While supportive of Amylyx’s acquisition of a GLP-1 drug, analysts say the company’s future hinges on key upcoming readouts from multiple products in its pipeline.
After withdrawing its only commercial product from the market in April—a potentially fatal setback for a young biotech—Amylyx has since regained ground, announcing positive early results for the same product in another indication and inking a deal for a new asset in one of biotech’s hottest spaces.
In March, the Cambridge, Mass.–based company revealed that its recently approved amyotrophic lateral sclerosis (ALS) drug Relyvrio (AMX0035) failed its Phase III trial and quickly made the decision to pull the product from the U.S. and Canadian markets. A week after that decision, the company got a glimmer of hope when AMX0035 improved pancreatic function and glycemic control in adult patients with Wolfram syndrome, a rare, inherited neurodegenerative disease.
This month, Amylyx was back in the news, announcing its entrance into the lucrative GLP-1 space with the $35.1 million acquisition of avexitide, a glucagon-like peptide-1 receptor antagonist (the opposite of the mechanism of the blockbuster weight-loss drugs Wegovy and Zepbound, which are GLP-1 receptor agonists), from the now defunct Eiger BioPharmaceuticals.
With these moves, the company may be a step closer to realizing one analyst’s assertion that some biotechs have nine lives, and that Amylyx might just be one of those companies.
Avexitide ‘Checked All the Boxes’
Amylyx has long sought out potential licensing opportunities to complement its pipeline, assessing hundreds of potential assets, co-CEO Justin Klee told BioSpace. On the checklist: a clear match between the mechanism of the drug and mechanism of the disease, “compelling” preclinical and clinical data, and “an opportunity to make a real impact and help people with high unmet medical needs.”
“In many ways, this was the first asset that really checked all the boxes,” Klee said of avexitide.
While GLP-1 agonists like Eli Lilly’s Mounjaro and Novo Nordisk’s Ozempic spark insulin production by mimicking the GLP-1 hormone, avexitide blocks the receptors, thereby raising blood sugar levels. The drug has been studied in five clinical trials for post-bariatric hypoglycemia (PBH) and three trials for congenital hyperinsulinism (HI)—two diseases for which Klee said there are currently no specific treatments. Both are characterized by hyperinsulinemic hypoglycemia, for which Avexitide holds the FDA’s Orphan Drug Designation.
Amylyx co-CEO Josh Cohen said the ability to “move rapidly” into Phase III studies with avexitide was attractive. Amylyx plans to begin Phase III trials in PBH by the first quarter of 2025, with data expected in 2026. If all goes well, Cohen said the product could be on the market by 2027.
The acquisition also further entrenches Amylyx in the endocrine space. With the company’s work in Wolfram syndrome, “we’ve been learning more and more in the endocrine space, and we’re very excited to continue there, and again, in areas of high unmet need,” Klee said.
Analysts were supportive of the move. In an investor note published July 10, Bank of America Research Analyst Charlie Yang said “avexitide gives Amylyx more shots on goal to turnaround the company with a significantly lower development risk profile compared to [its other pipeline programs].”
“It makes good sense for them,” agreed Joel Beatty, a senior research analyst at Baird. “It’s a drug that can leverage a lot of the things that they’ve done well in the past, such as rare disease clinical development . . . history of good regulatory interactions . . . as well as rare disease marketing.”
However, Yang wrote, “we expect investors to continue to debate avexitide’s commercial opportunity given the lackluster development/interests from other manufacturers in this space as well as shrinking PBH market as more patients are treated with effective GLP-1s with bariatric-like weight loss efficacy.”
Persisting in Neuro
Klee and Cohen emphasized that Amylyx is not abandoning its founding focus on ALS and other neurological diseases. “This [avexitide] comes on top of the pipeline that we’re already building,” Cohen said.
In addition to its work in Wolfram, for which Amylyx anticipates full Phase II data this fall, the company is in pivotal trials with AMX0035 in progressive supranuclear palsy (PSP), a rare, degenerative neurological disorder, with an interim data analysis from the Phase III ORION study planned for mid-2025. And the company is taking another shot on the ALS goal with AMX0114, an antisense oligonucleotide targeting the gene encoding calpain-2, a key effector of axonal degeneration. Cohen said Amylyx hopes to begin a Phase I trial with this asset this year.
However, Yang expressed caution around some of these programs in an interview with BioSpace. He noted that due to the relatively small patient population for Wolfram syndrome, “it’s not really a big dollar opportunity.” While the commercial opportunity in PSP is more promising, the disease holds either the same or greater difficulty than ALS, he said, and as with the failure of Relvyrio, “my assumption is this trial will not work.” Yang added that the outlook for Amylyx would be a lot clearer following the Phase III PSP readout.
Beatty also noted that with the failure of Relvyrio, investor expectations for AMX0035 in other disease settings are now “fairly low.” He said avexitide gives Amylyx a drug that “looks like it has a higher probability of success.”
Going forward, Beatty said that obtaining good clinical data will be important for Amylyx in terms of investor perception, though he acknowledged that that regulatory clarity on clinical trial expectations would be helpful, particularly in Wolfram syndrome. “That might be a setting where there’s somewhat of a lower bar for success than you might see for some larger settings that already have drugs available.”
He also noted that across its pipeline, Amylyx will need time to generate those data. “Fortunately for Amylyx, they have the cash to get to those opportunities.” Amylyx had $371.4 million in cash, cash equivalents and short-term investments as of December 2023, according to an SEC filing.
