It's a big year ahead for Actinogen Medical (ACW: $0.056), with its Phase IIb/III Alzheimer's disease study underway, and results expected during the year.
The study with its drug candidate, Xanamem, has enrolled more than 240 patients across 35 sites in the US and Australia. The first sign of any potential benefit will be late next month, when the DSMB assesses the trial for safety and an efficacy futility on the blinded data. This will be based on the first 100 patients who have been on treatment for 24 weeks.
The last patient in the study is expected to be treated this month, with results from that patient 40 weeks later following 36 weeks on treatment. This unblinded, topline safety and efficacy data is then expected in November next year.
Key Efficacy Signal 1
There are two key factors in the data that has been achieved so far that support a positive potential outcome from this study. The first is that the company has proven target engagement (11beta-HSD1) in volunteers, starting at 5mg a day dose, and effective target inhibition at 10mg a day. Increasing the dose to 20mg a day showed little difference if target inhibition. This means the company has selected the correct dose, and that with oral delivery the drug is entering the brain.
Key Efficacy Signal 2
The second key positive data comes from a retrospective analysis of patients treated in a Phase IIa Alzheimer's disease trial. That study was completed in 2019 in 185 patients treated for 12 weeks with a 10mg a day dose. Statistically significant benefit over placebo was not achieved.
However three years later the company conducted a retrospective analysis of 72 patients' stored plasma from that study. It found that 34 patients had elevated pTau181 levels. Plasma levels of that biomarker had only recently been correlated with the onset of Alzheimer's disease. In those 34 patients, there was 0.62 point benefit (CDR-SB) in the slowing of cognitive decline (p=0.09) which is clinically meaningful, but not statistically significant. A larger trial enrolling only those patients with higher pTau181 levels is expected to achieve statistical significance.
Other Positive Factors
There is other data that supports Actinogen's approach. A six year prospective Australian study reported in 2017 (AIBL) found that higher cortisol levels correlates with a much greater disk of developing Alzheimer's disease. Higher cortisol levels are also associated with more rapid clinical development in patients with Alzheimer's disease, which makes the longer trial data of more interest.
Actinogen is seeking to position its drug candidate as an additional therapy to help boost the modest effect from the current beta amyloid binding drugs on the market, Leqembi and Kisulna.
Of particular interest in the current Alzheimer's trial, which will treat patients for 36 weeks (not 12 weeks as in the previous study) is the impact of the treatment over this longer period, and the anticipated divergence from the placebo group.
One of the unknowns with Xanamem is that if an effect in Alzheimer's is shown, what will be the duration of the effect, and will there be any evidence of disease modification. A positive outcome in this study may not just position the program for a pivotal study; it may open up other disease areas for the company to explore, with elevated cortisol linked to range of health disorders.
GLP-1 Drugs Bow Out of Alzheimer's Disease
There was some expectation that GLP-1 agonist drugs such as Ozempic could have an impact in Alzheimer's disease, following some anecdotal evidence, and scientific rational that the class of drugs could impact brain insulin sensitivity and the accumulation of toxic proteins.
However last month Novo Nordisk announced results from Phase III studies in Alzheimer's disease which showed no benefit over placebo. These were two year studies following 3,800 patients. The extension study will now be discontinued.
Summary
Actinogen Medical has been building the data around its cortisol inhibitor for a decade with the aim of achieving a statistically significant outcome in Alzheimer's disease. Identifying a more responsive target population (those with elevated pTau181 levels), selecting the correct dose, and a longer treatment period should very well test the benefit of this drug in this indication.
As with most drugs that target the central nervous system, the development pathway is rarely linear, which has been the case for Actinogen. However it is a massive market opportunity for the company, and one that could broaden further into other indications should there be clear signs of efficacy in this study. The safety profile of the Xanamem has now been well established, having been trialed in 500 patients.
Actinogen Medical is capitalized at $178 million. It had a proforma cash balance at the end of October of $12.4 million (including a forthcoming R&D tax rebate). The company also has options exercisable at $0.0375 (expiring September 2026, $6 million total) and $0.05 (expiring in May and September 2027, total $23 million) that could deliver an additional $28 million of funding.
Bioshares recommendation: Speculative Buy Class B
Disclaimer:
Information contained in this newsletter is not a complete analysis of every material fact respecting any company, industry or security. The opinions and estimates herein expressed represent the current judgement of the publisher and are subject to change. Blake Industry and Market Analysis Pty Ltd (BIMA) and any of their associates, officers or staff may have interests in securities referred to herein (Corporations Law s.849). Details contained herein have been prepared for general circulation and do not have regard to any person’s or company’s investment objectives, financial situation and particular needs. Accordingly, no recipients should rely on any recommendation (whether express or implied) contained in this document without consulting their investment adviser (Corporations Law s.851). The persons involved in or responsible for the preparation and publication of this report believe the information herein is accurate but no warranty of accuracy is given and persons seeking to rely on information provided herein should make their own independent enquiries. Details contained herein have been issued on the basis they are only for the particular person or company to whom they have been provided by Blake Industry and Market Analysis Pty Ltd. The Directors and/or associates declare interests in the following ASX Healthcare and Biotechnology sector securities: Analyst MP: 1AD, ACR, AVR, CGS, CYC, CYP, CUV, CC5, DXB, IMM, MX1, NEU, PAB, SNT, CHM, ATX. These interests can change at any time and are not additional recommendations. Holdings in stocks valued at less than $100 are not disclosed.