J&J takes stake in Locus’ CRISPR-based ‘Pac-Man’ antimicrobials

Just over a year after its first-round financing, CRISPR company Locus Biosciences has signed up Johnson & Johnson as its first big pharma partner and pocketed a $20 million upfront fee.

While most CRISPR companies are looking at applying the CRISPR-Cas9 gene-editing technology to human diseases, Locus is taking a different tack. It’s using another pathway—CRISPR-Cas3—to tackle the issue of rising resistance to the current antimicrobial armamentarium at a time when many companies have backed away from researching new drugs.

While still in the early stages of development, J&J must like what it has seen from Locus’ programs. Along with the $20 million upfront fee, the drugmaker is offering another $798 million in milestones for CRISPR-Cas3 drugs targeting two bacterial pathogens.

When Locus raised $19 million in a series A toward the end of 2017, CEO Paul Garofolo likened the company’s technology to Pac-Man, with the CRISPR drugs chewing up the target bacteria’s DNA and causing cell death, while leaving other bacteria in the microbiome unscathed.

Since then, the Research Triangle Park biotech has extended its technology platform by buying EpiBiome’s discovery platform, allowing it to isolate characterize bacteriophages—a type of virus that infects and destroys bacteria—more rapidly.

Phages are central to Locus’ therapeutic approach as they are highly specific to the bacteria they infect, allowing CRISPR to be delivered only to the target pathogen. Once in the bacteria, the enhanced phage hijacks the cellular machinery to produce more copies of itself to help eradicate the infection.

The company’s deal with J&J’s Janssen Pharma unit centers on the development of CRISPR-Cas3-engineered phage (crPhage) drugs against bacterial pathogens “in the microbiome of the lungs and other organ systems in the context of diagnosed microbiome dysbiosis”—in other words where a normal healthy microbiome population is disturbed allowing disease-causing bacteria to gain a foothold.

The specific identity of the pathogens hasn’t been divulged, but Locus’ current pipeline includes crPhage drugs to treat Escherichia coli urinary tract infections, recurrent Clostridium difficile infections, Pseudomonas aeruginosa in the lungs and Enterobacteriaceae. This is thought to be the first big pharma collaboration to advance a bacteriophage therapy into the clinic.

“Our collaboration with Janssen…reflects the importance of the crPhage platform and its potential to revolutionize the treatment of disease and extend human life,” said Garofolo.

“Our platform is uniquely positioned to selectively eradicate pathogenic bacteria of choice while preserving an otherwise healthy microbiome in patients, and this collaboration with Janssen will enable us to further develop products on the platform to help patients in need around the world.”

Another CRISPR specialist with antimicrobial drugs in its sights, Eligo Bioscience, raised $20 million in a series A in September 2017 but is focusing on the CRISPR-Cas9 system.