Clinical Development Pipeline

The Xanamem® Pipeline


Major Depressive

Fragile X

Diseases to be studied

Phase 2 placebo-controlled trials


Cognitive impairment in early

Alzheimer’s Disease

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Biomarker analysis in patients with mild AD

Cognitive benefit in patients with early stages of AD

Pivotal trials focused on cognitive enhancement

Diseases to be studied

Phase 2 placebo-controlled trials



with cognitive impairment

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Depression and cognitive impairment

Pivotal trials assessing both depression and cognitive impairment

Diseases to be studied

Phase 2 placebo-controlled trials


Anxiety, sleep &
behavioral problems in

Fragile X Syndrome

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Proof of concept in adolescent and young adult males

Pending alternative funding e.g. partnerships or grants

Alzheimer's Disease

Alzheimer’s Disease is a chronic degenerative condition of the brain affecting more than 50 million people worldwide. It leads to gradual or rapid loss of cognitive ability i.e. the ability to perform tasks, think and remember clearly.

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Participate in trial

Major Depressive Disorder

Depression is one of the most common and burdensome psychiatric disorders worldwide, with an estimated 5% of the population affected. Depression is a complex disease characterized by emotional, physical and cognitive symptoms. Persons with depression often experience impairment in cognitive function in several domains, including executive functioning, processing speed, concentration/attention, learning, and memory not only before and during depressive episodes but also after remission of mood symptoms

Higher levels of cortisol have been associated with severity of depressive symptoms, suggesting a possible therapeutic role for Xanamem to lower cortisol in the brain.  Attempts to modify cortisol signaling in the brain via other mechanisms have met with mixed results for depression.

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Fragile X Syndrome

Fragile X Syndrome (FXS) is the most common inherited cause of autism and intellectual disabilities worldwide. It is a life-long genetic disorder caused by alterations in the Fragile X gene (FMR1) that cause the brain to fail to develop as it should. The syndrome usually affects males more seriously than females. Persons affected have issues with autism symptoms, anxiety, difficulty thinking and concentrating, and “sensory overload”.

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Patient Portal

All of our clinical trials are registered with, a regulated website that is managed and overseen by the US Food and Drug Administration (FDA).

The Actinogen phase 2 depression trial has closed recruitment

The Actinogen phase 2b Alzheimer's disease trial is now recruiting

Completed Clinical Trials

To find out more about our completed Phase 1b XanaMIA-DR study in Healthy Elderly Volunteers (NCT04983368), please click here.

To find out more about our completed Phase 2 XanADu study in Mild Alzheimer’s Disease Patients (NCT02727699), please click here.

To find out more about our completed Phase 1 XanaHES study in Healthy Elderly Volunteers (NCT03830762), please click here.

To find out more about our completed Phase 1 Multiple Ascending Dose in Healthy Volunteers (MAD) study (NCT02616445), please click here.

To find out more about our completed Phase 1 Single Ascending Dose (SAD) study in Healthy Volunteers (NCT01770886), please click here.


Contact Us

If you have any enquiries regarding our trials please reach out to us at


Clinical pharmacology and development of Xanamem, a tissue specific inhibitor of 11β-HSD1

Paul Rolan, Jack Taylor, Jonathan Seckl, John Harrison, Christopher Li-Hsian Chen, Colm Farrell, Paul Maruff, Michael Woodward and Dana Hilt. Academic poster presented at the Australian Dementia Research Forum (ADRF2024) on the Gold Coast, Australia from 3 to 5 June 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


Cognitive and disease-modifying effects of 11β-hydroxysteroid dehydrogenase type 1 inhibition in male Tg2576 mice, a model of Alzheimer’s Disease

Sooy, K., Noble, J., McBride, A., Binnie, M., Yau, J. L. W., Seckl, J. R., Walker, B. R., & Webster, S. P. 2015. Endocrinology, 1-12.


Selection and early clinical evaluation of the brain-penetrant 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) inhibitor UE2343 (Xanamem™)

Scott P Webster, AndrewMcBride, Margaret Binnie, Karen Sooy, Jonathan R Seckl, Ruth Andrew, T David Pallin, Hazel J Hunt, Trevor R Perrior, Vincent S Ruffles, J William Ketelbey, Alan Boyd and Brian R Walker 2017. British Journal of Pharmacology.


Discovery and biological evaluation of adamantyl amide 11β-HSD1 inhibitors

Webster, S. P., Ward, P., Binnie, M., Craigie, E., McConnell, K. M., Sooy, K., Vinter, A., Seckl, J.R. & Walker, B. R. 2007. Bioorganic & medicinal chemistry letters, 17(10), 2838-2843.


Midlife stress alters memory and mood-related behaviors in old age: Role of locally activated glucocorticoids

Nicola Wheelan, Christopher J. Kenyon, Anjanette P. Harris, Carolynn Cairns, Emad Al Dujaili, Jonathan R. Seckl, Joyce L.W. Yau 2018. Psychoneuroendocrinology 89 (2018) 13–22.


11β-hydroxysteroid dehydrogenase inhibition improves cognitive function in healthy elderly men and type 2 diabetics

Sandeep, T. C., Yau, J. L. W., MacLullich, A. M. J., Noble, J., Deary, I. J., Walker, B. R., & Seckl, J. R. 2004. PNAS, 101(17), 6734-6739.


Cognitive and disease-modifying effects of 11β-hydroxysteroid dehydrogenase type 1 inhibition in male Tg2576 mice, a model of Alzheimer’s Disease

Sooy, K., Noble, J., McBride, A., Binnie, M., Yau, J. L. W., Seckl, J. R., Walker, B. R., & Webster, S. P. 2015. Endocrinology, 1-12.


Inhibiting 11β-hydroxysteroid dehydrogenase type 1 prevents stress effects on hippocampal synaptic plasticity and impairs contextual fear conditioning

Sarabdjitsingh, R. A., Zhou, M., Yau, J. L., Webster, S. P., Walker, B.R., Seckl, J. R., Joëls, M., & Krugers, H. J. 2014. Neuropharmacology, 81, 231-6.


11beta-hydroxysteroid dehydrogenase type 1 deficiency prevents memory deficits with aging by switching from glucocorticoid receptor to mineralocorticoid receptor-mediated cognitive control

Yau, J. L., Noble, J., & Seckl, J. R. 2011. Journal of Neuroscience, 31(11), 4188 – 4193.


11β-hydroxysteroid dehydrogenase type 1, brain atrophy and cognitive decline

MacLullich, A. M. 1., Ferguson, K. J., Reid, L. M., Deary, I. J., Starr, J. M., Wardlaw, J. M., Walker, B. R., Andrew, R., & Seckl, J. R. 2012. Journal of Neurobiological Aging, 33(1), 5406-13.


Acute inhibition of 11beta-hydroxysteroid dehydrogenase type-1 improves memory in rodent models of cognition

Mohler, E. G., Browman, K. E., Roderwald, V. A., Cronin, E. A., Markosyan, S., Scott Bitner, R., Strakhova, M. I., Drescher, K. U., Hornberger, W., Rohde, J. J., Brune, M. E., Jacobson, P. B., & Rueter, L. E. 2011. Journal of Neuroscience, 31(4), 5406-13.


11beta-hydroxysteroid dehydrogenase type 1 expression is increased in the aged mouse hippocampus and parietal cortex and causes memory impairments

Holmes, M. C., Carter, R. N., Noble, J., Chitnis, S., Dutia, A., Paterson, J. M., Mullins, J. J., Seckl, J. R., Yau, J.L. 2010. Journal of Neuroscience, 30(20), 6916-20.


Partial deficiency or short-term inhibition of 11β-hydroxysteroid dehydrogenase type 1 improves cognitive function in aging mice

Sooy, K., Webster, S. P., Noble, J., Binnie, M., Walker, B. R., Seckl, J. R., & Yau, J. L. W. 2010. Journal of Neuroscience, 30(41), 13867-13872.


Circulating cortisol and cognitive and structural brain measures

Echouffo-Tcheugui, Justin B., Sarah C. Conner, Jayandra J. Himali, Pauline Maillard, Charles S. DeCarli, Alexa S. Beiser, Ramachandran S. Vasan, and Sudha Seshadri 2018. Neurology: 10-1212.


Plasma Cortisol, Brain Amyloid-β, and Cognitive Decline in Preclinical Alzheimer’s Disease: A 6-Year Prospective Cohort Study

Robert H. Pietrzak, Simon M. Laws, Yen Ying Lim, Sophie J. Bender, Tenielle Porter, James Doecke, David Ames, Christopher Fowler, Colin L. Masters, Lidija Milicic, Stephanie Rainey-Smith, Victor L. Villemagne, Christopher C. Rowe, Ralph N. Martins, and Paul Maruff, for the Australian Imaging, Biomarkers and Lifestyle Research Group 2017. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging 2(1): 45-52.


Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer’s type

Popp, J., Wolfsgruber, S., Heuser, I., Peters, O., Hull, M., Schroder, J., Moller, H. J., Lewczuk, P., Schneider, A., Jahn, H., Luckhaus, C., Perneczky, R., Frolich, L., Wagner, M., Maier, W., Wiltfang, J., Kornhuber, J., & Jessen, F. 2015. Neurobiology of Aging, 36, 601-607.


Cortisol levels during human aging predict hippocampal atrophy and memory deficits

Lupien, S. J., de Leon, M., de Santi, S., Convit, A., Tarshish, C., Nair, N. P. V., Thakur, M., McEwen, B. S., Hauger, L., & Meaney, M. J. 1998. Nature Neuroscience, 1(1), 69-73.


Plasma cortisol and progression of dementia in subjects with Alzheimer-type dementia

Csernansky, J. G., Dong, H., Fagan, A. M., Wang, L., Xiong, C., Holtzman, D. M., & Morris, J. C. 2006. American Journal of Psychiatry, 163, 2164-2169.


Salivary cortisol, brain volumes, and cognition in community-dwelling elderly without dementia

Geerlings, M. I., Sigurdsson, S., Eiriksdottir, G., Garcia, M. E., Harris, T. B., Gudnason, V., & Launer, L. J. 2015. Neurology, 85(11), 976-983.


Plasma cortisol levels, brain volumes and cognition in healthy elderly men

MacLullich, A. M., Deary, I. J., Starr, J. M., Ferguson, K. J., Wardlaw, J. M., & Seckl, J. R. 2005. Psychoneuroendocrinology, 30(5), 505-515.


Effects of stress throughout the lifespan on the brain, behaviour and cognition

Lupien, S. J., McEwen, B. S., Gunnar, M. R., & Heim, C. 2009. Nature reviews neuroscience, 10(6), 434-445.


Decrease in cortisol reverses human hippocampal atrophy following treatment of Cushing’s disease

Starkman, M. N., Giordani, B., Gebarski, S. S., Berent, S., Schork, M. A., & Schteingart, D. E. 1999. Biological psychiatry, 46(12), 1595-1602.


Translational Research in Stress Neuroendocrinology: 11β‐Hydroxysteroid Dehydrogenase 1 (11β‐HSD1), A Case Study

Reynolds, R. M., & Webster, S. P. 2015. Neuroendocrinology of Stress, 327-350.


Glucocorticoids increase amyloid beta and tau pathology in a mouse model of Alzheimer’s Disease

Green K.N., Billings L.M., Roozendaal B. et al. 2006. J. Neurosci. 26: 9047–56.


Combined plasma and cerebrospinal fluid signature for the prediction of midterm progression from mild cognitive impairment to Alzheimer Disease

Lehallier, B., Essioux, L., Gayan, J., Alexandridis, R., Nikolcheva, T., Wyss-Coray, T., & Britschgi, M. 2016. JAMA neurology, 73(2), 203-212.


Long-term cortisol measures predict Alzheimer Disease risk

Ennis, G. E., An, Y., Resnick, S. M., Ferrucci, L., O’brien, R. J., & Moffat, S. D. 2017. Neurology, 88(4), 371-378.


Hippocampal damage associated with prolonged glucocorticoid exposure in primates

Sapolsky RM, Uno H, Rebert CS et al. 1990. J Neurosci. 10: 2897–2902.


Environmental novelty exacerbates stress hormones and Aβ pathology in an Alzheimer’s model

Kimberley E. Stuart, Anna E. King, Carmen M. Fernandez-Martos, Mathew J. Summers & James C. Vickers 2018. Nature Scientific Reports 7: 2764.


Intellectual functioning and behavioural features associated with mosaicism in Fragile X Syndrome

Baker, E. K., Arpone, M., Vera, S. A., Bretherton, L., Ure, A., Kraan, C. M., Bui, M., Ling, L., Francis, D., Hunter, M. F., Elliott, J., Rogers, C., Field, M. J., Cohen, J., Santa Maria, L., Faundes, V., Curotto, B., Morales, P., Trigo, C., Salas, I., Alliende, A. M., Amor, D. J. & Godler, D. E. 2019. Journal of Neurodevelopmental Disorders, 11, 15.


Biobehavioral composite of social aspects of anxiety in young adults with Fragile X Syndrome contrasted to autism spectrum disorder

Roberts, J. E., Ezell, J. E., Fairchild, A. J., Klusek, J., Thurman, A. J., Mcduffie, A. & Abbeduto, L. 2018. American Journal of Medical Genetics Part B-Neuropsychiatric Genetics, 177, 665-675.


Cortisol profiles differentiated in adolescents and young adult males with Fragile X Syndrome versus autism spectrum disorder

Matherly, S. M., Klusek, J., Thurman, A. J., Mcduffie, A., Abbeduto, L. & Roberts, J. E. 2018. Developmental Psychobiology, 60, 78-89.


Fragile X Syndrome

Hagerman, R. J., Berry-Kravis, E., Hazlett, H. C., Bailey, D. B., Moine, H., Kooy, R. F., Tassone, F., Gantois, I., Sonenberg, N., Mandel, J. L. & Hagerman, P. J. 2017. Nature Reviews Disease Primers, 3, 19.


HPA axis function predicts development of working memory in boys with FXS

Scherr, J. F., Hahn, L. J., Hooper, S. R., Hatton, D. & Roberts, J. E. 2016. Brain and Cognition, 102, 80-90.


Cortisol and behavior in Fragile X Syndrome

Hessl, D., Glaser, B., Dyer-Friedman, J., Blasey, C., Hastie, T., Gunnar, M. & Reiss, A. L. 2002. Psychoneuroendocrinology, 27, 855-872.


Cortisol and social stressors in children with Fragile X: A pilot study

Wisbeck, J. M., Huffman, L. C., Freund, L., Gunnar, M. R., Davis, E. P. & Reiss, A. L. 2000. Journal of Developmental and Behavioral Pediatrics, 21, 278-282.


Effect of glucocorticoid and 11β-hydroxysteroid-dehydrogenase type 1 (11β-HSD1) in neurological and psychiatric disorders

Dodd S, Skvarc D R, Dean OM, Anderson A, Kotowicz M, Berk M 10 Feb 2022. Int J Neuropsychopharmacol. doi: 10.1093/ijnp/pyac014.


Presence of individual (residual) symptoms during depressive episodes and periods of remission: a 3-year prospective study

J. Conradi, J. Ormel and P. de Jonge 2011. Psychological Medicine, 41, 1165–1174.


Depression and Hypothalamic-Pituitary-Adrenal Activation: A Quantitative Summary of Four Decades of Research

Cinnamon Stetler, PhD, And Gregory E. Miller, PhD 2011. Psychosomatic Medicine 73:114–126.


Central CRH system in depression and anxiety — Evidence from clinical studies with CRH1 receptor antagonists

Florian Holsboer, Marcus Ising 2008. European Journal of Pharmacology 583, 350–357



Malhi, G.S. and J.J. Mann 2018. The Lancet 392(10161): p. 2299-2312.


Unipolar major depression in adults: Choosing initial treatment

Rush, A.J 2020. UpToDate


Toxic effects of depression on brain function: Impairment of delayed recall and the cumulative length of depressive disorder in a large sample of depressed outpatients

Gorwood, P., et al., 2008. American Journal of Psychiatry 165(6): p. 731-739.


Cognitive function following a major depressive episode: a systematic review and meta-analysis

Semkovska, M., et al. 2019. The Lancet Psychiatry 6(10): p. 851-861.


Neurocognitive deficits and disability in major depressive disorder

Jaeger, J., et al. 2006. Psychiatry Res 145(1): p. 39-48.


Cortisol as a predictor of psychological therapy response in depressive disorders: systematic review and meta-analysis

Fischer, S., et al. 2017. Br J Psychiatry 210(2): p. 105-109.


Psychiatric symptoms in Cushing’s syndrome: A systematic review

Lin, T.Y., J. Hanna, and W.W. Ishak 2020. Innovations in Clinical Neuroscience 17(1-3): p. 30-35.


Global economic burden of schizophrenia: a systematic review

Chong, Huey Yi et al. Neuropsychiatric disease and treatment vol. 12 357-73. 16 Feb. 2016, doi:10.2147/NDT.S96649.


Spotlight on brexpiprazole and its potential in the treatment of schizophrenia and as adjunctive therapy for the treatment of major depression

Bruijnzeel, D, and R Tandon. 2016. Drug Design, Development and Therapy 10: 1641-1647.


Cognitive and Disease-Modifying Effects of 11-beta Hydroxysteroid Dehydrogenase Type 1 Inhibition in Male Tg2576 Mice, a Model of Alzheimer’s Disease

Sooy, Karen. 2015. Endocrinology 156 (12): 4592-4603.


Efficacy of different types of cognitive enhancers for patients with schizophrenia: a meta-analysis

Sinkeviciute, I et al. 2018. NPJ Schizophrenia 4: 22.


Anti-dementia Drugs for Psychopathology and Cognitive Impairment in Schizophrenia: A Systematic Review and Meta-analysis

Kishi, T, and et al. 2018. International Journal of Neuropsychopharmacology 21 (8): 748-757.

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