ALS upstart Amylyx gains $3M grant to start combo trial

Brain imaging
Amylyx CEO Joshua Cohen

Cambridge, MA-based startup Amylyx Pharmaceuticals has been given charity backing to run its first in-human clinical trial for the biotech's oral combination ALS candidate AMX0035.

The biotech, which came into being back in 2013, has been handed a $2.96 million grant from the ALS Association and ALS Finding a Cure, which will go toward funding a Phase II trial for the drug.

This also builds on the $1.3 million it raised last November and the $600,000 from the ALS Finding a Cure Foundation and the Cure Alzheimer’s Fund.

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The Phase II trial is set to be run by Massachusetts General Hospital; the startup’s scientific advisory board is in fact chaired by Dr. Rudolph Tanzi, director of the genetics and aging research unit at MGH.

AMX0035 is a combination of two meds: sodium phenylbutyrate and tauroursodeoxycholic acid. Sodium phenylbutyrate, also known as Buphenyl, is currently marketed by Horizon Pharma to help treat urea cycle disorders, while tauroursodeoxycholic acid is used in the treatment of certain liver diseases.

Speaking to FierceBiotech, Justin Klee, president and co-founder of Amylyx, said that in preclinical studies the company had seen “strong results” in cellular and animal models, “suggesting the two drugs work synergistically to reduce cell death and inflammation in multiple insult models mimicking some of the pathology observed in ALS.”

He admits that it is “certainly true that many drugs have shown some initial promise in the clinic only to fail in later stage trials,” but believes his company’s plans will put it on the path to success.

“Amylyx is addressing the clinical challenge in several ways: Our initial trial will be fairly large so that a signal from it will be relatively robust; and we are selecting a specific group of patients early on. There is some thinking that some trials have failed due to an inability to select the patients best able to benefit from the drugs.”

The trial, which is expected to begin later this year, will test the safety and tolerability of AMX0035, as well as functional outcomes.

Analysis of biomarkers of cell function, neuronal damage, and inflammation will be included as a major part of the trial, along with a new measure of muscle strength that has been shown to be related with disease progression.

Joshua Cohen, CEO of the biotech, tells FierceBiotech that while this is the first time the cocktail treatment will enter the clinic, they already have more than just hope that it will perform.

Cohen explains: “So in a sense while it is a first-in-patient there is prior clinical data in this population at least on the individual agents. We expect the combination will, however, perform significantly better than either agent alone.

“Because of this, it makes sense to go directly into a fairly large trial that could show efficacy. We are, however, still finalizing the trial details and will update on these at a later point.

“Some of the exciting aspects of the trial we can share include a ‘piloting’ of a central IRB for the study. This will be the first ALS study to use this and should accelerate future study start times and reporting cycles. We are including a novel functional endpoint, ATLIS, which may be able to improve the ability to measure ALS.

“We are also including biomarkers for cell death and neuroinflammation which have yet to be studied in such a large therapeutic trial. Amylyx is treating a specific group of patients which were selected to improve the homogeneity of the patient population and the ability to measure an effect.”

On the business side, Cohen did not say that the company was looking to go public right now.

“Amylyx is focused on the current financing to support our upcoming clinical trial,” he said. “We will keep our options open but our strategy at this time is to run a top-quality trial and if that is successful, I think we will have many options.”

But Klee admitted that the biotech would need more external investment to fund its future. He said the company is grateful for the grant financing from ALSA and ALS Finding a Cure, something which “will cover the majority of the costs of the trial.”

But he said additional financing “will be necessary to support us through the end of the trial and complete additional projects, which we will need to have in place to support our development if the trial is successful.”

He added that the biotech is currently in the process of closing a Series A financing to support this trial and “will be excited to update on it shortly.”

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive neurodegenerative disorder that causes muscle weakness, paralysis, and ultimately, respiratory failure.

Most people with ALS live 2 to 5 years after their first signs of disease. About 10% of people with ALS survive at least 10 years. Currently only one med is on the market for the condition--Rilutek (riluzole)--which works by stopping the release of glutamate. The drug however only extends survival by around 2 to 3 months.

There have been a number of research setbacks in this difficult-to-treat therapy area. Most recently in May of this year, stem cell biotech Neuralstem ($CUR) said it was to ax staff across all divisions to save cash after data for its ALS candidate NSI-566 was found to be weaker than first thought.

There was also initial hope that small biotech Genervon and its candidate GM604 had shown some efficacy in an early trial of a dozen patients after some loud noises were made by the company, but strong data were never released, and some questioned its case for efficacy given the smallness of the study.

- check out the release

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