Actinogen XanaCIDD Phase 2a trial in patients with depression and cognitive impairment: enrolment accelerating and on track for results in second quarter of 2024

US$3.2 million (A$4.8m) R&D tax incentive rebate received from Australian Tax Office and XanaMIA Phase 2b Alzheimer's disease trial to commence shortly with initial results expected in first half of 2025  

SYDNEY, Nov. 28, 2023 /PRNewswire/ -- Actinogen Medical Limited (ASX:ACW) announces that enrolment in the XanaCIDD Phase 2a proof-of-concept trial in 160 participants with cognitive impairment associated with persistent major depressive disorder (MDD) now exceeds 50 percent (that is, more than 80 participants enrolled to date). Results remain on track for release in the second quarter of 2024.

Highlights of XanaCIDD trial:

• Double-blind, placebo-controlled randomized trial design
• 10mg Xanamem^® daily dose versus placebo for six weeks (a common duration for Phase 2a trials in MDD)
• Participants have a history of persistent MDD despite previous treatment and objective cognitive impairment
• 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 XanaMIA Part A and XanaHES trials
• The key secondary endpoint for the trial is the MADRS structured interview evaluating MDD symptoms and is a fundamental endpoint used for regulatory approvals of anti-depressant medication
• Recruitment in the UK is now accelerating (previously site activation was impacted by industry-wide delays at the UK regulator)
• Recruitment in Australia is further accelerating due to enhanced screening and recruitment procedures.

US$3.2 million R&D tax incentive rebate received

Actinogen also announced today that it has received a research and development (R&D) tax incentive rebate of US$3.2 million (A$4.8 million) from the Australian Tax Office for the 2023 financial year.

The R&D tax incentive is an Australian federal government program under which companies receive cash refunds for eligible research and development expenditure.

Actinogen's CEO Dr Steven Gourlay MBBS, PhD said:

 "We are looking forward to sharing the results of the XanaCIDD trial in approximately six months' time in the second quarter of 2024. This trial represents the first large scale test of whether lowering tissue cortisol in the brain can improve cognition and depression in patients with major depressive disorder (MDD). We are optimistic that Xanamem treatment will benefit patients, in part because the primary endpoint of the trial is the attention composite previously shown to be a sensitive measure of Xanamem effect."

"The receipt this year of a US$3.2 million Australian R&D tax incentive rebate represents a significant contribution by the Australian government towards our Phase 2 clinical-stage research exploring the potential benefits of Xanamem treatment for cognitive impairment associated with depression and Alzheimer's disease."

XanaMIA Phase 2b Alzheimer's disease trial site activation imminent and interim analysis on track for the first half of 2025

Clinical site startup activities continue at Australian sites for the XanaMIA Phase 2b Alzheimer's disease trial. Patient recruitment is expected to commence before the end of the year. The trial will enrol 220 participants with mild to moderate Alzheimer's disease and elevated blood pTau evenly randomized to treatment with 10mg of Xanamem or matching placebo daily for 36 weeks.

When approximately 100 patients reach 24 weeks of treatment, the Company will conduct an interim analysis and is expected to announce the results of that analysis in the first half of 2025.

Final results are anticipated in the second half of 2025.

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 and Upcoming 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 300 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.