Actinogen to present progress on Cognitive Impairment in Depression and Alzheimer's Disease Phase 2 trials at the BIO International Convention

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,May 31,2023 -- Actinogen Medical Limited (ASX: ACW) CEO Dr Steven Gourlay and CMO Dr Dana Hilt will present at the BIO International Convention,to be held at the Boston Convention & Exhibition Center from June 5-8,2023. The Actinogen presentation is scheduled at 4pm EST Monday June 5,in Room 403.

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

XanaCIDD Phase 2a trial of cognitive impairment in major depressive disorder

This Phase 2a,proof-of-concept trial commenced in December 2022 and will treat 160 patients with Major Depressive Disorder (MDD) who also have cognitive impairment. 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 and the UK and will treat 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 of mild-moderate Alzheimer's Disease (AD)

Having completed a number of key steps to develop a global syndicate of investigators and trial sites for the upcoming Phase 2 trial,Actinogen is making several improvements to the trial design. The first patient is expected to be treated in the coming months and results are expected in the second half of 2025.

Key features of the XanaMIA Phase 2b trial:

The newly manufactured to-be-marketed tablet formulation will be used

330 patients will be enrolled for a longer,36-week double-blind treatment period (24 weeks previously) to improve initial assessment of disease-modification effects in addition to those on cognitive preservation and enhancement

Patients will be randomized 1:1:1 to Xanamem 10 mg,5 mg,or a matching placebo

Results of an interim analysis will be announced around the midpoint of the trial

Patients with "mild-moderate AD" are now included to match the Phase 2a population with elevated blood pTau biomarker levels used to simulate the next trial and previously reported to have a large Xanamem effect on the CDR-SB endpoint of function and a test battery measuring cognition

Elevated pTau level will be used to confirm AD diagnosis and amyloid PET scans will not be required

Following extensive data analysis of prior trial data,the primary endpoint will be a cognitive composite of several tests,reflecting the strong cognitive effects of Xanamem in prior trials. The CDR-SB functional score remains a key secondary endpoint along with the assessment of activities of daily living.

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.

"Our high quality randomized XanaMIA Phase 2b trial will be conducted in 330 biomarker-positive patients with mild-moderate AD most likely to progress and will commence in the coming months.

"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.

"We are excited to be implementing our high-quality programs in both Alzheimer's and cognitive impairment in depression and believe they will demonstrate and confirm the potent clinical benefit of Xanamem therapy."

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.

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 its capsule.

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.

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® Xanamem is a registered trademark of Actinogen Medical Limited