Alzheon Gets $10M to Take Castoff Alzheimer’s Drug Into Pivotal Test

Xconomy Boston — 

Run by a veteran of drug R&D for Alzheimer’s disease, Alzheon is betting that a smart trial design and a little chemistry work could turn a failed drug for the memory-robbing disorder into a success.

The company now has its first round of financing to test that theory on a revamped version of tramiprosate, which washed out of clinical trials several years ago. Its $10 million Series A round will help it get closer to a Phase 3 trial, where so many Alzheimer’s drugs have crashed and burned in the past.

The financing was led by Ally Bridge Group, a Hong Kong-based private equity group, and other unnamed new and existing backers. In conjunction with the round, Alzheon is moving its headquarters to Framingham, MA, from Lexington.

Alzheon president and CEO Martin Tolar says the company will spend the next six months “fine tun[ing]” things, like developing a once-a-day pill of its drug, now called ALZ-801. Then it’s on to a Phase 2/3 trial, which Alzheon aims to start by the end of the year. The $10 million will get Alzheon to that point—Tolar says Alzheon plans to raise more cash later this year to push through the coming trial.

The cash represents the first significant financing round for Alzheon since it emerged from stealth in October 2013. Former Pfizer, CoMentis and Knome executive Tolar formed the company with former colleagues John Hey and Mark Versavel. Their plan: target stalled Alzheimer’s drug programs that have already showed potential in clinical trials, refine them, and find the specific patient groups they might work best for.

The idea is to reduce the risk, expense, and development time involved in Alzheimer’s drug development, which has seen billions of dollars in research and little in the way of approved drugs to show for it. Tolar puts the company’s potential expenses for a pivotal study in the “tens of millions [of dollars],” a “fraction” of what it would cost to develop an Alzheimer’s drug from scratch.

ALZ-801 is Alzheon’s first attempt to prove this approach can work. The startup picked up ALZ-801 through a licensing deal with Quebec-based Bellus Health, formerly known as Neurochem.

Several years ago, Neurochem tested tramiprosate—a chemically modified form of the amino acid taurine naturally found in seaweed—in a 2,000-patient, late-stage trial for people with mild-to-moderate Alzheimer’s. Tramiprosate binds to beta amyloid, a protein that misfolds and clumps up in the brains of Alzheimer’s patients. The so-called “amyloid hypothesis,” which has driven much of Alzheimer’s drug development in this century, holds that removing the plaques would improve patients’ lives.

But that hasn’t held true in big tests, including Neurochem’s study. While tramiprosate was safe to use, it failed to improve cognitive function in a statistically significant way. Neurochem later morphed into Bellus, with a focus on orphan diseases, and flipped the tramiprosate program—and all the data the drug accrued over time—to Alzheon for an undisclosed sum. (Bellus will earn royalties should Alzheon succeed.)

Alzheon has made modifications, creating what’s known as a “prodrug”—an inactive substance that machinery in the body converts into a drug—that Alzheon believes will perform better than the original tramiprosate.

Tolar says a major reason tramiprosate failed is “subject variability”—the drug affected different people unpredictably, “blunting” its overall effectiveness in the Neurochem studies. Alzheon believes it has solved that problem with a version designed to last much longer in the body and avoid that unpredictability, he says.

The startup also dug through Bellus’s old tramiprosate data and found that people with a variant of the Apolipoprotein E gene called ApoE4—which puts them at a higher risk of developing Alzheimer’s—improved on standardized scores (such as the Alzheimer’s Disease Assessment Scale-cognitive subscale) testing their cognition after 78 weeks, compared to placebo.

Alzheon also says in previous Phase 3 testing, tramiprosate didn’t cause edema in the brain, which is swelling caused by leaky blood vessels that has been seen in a number of antibody drugs that, like tramiprosate, aimed to clear out amyloid plaques.

This edema is one of the red flags that Biogen (NASDAQ: BIIB) saw in data from its own recently released Alzheimer’s study, and a reason Biogen might have to use a lower dose of its drug going forward.

Tolar says the most significant side effects in Bellus’s tramiprosate program were gastrointestinal problems (like nausea and vomiting), which Alzheon believes its prodrug approach will help. The implication—which hasn’t been proven yet—is that ALZ-801 will be just as safe as tramiprosate, and at least just as effective at slowing cognitive decline in ApoE4 carriers (about 40 percent of people with late-onset Alzheimer’s have a copy of the ApoE4 variant, according to the National Institute on Aging). Alzheon will exclusively target those patients in the coming trial.

“We just need to run a very streamlined, straightforward study to confirm [what was seen with tramoprisate]—that’s it,” Tolar says.

Photo “My Mother’s Hands” courtesy of Ann Gordon via a Creative Commons license.