A longitudinal dataset indicating the utility of plasma pTau for patient selection in clinical trials of patients with mild Alzheimer's Disease (AD) and the likely therapeutic benefit of oral Xanamem in this population

SYDNEY, March 30, 2023 /PRNewswire/ -- Actinogen Medical ASX: ACW ("ACW" or "the Company") is pleased to announce that its Chief Medical Officer, Dr Dana Hilt will make an oral presentation to the International Conference on Alzheimer's and Parkinson's Diseases and related neurological disorders (ADPD 2023) later today in Gothenburg, Sweden.

Dr Hilt was invited to present Actinogen's novel Phase 2a data as an oral presentation in a symposium session entitled AD Drug Development Clinical Trials. The presentation details the unique longitudinal dataset demonstrating 1) the utility of using the plasma biomarker pTau181 for selection of patients with a more progressive form of mild AD in clinical trials and 2) an encouraging beneficial effect of Xanamem on clinical endpoints of function (CDR-SB^[1]) and cognition (NTB^[1]) in these patients.

In his presentation Dr Hilt analyses four studies that have shown positive results for ACW's small molecule drug Xanamem that pave the way for the 330-person XanaMIA Phase 2b AD trial to commence in the coming months. Key points include:

• Most anti-amyloid therapies have failed and recent data for lecanemab shows only a modest beneficial effect, suggesting the utility of the "amyloid hypothesis" in AD is limited
• There is a strong scientific rationale for the targeted modulation of brain cortisol in several brain diseases including AD and depression - the "cortisol hypothesis"
• Xanamem is a brain-penetrant small molecule inhibitor of tissue cortisol synthesis that does not disturb normal cortisol homeostasis regulated by adrenal gland production
• Four independent clinical studies have shown positive results:
• A human PET study visualized high levels of target engagement in the brain thereby establishing the suitability of low doses of 5 mg and 10 mg daily for clinical investigation
• Two randomized, placebo-controlled trials showed the same pattern of improved attention and working memory, both key aspects of cognition, in older, cognitively normal volunteers
• Analysis of biomarker-positive (plasma pTau181) patients with mild AD in a Phase 2a trial showed clinically significant benefits on function (CDR-SB) and cognition (NTB).
• Excellent safety and tolerability profile in more than 300 people treated

The upcoming XanaMIA Phase 2b trial will study 330 individuals treated with 5 mg, 10 mg or placebo over 24 weeks. Patients will have early stage, progressive AD defined as mild cognitive impairment (MCI) or mild AD and elevated plasma pTau181. Key endpoints will be a cognitive composite based on the NTB described in Dr Hilt's presentation and the CDR-SB.

Dr Hilt's presentation will be available at https://actinogen.com.au/corporate-presentations/

Dr Steven Gourlay, Actinogen's CEO and MD, said:

"Actinogen is excited to present its novel Phase 2a dataset that is one of the first to show that the blood pTau biomarker is a highly effective method for selection of patients with a progressive form of mild Alzheimer's disease. As a simulation of the upcoming Phase 2b XanaMIA trial the data give us confidence in our study design, endpoints and patient selection criteria."

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.

About Xanamem

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

Chronically elevated cortisol is associated with cognitive decline in Alzheimer's Disease, and Xanamem has shown the ability to enhance cognition in healthy, older volunteers. 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 11-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 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.

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