Neurocentrx Reports Positive Top-line Results from Phase 1 Clinical Study of its Lead Oral Ketamine Capsule Programme

• KET-IR (oral ketamine immediate-release formulation) was generally well-tolerated with no serious adverse events reported following single ascending doses in healthy males and females
• Pharmacokinetic properties were similar to those reported for other ketamine formulations
• Results support potential to evaluate KET-IR efficacy in people with treatment-resistant depression and in other major mental health conditions
• Phase 2 clinical trials of an abuse-deterrent oral IR formulation are planned for H1 2024

EDINBURGH, Scotland--(BUSINESS WIRE)-- Neurocentrx, a biopharmaceutical company focused on the development of oral ketamine for the treatment of mood disorders and other indications, today announced positive topline results from its Phase 1 clinical study of KET-IR, its novel oral ketamine immediate-release (IR) formulation to treat major mental health conditions, including treatment-resistant depression.

KET-IR was generally well tolerated in healthy volunteers at all dose levels tested and no serious adverse events were reported following single doses. At several KET-IR dose levels, ketamine and ketamine metabolite blood concentrations were similar to those reported for intranasal esketamine, which is used to treat patients with treatment-resistant depression, and with intravenous ketamine.

Pharmacodynamic effects known to be associated with ketamine therapy, such as dissociation and mild sedation, were apparent at several doses. These effects resolved within hours following a KET-IR dose. Cognitive function tests revealed no significant changes across multiple objective measures of attentiveness, response time, or executive memory function during KET-IR dosing or participant follow-up (through 10 days following the final dose).

Professor Allan Young, Chair of Mood Disorders and Head of Academic Psychiatry at the Centre for Affective Disorders, Institute of Psychiatry, Psychology & Neuroscience at King’s College London, and study co-investigator, said: “The Phase 1 study has shown that KET-IR, Neurocentrx’s oral ketamine immediate-release formulation, is suitable for additional clinical studies in treatment-resistant depression. These clinical results are very encouraging for studies in patients with other major mental health conditions, such as bipolar depression.”

Neurocentrx’s collaborators at King’s College London will present the results of the trial at the International Society for Affective Disorders Conference on 14-16 December 2023 in Milan.

The Phase 1 trial was a first-in-human, randomised, double-blind, placebo-controlled clinical study of the safety, tolerability, pharmacokinetic and pharmacodynamic effects of single ascending doses of KET-IR in healthy males and females (EudraCT no 2019-001019-22). Neurocentrx sponsored the study in part via Innovator Award funding from the Wellcome Trust.

Neurocentrx has obtained MHRA guidance that KET-IR and an abuse-deterrent immediate-release formulation may be suitable for immediate Phase 3 pivotal efficacy studies. However, the company will next conduct Phase 2 studies in people with treatment-resistant depression, bipolar depression, and potentially other psychiatric disorders.

“We are encouraged by the results of our phase 1 study of KET-IR.”, added Graeme Duncan, Head of Clinical Development at Neurocentrx. “Currently, we are working with regulators on a clear development pathway to achieve commercial-scale manufacturing and marketing approval of KET-IR and a new ketamine formulation to treat depression in line with the USA FDA abuse deterrence guidelines.”

In the first half of 2024, Neurocentrx plans to initiate Phase 2 efficacy and safety studies of KET-IR and their abuse-deterrent oral immediate-release ketamine formulation (AD-KET-IR) in multiple mental health indications.

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Notes to Editors

Summary of Preliminary KET-IR Phase 1 Study Results:

• Single Ascending Dose (SAD) Study: In the SAD study, KET-IR was administered as an oral capsule at doses between 40 and 240 mg in 6 double-blind placebo-controlled cohorts enrolling a total of 18 healthy volunteers. Based on pre-specified dose escalation stopping criteria, a maximum tolerated dose (MTD) was not established.
• Safety, Tolerability and Pharmacokinetics:
  KET-IR was generally well tolerated following dose escalation from 40mg to the final planned dose of 240 mg. Blood levels of ketamine and ketamine metabolites were similar to levels associated with therapeutic ketamine administration at several dose levels (Perez-Ruixo et al. 2020 and Singh et al. 2016).
  All adverse events reported were mild or moderate in intensity and resolved within hours without study interruption or medical intervention. No serious adverse events were reported. Measures of clinical activity known to be associated with ketamine treatment were observed at several dose levels, including dissociation and mild sedation.

• Several dose levels showed a pharmacokinetic profile suitable for continuous dosing regimens, with dose linearity across all levels tested. Furthermore, rapid drug exposure and clearance properties were consistent with those reported for immediate-release ketamine formulations (Perez-Ruixo et al. 2020 and Singh et al. 2016).

About Neurocentrx

Neurocentrx is an Edinburgh-based biopharmaceutical company focused on the development of oral ketamine for the treatment of major mental health conditions, including mood disorders. The Company aims to gain regulatory approval for the first prescription form of oral ketamine to treat depression and has developed a novel and proprietary abuse-deterrent ketamine oral formulation. Neurocentrx is a growth-phase company headquartered in the UK and is seeking corporate partners and investors to support future clinical development. For more information, please visit the website: www.neurocentrx.com.

About KET-IR and AD-KET-IR

KET-IR and AD-KET-IR are Neurocentrx’s proprietary oral ketamine immediate-release formulations for the treatment of major mental health conditions. AD-KET-IR is an oral ketamine capsule formulation being developed under FDA guidance to limit the potential for misuse and diversion of controlled substances. Since launching operations in 2013, Neurocentrx continues to expand its patent and intellectual property estate portfolio covering novel compositions and methods for delivering oral ketamine therapy for patients and healthcare providers across diverse care and community settings.

About Wellcome

Wellcome supports science to solve the urgent health challenges facing everyone. We support discovery research into life, health and wellbeing, and we’re taking on three worldwide health challenges: mental health, infectious disease and climate and health.

About King’s College London and the Institute of Psychiatry, Psychology & Neuroscience

King’s College London is amongst the top 35 universities in the world and top 10 in Europe (THE World University Rankings 2023), and one of England’s oldest and most prestigious universities.

With an outstanding reputation for world-class teaching and cutting-edge research, King’s maintained its sixth position for ‘research power’ in the UK (2021 Research Excellence Framework).

King’s has more than 33,000 students (including more than 12,800 postgraduates) from some 150 countries worldwide, and some 8,500 staff. The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s is a leading centre for mental health and neuroscience research in Europe. It produces more highly cited outputs (top 1% citations) on psychiatry and mental health than any other centre (SciVal 2021), and on this metric has risen from 16th (2014) to 4th (2021) in the world for highly cited neuroscience outputs. In the 2021 Research Excellence Framework (REF), 90% of research at the IoPPN was deemed ‘world leading’ or ‘internationally excellent’ (3* and 4*). World-leading research from the IoPPN has made, and continues to make, an impact on how we understand, prevent and treat mental illness, neurological conditions, and other conditions that affect the brain.

www.kcl.ac.uk/ioppn | Follow @KingsIoPPN on Twitter, Instagram, Facebook and LinkedIn

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