Clinical trial flops have become the norm for Alzheimer’s disease treatments, despite the billions put into research for the memory-robbing disorder. But a new Lexington, MA-based startup called Alzheon sees opportunity in all of those high-profile failures of the past. Its belief is that these failures have left behind a treasure trove of clinical data, and stalled drug candidates, that can be plucked, refined, and developed to work for more specific groups of patients.
Alzheon officially emerged from stealth today, backed by an undisclosed initial seed funding from two unnamed private investors.
“We’re taking on assets that are mature, but are usually in hands where it’s just not the right fit,” says Alzheon president and CEO Martin Tolar.
Alzheon is starting up with one such drug already in its portfolio. It in-licensed a compound called ALZ-801 (previously BLU8499) from Quebec-based Bellus Health that is the successor to an earlier Alzheimer’s drug that failed a big clinical trial in 2007. Alzheon didn’t disclose the financial terms of the deal, other than to say Bellus stands to receive a royalty stream on potential sales of the drug in the future, should things pan out. But Alzheon will now develop ALZ-801, believing it can design a trial program that targets the patients that are most likely to respond to it. And Tolar says the company has enough cash in the bank to add a few more programs as well.
Tolar is a neuroscientist by training and a Pfizer veteran that has worked on a number of Alzheimer’s drug programs. He and Alzheon chief scientific officer John Hey, for instance, helped develop an Alzheimer’s drug candidate for CoMentis that led to a big licensing deal with Astellas Pharma in 2009. Tolar later had stints leading Wellesley, MA-based startup NormOxys, and most recently Cambridge, MA-based genomics startup Knome. He says he always had his eye on coming back to drug development—and specifically, Alzheimer’s. So he stayed in contact with the teams he worked with at Pfizer and CoMentis, and came up with the idea for Alzheon. Tolar left his post at Knome, staying for just about a year and a half, and Alzheon was incorporated in August. Hey joined on as CSO, and former Pfizer coworker Mark Versavel came on as chief medical officer.
“This is a team that’s been together for a long time,” Tolar says. “We jelled before founding this. We felt we could provide a new approach to [Alzheimer’s drug development],”
Through that approach, Alzheon isn’t starting from scratch. Rather, it is targeting stalled drug programs that have been tested already in clinical trials. The drugs have already been shown to have good safety profiles, meaning they can quickly be advanced into studies that show whether they’re any good.
“The main criteria is to have clinical data in patients that could convince us that there is a signal here, that there is a population or subpopulation that would benefit from treatment, and that there is a trial design where we can, practically [speaking], make it happen,” Tolar says. “This tremendously reduces the risk, and allows us to run much smarter trials.”
Alzheon’s first foray into this plan is with ALZ-801. The compound is 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.
“We’ll see how far we want to take them,” Tolar says. “For us, really, execution is the main challenge.”