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a prodrug—or, an inactive substance that enzymes or other chemicals in the body chop up into a drug. In this case, the active ingredient is tramiprosate, which itself is a chemically modified form of taurine, an amino acid naturally found in seaweed. The compound binds to beta amyloid, the protein that forms the plaques in the brain that many experts believe is the main culprit for Alzheimer’s.
Tramiprosate already has a long history, and not necessarily a good one. Bellus, when it was known as Neurochem, tested tramiprosate in a big, 2,000-patient late-stage clinical trial for people with mild-to-moderate Alzheimer’s, hoping that it would stop beta-amyloid plaques from forming, and thus slow down the progression of Alzheimer’s. That trial failed. While tramiprosate was safe to use, it didn’t improve cognitive function. So rather than push forward with another long, expensive, risky Phase III study, then-Neurochem did two things: first, the trial showed signs that tramiprosate might help protect the brain’s hippocampus from shrinking during Alzheimer’s. Since tramiprosate is a natural product, the company began selling it as a nutraceutical, or “medical food,” which isn’t subject to the same regulatory scrutiny as prescription drugs. It’s sold under the name Vivimind. Bellus is divesting that product today in a separate deal.
Second, what was left of Neurochem morphed into a new company called Bellus, and started going after orphan diseases. It only kept the Alzheimer’s program alive through a small development deal with U.K.-based Asclepios Bioresearch, which was going to help it run a midstage study of the tramiprosate prodrug. Alzheon is now taking those duties over, and refining the prodrug.
“With a prodrug we can actually improve on the performance, which a lot of the time, is really the difference between having a biological effect on a patient or not,” Tolar says. “That, frankly, had been a problem for [tramiprosate].”
Alzheon is designing a new trial program for ALZ-801 based on a deep dive into the data of the old trials, analyses of subpopulations from those studies, and with the help of biomarkers and other tools that just weren’t available when Neurochem ran its big trial in 2007. Tolar wouldn’t say specifically the analytical work it has done, what type of study Alzheon envisions, or even the group it plans to target. But he did note, for instance, that the parent drug showed signs of efficacy in patients with a form of the Apolipoprotein E, or APOE gene that is implicated in Alzheimer’s. So in theory, Alzheon would be running smaller, more targeted studies for its drug candidates. That should translate into trials that take less time and money to yield a result.
Of course, any Alzheimer’s trials are a massive financial undertaking—typically far too big and costly for a little startup. So Alzheon is hoping for two things: one, by running more targeted studies, it can get a signal early on that the drug either works, or doesn’t. Two, if it successfully picks the right drugs and designs the right trials, it could theoretically try to cut a deal with a pharmaceutical company to pick up the tab for further studies necessary to win FDA approval.