Clinical Dementia Rating Scale - Sum of Boxes effect of 0.6 to 0.8 points observed in patients with elevated pTau biomarker with once daily, 10 mg, oral therapy

Actinogen Medical Ltd (ASX:ACW)

SYDNEY, NSW, AUSTRALIA, October 11, 2022 /EINPresswire.com/ -- Sydney, Actinogen Medical Limited (ASX: ACW) announces positive Phase 2a clinical data from its Alzheimer’s Disease (AD) biomarker study, which validates the Company’s planned Xanamem program in AD.

Key points:

• Phase 2a placebo-controlled trial re-run in biomarker-positive patients using available blood biomarker levels in 72 patients from the prior XanADu study of 185 patients with mild AD over 12 weeks

• Used a pre-specified analysis plan and protocol to avoid bias

• Patients with elevated blood pTau above the median value showed a clinically significant Xanamem effect on the CDR-SB endpoint plus trends in a Neurologic Test Battery (NTB) and the Mini Mental State Exam (MMSE)

• CDR-SB effect size of 0.6 - 0.8 points is larger than the 0.45 points reported recently for the anti-amyloid antibody lecanemab and represents a 60-80% reduction in progression over 12 weeks compared with placebo (lecanemab reported to show 27% over 18 months)2

• Twice as many patients in the Xanamem group (56%) were stable or improved compared with placebo

• CDR-SB will be a primary endpoint in the upcoming Phase 2b trial of 6 months duration

• Regulatory path to approval in AD is clear and uncontroversial using CDR-SB

• Findings significantly de-risk and improve AD program efficiency.

Eminent world-leading authority on dementia, Associate Professor Michael Woodward, commented:

“The positive data for CDR-SB and other endpoints are encouraging and indicate a likely therapeutic effect of Xanamem in patients with the early stages of AD. The use of pTau blood levels to confirm the diagnosis of AD in future trials represents a practical and efficient method to select patients at risk of disease progression and in whom a treatment effect is more likely to be observed.”

Professor Paul Rolan, Actinogen’s Chief Medical Officer, said:

“These clinical results provide further validation of our Alzheimer’s Disease program and are a significant step forward in the development of Xanamem as a new treatment for Alzheimer’s Disease with a novel, amyloid-independent mechanism of action.

We are very pleased to see such positive clinical data for patients with biomarker-positive, mild Alzheimer’s Disease. The results extend findings of therapeutic effects on cognition in two prior trials of cognitively normal, older volunteers to patients with early Alzheimer’s Disease. The data also validate the dose range planned for our upcoming trials in Alzheimer’s Disease and Depression.”

Biomarker study results in detail

The goals of the study were to:

1. measure Xanamem effects in patients with biomarker-positive AD by excluding the ’noise’ from patients with other types of dementia who were unlikely to progress during the trial, and

2. establish if there was any short-term effect of Xanamem on the levels of blood biomarkers themselves. A short-term effect of Xanamem on protein biomarkers was considered unlikely because its mechanism is not via direct action on amyloid and tau proteins in the brain.

The primary finding of the study was:

Blood pTau levels above the median value of 6.74 pg/mL (n=34) or a published cutoff of 10.2 pg/mL (n=9) identified patients who had a clinically significant therapeutic benefit from Xanamem with an average effect size of 0.6 to 0.8 points on the CDR-SB scale, measuring cognition and function, which is widely used in modern trials of early-stage AD (Cohen’s d = 0.41, p = 0.09).

Dr. Steven Gourlay
CEO & Managing Director
P: +61 2 8964 7401
E. steven.gourlay@actinogen.com.au

Announcement authorised by the Board of Directors of Actinogen Medical

About Actinogen Medical & Xanamem

Actinogen Medical (ACW) is an ASX-listed, biotechnology company developing a novel therapy for neurological and neuropsychiatric diseases associated with dysregulated brain cortisol. Xanamem has shown the ability to enhance cognition in healthy, older volunteers and now in patients with mild AD. There is a strong association between cortisol & detrimental changes in the brain, affecting cognitive function, harm to brain cells & long-term cognitive health.

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.

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. 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 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. Do 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. 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.

Michael Roberts
Actinogen Medical Ltd
+61 423 866 231
email us here

The recent webcast outlines in more detail the positive Phase 2a clinical data from our Alzheimer's Disease biomarker study