Nexo launches with oncology drug discovery program

Nexo Therapeutics has launched with $60 million in series A financing to treat cancer by developing covalent drugs for previously intractable protein targets.

Covalent drugs strongly bind to protein targets, shutting down their disease-causing activity. In comparison to noncovalent drugs, these drugs are more potent at lower doses, with longer lasting therapeutic effects. The challenge is finding a binding site on the target protein that’s selective enough to avoid unwanted off-target effects.

The amino acid cysteine is commonly used as a covalent drug target, but it is an underrepresented amino acid with approximately 2% natural abundance in proteins. Other amino acids have an abundance closer to 5%. Another challenge is that cysteines can often be located in the core of the protein, making them hard to get to.

Nexo will use its covalent discovery and optimization (CODON) engine, a proprietary library of fragments targeting all ligandable amino acids, which includes cysteine, tyrosine, lysine, glutamic acid, and aspartate.

Nexo says no other company has created a systemic program to use these ligands for drug discovery. “We’re agnostic about the amino acids we use as a starting point,” says Andrew Phillips, Nexo’s CEO. “Getting that first handhold is the most important thing,” he says.

The company may switch from an initial covalent hit to a noncovalent drug candidate as the development program requires, he says.

The second prong of Nexo’s approach is its Informed Profile Before Initiation of Target (INFINI-T) platform, which Nexo’s researchers can use to modulate chimeric fusion proteins with small molecules. The results help the scientists to understand how much a drug needs to inhibit a target, and for how long, to achieve the desired therapeutic effect.

The traditional approach to studying binding relies on biological models developed after an initial target is identified. Nexo says the advantage of its platform is that it can run in parallel with ligand discovery to give a more complete picture.

Nexo has also announced that it is entering a partnership with the University of Texas MD Anderson Cancer Center to combine their expertise and develop drugs to address unmet needs in oncology. The company, based in Watertown, Massachusetts, plans to expand its workforce to about 20 people by year-end.