existing antipsychotic drugs. HTL’149 achieves this profile through selectively targeting the orphan GPR52 receptor in the brain to address positive symptoms (e.g. psychosis, delusions, hallucinations), negative symptoms (e.g. social withdrawal) and cognitive impairment (e.g. attention, working memory and executive function) associated with schizophrenia.

Through this novel mechanism of action, HTL’149 aims to address the significant proportion of schizophrenia patients who do not respond to or suffer side effects leading to compliance issues from using existing antipsychotics. Furthermore, current antipsychotic drugs do not effectively treat the negative or cognitive symptoms of disease.

The Phase I trial is a two-part, randomized, double-blind, placebo-controlled, single- and multiple-ascending dose study to assess the safety, pharmacokinetics, and pharmacodynamics of oral HTL’149 in healthy volunteers aged 18-55 years. The trial will be conducted in the UK and is expected to read-out initial data in 12-18 months.

Matt Barnes, President of Heptares Therapeutics and Head of UK R&D, said: “The progression of this wholly owned, first-in-class asset into clinical trials is a very important milestone for Sosei Heptares. It is the culmination of a rigorous internal program that began with the selection of GPR52 as the right target to address the significant unmet needs of schizophrenia patients and the subsequent design of a novel and potentially first-in-class agonist molecule with the right therapeutic profile. Progression of HTL’149 from discovery into clinical trials is a great example of the power of our StaR/SBDD platform to generate high-quality candidates utilizing the combined expertise of our platform, discovery and translational medicine teams.”