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Schenectady biotech researcher wins $3M grant to fight E. coli

Schenectady biotech researcher wins $3M grant to fight E. coli

Schenectady firm is devising antibody technique to defeat drug-resistant strains
Schenectady biotech researcher wins $3M grant to fight E. coli
Facilities Manager, Steve Fikes with cultures in one of the lab areas at the Institute for Clinical Pharmacodynamics.
Photographer: MARC SCHULTZ/GAZETTE PHOTOGRAPHER

SCHENECTADY — A Schenectady biotech firm has received a $3 million grant to research a treatment for drug-resistant infections, and may get $6.2 million more if it demonstrates progress toward the goal.

Bravos BioSciences is receiving the money from CARB-X, a worldwide nonprofit partnership led by Boston University that is searching for a way to deal with the growing number of pathogens that can’t be killed with antibiotics.

Bravos is a new company that has the same ownership, leadership and quarters as the Institute for Clinical Pharmacodynamics, based on Broadway in downtown Schenectady for the last three years.

It’s looking for a way to use antibodies — germ killers created by the body’s immune system — rather than antibiotics to fight bacterial infections, in much the same way scientists have adapted antibodies to fight cancer cells. 

ICPD President Paul Ambrose said the goal is to develop external antibodies that can be administered to patients like a drug to attack the pathogens that are making them ill.

The target is a particularly virulent variety of Escherichia coli, or E. coli. Many varieties occur naturally in the gut and are harmless or even beneficial, unless they get into the bloodstream. Others when ingested cause severe abdominal distress, urinary tract infections and other problems.

In the infamous Capital Region outbreak 20 years ago this month, more than 1,000 people were sickened by E. coli O157:H7 traced to ground water from the Washington County Fairgrounds. One young child and one elderly man died, and several children sustained permanent kidney damage.

Bravos is targeting E. coli ST131-O25B.

“The main reason is because it’s a major cause of disease, second because so much of it has become drug-resistant,” Ambrose said.

“There are other drug-resistant strains but none so strong or lethal.”

Statistics show 80% of ST131-O25B infections are multidrug-resistant — 90% to fluoroquinolone and 65% to cephalosporins, the two preferred antibiotic treatments for E. coli infections.

The U.S. Centers for Disease Control and Prevention calls antibiotic resistance “one of the biggest public health challenges of our time,” noting that at least 2 million Americans contract an antibiotic-resistant infection each year and at least 23,000 die from it.

The major for-profit drugmakers and researchers have backed off antibiotic research because antibiotics are a short-term drug, which limits the financial return on the major investment to develop them, Ambrose said. Small pharmaceutical companies lack funding and/or go out of business with some regularity, he added.

The CARB-X grant lessens the financial risk for Bravos, whose subsidiary BB100 LLC is actually the recipient of the $3 million grant. It has to make a $1.3 million match, and would have a $2.7 match if it wins the $6.2 million follow-up CARB-X grant.

ICPD, formed in 2004 and previously based in Latham, has long conducted research on effective dosing of other companies’ drugs.

“We decided we wanted to go into it ourselves,” Ambrose said.

During the planning stages for the move, he told city officials his goal was to have a drug company based in downtown Schenectady, and that still is the goal. He said ICPD has gotten a lot of help from the city, Metroplex and Pioneer Bank along the way.

Bravos and BB100 were created to be spun off if needed to get a product to market more easily, should a product reach that stage of development.

Bravos applied for the grant more than a year ago, and underwent extensive vetting before winning the $3 million award.

“Patients urgently need new life-saving products and the BB100 approach represents a potential alternative to antibiotics to treat serious infections,” CARB-X Executive Director Kevin Outterson said in a release.

CARB-X calls itself the world’s largest antibacterial development effort, with 30 projects underway in five countries. It has awarded $130 million for 45 projects since its formation in 2016 and expects the total to reach $500 million by 2021.

Bravos has identified a cell line that produces a humanized antibody that defeats E. coli ST132-O25B. In simplified terms, the challenge now is to genetically modify and multiply the cell line to produce usable quantities of the antibody, then determine what dosage would be both safe and effective.

The hope is to start human testing within three years, Ambrose said.

Behind the facade at 242 Broadway, which is marked only “ICPD” without any further hint what goes on inside, about 30 people are working behind two layers of locked doors, including physicians, doctoral-level pharmacists and researchers, lab technicians and support staff.

It’s a biosafety level 2 facility, Ambrose said, with sanitary precautions such as negative air pressure lab space.

A BSL-3 facility would have enhanced safety measures for researching diseases such as tuberculosis, while the handful of BSL-4 labs around the world are designed for safely analyzing super-pathogens such as the Ebola virus.

The BSL-2 lab at ICPD handles some fairly nasty pathogens, but not exotic ones — they are commonly found in humans and animals in this part of the world. 

This new E. coli grant, however, is a source of pride and excitement, Ambrose said.

“This is singular,” he said. “If it works, a lot a lot of patients are going to benefit. It will be paradigm-changing.”

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