Head-to-head Trial of Prolonged-Release Oral Ketamine Formulation, KET01, and Intranasal SPRAVATO®, Finds Less Incidence of Dissociation or Cardiovascular Effects with Oral Treatment, at doses used for Treatment-Resistant Depression

Results Suggest Formulation Potentially Suitable for At-Home Administration

Ketabon Also Releases In-Depth Data from Phase 2 KET01 Trial 

MUNICH, Germany, Nov. 13, 2023 (GLOBE NEWSWIRE) — Ketabon GmbH (“Ketabon” or “the Company”), a joint venture between HMNC Brain Health and Develco Pharma, announced today favorable results from its head-to-head trial with KET01, the Company’s proprietary lead asset, versus SPRAVATO^®, the FDA-approved intranasal spray for patients with Treatment-Resistant Depression (TRD). KET01 is an IP protected oral prolonged-release formulation of ketamine and is being studied in patients with TRD. Due to its unique metabolite profile, the incidence of dissociation with KET01 was very low and statistically significantly lower relative to SPRAVATO^®, pointing to a clinically meaningful difference, which could offer the potential for a safe at-home unsupervised administration. During the summer Ketabon also released data from its Phase 2 KET01-02 trial with KET01, which demonstrated rapid and durable improvements in depressive symptoms in TRD. 

“KET01’s near complete absence of dissociative effects as measured by the Clinician-Administered Dissociative States Scale, suggests that the formulation can be suitable for administration outside of a medical setting, in the comfort of a patient’s home,” said HMNC Brain Health’s Chief Medical Officer, Dr. Hans Eriksson. “As we are seeking alternative treatment options for patients suffering from TRD, we are hopeful KET01 has the potential to vastly change the treatment paradigm given its favorable tolerability at doses associated with antidepressant efficacy.”

Both studies were presented at the CNS Summit in Boston this week by Dr. Eriksson.

KET01-03 Versus SPRAVATO^® Key Findings: 

The trial investigated the tolerability of a single dose of KET01 (240 mg) compared to intranasal esketamine (84 mg; active comparator) with respect to dissociative symptoms assessed by the change in Clinician-Administered Dissociative States Scale (CADSS) total score in healthy male subjects. Both doses are associated with antidepressant efficacy.

The trial was conducted under controlled conditions to investigate the tolerability of KET01 (ketamine) and SPRAVATO^® (esketamine), with respect to dissociative symptoms, with emphasis on the time points after administration presumed for maximum plasma concentrations of ketamine and esketamine, respectively. A total of 26 participants at a single center were randomized to receive two single doses, KET01 (240 mg) and intranasal placebo nasal spray, or intranasal esketamine nasal spray (84 mg) and placebo tablet. All doses were sequence balanced, with a 2-to-4-week washout period between doses. No serious adverse effects were reported. 

KET01-02 Phase 2 Trial: Data Results of a Randomized Placebo-Controlled Double-Blind Phase 2 Trial

In August 2023, Ketabon revealed topline results from its Phase 2 trial of KET01, an oral prolonged-release ketamine formulation, which demonstrated early improvements in depressive severity and included minimal incidences of dissociation or cardiovascular effects. 

The trial investigated the efficacy, safety, and tolerability of KET01 in 122 outpatients with current major depressive episodes not responding to a minimum of two standard antidepressants, thereby fulfilling criteria for TRD. Patients were administered doses of 120 mg/day KET01, 240 mg/day KET01, or placebo given once daily in addition to their ongoing standard antidepressant treatment over a three-week period. The trial was conducted across 29 sites in Germany, Poland, and the Czech Republic.

Results showed that KET01, at a 240mg/day dose, demonstrated rapidly occurring and clinically relevant improvements in depressive severity 7 hours after the first dosing with a statistically significant separation on Day 4 and Day 7. The improvements from baseline were sustained while on active treatment until Day 21, and also after the 4-week follow-up period. The mean Montgomery-Åsberg Depression Rating Scale (MADRS) score improved in placebo-treated patients during the trial, but at the primary endpoint, after 21 days, the separation versus placebo did not reach statistical significance. Only minimal signs of dissociative symptoms were detected by the CADSS scale, and no changes in cardiovascular parameters were detected. 

Additionally:

• There was no difference in mean CADSS scores between the groups at any assessment time point including during Day 1 when the scale was administered 1, 4, and 7 hours after dosing, with mean scores in the different treatment groups ranging from 0.2 to 1.3.
• There was no difference in mean heart rate, diastolic blood pressure, or systolic blood pressure between the groups at any assessment time point, including during Day 1.
• KET01 was well tolerated with treatment-emergent adverse events (TEAEs) reported by 47.5% of the placebo group, by 50.0% of the 120 mg/day KET01 group, and by 62.5% of the 240 mg/day KET01 group. The most commonly reported TEAEs per treatment arm were headache (17.5%) in the placebo group, headache (11.9%) in the 120 mg/day KET01 group; and dizziness (17.5%), in the 240 mg/day KET01 group.
• TEAEs potentially related to dissociation were reported by 0% of the patients in the placebo group, by 0% of the patients in the 120 mg/day KET01 group, and by 12.5% of the patients in the 240 mg/day KET01 group.

“Data continues to suggest rapid and clinically relevant reduction of depressive symptoms after oral treatment with 240 mg/day of KET01. We believe that KET01 has the potential to be developed as an efficacious take-at-home treatment for TRD,” said Dr. Eriksson. “Together with the SPRAVATO head-to-head trial findings, it can be hypothesized that the low maximal ketamine concentration obtained with the prolonged-release oral ketamine formulation results in less dissociative effects and a positive benefit/risk, compared with ketamine-based treatments administered in a clinic.”

For additional details on the trial, please email HMNCBrain@kcsa.com. For more information on the Ketabon program, please visit https://www.ketabon.health/ 

About HMNC Brain Health 
HMNC Brain Health (HMNC Holding GmbH) is a global precision psychiatry biopharma company headquartered in Munich, Germany which is pioneering the development of personalized therapies powered by predictive companion diagnostics, leading to higher remission rates. The company develops a unique pipeline for targeting both Major Depressive Disorder (MDD) and Treatment-Resistant Depression (TRD). The company has presence in both Germany and the U.S. and is backed by a renowned global VC, several family offices, and a strategic healthcare investor. More information at www.hmnc-brainhealth.com

About Develco Pharma
Develco Pharma is a Swiss-German pharmaceutical company headquartered in Pratteln, Switzerland, specializing in the development and manufacture of orally administered modified, prolonged & chrono-release drugs containing known active ingredients. Established in 2006, today the company has a workforce of 130 employees. A state-of-the-art production facility for analgesics and drugs for the treatment of other indications has been in operation in Schopfheim, in Germany, since 2016. Develco identifies and defines pharmaceutical products containing known active ingredients and develops generic, hybrid, value-added, and innovative formulations backed by clinical data for the delayed or modified release of active ingredients. On the strength of its experience and innovativeness, the company has emerged as an internationally recognized provider of pharmaceuticals for the treatment of several disease areas. The customer base of Develco Pharma includes global pharmaceutical groups. The company has some 180 market approvals in all (products of different dosages) in Europe, the US, Middle East, South Africa, Asia, and Australia. More information at www.develco.ch

About the Ketabon Program 
The Ketabon program, a joint venture between HMNC Brain Health and Develco Pharma comprises an oral prolonged-release formulation of ketamine for TRD (KET01) with minimal dissociative side effects, that could make it the first ketamine treatment for depression suitable for use at home. The pharmacokinetic profile of the prolonged-release formulation could significantly improve the risk profile and patient convenience, by minimizing dissociative side effects compared to the currently applied intravenous and intranasal ketamine therapies resulting in a decreased need for monitoring under medical supervision. TRD patients with insufficient response to standard antidepressants represent close to 30% of an overall estimated number of 320 million patients worldwide suffering from major depressive disorder. Clinical development of oral prolonged-release ketamine could also be potentially expanded into other indications beyond depression, such as anxiety, aggression, PTSD, and panic disorder.

Media contacts (U.S.):
McKenna Miller
+949-606-6585
hmncbrain@kcsa.com
Investor Contact (U.S.)
Sophia Bashford
+1 347-487-6788
sbashford@kcsa.com