Demonstrates changes in brain activity, therapeutic window and M1 receptor selectivity
Tokyo, Japan –10 February 2016: Sosei Group Corporation (“Sosei”; TSE Mothers Index: 4565) today reports that Heptares Therapeutics (“Heptares”), the wholly-owned subsidiary of Sosei Group Corporation, announces positive findings from its Phase 1b clinical study with HTL9936. HTL9936 is the first selective muscarinic M1 receptor agonist, designed using Heptares StaR® technology, which has entered clinical development as a new treatment for cognitive impairment in patients with dementia and schizophrenia.
These positive results provide strong evidence of a therapeutic window for the selective M1 agonist mechanism in general, and for progression of HTL9936 and similar molecules as medicines to treat cognitive disorders.
The Phase 1b precision medicine study involved 28 healthy elderly subjects who received different doses of HTL9936 and was designed to test the effect of drug on measures of brain activity while simultaneously monitoring side effects.
In the study, HTL9936 exhibited robust and statistically significant changes in brain electrical activity measured using multiple electroencephalography (EEG) biomarkers relevant to cognition, including effects on the P300 evoked response potential (p=0.0052). These procognitive effects were seen at low doses and low blood concentrations that were safe and well tolerated.
M1 receptor selectivity was also confirmed across the dose range studied through the absence of gastrointestinal side-effects (such as diarrhoea and vomiting) typically attributed to the stimulation of M2 and M3 receptors. Such side effects are dose-limiting in standard-of care acetylcholinesterase inhibitors, which likely work through non-selective muscarinic receptor stimulation.
Heptares is also developing a second patentably distinct M1 agonist, HTL18318, which is in Phase 1 and for which results are expected later this year. Phase 2 studies in dementia and schizophrenia patients are expected to commence in late 2016.
“The results from this Phase 1b study reinforce our earlier findings from clinical and preclinical studies, providing compelling evidence to support the therapeutic potential of Heptares’ selective M1 agonists for improving cognitive function in patients with dementia and schizophrenia,” commented Tim Tasker, Chief Medical Officer of Heptares. “We are excited by these findings and look forward to progressing the M1 programme into patient studies later this year.”
Malcolm Weir, Heptares CEO, added: “We are greatly encouraged by these findings from our lead M1 agonist programme. We have generated a diverse portfolio of selective agonists that includes not only M1 but M4 agonists for treating psychosis in schizophrenia and Alzheimer’s disease patients, and dual M1/M4 agonists for both psychosis and cognitive impairment in these patients; we expect these to reach the clinic from early 2017 onwards. We believe this is a programme with the potential to deliver medicines of immense clinical and commercial significance.”