Amino acids play important roles in tumors, so targeting these molecules makes sense for cancer drug research. But much of this research has focused on just one of the 20 amino acids found in humans. It’s a key one to be sure, but Andrew Phillips, founder and CEO of Nexo Therapeutics, contends a broader approach is a better way to find new drugs capable of addressing some of cancer’s toughest targets.
Nexo isn’t disclosing its targets for now, but the company is ready to share some details about its research. The Versant Ventures-founded startup emerged from stealth this week with $60 million in Series A financing and an alliance with The University of Texas MD Anderson Cancer Center.
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“It really is to innovate chemistry and chemical biology to work on some of these elusive targets,” Phillips said. “None of us are fans of the term ‘undruggable.’ Many targets are viewed as undruggable for technology reasons. That’s not us.”
Nexo, which is based in Littleton, Colorado, and has research labs in Watertown, Massachusetts, is working on what Phillips describes as the next wave of covalent drug discovery. Small molecules that form covalent bonds have a stronger connection to their targets. In addition to making the drugs more potent, covalency makes them more selective, meaning they’re less likely to hit other targets and cause adverse effects.
The AbbVie and Janssen Biotech drug Imbruvica, Tagrisso from AstraZeneca, and Amgen’s Lumakras each address different cancer targets. However, these drugs all work by forming covalent bonds with an amino acid on their targets called cysteine. Other research efforts are underway targeting cysteine in some manner as a way of treating cancer. Nexo aims to go beyond cysteine.
While chemistries exist to target other amino acids, no one has put them together into a single technology platform, Phillips said. Nexo actually has two platforms. The chemistry platform, called CODON, screens a library of covalent fragments at scale to find ligands, the molecules that can bind to a target. The chemical biology platform, called INFINI-T, yields insight into how deeply and how long a molecule most interact with its target to have a pharmacological effect.
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Phillips likened Nexo’s approach to mountain climbing. A climber must choose the best route to take for the ascent. An undruggable or difficult-to-drug target is like a cliff face with no clear place to start a climb. The Nexo technologies help the startup find starting points for its drugs.
“Covalency gives us that handhold on the cliff face,” Phillips said. “With that handhold on the cliff face, we can optimize our leads.”
There are other companies also trying to bring covalent chemistry to additional amino acids. The research of South San Francisco-based Terremoto Biosciences focuses on developing small molecules that target lysine. Umbra Therapeutics, based in Lexington, Massachusetts, is researching approaches to both tyrosine and lysine. Carlo Rizzuto, managing director at Versant and a Nexo board member, said Nexo can stand apart by taking a broader view of the amino acids that are key to cancer.
“Those companies are taking a very focused approach with a specific chemistry for one amino acid,” he said. “What we’re trying to do is be more comprehensive.”
Phillips was the president and CEO of C4 Therapeutics, a clinical-stage biotech developing drugs that employ an approach called targeted protein degradation. In 2020, he joined Cormorant Asset Management. While there, he met the Versant team. Rizzuto said he and Phillips became excited about the opportunity to take covalent drug research beyond cysteine and they formed Nexo.
Cancer is just the start for Nexo. Phillips said going beyond cysteine could also take the startup into immunology and perhaps neuroscience. Some of that research could be done through partnerships, he added. In the nearer term, the MD Anderson partnership will help Nexo bring its cancer drugs into the clinic. The startup will leverage MD Anderson’s Translational Research to Advance Therapeutics and Innovation in Oncology (TRACTION) platform, which gives the startup access to in vitro and in vivo models for its research.
MD Anderson has similar agreements with other biotech companies. In 2021, the cancer center began a three-year alliance focused on an experimental Blueprint Medicines cancer therapy. Like the Blueprint deal, Nexo will provide MD Anderson with research funding and the cancer center is eligible to receive milestone payments and royalties from sales of commercialized products that stem from the collaboration. Nexo will keep all rights to its programs.
Nexo’s new financing was led by Versant. New Enterprise Associates and Cormorant Asset Management also participated in the startup’s funding round.
Photo by poncho via Getty Images
