No IPO? No problem: Alzheon bags $47M NIH grant to bankroll Alzheimer's trial

A grant from the National Institutes of Health’s National Institute on Aging will support a phase 3 study of Alzheon's lead Alzheimer's disease program in a genetically defined patient population. (NIH)

Alzheon has been trying to go public for years, calling off its IPO in April 2018 and aborting its second attempt in January last year. Now, public markets be damned, the company is moving forward with a phase 3 study of its lead Alzheimer’s disease program thanks to a $47 million grant from the National Institutes of Health’s National Institute on Aging (NIA).

Over five years, the grant will support a study of ALZ-801, a pill that blocks the formation of amyloid oligomers, or soluble amyloid molecules, in the brain, which is thought to lead to Alzheimer’s disease. Amyloid oligomers are clusters of individual amyloid proteins and represent a target drugs can hit before full-blown amyloid plaques form. Many companies have tried—and many have failed—to effectively target amyloid plaques, highlighting the need for new approaches in Alzheimer’s drug development.

ALZ-801 is a prodrug of tramiprosate, meaning the pill is metabolized inside the body to produce the drug. Tramiprosate has been tested in more than 2,000 patients with mild to moderate Alzheimer’s but didn’t move the needle in a general population. That’s why Alzheon is taking a precision medicine approach with ALZ-801.

The phase 3 study will enroll 300 patients with early Alzheimer’s disease who also have two copies of the APOE4, or apolipoprotein E, gene variant. It’s doing so for two reasons, Alzheon said in a statement. First, people with this variant are at higher risk of their disease worsening quickly, and second, drugs like ALZ-801 that target amyloid oligomers are more likely to work in this patient group, the company said.

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Alzheon plans to begin the study in the first quarter of 2021. Patients will receive either ALZ-801 or placebo twice daily for 18 months. To meet the study’s primary endpoint, Alzheon’s pill will have to beat placebo at slowing clinical decline on a dementia-rating scale called the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog). The study will also look at other functional and behavioral endpoints, as well as biomarkers, such as levels of amyloid and tau proteins, in patients’ blood and cerebrospinal fluid.

“We have designed this study to have a higher probability of success than previous trials in Alzheimer’s patients. We are applying precision medicine by targeting Alzheimer’s patients who can be readily diagnosed, who develop the disease earlier when they are less likely to have comorbidities, and who are likely to benefit from the treatment,” said Alzheon Chief Medical Officer Susan Abushakra, M.D., who will serve as the principal investigator.

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The company is looking at biomarkers to better understand how ALZ-801 affects the progression of Alzheimer’s disease in this patient subgroup, Abushakra added. In the future, the company will consider testing the drug in people who have just one copy of the APOE4 gene and in healthy people who are at high risk of developing Alzheimer’s.

“Proposals to NIA are highly competitive and this award recognizes the contribution of Alzheon scientists to the targeting of toxic beta amyloid oligomers, which are now established as key triggers of cognitive decline in Alzheimer’s patients,” Alzheon CEO Martin Tolar, M.D., Ph.D., said in the statement. “We are proud that Alzheon has stayed the course and, after seven years of pathbreaking efforts, emerged as a frontrunner in the development of the first oral treatment for Alzheimer’s that can slow or stop the progression of the disease.”

Alzheon picked up the rights to ALZ-801 from Neurochem, now known as Bellus Health, in 2013. The company took aim at an $81 million IPO in March 2018, with plans to use the funding to move ALZ-801 into phase 3, only to call it off a month later. The company teed up a second attempt in August 2018, downsizing its goal to $40 million, but canned that plan in January 2019.