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Drug Discovery

Aizen Therapeutics launches to develop mirror peptides

Mirror peptide–based biologics could be stabler than traditional peptide-based drugs

by Sarah Braner
November 26, 2024

 

A photo of David Van Valen.
Credit: Caltech
The company was cofounded by David Van Valen from the California Institute of Technology.

Biotech Aizen Therapeutics has spun out of the lab of David Van Valen at the California Institute of Technology with $13 million in seed funding.

Aizen is using generative artificial intelligence to discover mirror peptides made entirely out of d-amino acids. Like proteins, peptides are made of amino acids, but they are shorter chains than proteins, which can be hundreds of amino acids long. Mirror peptides are similar to their naturally occurring counterparts but are nonsuperimposable.

“We’re in a renaissance for peptide therapeutics,” Van Valen says. He notes that beyond their use in weight-loss medications, peptides have gained attention because they “hit a sweet spot”—they can target enough of a receptor to induce an effect but are small enough to penetrate well into tissues.

Peptide-based biologics aren’t very stable in the body because protease enzymes have evolved to break them down. But these proteases haven’t evolved to degrade the mirror versions of these peptides, so mirror peptides are stabler. And because proteases don’t break down mirror peptides, those peptides remain too big for an antigen-presenting cell—which kicks off the immune response by presenting a fragment of a foreign substance to immune lymphocytes—to activate an immune response.

While US regulators have approved some therapies using d-amino acids, such as the blood thinner bivalirudin, there is no approved therapy using mirror peptides made entirely out of d-amino acids. One reason that development has been slow is that creating mirror peptides in silico requires large datasets based on interactions between mirror peptide and regular proteins, and those data are simply not easily available. But the prospect of building mirror peptide drugs remains attractive because the more d-amino acids a peptide contains, the stabler it is and the less likely it will be broken down by proteases.

Van Valen says Aizen solves this problem using generative AI-enabled drug discovery techniques, but he would not elaborate. He confirmed that the start-up is currently targeting the neuroscience and solid tumor areas.

Aizen’s work uses “the next wave of AI-enabled drug discovery tools that had their foundation in the work that won the Nobel Prize this year,” says Ajay Kshatriya, Aizen’s CEO. “This is the continuation of that trajectory, of how and where AI can impact drug discovery and development.”

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