Actinogen to present progress on Phase 2 trials at the BIO Investor Forum, San Francisco and Clinical Trials on Alzheimer's Disease (CTAD) Conference, Boston

Xanamem^® is an oral, brain-penetrant tissue cortisol synthesis inhibitor that has shown promising safety and clinical activity in three placebo-controlled trials and has the potential to treat a variety of neurodegenerative and neuropsychiatric diseases

SYDNEY, Oct. 13, 2023 /PRNewswire/ -- Actinogen Medical Limited (ASX: ACW) CEO Dr Steven Gourlay will conduct a series of meetings at the BIO Investor Forum, San Francisco on October 17-18, 2023.  The following week, Dr Gourlay and CMO Dr Dana Hilt will participate in the 16th annual CTAD conference in Boston where they will present a scientific poster on October 25 and conduct a number of stakeholders meetings.

Dr Gourlay and Dr Hilt will be discussing progress made with the Company's two ongoing Phase 2 trials:

XanaCIDD Phase 2a trial in patients with cognitive impairment and major depressive disorder

Enrolment continues in the XanaCIDD Phase 2a proof-of-concept trial in 160 patients with cognitive impairment associated with persistent Major Depressive Disorder (MDD). Cognitive impairment is common in MDD and currently there are no anti-depressant drugs approved for its treatment, although some companies have reported trials to assess effects of their anti-depressants on cognition. Consequently, there is a high unmet need for novel and safe treatments for this indication.

The trial is being conducted in Australia, the UK and the USA. It is treating patients with 10 mg of Xanamem or placebo once daily for six weeks as monotherapy or added to stable background anti-depressant therapy. The primary endpoint is an attention composite of three computerized cognitive tests measuring attention and working memory. Depression is assessed as a key secondary endpoint using the MADRS scale.

The trial is expected to report results in the first half of 2024.

XanaMIA Phase 2b trial in patients with mild-moderate Alzheimer's Disease (AD)

On 26 September Actinogen announced that it had redesigned operational features of the XanaMIA Phase 2b clinical trial of Xanamem in patients with mild to moderate AD to reduce the cost and time to initial results.

Key features of the revised XanaMIA Phase 2b trial:

• The trial will enrol patients with an elevated blood pTau biomarker (the same group shown to have a large Xanamem clinical effect in the previous Phase 2a biomarker trial) and keeps the same endpoints and 36‑week treatment length. The removal of the 5mg dose arm reduces patient numbers by one-third to 220 patients, who will receive either 10mg or placebo daily
• Enrolment of the first 100 patients will take place at Australian sites and initial efficacy and safety results from an administrative interim analysis will occur when approximately 100 patients reach 24 weeks of treatment, expected in the first half of 2025
• Collectively, these changes reduce trial costs significantly and increase forecast receipts from Australian R&D tax incentive cash refunds by focusing on Australian R&D activities in the near term. Net forecast savings between now and June 2025 will be in the order of A$30 million compared to the original plan
• The XanaMIA Phase 2b trial will finalize Australian clinical site start up activities as soon as possible, with site activation expected before the end of the year
• Final results are anticipated in the second half of 2025.

Dr Steven Gourlay, Actinogen CEO and MD, commented:

"Actinogen is at an important juncture in the world of drug development with its promising oral therapy Xanamem. While recent positive data on new amyloid antibody infusions give Alzheimer's patients hope, they do not halt disease progression, highlighting the continued and urgent need to find effective and safe non-amyloid therapies to arrest cognitive decline.

"Our high quality randomized XanaMIA Phase 2b trial will be conducted in 220 patients with mild-moderate AD who are biomarker-positive and thus likely to have progressive disease.  We will finalize Australian clinical site start up activities as soon as possible, with site activation expected before the end of the calendar year.

"Our XanaCIDD Phase 2a trial assessing the effects of Xanamem on cognition and depression represents a novel and important approach towards treating patients with MDD with the hope that the therapy will be rapidly acting on cognition, as we have seen in two prior trials in cognitively normal people, and also have effects on depression itself."

Announcement authorised by the Board of Directors of Actinogen Medical

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 the pTau181 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 a 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.

^®  Xanamem is a registered trademark of Actinogen Medical Limited