Actinogen Medical Limited announces the full enrolment of 167 participants in the Company's XanaCIDD phase 2a clinical trial in patients with cognitive impairment in major depressive disorder (MDD). The XanaCIDD trial is a proof-of-concept, placebo-controlled, parallel group trial with a six-week treatment period and four weeks of follow up. This is an important and unique trial in the neuropsychiatric field because of its focus on the ability of the Company's novel small molecule Xanamem® to improve cognitive function in patients with MDD by reducing levels of the "stress hormone", cortisol, in the brain, while leaving normal cortisol stress response intact in the body.

Xanamem does this by inhibiting tissue cortisol synthesis in the brain by an enzyme called 11ß-HSD1, without affecting cortisol synthesis by different enzymes in the adrenal gland. Cognitive impairment, or "foggy thinking" is reported by the majority of patients with MDD and may not respond to traditional anti-depressant therapy. Xanamem is being developed as an easy-to-use, oral therapy to improve cognitive impairment associated with MDD and Alzheimer's disease.

It has potential uses in other diseases where cognitive impairment is a significant problem such as schizophrenia and other types of dementia. The XanaCIDD trial is a phase 2a, proof-of-concept, placebo-controlled, parallel group trial in patients with persistent MDD and measurable cognitive impairment. Xanamem (10 mg) or placebo is added to the existing anti-depressant therapy or, in patients with a previous history of anti-depressant treatment, as a stand-alone treatment.

Results are expected in early Third Quarter 2024. The primary endpoint for the trial is the computerized Cogstate "attention composite" test battery, measuring attention and working memory and shown previously to be a sensitive measure of Xanamem benefit in the prior XanaMIA Part A and XanaHES trials. Attention and working memory, sometimes characterized as the ability to focus, are critical and essential components of cognitive ability.

The key secondary endpoint is the Montgomery-Asberg Depression Rating Scale (MADRS) which is a structured interview evaluating MDD symptoms and is a fundamental endpoint used for regulatory approvals of anti-depressant medication. Other secondary endpoints include an executive function cognitive composite, a memory function cognitive composite, proportions of responders and global clinical assessment scores. Actinogen's second on-going randomized trial, a phase 2b of 36 weeks duration in patients with mild to moderate, biomarker-positive Alzheimer's disease, is expected to provide interim results mid-2025 and final results in 2026.

The XanaCIDD Phase 2a depression trial is a double-blind, six-week proof-of-concept, placebo-controlled, parallel group design trial in 167 patients. Participants are evenly randomized to receive Xanamem 10 mg once daily or placebo, in some cases in addition to their existing antidepressant therapy, and effects on cognition and depression are assessed. The XanaMIA Phase 2b Alzheimer's disease trial is a double-blind, 36-week treatment, placebo-controlled, parallel group design trial in 220 patients with mild to moderate AD and progressive disease, determined by clinical criteria and confirmed by an elevated level of a pTau protein biomarker in blood.

Patients receive Xanamem 10 mg or placebo, once daily, and effects on cognition, function and progression of Alzheimer's disease are assessed. Thus, Xanamem is being assessed in this trial for its potential effects as both a cognitive enhancer and a disease course modifier.