Tokyo, Japan and London, UK, 18 September 2018 – Sosei Group Corporation (“Sosei” or the “Company”; TSE Mothers Index: 4565), the world leader in GPCR medicine design and development, announces that the Company and Allergan, its license partner for HTL0018318, have decided to voluntarily suspend clinical development activities with HTL0018318 pending the investigation of an unexpected toxicology finding in an animal study involving non-human primates. This voluntary suspension is not based on any human findings. Sosei’s programs with other partners as well as its in-house pipeline are not impacted by the finding announced today.
HTL0018318 is a selective small molecule muscarinic M1 receptor agonist under clinical investigation as a potential new symptomatic treatment for cognitive impairment in patients with Alzheimer’s disease (AD) and other dementias, including dementia with Lewy bodies, (DLB).
The compound is in Phase 1 clinical development in the US (sponsored by Allergan), and in a Phase 2 clinical study in Japan in patients with DLB. A further Phase 1b study in AD patients has completed its clinical phase in Europe and the data is being analysed (sponsored by Sosei’s subsidiary Heptares Therapeutics).
To date, HTL0018318 has been investigated in approximately 310 human subjects in the US and Europe, including healthy volunteers and patients with mild/moderate AD. Data available from the human studies have found it to be well tolerated and with no serious adverse effects at the tested doses for up to 28 days.
Patient safety is of the utmost importance to Sosei and Allergan. The decision by Sosei and Allergan to voluntarily suspend clinical development activities with HTL0018318 was taken as a precaution based on emerging results from a single animal toxicology study in non-human primates. This animal toxicology study was investigating different dosing levels of HTL0018318 over a nine-month period. The toxicological finding (neoplastic, rare tumor) was observed at doses and durations exceeding those used clinically in humans to date. No serious safety findings were observed in any species in any other animal toxicology studies with HTL0018318 extending as long as six months. Scientists from both Sosei and Allergan will be investigating these findings, which are currently of unknown cause.
Sosei and Allergan have reported the safety finding of the study to the US Food & Drug Administration (FDA) and the Japan Pharmaceutical & Medical Devices Agency (PMDA). Other regulatory authorities in countries where studies that have been completed were also informed. The Company is undertaking a thorough investigation to identify the significance and cause of the safety finding and determine the next steps. Data from previous preclinical and clinical studies will be reviewed as part of the investigation.
Dr Tim Tasker, Chief Medical Officer of Sosei, said: “We were very surprised to see these results given the safety profile HTL0018318 has exhibited across all previous animal and clinical studies. We have taken these steps in the best interests of patient safety, which is our number one priority. We are committed to working with clinical investigators, R&D teams and regulatory authorities to understand better the reason for the findings from this animal toxicology study and so enable the human clinical development program with HTL0018318 to continue as soon as possible. We remain confident that this compound has the potential to deliver important benefits to patients with AD and DLB.”
This toxicology finding, and subsequent investigations, will delay the start of planned Phase 2 studies in AD and DLB patients by at least six months. Because of this delay, there will be a revenue impact next year as the Company no longer expects to receive a major milestone payment from Allergan in 2019 relating to progress of the partnered muscarinic M1 agonist program for AD. The costs associated with investigating this safety finding are covered under the terms of our 2016 global R&D and commercialization agreement with Allergan. Regarding the nine-month period to 31 December 2018, we expect R&D expenses will decline because of reduced external spending. The voluntary suspension of clinical development activities with HTL0018318 does not automatically trigger impairment of assets or goodwill. We will fully assess the financial impact of the voluntary suspension and make adjustments to the carrying value of relevant assets, if any, in our results for the quarter ended 30 September 2018, which will be reported on 8 November 2018. We will also provide an update on the outlook for the accounting period ended December 2018 at that time.
The Company will host a video webcast today at 4:30 p.m. JST. To view, please access the following web address http://www.c-hotline.net. A replay of the video webcast will be available from 6:30 p.m. on the Investor Relations section of the Sosei website at www.sosei.com/en/ir.