Xanamem’s novel mechanism of action sets it apart from other therapies for Alzheimer’s Disease. It works by blocking the excess production of cortisol – the stress hormone – inside brain cells through blocking of the 11β-HSD1 enzyme. There is a strong association between cortisol and changes in brain structure, affecting memory. The 11β-HSD1 enzyme is present at high levels in the hippocampus and frontal cortex, the areas of the brain associated with cognitive impairment in neurological diseases, including Alzheimer’s Disease.

In the Company’s recent XanaMIA Phase 1b trial, Xanamem showed rapid improvements in cognition for attention tests, pharmacodynamic activity (ACTH) and good tolerability in healthy older volunteers treated with 5 mg or 10 mg Xanamem daily. This confirms results from the XanaHES Phase 1 trial in healthy older volunteers treated with 20mg Xanamem daily, and from recent human target engagement imaging for the drug’s action in the brain. The Company plans to initiate a range of Phase 2 studies evaluating Xanamem in 5mg and 10mg daily doses in the treatment of cognitive impairment associated with Alzheimer’s Disease, Major Depressive Disorder, Fragile X Syndrome and other neurological indication(s) with a strong scientific rationale.

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.


To see our Xanamem clinical development pipeline click here


The Cortisol Hypothesis

Xanamem was developed in response to evidence that there is a strong association between chronically raised cortisol levels in the blood and in the brain, and the development of cognitive impairment in Alzheimer’s Disease.

Cortisol is more commonly known as the “stress hormone” and is produced in times of physical and mental stress. While this response is normal, if cortisol levels remain increased for long periods of time, it can become toxic to the neurons (nerve cells) in the brain. Individuals with raised cortisol include those with diabetes, with depression, schizophrenia, bipolar disorder, PTSD, and many patients with Alzheimer’s Disease. Interestingly, blood cortisol levels are known to rise naturally with normal aging, with 50% of those over 65 years old having persistently raised cortisol.

Data from several major studies have consistently shown an association between increased cortisol levels and the cognitive decline associated with a number of neurological, psychiatric and metabolic diseases. Additionally, persistently raised cortisol is associated with the development of the abnormal β-amyloid protein plaques and neurotoxicity in the brain – the hallmarks of Alzheimer’s Disease.

Some of the most compelling evidence supporting the cortisol hypothesis was provided by the Australian Imaging, Biomarker & Lifestyle Study of Ageing (AIBL) study published in early 2017. This study, funded by the CSIRO and several universities and medical research institutes demonstrated that healthy, elderly individuals with high cortisol levels were significantly more likely to develop Alzheimer’s Disease than those with lower cortisol levels. The study authors concluded that therapies aimed at lowering cortisol levels should be considered as a potential way of preventing the development of Alzheimer’s Disease.

Mechanism of Action

Xanamem is designed to cross the blood-brain-barrier in adequate amounts to target and block the 11β-HSD1 enzyme in the brain, and thus reduce the production of cortisol (the “stress hormone”) in neurons (brain cells). The enzyme is present in high concentrations in the hippocampus, frontal cortex and the cerebellum, the regions of the brain associated with recent memory and behaviour, and most affected by Alzheimer’s Disease. Excess cortisol is toxic to brain cells and associated with disease progression in Alzheimer’s Disease.



11β-HSD1 enzyme and cognition

Cortisol and Alzheimer’s/MCI

Cortisol and Depression

Cortisol and Fragile X

Cortisol and Other Diseases

Design of a state-of-the-art Phase 2b trial to evaluate the efficacy of a specific inhibitor of 11β-HSD1, Xanamem™, in mild and moderate Alzheimer’s Disease

Dana Hilt, Jack Taylor, Tamara Miller, John Harrison, Christopher Chen and Craig Ritchie. Academic poster presented at Alzheimer’s and Parkinson’s diseases conference (ADPD) 6 March 2024.


Brain 11-Hydroxysteroid Dehydrogenase Type 1 Occupancy by Xanamem™ Assessed by PET in Alzheimer’s Disease and Cognitively Normal Individuals

Victor L. Villemagne, Vincent Doré, Lee Chong, Michael Kassiou , Rachel Mulligan, Azadeh Feizpour , Jack Taylor, Miriam Roesner, Tamara Miller and Christopher C. Rowe. Article published to the Journal of Alzheimer’s Disease 19 January 2024.


Rationale and design of a Phase 2b trial to evaluate the efficacy of a specific inhibitor of 11β-HSD1, Xanamem®, in mild/moderate AD

Dana Hilt, Jack Taylor, Tamara Miller, John Harrison, Christopher Chen, Craig Ritchie. Academic poster presented to Clinical Trials on Alzheimer’s Disease (CTAD) 24 – 27 October 2023.


Xanamem shows pro-cognitive activity with clinically meaningful effect sizes across 3 independent, placebo-controlled clinical trials

Dana Hilt; Jack Taylor; Paul Rolan; Tamara Miller; Mark Jaros; John Harrison; Craig Ritchie. Academic poster presented to Alzheimer’s Association International Conference 17 July 2023.


XanaMIA-DR: A Double-Blind, Placebo-Controlled, Dose Ranging Study to Assess the Efficacy, Pharmacodynamics and Safety of Xanamem in Healthy Elderly Volunteers

Michael Woodward; Paul Rolan; Jack Taylor; Tamara Miller; John Harrison; Dana Hilt; Paul Maruff. Academic poster presented to Clinical Trials on Alzheimer’s Disease (CTAD) Conference 2 December 2022


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