Clinical Trials

* On February 10, 2016, Heptares Therapeutics announced positive findings from its Phase 1b clinical study with HTL9936. 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 pro-cognitive 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.

* On June 17, 2015, Sosei Group announced that its wholly-owned subsidiary Heptares Therapeutics has reported the positive outcome of its Phase 1a study with HTL9936, the first-ever fully selective muscarinic M1 receptor agonist to enter clinical development. Key findings were:

- Early evidence of increased brain activity, as measured by electroencephalography (EEG), was seen after dosing and gave signals similar to those seen with other cognitive enhancing agents1.

- HTL9936 was well tolerated at drug levels that result in the increased brain activity observed without side effects.

- HTL9936 demonstrates good penetration into the brain, as indicated by levels found in cerebrospinal fluid.

- M1 selectivity was demonstrated with, unlike earlier muscarinic agonists3, no adverse effects seen from stimulation of other muscarinic receptors.
These preliminary data suggest that the selective M1 agonist product profile of HTL9936 predicted from preclinical studies translates to humans. Heptares is now putting in place a series of further clinical studies with the objective of demonstrating clinical proof of concept in patients, and moreover is advancing its diverse portfolio of follow-on selective muscarinic agonists that target M1, M4, and both M1/M4 to the clinic. Heptares now looks forward to advancing HTL9936 and the M1 agonist programme into further clinical studies.

* On December 9, 2013, Heptares Therapeutics has announced that it has initiated a Phase 1 clinical study of HTL9936, a fully selective muscarinic M1 receptor agonist to enter clinical development. Heptares plans to develop HTL9936 as a novel treatment for improving cognitive function (memory and thinking abilities) in patients with Alzheimer’s disease and other diseases associated with dementia and cognitive impairment.