Amphista demonstrates protein degraders’ ‘rapid’ efficacy against tumor, CNS targets in animals

Amphista Therapeutics has unveiled new data demonstrating the potential of its protein degraders in animal models, a step toward bringing the tech to the clinic. 

The findings showed the therapies reduced tumor size and boosted survival, the biotech said in a Jan. 24 release. The degraders also successfully knocked down target proteins in the brains of dogs and monkeys, “which has been a challenge across the [targeted protein degradation field],” an Amphista spokesperson told Fierce Biotech Research in an email.

“Amphista has now successfully shown that it can do this … through improved [physical chemical] properties of its degraders,” the spokesperson said. “These learnings will drive Amphista’s early [central nervous system] portfolio—a focus moving forward.” 

Targeted protein degraders, or TPDs, are exactly what they sound like: drugs that work by completely destroying disease-causing proteins rather than inhibiting their function. Proteolysis-targeting chimeras (PROTACs) and some molecular glues both fall under the TPD umbrella, as do some small molecules.

The FDA hasn’t greenlit any TPDs yet, but several are in clinical trials, such as Arvinas and Pfizer’s PROTAC vepdegestrant—under study for use in breast cancer—and Nurix Therapeutics’ small molecule NX-2127, which is being tested in B-cell malignancies. 

Amphista’s TPDs are small molecules too. The company describes them as novel, bifunctional “plug and play” molecules that can be used in a wider range of tissues and disease indications than first-generation TPDs. Amphista also claims its therapies carry a lower risk of tumor resistance than their forebears, as they target proteins that are required for tumor cell growth.

The new data shows that a single oral daily dose of its TPDs was enough to reduce tumor size and improve survival in “multiple in vivo disease models,” according to Amphista's press release, although the biotech declined to disclose to Fierce the types of animal models and cancers they tested them against. The release explains that the molecules induced a large amount of degradation “rapidly after dosing” and were also specific for the target protein even at 100-fold greater concentrations of the amount needed to degrade 50% of it.

For the degraders that the company hopes to use in neurodegenerative disease, Amphista said it has evidence that the drugs penetrated the central nervous system “across multiple targets.” A target protein was degraded rapidly in the brains of primates and dogs when given intravenously, the company added. 

While a spokesperson confirmed to Fierce that the new data is on products that Amphista has developed and tested in-house, the company has partnerships in place with Merck KGaA and Bristol Myers Squibb valued at a combined $2.3 billion.