Locus and Janssen Ink Potential $818 Million Deal to Develop CRISPR-Based Antibacterials

Johnson & Johnson logo on outdoor sign

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Locus Biosciences, based in Research Triangle Park, NC, inked a collaboration and license deal with Janssen Pharmaceutical, a Johnson & Johnson company. The companies will work to develop precision antibacterial therapies based on CRISPR-Cas3-enhanced bacteriophage.

Under the terms of the deal, Janssen is paying Locus $20 million up front. Locus will be eligible for up to a total of $798 million in development and commercial milestones, as well as royalties on any product sales.

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Locus focuses on using Type 1 CRISPR-Cas3 to degrade the DNA of target bacteria, which quickly kills them. One advantage of this approach over antibiotics is it targets the specific bacteria without wiping out the desirable “good” bacteria in the body.

“Our collaboration with Janssen on the development of products to treat deadly infections and potentially other microbiome dysbiosis associated conditions reflects the importance of the crPhage platform and its potential to revolutionize the treatment of disease and extend human life,” stated Paul Garofolo, Locus’s chief executive officer. “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.”

CRISPR is a form of gene editing. Most companies have focused on using the technique to modify human genes to treat diseases, although that is largely in its earliest stages. The technique has been in the spotlight with the controversial announcement that Chinese researcher He Jiankui had used CRISPR-Cas9 to alter the DNA of embryos for seven couples, with the resultant birth of a set of twins and another pregnancy.

Locus’ approach is CRISPR-Phage (crPhage), which uses CRISPR and a different enzyme, Cas3. Phages are viruses that infect bacteria. Cas3 is actually the most common CRISPR-Cas system in nature, while CRISPR-Cas9 is relatively rare. Cas3 is more effective at shredding target DNA beyond any chance of repair.

In November 2017, Garofolo told FierceBiotech, “Selecting the right tool for the job at hand is critical for success. Both Cas3 and Cas9 are very capable solutions in their own rights, but Cas3 causes irreversible DNA damage—think Pac-Man chewing up the target bacteria’s DNA—resulting in cell death. As such, it is the overwhelming correct choice for an antibacterial product.”

Locus has several programs focused on E. coli for urinary tract infections and C. difficile for C. diff infections. The Janssen programs will apparently focus on respiratory and other infections.

The company also has a second area focused on microbiome-related diseases. These include programs relevant to inflammatory bowel disease (IBD) and other diseases caused by problems in the microbiome in gastrointestinal, immunology, oncology, and central nervous system therapy areas.

The company hopes to launch clinical trials sometime this year.

Locus raised $19 million in a Series A financing in late 2017. It was led by Artis Ventures with participation from Tencent Holdings, Abstract Ventures and the North Carolina Biotechnology Center. In January, Locus partnered with IDbyDNA to develop a companion diagnostic using its next-generation sequencing platform, Explify. The test will be used to help select patients for Locus’ LBx-PAO1 antimicrobial product that targets Pseudomonas aeruginosa. In July 2018, Locus acquired EpiBiome’s discovery platform, which allowed it to isolate bacteriophages more quickly.

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