Press release

Jun 17, 2015

Sosei subsidiary Heptares announces positive outcome of Phase 1a study with first-ever selective muscarinic M1 receptor agonist for improving cognition in patients with Alzheimer’s disease

Early evidence of enhanced brain activity seen at dose levels that are well tolerated

Tokyo, Japan – 17 June 2015: Sosei Group Corporation (“Sosei”; TSE Mothers Index: 4565) is pleased to announce that its wholly-owned subsidiary Heptares Therapeutics (“Heptares”) 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.

The Phase 1a study assessed the safety, tolerability and pharmacokinetics of HTL9936 in relation to dose in 84 healthy volunteers, while also evaluating preliminary signs of efficacy (increase in brain activity). 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 agents1,2.
 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.

“HTL9936 was designed and developed specifically to be a first-in-class oral agent to improve cognitive function (memory and thinking abilities) in patients with serious neurological diseases, such as Alzheimer’s disease and dementia,” said Tim Tasker, Chief Medical Officer of Heptares. “We are therefore delighted with the outcome of this first clinical study, the results of which provide important validation of our GPCR-directed structure-based design platform and approach to create important new medicines in areas of unmet need. We look forward to advancing HTL9936 and the M1 agonist programme into further clinical studies to confirm the efficacy and safety observed.”

References:

1. Chang YS et al. Parallel improvement of cognitive functions and P300 latency following donepezil treatment in patients with Alzheimer's disease: a case-control study. J Clin Neurophysiol. 2014 31(1):81-5.

2. Werber EA et al. The clinical use of P300 event related potentials for the evaluation of cholinesterase inhibitors treatment in demented patients. J Neural Transm. 2003 110(6):659-69.

3. Bodick NC et al. Effects of xanomeline, a selective muscarinic receptor agonist, on cognitive function and behavioral symptoms in Alzheimer disease. Arch Neurol. 1997 54(4):465-73.

4. Schretlen DJ, Adv Stud Med. 2007;7(3):72-78 5. Lewy Body Dementia Association, Inc. www.lbda.org.

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