A Boston University School of Law (LAW)–based public-private partnership to spur the development of new antimicrobials awarded $24 million to 11 biotech companies and research teams in the United States and the United Kingdom on March 30, 2017, for their work on urgently needed new antibiotics and diagnostics aimed at drug-resistant superbugs. The same day, Wellcome Trust, a global charitable foundation headquartered in London, pledged $155 million over five years to BU for the partnership—called Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator, or CARB-X—bringing its total funding to $450 million.
Kevin Outterson, CARB-X executive director and principal investigator, says the projects “are in the early stages of research, and there is always a high risk of failure. But if successful, they hold exciting potential in the fight against the deadliest antibiotic-resistant bacteria.”
Outterson, a LAW professor of law and a researcher in pharmaceutical markets, announced the 11 awardees—representing the nonprofit partnership’s first round of grants and including five Boston-area companies—at an event at the Washington office of Pew Charitable Trusts. The Wellcome Trust contribution was announced at the same event.
“Drug-resistant infection is already a huge global challenge—and it’s getting worse,” says Tim Jinks, Wellcome Trust head of drug resistant infection. “Without effective drugs, doctors cannot treat patients. Through CARB-X, we are filling the void for early discovery support. And with this first portfolio, we have taken bold decisions to ensure a broad range of approaches to finding new ways to treat and diagnose resistant infection.”
“We are deeply honored that Wellcome Trust chose Boston University for this groundbreaking gift,” says Outterson, LAW’s N. Neal Pike Scholar in Health and Disability Law. “The vast majority of these funds will directly fund cutting-edge research coordinated by BU.”
Identified by the World Health Organization (WHO) and the Centers for Disease Control and Prevention (CDC) as one of the greatest threats to public health worldwide, antibiotic resistance each year kills an estimated 23,000 Americans and 700,000 people worldwide. Even while the pace of resistance is outstripping the supply of new drugs, the lack of a clear financial reward has led the pharmaceutical industry to all but abandon the development of new antibiotics. CARB-X, which launched in July 2016 and is the world’s largest public-private partnership focused on antibiotics, is a joint project of the BU School of Law, the US Department of Health and Human Services (HHS), the HHS Biomedical Advanced Research Authority (BARDA), and the National Institute of Allergy and Infectious Diseases (NIAID) in the United States, and Wellcome Trust in the United Kingdom. BARDA has committed up to $250 million over five years. NIAID is committing to $50 million in preclinical services.
“NIAID welcomes the opportunity to lend its preclinical expertise to the new CARB-X awardees and work with our partners to find and develop a new generation of safe and effective antibiotics,” says NIAID director Anthony S. Fauci.
“With CARB-X, we built on our track record of innovative partnerships to enhance national security preparedness for chemical, biological, radiological, and nuclear threats,” says Rick Bright, director of BARDA. CARB-X has begun “accelerating novel antibacterial products and technologies from early stage development toward the clinic. This portfolio will ensure that the United States and the world are better prepared to treat drug-resistant bacterial infections.”
If the 11 awardees successfully reach a series of milestones, CARB-X will award them up to $24 million in additional payments over three years. The companies themselves will contribute varying amounts of money to their projects; those funds total an additional $26 million.
The companies CARB-X awarded were selected from among 168 US and international applicants by the partnership’s scientific advisory board, whose members include scientists from all over the world. The board is led by physician scientist and former Cubist Pharmaceuticals executive Barry I. Eisenstein, who helped lead the Food and Drug Administration (FDA) approval process for Cubicin (daptomycin), among the most successful antibiotics for life-threatening infections caused by drug-resistant bacteria, like MRSA (methicillin-resistant Staphylococcus aureus), in the last 25 years.
For the most part, the 11 CARB-X grantees are small companies with limited access to funding. “These people are starving for money,” Outterson says.
One of them, San Diego’s two-year-old Forge Therapeutics, Inc., a seven-person biopharmaceutical company that is developing a novel antibiotic, managed to raise $5.5 million in seed money. CARB-X will give Forge $4.8 million over 15 months to accelerate its work, and potentially up to $4 million over the following 18 months. “We’ve got a chemistry solution that pharma’s been working on for 20 years,” says chemist and microbiologist Zach Zimmerman, Forge CEO. “This nondiluted money from CARB-X is going to rapidly advance our program. The stamp of approval from CARB-X also provides scientific validation.”
Along with the others awarded in this first round, Forge went through an exhaustive screening process by the CARB-X scientific advisory board. To be considered for funding, projects must target one of the deadly antibiotic-resistant bacteria on the CDC’s Serious or Urgent Threat List or on the WHO Priority Pathogens List.
In the first year, the CARB-X portfolio priorities are weighted towards Gram-negative bacteria, which are resistant to multiple drugs and can cause infections such as pneumonia, surgical site infections, and meningitis in health care settings, and towards nontraditional approaches.
“You’ve seen the TV show Shark Tank?” Zimmerman says. The CARB-X screening process his company underwent “was a little like that. There were short applications, long applications, face-to-face meetings. You had people with 30, 40 years of experience in pharmaceuticals reading your application, going through not just your science, but your personnel.”
And according to Outterson: “We wanted it to be the most rigorous screening process in the world.”
One of the UK awardees, Proteus IRC, is developing technology to rapidly visualize bacteria and the host response in the deepest part of human lungs. “The CARB-X award opens up a lot of opportunities,” says Mark Bradley, a Proteus director and principal investigator. “It’s like becoming part of a big family.” He says his team is looking forward to working with scientists at CARB-X partner institutions. “This offers us a lot of expertise,” he says. “We haven’t taken things into big clinical trials before. We’re hoping this will open up a large-scale repository of knowledge.”
Proteus and the other CARB-X awardees have to commit to being “good stewards” of the molecules they develop, Outterson says, so they are not wasted through inappropriate use—in agriculture, for example—and so that global access is provided. “They can’t plan to just sell it in high-income countries and ignore sub-Saharan Africa,” he says. “We’re not going to tell them how to do that, but we are requiring them to come up with a plan and that plan will be published on our website.”
Forge is one of three companies getting funding from CARB-X that are working on the development of what would be new classes of antibiotics aimed at superbugs—or Gram-negative bacteria. Another four are working on novel approaches to combating superbugs. The last new class of antibiotics aimed at superbugs to make it through the regulatory process and reach consumers was developed in 1962. “If any one of those seven makes it all the way to FDA approval,” Outterson says, “they would be considered one of the most innovative things we’ve seen since 1962. Multiple groups of people are chasing new classes of antibiotics, but no one has made it to the finish line since 1962.”
CARB-X aims to award $450 million to develop innovative antimicrobials, diagnostics, and vaccines over the next four years, with the goal of accelerating the preclinical discovery and development of at least 20 antibacterial projects—and of advancing at least 2 new projects into human trials. As with the other funding, the $155 million from Wellcome Trust will go directly to BU, which is responsible for its distribution.
Other CARB-X partners include the Broad Institute of MIT and Harvard, the Massachusetts Biotechnology Council (MassBio), the California Life Sciences Institute (CLSI), RTI International, and the UK’s Antimicrobial Resistance Centre (AMR).
Cidara Therapeutics, Inc., San Diego, Calif. $3.9M over 13 months, and potentially up to $3M in the following 11 months.
ContraFect Corporation, Yonkers, N.Y. $1.1M over 15 months, and potentially up to $1.1M in the following 9 months.
Entasis Therapeutics, Inc., Waltham, Mass. $2.1M over 9 months, and potentially up to $4.2M in the following 12 months.
Forge Therapeutics, Inc., San Diego, Calif. $4.8M over 15 months, and potentially up to $4M in the following 18 months.
Microbiotix, Inc., Worcester, Mass. $1.6M over 12 months, and potentially up to $1.6M in the following 12 months.
Oppilotech, Ltd., London, United Kingdom. $120,000 over six months.
Proteus IRC., Edinburgh, Scotland. $640,000 over 21 months, and potentially up to $480,000 in the following 20 months.
Redx Pharma Plc., Alderley Park, United Kingdom. $1M over 18 months.
Spero Therapeutics LLC., Cambridge, Mass. $1.6M over 12 months, and potentially up to $5.4M in the following 24 months.
Tetraphase Pharmaceuticals Inc., Watertown, Mass. $4M over 18 months.
Visterra, Inc., Cambridge, Mass. $3M over 12 months, and potentially up to $4.2M in the following 12 months.