The key to Athira Pharma’s approach to Alzheimer’s disease is already inside each of us: a repair mechanism that can regenerate damaged neurons. What’s needed to begin the process is a pharmacological kickstart.
Athira (NASDAQ: [[ticker:ATHA]]) is developing a drug intended to turn on the repair pathway. The company’s experimental therapy is a small molecule that crosses the protective blood-brain barrier to reach its target. Leen Kawas, the founder and CEO of Seattle-based Athira, says that whereas previous drug research efforts aimed to slow the disease’s progression, Athira’s tack offers the potential to reverse the effects of Alzheimer’s.
“We hope to slow down the disease progression, but we do believe our approach has the ability to show improvement,” in cognition and other measures, Kawas says. “We’re focused on overall recovery of brain function.”
Data from a small clinical trial indicate the therapy might be working. Athira plans to learn more from larger studies, and to develop other neuroscience drugs based on the same drug discovery technology that yielded its lead compound, ATH-1017. Athira will finance its research with the $204 million it raised from its IPO, which closed Tuesday. Xconomy caught up with Kawas, and she discussed how Athira’s science offers a chance for the company to stand apart from the long list of drug development failures littering the field of Alzheimer’s drug development.
The target of Athira’s lead drug candidate is hepatocyte growth factor (HGF), a protein that regulates cell growth. It was initially discovered in the liver but is found throughout the body. Hitting this protein activates MET, a biological process that has been studied for regenerative medicine applications. Research by others has evaluated drug candidates that activate HGF/MET for addressing heart, respiratory, central nervous system, and neurological disorders. Kawas says that while those studies validate the pathway as a drug target, many of them tried to drug the pathway with biological compounds—large molecules that are more complex and expensive to manufacture and come in formulations that must be injected or infused. Kawas says that by developing small molecules, Athira is moving forward with a drug formulation that is less complex to manufacture and comes as an easier-to-take pill.
Biologic drugs can be engineered to target specific cells. Small molecule drugs aren’t like that. They travel in the bloodstream, potentially sparking effects around the body. Mark Litton, Athira’s chief operating officer, says that although ATH-1017 circulates throughout the body, it doesn’t activate the HGF/MET mechanism everywhere. The pathway presents itself only in the presence of injury, he says. Once repairs are done, the receptor breaks down and is no longer available to bind to the drug.
When ATH-1017 reaches the brain, the drug’s chemistry enables it to cross the blood-brain barrier, Kawas says. Inside the brain, the drug activates the repair pathway to promote neuron regeneration. The goal is to help restore some of the brain function that was lost to Alzheimer’s. That’s different than other drugs that aim to break up beta amyloid and tau proteins to slow the disease’s progression. Many such drugs failed in late-stage clinical trials. Biogen (NASDAQ: [[ticker:BIIB]]), Eli Lilly (NYSE: [[ticker:LLY]]), and Roche are among the companies that still have active programs targeting those proteins. In its IPO filing, Athira says it does not view those antibody therapies as competitors, adding that they are potentially complementary to the company’s approach.
So far, Athira has tested its lead drug in a Phase 1 study whose 88-patient enrollment included 11 Alzheimer’s patients. The drug was found to be safe and well tolerated, but it was the results in the 11 Alzheimer’s patients that stirred interest in the scientific community when they were presented late last year during Clinical Trials on Alzheimer’s Disease conference. Those patients were evaluated with
