HTL0009936 / Nxera Pharma - LARVOL DELTA

From structure to clinic: Design of a muscarinic M1 receptor agonist with potential to treatment of Alzheimer's disease. (PubMed, Cell) - "Through this approach, we rationally designed the optimal properties, including selectivity and partial agonism, into HTL9936-a potential candidate for the treatment of memory loss in Alzheimer's disease. More broadly, this demonstrates a strategy for targeting difficult GPCR targets from structure to clinic."

Journal • Alzheimer's Disease • CNS Disorders

Safety, pharmacokinetics and pharmacodynamics of HTL0009936, a selective muscarinic M -acetylcholine receptor agonist: a randomized cross-over trial. (PubMed, Br J Clin Pharmacol) - "HTL0009936 showed well-characterized pharmacokinetics and single doses were safe and generally well-tolerated in healthy elderly subjects. Due to physostigmine tolerability issues and subject burden, the study design was changed and some pharmacodynamic assessments (neurocognitive) were performed at suboptimal drug exposures. Therefore no clear conclusions can be made on pharmacodynamic effects of HTL0009936, although an effect on P300 is suggestive of central target engagement."

Clinical • Journal • PK/PD data • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

Sosei Heptares to Regain Worldwide Rights to Muscarinic Agonist Programs (PRNewswire) - "Sosei Group Corporation...announces it is to regain the worldwide rights to its muscarinic agonist programs. The program was licensed to Allergan in April 2016, and Allergan was acquired by AbbVie in May 2020. This decision to return worldwide rights was based on business decisions regarding AbbVie’s pipeline strategy and not on any efficacy, safety or other data related to the collaboration programs....Sosei Heptares will now conduct a full internal review to determine a strategy for the further development and re-partnering of the program."

Licensing / partnership • Alzheimer's Disease • CNS Disorders • Schizophrenia

Deal watch: Immuno-oncology double-header at Bristol with Rigel, Flexus deals (Pink Sheet - Informa) - “Its (Heptares) M1 agonist for cognitive disorder associated with Alzheimer’s is furthest advanced in development, with Phase Ib results due this summer.”

Anticipated P1 data • Alzheimer's Disease