Scilex Bio is advancing KDS2010, a novel oral tablet, through Phase 2 clinical trials for both obesity and Alzheimer's disease, with plans to expand trials to the U.S. in 2025. The drug's unique mechanism of action, targeting Monoamine Oxidase B (MAO-B) and astrocytic GABA production, offers a potentially new approach to treating these conditions.
KDS2010 for Obesity
The Phase 2 obesity trial is currently enrolling approximately 75 overweight or obese patients in South Korea and is designed as a randomized, double-blind, placebo-controlled study. KDS2010 (Tisolagiline) functions as a selective, reversible MAO-B inhibitor, blocking GABA production in reactive astrocytes and eliminating neuronal inhibition in the Lateral Hypothalamic Area. This mechanism stimulates metabolism and energy expenditure without affecting appetite, potentially offering advantages over current obesity treatments like GLP-1 agonists, which can cause side effects such as loss of appetite and gastrointestinal issues.
Phase 1 trials, completed with 88 subjects, demonstrated favorable safety, tolerability, and suitable pharmacokinetics for once-daily dosing. According to IQVIA, the global obesity drug market is projected to reach $150 billion by the early 2030s, making the development of new treatments like KDS2010 highly significant.
KDS2010 for Alzheimer's Disease
KDS2010 is also in Phase 2 clinical trials for Alzheimer's disease, currently enrolling 114 patients in South Korea, with a U.S. cohort to be added in 2025. In neurodegenerative diseases like Alzheimer’s, altered GABAergic activity and dysfunction in astrocytic regulation of neurotransmitter systems contribute to cognitive decline and neuroinflammation. By inhibiting astrocytic GABA signaling, KDS2010 helps to reduce neuroinflammation and normalize the balance between excitatory and inhibitory signals in the brain, potentially leading to enhancing cognitive function in Alzheimer's disease.
Preclinical studies have shown that long-term treatment with KDS2010 significantly attenuates increased astrocytic GABA levels and astrogliosis, enhances synaptic transmission, and improves learning and memory in APP/PS1 mice. Richard Lipton, MD, Professor of Neurology at the Albert Einstein College of Medicine, noted that current treatments in development for Alzheimer’s Disease are mostly injectable antibodies or peptides targeting amyloid, tau or neuroinflammation and that a small molecule with great potential to improve cognitive function that can be delivered with once-daily oral dosing holds promise for people living with Alzheimer's disease.
Mechanism of Action
KDS2010 is a potent, selective, and reversible Monoamine oxidase B (MAO-B) inhibitor of new generation, which overcomes the drawbacks of existing irreversible and reversible MAO-B inhibitors. MAO-A regulates dopamine levels, whereas MAO-B controls tonic levels of GABA, gamma-aminobutyric acid, a chief inhibitory neurotransmitter in the central nervous system. Selective inhibition of astrocytic GABA is a molecular target for treating obesity and Alzheimer's.
Market Potential
According to health care analyst reports, the Alzheimer’s global drug market size is expected to rise above $15 billion by 2030 in the eight major markets, as new drugs show promise and are being launched with FDA approval to slow cognitive decline. The global obesity drug market is projected to reach $131 billion by 2028, and $150 billion by early 2030s. KDS2010's oral administration and potentially better safety profile could give it a competitive edge in this rapidly growing market.
Ongoing Clinical Trials
A Randomized, Double-blind, Placebo-controlled, Dose Finding, Phase 2 Clinical Trial to Evaluate the Efficacy and Safety of KDS2010 in Overweight or Obese Patients is ongoing in South Korea and will be expanding to the USA in 2025. The trial investigates 12-week treatment in 75 patients with high BMI (Body Mass Index) and at least one of the weight-related comorbidities (hypertension, dyslipidaemia, or cardiovascular disease), assessing body weight change from the baseline, proportion of patients with reduction in body weight, and other parameters.
A Randomized, Double-Blind, Placebo-Controlled, Dose-Finding, Phase 2 Clinical Trial to Evaluate the Safety and Efficacy of KDS2010 in Patients with Alzheimer’s Disease with Mild Cognitive Impairment and Mild Dementia is currently recruiting in South Korea in 114 patients and U.S. cohort will be added in 2025.
