Next month Actinogen Medical (ACW: $0.045) will release results from its Phase II/III study in patients with mild-moderate Alzheimer's disease with its drug candidate Xanamem.
A total of 247 patients have been recruited into the study across Australia and the US, with approximately half receiving the drug candidate and the other half receiving placebo. Patients are being treated for 36 weeks, which should be a reasonable period to gauge effect of the investigational therapy.
In January this year an unblinded interim analysis was conducted by an independent Data Monitoring Committee which recommended the trial continue unchanged. This was encouraging, suggesting that the study is on track to deliver a potential efficacy signal.
In August the company reported that 89% of the trial participants who had completed the study had elected to move into the Open Label Extension phase to received Xanamem for up to 25 months. That equated to 108 patients. The last patient in the full study completed treatment at the end of September.
Study Design to Improve Changes of Success
Alzheimer's disease has been a difficult therapeutic area to make advances in, with existing beta-amyloid drugs yielding just modest improvements. It is very likely to become a disease that will benefit from a multi-therapy approach, which may include Actinogen's drug candidate.
What is assisting with drug development is better identification of patients. In previous studies by others, as much as 30% of patients did not have the disease. However the emergence of relevant blood markers is helping refine the patient pool and improve the clinical trial process.
Actinogen has improved its chances of success in two ways. The first is by ensuring all patients recruited had elevated pTau181 levels in their bloodstream. Whilst not a definitive test for the disease, it is a very good indicator of disease pathology. In a previous Phase II study, Actinogen failed to achieve an efficacy readout in Alzheimer's disease. However when only the subjects with elevated pTau181 levels were considered, the result was a 0.6 unit benefit in function as measured by the test batter CDR-SB after 12 weeks.
This compares to just a 0.39 point benefit from the approved drug aducanumab (Aduhelm) from Eisai and Biogen at 18 months and 0.6 point benefit with Kisulna (from Eli Lilly) over the same period. The result for Actinogen was not statistically significant (p=0.09) with just a small sample size of 34 subjects.
The second factor in the company's favour is that it has shown target (11beta-HSD1) inhibition in the brain beginning at a daily dose of 5mg. Actinogen is using double that dose in the current study (10mg per day).
Selectively Lowering Cortisol Production in the Brain
Xanamem works by lowering the stress hormone cortisol in the brain. Actinogen CEO Steven Gourlay said that chronic elevated levels of cortisol in the brain are toxic, and that it is the locally produced cortisol that is the issue (Source: Bioshares Biotech Summit, August 2026). Xanamem controls the concentration of cortisol in the brain tissue by blocking 11beta-HSD1. It is not seeking to control overall blood cortisol levels (produced by the adrenal glands), but reduce the excess cortisol produced in the brain.
Cortisol in the brain is known to have an impact on increasing the damaging beta-amyloid and tau proteins in the brain. It also causes brain atrophy and neuroinflammation, as well as chronic brain aging.
In mice, an 11beta-HSD1 inhibitor has shown to prevent age-related cognitive decline in mice. Gourlay said that the company could be seen as developing an anti-aging drug but it is starting in Alzheimer's disease.
In a German study (Popp et al, 2015), Gourlay said that elevated cortisol levels in the CSF were proportionally elevated in patients with pre-Alzheimer's and Alzheimer's disease.
In a converse study two decades ago, 138 patients with mild-moderate Alzheimer's disease were given cortisol (as prednisolone) but it was found to have a negative impact on cognition, dementia and depression. It is now known that prednisolone used to treat inflammation has a negative impact on many areas of brain function, including memory and concentration.
Benefit Seen in Depression Study with Xanamem
Another example of brain activity is from a study in depression. In the 76 patients on SSRI treatment, there was a benefit in depression symptoms (MADRS scale) at six weeks over placebo. However this looks to have been impacted by a placebo effect. Four weeks after the treatment stopped, the benefit in the Xanamem group increased considerably to statistical significance (p=0.03). Gourlay said that the continued effect after treatment cessation is consistent with the time for the cortisol inhibition in the brain to take effect.
Gourlay said Xanamem has a 'game changing product profile' that 80% of US neurologists surveyed indicated they would prescribe the product within the first six months if approved. Gourlay said that it is a safe and known therapy that would potentially be multiple times better than other current options.
On the aspect of safety, the drug profile has been well established with over 500 people having been given the drug candidate across eight clinical studies.
Gourlay said that the trial readout will be the culmination of 30 years of work in the field around cortisol inhibition. "But no one has ever had a drug like Xanamem that gets into the brain, inhibits its target at a high level (and) has good clinical safety."
Actinogen is capitalized at $162 million.
Bioshares recommendation: Speculative Buy Class B
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