Actinogen Medical Limited announced that the first patient has been randomized and treated in the XanaMIA phase 2b clinical trial in patients with biomarker-positive mild to moderate Alzheimer's disease (AD). This represents the culmination of the site and screening setup phase of the trial when patient pre-screening for elevated levels of the pTau blood biomarker commenced at multiple clinical sites. The XanaMIA trial is a double-blind placebo-controlled randomized trial design which will enrol 220 participants with mild to moderate AD and elevated levels of plasma pTau.

The trial measures the effects of a Xanamem®? 10 mg daily dose versus placebo on safety and its ability to preserve cognition and function over a 36-week treatment period. The primary endpoint is a cognitive test battery comprising seven different digital assessments (previously, Xanamem benefits on cognition were observed in three separate placebo-controlled trials including an initial study in AD).

A key secondary endpoint is the Clinical Dementia Rating - Sum of Boxes scale (CDR-SB), a validated combined cognitive and functional measure, used by the FDA and many companies as a primary or secondary endpoint for regulatory approval. Previously, in an analysis of biomarker-positive patients with mild AD treated with Xanamem, clinically significant benefits were seen on cognition and the CDR-SB endpoint. A variety of other secondary endpoints include the Amsterdam Activity of Daily Living scale, which measures the ability to perform everyday tasks.

Based on encouraging safety and clinical activity seen in multiple prior trials of Xanamem, and a strong scientific rationale for reducing brain cortisol levels, the company is confident that the trial will confirm clinically and statistically meaningful results. Actinogen awarded UK Innovation Passport for Xanamem: Actinogen has also received approval from the UK Medicines and Healthcare products Regulatory Agency (MHRA) of its application for an Innovation Passport as part of the Innovative Licensing and Access Pathway (ILAP) for Xanamem in the treatment of Alzheimer's disease. Key benefits of this approval include: Entry point to the ILAP which aims to accelerate time to market; Linkage to a portfolio of activities through the product-specific creation of the Target Development Profile (TDP) in conjunction with the MHRA; Opportunities for enhanced regulatory and other stakeholder input including from partner agencies such as the MHRA and National Institute for Health and Care Excellence (NICE).

The XanaCIDD Phase 2a depression trial is a double-blind, six-week proof-of-concept, placebo-controlled, parallel group design trial in 160 patients. Patients 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. cognitive impairment is also a feature in Depression and many other diseases.

Cortisol itself is also associated with depressive symptoms and when targeted via other mechanisms has shown some promise in prior clinical trials. The Company has studied 11b-HSD1 inhibition by Xanamem in more than 350 volunteers and patients, so far finding a statistically significant improvement in working memory and attention, compared with placebo, in healthy, older volunteers in two consecutive trials and clinically significant improvements in functional and cognitiveability in patients with biomarker- positive mild AD. A series of Phase 2a trial is a double- blind placebo-controlled, placebo-controlled, parallel Group design trial in 160 patients.

The XanaCIDD phase 2a depression trial is a triple-blind, double-blind, three-week proof-of- concept, placebo-controlled, parallel groups design trial in 160 patients. Patients 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.