Reinforcing the neurons attacked by Alzheimer’s disease and ALS.
Co-CEOs: Josh Cohen and Justin Klee
Based: Cambridge, Massachusetts
Clinical focus: Supporting the inner workings of brain cells to hold off declines in cognition and motor skills.
The scoop: Using a novel pairing of previously known compounds, Amylyx Pharmaceuticals aims to support the health of individual neurons under siege from degenerative conditions such as Alzheimer’s disease and amyotrophic lateral sclerosis, or ALS.
The company’s lead candidate, AMX0035, combines two orphan drugs—one an acid and one a base, which presents its own set of chemical manufacturing challenges—into a single oral medication focused on neurons’ organelles.
Taurursodiol, also known as tauroursodeoxycholic acid, works to protect brain cells’ energy-producing mitochondria, which can self-destruct during the early stages of degenerative diseases. Meanwhile, sodium phenylbutyrate, sold as Buphenyl, helps to boost the endoplasmic reticulum, which surrounds the nucleus and works to make sure any constructed proteins are correctly folded and operate properly.
The endoplasmic reticulum’s pathways, capable of triggering the death of the cell if it fails to clear out malformed proteins, have long been considered a target for potential cancer treatments, when too many cells and out-of-control growth are the problem.
Amylyx, however, is looking at the other side of the coin, where the rampant death of neurons and loss of brain tissue affects cognition and a person’s ability to talk, move and breathe.
Their approach recently showed that it could slow the decline seen in patients with ALS by about 25%, with a phase 2/3 study published in the New England Journal of Medicine. After six months, those who received AMX0035 retained more function according to a commonly used clinical metric that measures a person’s ability to walk, dress and feed themselves.
What makes Amylyx fierce: ALS has been a difficult mountain to climb, as a majority of clinical attempts have failed to make significant progress against the disease over the past two decades. In addition, declines in motor skills and function can be rapid, with those diagnosed typically surviving for two to five years.
The functional rating scale used in Amylyx’s study adds up points across 12 categories measuring the ability to complete different aspects of daily life.
“Each one-point drop is very significant,” said Amylyx co-CEO Justin Klee. “If you look at speech, you can quickly go from speaking with issues to not being able to speak at all. Or you might go from changing the type of food you eat, to needing a feeding tube. The drops are quite dramatic.”
Given alongside currently available therapies, participants receiving AMX0035 saw an average drop of about 1.24 points per month, compared to 1.66 points per month with placebo. After six months, treated patients had total scores about 2.32 points higher, with gains seen in categories covering fine motor skills.
“That's if the patient can feed themselves, or if they can type on a laptop—it's how you interact with the world,” Klee said. That study was backed by money raised from the Ice Bucket Challenge, alongside support from the ALS Association and ALS Finding a Cure.
At the same time, the company finished recruiting enough patients over the summer for a separate study in Alzheimer’s disease, which is expected to produce preliminary results before April 2021.
“The mechanism of action is theoretically similar,” said co-CEO Josh Cohen. “Alzheimer's undergoes pretty profound degeneration of the hippocampus, with patients losing significant tissue volume by the time they’re diagnosed. Hopefully our combination will slow that down.”
It’s been a long road for Amylyx since being founded by Klee and Cohen in their dorm room at Brown University in 2013—with the majority of those years counting just two or three employees, themselves included.
But over just the past year-and-a-half, the company’s staff has grown to over 20—adding executives from Biogen, Ironwood and BlueRock—and has collected resources and financial support from a network of patient groups, foundations and funds focused on ALS and Alzheimer’s disease.
“Especially in ALS, it’s a community we know really well,” Klee said. “We had over 50 co-authors on our [NEJM] paper—and there really aren’t all that many ALS specialists in the country.”
By the time they hope to launch the drug, Cohen said Amylyx plans to scale up its headcount to just over 100.
“We are fiercely independent,” said Klee. “And we plan to be around for a long time.”
Investors: Morningside Ventures led a $30 million series B round in July, with participation from other unnamed investors.