ROCKVILLE, Md.—Synthetic Biologics Inc., which specializes in therapeutics that preserve the microbiome, shared positive data in late April for SYN-005, its orphan drug program for the prevention and treatment of pertussis (whooping cough). SYN-005 combines hu1B7 and hu11E6, two highly synergistic humanized monoclonal antibodies, to target and possibly inactivate the pertussis toxin that causes disease symptoms. The company was granted Orphan Drug designation for SYN-005 for the treatment of pertussis in September 2014 by the FDA.
Synthetic Biologics evaluated the compound in a nonhuman primate study designed to test if administration of hu1B7, one component of SYN-005, at two days of age could protect animals from a pertussis infection. Pertussis is caused by the Bordetella pertussis bacteria.
In the study, control animals infected with B. pertussis at five weeks of age showed significant increases in white blood cell counts, with most also demonstrating symptoms of pertussis, such as coughing and diminished activity. The animals treated with hu1B7 at two days of age and then infected five weeks later presented with markedly lower peak white blood cell counts that stayed within normal ranges or were only slightly elevated. All seven of the animals that were administered hu1B7 appeared healthy and displayed no behavioral signs of disease.
One additional animal was treated with hu1B7 at two days of age, though for this case, infection with B. pertussis was delayed until hu1B7 could no longer be detected in the blood. In the absence of hu1B7, the animal developed a high white blood cell count and behavioral signs of pertussis.
In light of the animal study results, Synthetic Biologics has initiated preclinical testing of a modified version of hu1B7 that could extend the plasma half-life and substantially reduce the required dose of SYN-005. The company also previously reported that the compound had proved highly efficacious as a therapeutic in non-human primates infected with B. pertussis.
“We are greatly encouraged by these results, which clearly demonstrate hu1B7, a humanized anti-pertussis toxin monoclonal antibody, protected neonatal primates from developing pertussis for at least five weeks,” said Dr. Jennifer Maynard, associate professor in the McKetta Department of Chemical Engineering at the University of Texas at Austin. “These data give us increased confidence that pertussis prophylaxis using hu1B7 may be a viable option to protect newborns for several months after birth when the risk of pertussis mortality is highest.”
Synthetic Biologics is developing SYN-005 through its Exclusive Channel Collaboration with Intrexon Corp. and researchers led by Maynard. The goal of the collaboration is the prevention of pertussis in at-risk newborns and a method for targeting and neutralizing the pertussis toxin in hopes of reducing morbidity and mortality in infected infants. In 2015, UT Austin received a grant from The Bill & Melinda Gates Foundation to generate preclinical proof-of-concept data to test the hypothesis that antibody administration at birth could be a tactic for preventing pertussis. Maynard is principal investigator of the 2015 grant and this prophylaxis study.
Pertussis is highly contagious and can be fatal in infants and children. Symptoms include chronic coughing and breathing difficulties. The World Health Organization estimates that there are 50 million cases of whooping cough globally each year, and that an estimated 300,000 die from this condition, primarily young, unvaccinated infants.
“There is a pressing need for new and innovative agents to address the re-emergence of pertussis as a rising global health concern, particularly in the developing world where the mortality rate for at-risk newborns is highest,” said Jeffrey Riley, Synthetic Biologics president and CEO. “Positive results from this non-human primate study suggest that SYN-005 may be able meet this need by preventing pertussis infection among high risk individuals. These data, along with those from our earlier therapeutic studies, provide strong support for advancing SYN-005 to clinical trials for both the prevention and treatment of pertussis, especially in newborns.”
In similarly encouraging news, the company announced on May 11 that the FDA had awarded a Breakthrough Therapy designation for SYN-004 for the prevention of Clostridium difficile infection. The compound is a first-in-class oral enzyme designed to protect the gut microbiome from being disrupted by certain intravenous beta-lactam antibiotics. This special designation is based on a Phase 2b clinical trial in which SYN-004 met its primary endpoint of markedly reducing C. diff. infection.