Ann: ACW randomizes first US participant in Alzheimers trial, page-4

Cassava Sciences announced recently its experimental Alzheimer’s disease drug Simufilam showed no signs of working in a phase 3 clinical trial. Simufilam, which was supposed to counteract protein changes driving Alzheimer’s, failed to meet any primary, secondary, or exploratory end points, the company said. Besides failing to reduce symptoms, it showed no signs of beneficial effects on biomarkers associated with Alzheimer’s. At the time science.org noted the company has only one drug in development, making its future uncertain at best. Its stock plummeted by more than 80% on the news—dropping about $1 billion in value. The platform went on to quote Rick Barry, the company’s CEO, from a conference call, where he is reported as saying “This is by no means the news we were hoping for.”

I guess this may come as no surprise for followers of Alzeihmers clinical trials, or in particular Alzeihmers trial candidates. Since 2003, 98% of Alzheimer’s disease (AD) treatment clinical trials have failed, showing a disappointing 2% success rate. One of the biggest issues, according to clinicalleader.com is One of the biggest issues that AD clinical trials have faced is the over reliance on treatments targeting amyloid protein that has given, at best, modest success. At least five other causes of neurodegeneration — neuroinflammation, mitochondrial dysfunction, lysosomal dysfunction, insulin resistance, and lipid abnormalities — drive the disease. Each may work alone, but they most likely work in concert with amyloid. Amyloid is only part of the problem.

As investors in Actinogen are aware, unlike the above mentioned Simufilam, or the recently AD drug Leqembi, Xanamem, Actinogen’s leading candidate works on reducing cortisol in the brain, as opposed to taking the amyloid route. And unlike Leqembi, which has been rejected in some domiciles due to the side effects associated with the drug, Xanamem has no significant side effects. But it goes without saying Xanamem must prove efficacy in its ongoing trial both here and in the US for it to reach the approval status granted to Leqembi last July. At that time new information prompted the FDA to convert accelerated approval status to a full approval. Leqembi research showed that not only did many people treated with Leqembi have significantly reduced brain amyloid, they declined about half a point less than placebo-treated patients on one test, the Clinical Dementia Rating scale (CDR), showing a 27% slowing of disease progression. These results and the subsequent FDA decision meant Leqembi was the first official FDA drug for Alzeihmers disease. Which ostensibly means there is still a huge market for any drug able to crack the AD code as it were, and in doing so slow the progression of what is currently the seventh biggest killer in the US. In fact according to the National Institute on Aging, it’s a disease that research shows is more feared than cancer.

Today Actinogen announced the treatment of the first patient in their proposed 220 strong patient trial for AD. This comes off the back of fast track designation status for Xanamem in the US, excellent independent peer reviews in which the drug proved efficacious in treating AD patients with elevated PTau, and an exemplary safety track record. Yet as per usual Actinogen lags the market cap of similar stocks listed on other bourses striving to treat likeminded neurological disorders. Why even Cassava (SAVA -NASDAQ), despite the recent failure at $155m USD is still worth more than twice the market cap of Actinogen (ACW). Is the market going to wake up to Actinogen CEO Steve Gourlay’s prophecy that Xanamem has the potential to be much more effective in treating Alzeihmers than the existing Amyloid based treatments, without all the side effects? Time shall tell. But what is currently known following todays news is that Xanamem has moved one step closer to FDA Approval, if the current trial reiterates the data exhibited by the drug in earlier trials. Whilst July 2025 is just around the corner, that being the date when Actinogen believes it shall be in a position to post interim results from their XanaMIA Phase 2b/3 Alzeihmers Trial. Further to which the company's recent appointment of Andy Udell to commercialise the drug may make the ACW price even sweeter than the Edison Research price target of 21 cents, should all things go to plan in reaching some if not all of the primary endpoints outlined in the clinical trial synopsis. Udell was President of North America’s Callidatas Therapeutics, being responsible fro taking the Swedish company through phase 3 trials, market readiness and a successful US product launch. Clearly he is well equipped to repeat the performance with Actinogen’s Xanamem, having only recently hopped off the horse.

I guess most of wish the stock, ACW that is, were listed on the NASDAQ, where no doubt it would have a stronger following, given the recent hysteria surrounding Alzeihmers Disease in that market. Though I suppose the only upside is local investors can still afford to buy the stock here. It may well be unaffordable if listed on the NASDAQ, given the recent clinical trial failures, licensing rejections due to side effects, and ongoing complications faced by Xanamem’s AD competitors.

Best of luck to all long term holders.

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