Amplifier Launches to Bring First AMPK Activator to the Clinic

Pictured: Buildings on a city street/courtesy Getty Images

Pictured: Buildings on a city street/courtesy Getty Images

Just two months after its last pipeline company launch, Cambrian BioPharma unveiled another. Tuesday morning, the longevity biotech announced the debut of Amplifier Therapeutics, which is focused on developing a clinical-stage AMPK activator with broad potential. 

Cambrian's first clinical program, ATX-304 was acquired from Swedish biopharma Betagenon AB for $26 million USD. James Hall, CEO of Betagenon, will lead the Amplifier team to the clinic.

ATX-304 is a pan-AMPK activator. AMPK is activated in the body when energy levels in the cell are low to bring sugar from the blood into the cell and mobilize fat to produce energy. This occurs most often during exercise, fasting or reduced oxygen supply. The body’s innate ability to activate AMPK decreases with age.

AMPK activation is anticipated to have a broad range of therapeutic applications, particularly in conditions that increase with age, like cardiovascular and kidney disease, diabetes and cancer. When activated, the body enters a fast burn metabolic state, mimicking the effects of exercise.

“Endurance goes up, and cardiovascular health goes up,” James Peyer, CEO of Cambrian, told BioSpace.

“You can induce rapid, sustainable healthy weight loss and fat reduction without losing muscle or even gaining muscle. The function of almost every organ from liver to kidney improves.”

While initially targeting age and metabolic-related disease to get the drug through to commercialization as a “reactive medicine,” Peyer explained the indications are stepping stones to ultimately get the therapy to preventative medicine status. The company’s core vision is increasing humanity’s health span.

A Holy Grail Target

Pharma giants Eli Lilly and Pfizer also believe in the potential of AMPK activation. Nimbus Therapeutics netted close to $500 million from Lilly in October 2022 in a licensing deal to identify isoform-selective small molecule AMPK activators.

The deal came just a month after Nimbus scored a $125 million funding round with participation from Pfizer’s investment arm, Pfizer Ventures.

Jeb Keiper, CEO of Nimbus, called AMPK activation a “holy grail target in cellular energy balance” in a tweet after the company launch, a sentiment echoed by Peyer.

While Nimbus’s candidate is still in the preclinical stage, Amplifier’s is ready for the clinic. An advanced Phase Ib trial is already slated for later in 2023. The proof-of-concept study will enroll patients with metabolic dysfunction, but enrollment will not target a specific disease.

From there, the plan is to launch trials for multiple indications. Peyer said the team has "a few good ideas” in terms of target diseases but is not sharing details just yet.

ATX-304 has the potential to treat obesity. The treatments garnering attention in the obesity space right now, like Novo Nordisk’s Wegovy, are GLP-1 agonists that induce satiety to suppress appetite. Peyer said its AMPK activator “puts people on the opposite side of that coin” to make the body behave as though it is exercising.

“I think, if this drug continues to hold water, we may end up with a healthier alternative to those GLP-1 drugs... to induce a sustainable and healthier version of weight loss,” he said.

Last year, Morgan Stanley stated obesity treatments have the potential to become a blockbuster category. Its research arm predicted the market for obesity drugs will grow to $54 billion by 2030.

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