Plus, Actinogen receives approval of its application for a UK Innovation Passport as part of the Innovative Licensing and Access Pathway (ILAP) for Xanamem in the treatment of Alzheimer's disease

Enrolment in XanaCIDD phase 2a trial of cognitive impairment and depression has surpassed 90%

SYDNEY, April 15, 2024 /PRNewswire/ -- Actinogen Medical Limited (ASX: ACW) announces 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.

The trial has commenced at thirteen Australian sites and will subsequently expand to the USA. An interim analysis is planned for mid-2025 when approximately 100 patients reach 24 weeks of treatment, with final results anticipated in H1 2026.

Dr Steven Gourlay, Actinogen's CEO said:

"We are very pleased to announce the first patient treated in our phase 2b trial in patients with Alzheimer's disease. Based on encouraging safety and clinical activity seen in multiple prior trials of Xanamem, and a strong scientific rationale for reducing brain cortisol levels, we are confident that the trial will confirm clinically and statistically meaningful results."

"This phase 2b trial is designed to confirm that Xanamem is a safe and effective new treatment for Alzheimer's disease and represents a major opportunity for patients and the Company."

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).

Dr Steven Gourlay, Actinogen's CEO said:

"The MHRA's approval of the ILAP application validates our belief in Xanamem's unique and encouraging profile for the treatment of Alzheimer's disease. Following on from three prior trials showing promising activity, Actinogen's 220-person phase 2b trial in Alzheimer's is now underway and will report initial results in mid-2025."

The next step in the ILAP process will be to commence development of the TDP.

XanaCIDD phase 2a cognitive impairment and depression trial nears completion

• The XanaCIDD Phase 2a depression trial enrolment has surpassed 90%
• Full enrolment of approximately 160 patients is expected later in April
• Results to report in early Q3 2024

The XanaCIDD Phase 2a Depression trial is a six-week proof-of-concept, placebo-controlled, parallel group design trial in patients with persistent Major Depressive Disorder (MDD) and cognitive impairment.

Xanamem 10 mg daily or placebo is added to the existing anti-depressant therapy, if being used. Therapeutic effects on cognition, measured using an "Attention Composite" of the computerized Cogstate Cognitive Test Battery are assessed as the primary endpoint (a composite of the One Back, Identification and Detection tests). Effects on depression are measured using the Montgomery-Asberg Depression Rating Scale.

Previously, positive benefits on cognition were observed using the same Attention Composite endpoint in two independent, placebo-controlled trials of older, cognitively normal volunteers.

About Actinogen Medical

Actinogen Medical (ACW) is an ASX-listed, biotechnology company developing a novel therapy for neurological and neuropsychiatric diseases associated with dysregulated brain cortisol. There is a strong association between cortisol and detrimental changes in the brain, affecting cognitive function, harm to brain cells and long-term cognitive health.

Cognitive function means how a person understands, remembers and thinks clearly. Cognitive functions include memory, attention, reasoning, awareness and decision-making.

Actinogen is currently developing its lead compound, Xanamem, as a promising new therapy for Alzheimer's Disease and Depression and hopes to study Fragile X Syndrome and other neurological and psychiatric diseases in the future. Reducing cortisol inside brain cells could have a positive impact in these and many other diseases. The cognitive dysfunction, behavioural abnormalities, and neuropsychological burden associated with these conditions is debilitating for patients, and there is a substantial unmet medical need for new and improved treatments.

Current Clinical Trials

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.

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.

About Xanamem

Xanamem's novel mechanism of action is to block the production of cortisol inside cells through the inhibition of the 11β-HSD1 enzyme in the brain. Xanamem is designed to get into the brain after it is absorbed in the intestines upon swallowing.

Chronically elevated cortisol is associated with cognitive decline in Alzheimer's Disease and excess cortisol is known to be toxic to brain cells. 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 11β-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 cognitive ability in patients with biomarker-positive mild AD. Previously, high levels of target engagement in the brain with doses as low as 5 mg daily have been demonstrated in a human PET imaging study. A series of Phase 2 studies in multiple diseases is being conducted to further confirm and characterize Xanamem's therapeutic potential.

Xanamem is an investigational product and is not approved for use outside of a clinical trial by the FDA or by any global regulatory authority. Xanamem is a trademark of Actinogen Medical.

Disclaimer

This announcement and attachments may contain certain "forward-looking statements" that are not historical facts; are based on subjective estimates, assumptions and qualifications; and relate to circumstances and events that have not taken place and may not take place. Such forward looking statements should be considered "at-risk statements" - not to be relied upon as they are subject to known and unknown risks, uncertainties and other factors (such as significant business, economic and competitive uncertainties / contingencies and regulatory and clinical development risks, future outcomes and uncertainties) that may lead to actual results being materially different from any forward looking statement or the performance expressed or implied by such forward looking statements. You are cautioned not to place undue reliance on these forward-looking statements that speak only as of the date hereof. Actinogen Medical does not undertake any obligation to revise such statements to reflect events or any change in circumstances arising after the date hereof, or to reflect the occurrence of or non-occurrence of any future events. Past performance is not a reliable indicator of future performance. Actinogen Medical does not make any guarantee, representation or warranty as to the likelihood of achievement or reasonableness of any forward-looking statements and there can be no assurance or guarantee that any forward-looking statements will be realised.

SOURCE Actinogen Medical Limited