The past few days have been trying times for the global Alzheimer’s community. Biogen and Eisai Inc were forced to halt a stage 3 trial of a formerly promising compound when it became clear that the treatment, named Aducanumab, wouldn’t come close to meeting study endpoints. After much anticipation, it became clear that Aducanumab just doesn’t work. In just a few days, billions of dollar in R&D investment and badly needed revenue potential vanished into thin air. But hope persists. Here are four biotechs that are forging ahead with novel approaches to the dreaded disease.
“It’s not how many times you get knocked down that counts, but how many times you get back up.”
-General George Custer
1) Neurotrope, Inc. ($NTRP)
Rather than treating amyloid plaques directly, this scrappy startup is targeting another hallmark of demented patients; weakened or erased synaptic connections between brain cells. Think of Neurotrope as an electrician working to strengthen the electrical grid in a complex building.
$NTRP is moving forward with testing of it’s patented Bryostatin-1, an agent originally derived from jellyfish. One key advantage for Bryostatin-1 is that it has been studied in cancer patients for years, thus there are no fears of toxicity in humans. Neurotrope has successfully regrown brain wiring in mice, and already shown some tantalizing human results in a preliminary phase 2 study. A much larger phase 2 study is currently underway, with a readout expected before the end of 2019.
2) Denali Therapeutics, Inc. ($DNLI)
The scientists at Denali believe that many of the negative symptoms of Alzheimer’s are results of bad inflammation in the brain. Specifically, they are targeting a protein in the brain called RIPK1 that drives unhealthy inflammation. In mouse models, Denali has produced dramatic benefits by dialing down the effects of the RIPK1 protein. Can this same benefit be delivered in human test subjects? Denali describes it’s work with this drug candidate as “early clinical.” That is Pharma speak for “we shall see…”
3) Alector, Inc ($ALEC)
Alector was founded under the hypothesis that the immune system is a key driver of brain health. Thus, Alzheimer’s and other neuro maladies can be prevented or cured by modulating the immune system’s actions in the brain. $ALEC has two early stage drug candidates it is developing in partnership with Abbvie. If the Alector scientific team is proven correct, it would be nothing less than a revolution in our understanding of the human brain.
4) Biogen and Eisai ($BIIB) & ($ESALY)
Are you reading this correctly? Yes, you are. Fresh after enduring a stock market plunge that erased billions in shareholder wealth, the “dynamic duo” are at it again. The failure of Aducanumab has fueled a lot of speculation that the “amyloid plaque” hypothesis of Alzheimer’s is wrong. So many different drugs have been designed to prevent or remove amyloid plaques from the brain; all have failed to improve or prevent dementia in real world patients.
Now Biogen and Eisai are moving forward with yet another candidate that relies upon the Amyloid Hypothesis. Within hours of announcing the discontinuation of the aducanaub program, they announced a new phase three trial for BAN2401, a different agent that has been in development. Incredibly resilient? Or incredibly foolish? You be the judge.
Anyone who chooses to invest their hard earned capital in any of these companies must understand that the odds of success are long. Many billions of dollars have been lost in the quest to cure Alzheimer’s disease. Many scientific careers have died an ugly death on crushed hopes. Yet anyone who has experienced first hand the utter devastation caused by this cruel disease knows that we must continue to take these risks. A better world depends on us.
DISCLOSURE: the Sick Economist owns shares in $NTRP