HTL0018318 / Nxera Pharma - LARVOL DELTA

A phase 1b/2a multicenter study of the safety and preliminary pharmacodynamic effects of selective muscarinic M receptor agonist HTL0018318 in patients with mild-to-moderate Alzheimer's disease. (PubMed, Alzheimers Dement (N Y)) - "Postive effects of HTL0018318 were found on specific attention and memory endpoints. HTL0018318 was well tolerated in mild-to-moderate AD patients and showed positive effects on attention and episodic memory on top of therapeutic doses of donepezil."

Clinical • Journal • P1/2 data • PK/PD data • Alzheimer's Disease • CNS Disorders • Fatigue • Pain

Safety and Pharmacokinetics of HTL0018318, a Novel M Receptor Agonist, Given in Combination with Donepezil at Steady State: A Randomized Trial in Healthy Elderly Subjects. (PubMed, Drugs R D) - "HTL0018318 was well tolerated when given alone and in combination with donepezil. HTL0018318 and donepezil do not demonstrate pharmacokinetic or pharmacodynamic interactions, indicating that HTL0018318 can be safely administered in combination with donepezil."

Clinical • Combination therapy • Journal • PK/PD data • Alzheimer's Disease • CNS Disorders • Dementia

Safety, pharmacokinetics and exploratory pro-cognitive effects of HTL0018318, a selective M receptor agonist, in healthy younger adult and elderly subjects: a multiple ascending dose study. (PubMed, Alzheimers Res Ther) - "Multiple doses of HTL0018138 showed well-characterised pharmacokinetics and were safe and generally well-tolerated in the dose range studied. Pro-cognitive effects on short-term memory and learning were demonstrated across the dose range. These data provide encouraging data in support of the development of HTL0018138 for cognitive dysfunction in AD and DLB."

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

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

Sosei Heptares operational highlights and consolidated results for the nine months ended 30 September, 2019 (PRNewswire) - "Global R&D collaboration with Allergan update – programs continue to advance through development: multiple compounds with the potential to be new candidates generated. Clinical development of HTL0018318 in Alzheimer's disease remains voluntarily suspended while investigative work continues."

Discontinued • Alzheimer's Disease • CNS Disorders

First-in-man study to investigate safety, pharmacokinetics and exploratory pharmacodynamics of HTL0018318, a novel M -receptor partial agonist for the treatment of Dementias. (PubMed, Br J Clin Pharmacol) - "HTL0018318 showed well-characterized pharmacokinetics and following single doses were generally well tolerated in the dose range studied. These provide encouraging data in support of the development for HTL0018318 for AD and other dementias. Netherlands Trial Register identifier NTR5648."

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

Sosei Heptares operational highlights and consolidated results for the nine months ended 30 September, 2019 (PRNewswire) - "Phase 2 trial of HTL0018318 in DLB patients in Japan – decision made to withdraw study to minimize CRO expenditure while clinical trial activities are suspended. The Company remains committed to the DLB program in Japan and plans to resubmit a new clinical trial notification with the Japanese PMDA in the future."

New trial

DLB: A Study to Assess Safety, Tolerability, and Efficacy of HTL0018318 in Patients With Dementia With Lewy Bodies (clinicaltrials.gov) - P2; N=0; Withdrawn; Sponsor: Heptares Therapeutics Limited; N=172 ➔ 0; Suspended ➔ Withdrawn

Clinical • Enrollment change • Trial withdrawal

Sosei Heptares operational highlights and consolidated results for the first half of FY2019 (PRNewswire) - "Clinical development of HTL0018318 in Alzheimer's disease remains voluntarily suspended while investigative work is continuing...Update on Phase 2 trial of HTL0018318 in DLB patients in Japan – decision made to withdraw study in order to minimize CRO expenditure while clinical trial activities are suspended. The Company remains committed to the DLB program in Japan and plans to file a new clinical trial application with the Japanese PMDA in the future."

Trial status

That's a big fall back, major domestic securities down investment valuation (Minkabu Press Release) - "Sosei group...falls sharply. On 11th, SMBC Nikko Securities Co., Ltd. changed its investment...lowered its target price from 4,250 yen to 2,400 yen...HTL0018318, which had been developed for Allergan and had been developed for Alzheimer's disease, had unexpected toxicological findings (multiple changes to rare tumors in a study in monkeys in September 18) Confirmation was confirmed, and a voluntary interruption of development was announced to investigate the cause. The cause is still under investigation, and the probability of success has been lowered from 25% to 5%, taking into consideration that the development schedule continues to be unclear, and that other companies are continuing to stop developing the drug for treating Alzheimer's disease."

Clinical data • Stock price

DLB: A Study to Assess Safety, Tolerability, and Efficacy of HTL0018318 in Patients With Dementia With Lewy Bodies (clinicaltrials.gov) - P2; N=172; Suspended; Sponsor: Heptares Therapeutics Limited; Initiation date: Apr 2019 ➔ Jul 2019

Clinical • Trial initiation date