5 WAYS THAT BIOTECH CAN ATTACK ALZHEIMER’S

For centuries Alzheimer’s has been a disease almost too cruel to fathom. Killing its victims slowly, and often tearing families apart little by little as well, the dread scourge seemed incurable. Not only did families slowly lose loved ones in an excruciating fashion, but the field also yielded nothing but pain for researchers and investors brave enough to risk their blood sweat and tears in search of an effective treatment. The business world was littered with expensive, failed research projects.  

But that all started to change over the last few years with the approvals of Leqembi (by Biogen&Eisai) and Kisunla (by Eli Lilly). These are the first two drugs proven to meaningfully slow the memory robbing progression of the disease. Although these two drugs leave much to be desired, the approvals have inspired and motivated researchers, executives and investors to keep trying with Alzheimer’s. These approvals still leave patients and their families groping in the dark, but they do represent a pinprick of light at the end of the tunnel. 

There is nothing like just a taste of success to unleash the creativity of the scientific community; below we review five different avenues of attack that are being pursued in the battle against Alzheimer’s.

By The Sick Economist

1. Remove the Amyloid

The Amyloid plaque hypothesis of Alzheimer’s has long dominated research in the field. The general idea is that these dysfunctional, misfolded proteins build up in the brain, which then causes the cascade of deadly symptoms that lead to Alzheimer’s signature memory loss. 

Today this is a controversial theory that is heavily debated in neurology circles. Are the Amyloid plaques really the cause of the problem, or merely the symptom?  Amongst a long list of anatomic brain disturbances that can be observed in the Alzheimer’s brain, how important is Amyloid, anyhow? 

These matters are up for debate, but what is now beyond debate is that removal of the plaques themselves has provided some measurable cognitive benefit. This is the technique that led to the approval of Lequembi and Kisunla.

Researchers who adhere to this theory believe that the reason why these two new approved medicines only provide modest cognitive benefit is because they don’t do a good enough job of clearing the Amyloid plaques. In other words, they see these first two drugs as “version 1.0,”  mere practice runs to arrive at something much better. 

To this end, both Roche and Eli Lilly are well advanced in researching drugs that work in a similar method, but more powerfully. Both have drugs in phase II or phase III testing that have been demonstrated to remove plaques more swiftly, and more completely than the current approved drugs. There is no doubt that Roche and Lilly can do a better job at removing Amyloid plaques in the brain. But what is still not known, is if improved plaque removal will lead to better cognitive results. The two currently approved drugs slow cognitive decline by around 30%. If plaques are removed more completely and more quickly, can we slow cognitive decline by 50%? 70%? Even 90%? 

We just don’t know yet. But we will soon. Roche’s Trontinemab is currently in phase II testing, and Lilly’s Remternetug is in phase III testing. Definitive results of the trials are expected as early as Spring, 2026. 

2) Tearing out the Tao 

Another “protein gone wrong,” in the Alzheimer’s brain is called Tau. What is very clear to the broad research community is that dysfunctional Tau proteins are a big part of this disease process. But that may be the only thing that is clear. Are these Tau defects the cause, or the symptom, of the disease? How do Tau dysfunctions interact with the Amyloid plaques? How important is all of this to human cognition and memory? 

There are still so many unknowns. But that isn’t stopping biotech swashbucklers from taking a shot at this aspect of the disease. They are basically throwing Tau related therapies at the wall and praying that something sticks. While there are many companies working on these kinds of therapies, two that stand out are Voyager Therapeutics (VYGR) and AC Immune (ACIU). Voyager has four different research molecules related to Tau, with three being pre-clinical, and one already in phase I testing. Voyager is particularly excited about their TRACER platform, which allows them to quickly create AAV Capsids which can very precisely deliver medicine across the blood brain barrier. 

Meanwhile, rival AC Immune is hardly waiting to be left behind. They actually have five different Tau therapies in their pipeline. One is in phase I testing, while another is in phase II testing. The other three molecules are still pre-clinical, which means not quite ready for human trials. 

Thomas Edison is famous for saying, “There is no such thing as a failed experiment.”  So these kinds of small, daring biotechs are trying a lot of different experiments, to just see if anything works. With each failure, they will learn more and more, and inch closer to eventual success. Sooner or later, we will reach the real prize: a complete and thorough understanding of how exactly the Tau  protein works in the brain, and what we need to do to make it work correctly for sick patients. 

3) Sooth Raging Inflammation  

Yet another well known aspect of the Alzheimer’s brain is inflammation. For reasons that are still not fully understood, Alzheimer’s brains suffer redness, rawness and swelling in their brains more than people with clear minds. As usual, nobody quite knows if this is a cause or a symptom of Alzheimer’s; or if this inflammation is the cause of cognitive decline. 

Novo Nordisk (NVO), the famous creator of Ozempic, knows a thing or two about inflammation. In addition to its well known weight loss properties, Ozempic is proven to reduce inflammation across the body. More and more benefits are being discovered every day … .researchers have now proven that Ozempic provides tangible benefits for the heart, kidneys and liver…research is ongoing regarding osteoarthritis and a range of other maladies linked to inflammation.

Novo also has meaningful reason to believe that Ozempic can reduce brain inflammation as well, perhaps with exciting results. A number of small, preliminary studies have linked Ozempic use to lower rates of Alzheimer’s, and slower progression of the disease.  

But the most critical study is due to produce data this year. While other studies are suggestive of cognition saving benefit, they don’t yet meet the clinical “gold standard” of scientific proof: the double blind, placebo controlled trial. 

As we speak, Novo is working to remedy that problem. The EVOKE trial is designed to provide definitive evidence of Ozempic’s benefit against Alzheimer’s disease. No one knows quite yet how much Ozempic will reduce inflammation in the brain, or how much cognitive benefit that might provide, but we are slated to find out later this year. 

Novo is so confident of this approach, that they actually own a sister company that is formulating GLP-1 molecules, JUST for neurological treatments. You may remember, Ozempic was primarily designed for weight loss; only now are we understanding the wide range of benefits the medicine can trigger. But Novo’s sister company Kariya Therapeutics is custom making molecules just for specific diseases like Parkinson’s disease and Alzheimer’s. 

Novo Nordisk is not the only scientific team that believes that reducing inflammation may reduce the damage caused by Alzheimer’s. InMed Pharmaceuticals (INM) is utilizing a totally different method of action than Novo, but the target is the same: reduce inflammation in the brain. This company’s research is at a much earlier stage than Novo, but the fact that multiple companies are working on neuroinflammation lends some credibility to the approach. 

4) Fixing the Immune System 

Another theory of Alzheimer’s pathology that has become popular of late is the idea that Alzheimer’s is actually an auto-immune disease, like Lupus or Rheumatoid Arthritis. This hypothesis posits that all of the above-mentioned problems, the dysfunctional Beta Amyloid proteins, the pathogenic Tao proteins, and the apparent inflammation of the brain, are all symptoms of an underlying problem with the patient’s immune system. 

To that end, there are many young biotechs that are now pursuing this line of investigation. Two of the most promising are Coya Therapeutics (COYA) and Prothena, Inc. (PRTA)

Coya Therapeutics is working on a novel approach that focuses on TREGS, which are a form of lymphocyte that modulates the workings of the immune system.  So far they have one clinical stage agent that is in phase II testing against ALS disease. But they also have four pre-clinical agents in the early stage of testing vrs. different kinds of dementia. One of the four preclinical Alzheimer’s agents is currently at the IND enabling stage, which means it should enter the clinic in the near future. 

Prothena has a variety of anti-Alzheimer’s medicines in its pipeline, including one that is currently in stage II testing and partnered with Bristol Myers Squibb. Regarding the immune system, Prothena is just about to enter the clinic with a molecule named PRX123, which will be a vaccine that aims to train the body to remove unhealthy Beta Amyloid and Tau proteins. The hope would be that Prothena can train a patient’s body to seek and destroy unhealthy proteins that it is somehow missing on its own. 

These are very early stage biotechs, and represent great risks for investors. However, the rewards may very well be commensurate with the risk to capital. 

5) The Grab Bag

Lastly, there are many companies that don’t neatly fit into any of these therapeutic categories. They are boldly attempting to trailblaze a path forward based on half a dozen novel hypotheses regarding the poorly understood disease. 

One such company is Anavex (AVXL). This company claims to activate Sigma receptors in the brain, which then help the brain to clear away damaged or misfolded proteins. Of any of the companies listed here, Anavex may actually be the farthest along. In January 2025, they released shocking results of a stage III trial where they claim to demonstrate that their new agent slows Alzheimer’s progression by 36%, without any of the nasty side effects that have hampered the uptake of the new drugs Lequembi and Kinsula. 

While these are certainly some promising results, the investment and scientific community has met the claims with some scepticism. The stock has barely budged since the announcement. At this point, all we can say is that extraordinary claims require extraordinary evidence, so it would be wise to look for more and better data coming out of Anavex. 

Another company looking for a “silver bullet” that doesn’t conform to any one particular theory of Alzheimer’s is Vigil Neuro (VIGL). Vigil is focused on restoring the function of the microglia, which they describe as, “the sentinel immune cells of the brain that play a critical role in maintaining CNS health and responding to damage caused by disease.” To this end, they currently have a novel molecule in phase I testing. 

With a quick internet search, you can find many of these small, start up biotechs with fresh ideas about Alzheimer’s and big dreams. But you should be aware, these are risky bets, only appropriate for the most intrepid investors. 

All in all, the world of Alzheimer’s research is now racing along at warp speed. Even to use the phrase, “world of Alzheimer’s research” might have been too much just ten years ago, when the field was demoralized and stunted by a legacy of failure. There is no guarantee that it won’t all end the same way this time. But the breadth and depth of the clinical candidates being tested really bodes well. To overtake a powerful enemy, you must attack from all sides. And it certainly does seem like the biotech community is attacking with all her might in 2025.