[Updated 1/4/19, 9:10 p.m. PT. See below.] As strains of bacteria evolve to fight back against common antibiotics, a slew of biotechnology companies are working to develop ways to combat these “superbugs.”
San Diego’s Forge Therapeutics is among those targeting gram-negative bacteria, a type of bacteria that has a protective outer membrane that makes it especially resistant to drugs. Comparatively, gram-positive bacteria don’t have that extra membrane, and they’re easier to treat.
On Thursday, Forge announced it had been granted $5.7 million by public-private partnership CARB-X to evaluate treatments for serious lung infections caused by gram-negative bacteria, including multi-drug resistant P. aeruginosa, which the Centers for Disease Control and Prevention (CDC) has identified as one of the top 18 antibiotic resistance threats in the U.S.
Forge could later get up to $5.4 million more, based on the technical milestones it achieves. It’s the company’s second award from CARB-X, which funds research into and development of antibiotics and other antibacterial products.
CARB-X, based at Boston University’s School of Law, is putting more than $500 million toward innovation in antibacterial R&D. In addition to the university, the partnership is backed by organizations including the U.S. Department of Health and Human Services’ Biomedical Advanced Research and Development Authority, the National Institutes of Health, the Wellcome Trust, the California Life Sciences Institute, RTI, the Massachusetts Biotechnology Council, Boston University, the Bill & Melinda Gates Foundation, and the UK government.
The grant for Forge, which is developing medicines targeting metalloenzymes, a type of enzyme that contains a metal ion as part of its structure, is intended to support its development of inhibitors of LpxC, a zinc metalloenzyme found in the outer membrane of gram-negative bacteria. Forge says LpxC is an attractive target because it isn’t found in gram-positive bacteria or in human cells. Previous LpxC inhibitors evaluated by biopharma companies have been ineffective, and there are no FDA-approved therapeutics targeting LpxC, according to Forge. The company says it has made inhibitors of LpxC that are safe and effective in an animal model of gram-negative infection, and can destroy gram-negative superbugs that other antibiotics can’t. But Forge has a lot of work ahead to get the experimental products into clinical trials in humans and, if all goes well, eventually into the market.
[Updated to add more data about deaths from drug resistance.] According to the CDC, roughly 2 million people in the U.S. are diagnosed yearly with antibiotic-resistant infections, and about 23,000 die from those infections. That data is from 2013. An estimate published this month, however, puts the number of annual deaths from multidrug-resistant infections at more than 153,000—nearly sevenfold higher.
“The world urgently needs new classes of antibiotics, like those that Forge is developing, as well as other life-saving products to prevent, diagnose, and treat deadly infections,” said Kevin Outterson, CARB-X executive director and Boston University law professor, in a prepared statement about the grant.
Forge has other backers, too. It raised a $15 million Series A financing round led by MagnaSci Ventures, a Houston, TX-based investment fund, in 2017. The year prior, it established a “strategic alliance” with German drug discovery and development company Evotec.
Forge is headed by company co-founder Zachary Zimmerman, who previously held roles at San Diego-based Arcturus Therapeutics (NASDAQ: ARCT), Carlsbad, CA-based Regulus Therapeutics (NASDAQ: RGLS), Cambridge, MA-based Alnylam Pharmaceuticals (NASDAQ: ALNY), and Branford, CT-based 454 Life Sciences, which Roche acquired in 2007 for $140 million in cash.
Other companies are also aiming to tackle drug-resistant infections, including San Diego’s Zavante, which was working on an intravenous formulation of a currently available oral antibiotic when it was acquired in 2018 by Nabriva Therapeutics, and San Diego’s Qpex, which aims to develop new beta lactamase-blocking drugs to combine with proven antibiotics.