A couple of introduction pieces:

• 10 min Spotify podcast on the upcoming Alzheimer's trial and science overview. October 2024.
• Stockhead article from September (before the depression trial result which was not a home run). Some good colour on the twists and turns the company has already taken, and the depression and Alzheimer's landscape.

The very basics: Chronic cortisol is toxic to nerve cells. This drug inhibits an enzyme that something something reduces cortisol in the brain.

Why was the depression trial result not a home-run?

The drug has a good safety and side-effect profile so far in hundreds of patients.

They did see clinically and statistically significant improvements in 'depression symptoms'.

But, because the placebo group also improved over the 10 weeks of the trial in the cognition tests, they cannot make any claims about cognitive improvements in depression. In case this is confusing, 'cognitive impairment' is apparently a different aspect of depression than 'depression symptoms' and they are tested independently.

I think they want to circle back for a longer depression trial with a funding partner after the Alzheimer's trial, but they would have immediately been in a better bargaining position had they hit a home-run. They want to prove out the cognition side because that would broaden the market...a lot.

Regardless, they are focused on Alzheimer's now, and if they stick to the schedule, the trial is fully funded as an independent pivotal trial (one of 2 that would be required for FDA approval).

• 220 patients, 9 months, Aust and US sites
• Interim results expected in mid-2025
• Final results mid-2026

' The patients are assessed on both cognition and Alzheimer’s progression.

“We believe we have already validated the target by showing improved cognition in healthy older volunteers and potentially a big clinical benefit in biomarker-positive patients with Alzheimer’s,” Dr Gourlay says. '

CEO Dr Steven Gourlay put $1m into an $11m capital raising. From what I can gather, he now owns at least $2m in shares of a 75m market cap.

They state this should fund trials until late CY2026.

From what I can gather Dr Gourlay has worked in biomedical research for 30 years, including at the FDA and the European equivalent. He may have already done rather well if he had skin in the game at prior ventures, but he seems to have good experience anyway.

Actinogen is entering a Stage 2b/3 trial to test their compound Xaneman over 36 weeks targeting an inhibition of brain cortisol for Alzheimer's (as well as in depression).

I got interested here after hearing him chat with Alan Kohler and seeing the volatile share price after a recent depression trial. The market decided it didn't like the trial results. Results were somewhat promising in early weeks against 'depression' and the signal strength improved between 4 and 10 weeks. But they lucked out in a test of 'cognition' because the placebo control group also saw a positive result there. Not an expert but apparently placebo groups doing well in depression trials can be a thing, because taking action of any kind tends to help (including entering a trial).

They wheeled out the chief science officer who did a series of talks and then the price recovered (only to tank again at the announcement of the raise).

I am not a Doctor but: I am tempted to believe them, the theory makes sense that reducing brain cortisol would help a lot of people (and it doesn't interfere with non-brain cortisol). I imagine (guessing) that they can't go back to test depression for a longer period since the money is spent. So they are moving forward with Alzeimer's in a longer test (36 weeks).