Boehringer Ingelheim is significantly expanding its pipeline of potential schizophrenia therapies through new collaborations with Sosei Heptares and Autifony Therapeutics. These deals aim to address the unmet needs in treating the full spectrum of schizophrenia symptoms, including cognitive and negative symptoms which are poorly addressed by current antipsychotics.
Targeting Schizophrenia with Novel Agonists
Boehringer Ingelheim has secured an option to license a family of GPR52 agonists from Sosei Heptares for a deal potentially worth €755 million. This collaboration focuses on developing first-in-class therapies that could target the broad range of symptoms associated with schizophrenia. The portfolio of GPR52 agonists has the potential to treat not only positive symptoms such as delusions and hallucinations, but also negative symptoms like apathy and social withdrawal, as well as cognitive dysfunction.
GPR52 is a receptor expressed in the striatum and prefrontal cortex, brain areas associated with positive and negative symptoms, respectively. Agonists of GPR52 may “calm the striatum while boosting frontal cortical function,” according to the partners. The lead compound, HTL0048149, is currently in a phase 1a/1b trial in healthy volunteers in the UK.
Autifony Collaboration Focuses on Kv3.1/3.2 Modulation
In a separate deal, Boehringer Ingelheim is collaborating with Autifony Therapeutics to develop an early-stage schizophrenia drug and other compounds. Boehringer will fund R&D into Autifony’s voltage gated potassium channel modulator programme and has an option to purchase certain drugs to treat serious central nervous system disorders. The pharma company gets an exclusive option to buy Autifony’s Kv3.1/3.2 positive modulator platform, including lead compound AUT00206, a novel oral small molecule in phase 1b studies, including one in patients with schizophrenia.
Preclinical studies suggest that AUT00206 has the potential to treat cognitive and negative symptoms of schizophrenia, as well as positive symptoms with fewer side effects than current anti-psychotic drugs. Cognitive and negative symptoms are poorly treated by antipsychotic drugs and are associated with significant functional impairment and reduced quality of life for patients.
Boehringer's Broader Schizophrenia Pipeline
These collaborations add to Boehringer Ingelheim's existing schizophrenia pipeline, which includes both pharmacological and digital therapeutic (DTx) products. Iclepertin (BI 425809), a GlyT1 inhibitor with breakthrough designation from the FDA, is currently in the CONNEX phase 3 trial program, targeting the cognitive symptoms associated with schizophrenia. Results from these trials are expected later this year or in early 2025.
Additionally, the Click Therapeutics-partnered DTx CT-155, also with breakthrough status from the FDA, is in late-stage testing for the negative symptoms of schizophrenia. Results of the CONVOKE trial of the smartphone-based app are due in mid-2024.
Dr Jan Poth, therapeutic area head, CNS and Immunology, at Boehringer Ingelheim, said: “This partnership opens up the possibility of testing clinically an unprecedented therapeutic concept for the treatment of schizophrenia and to develop novel compounds with significant value to the patient.”
