The Biomedical Advanced Research and Development Authority (BARDA) is a division of the U.S. Department of Health and Human Services (HSS) and awards civilian R&D contracts.

One interesting contracted recently awarded in February, 2021 is an additional $13 million on top of an original payment of $9.5 million to BioFactura of Frederick, MD to continue development of a smallpox biodefense therapeutic.

BioFactura develops and manufactures high-value biosimilars, biodefense medical countermeasures, and client-selected novel drugs. For this contract, it met the initial milestone of successfully developing a monoclonal antibody and plans to use additional funds for manufacturing of the antibody and begin phase I trials with input from the FDA.

Funding of our first option confirms the commitment of BARDA to support development of this important product. We look forward to continuing our close collaboration with BARDA’s program and technical groups as we move into manufacturing and the regulatory pathway to FDA approval. -- Dr. Darryl Sampey, President and CEO of BioFactura

What is Smallpox? It is an infectious disease caused by the Variola virus and spreads by direct contact. Initial symptoms begin about 1-2 weeks after infection and include fever, headache, as well as whole body aches and pains. Soon after, a rash consisting of small pink bumps starts to spread until these bumps fill up with pus, crust over, and then scar the skin. This infection can lead to corneal ulcerations, blindness, and even brain inflammation. Thirty percent of those infected died. It was a devastating disease killing more than 300 million people in the 20th century, and those who survived had life-long scars.

Traces of smallpox pustules found on the head of the 3000-year-old mummy of the Pharaoh Ramses V. Photo courtesy of World Health Organization (WHO)

The origin is unknown and it is assumed to have been around for at least 3000 years. While Egyptian mummies were found to have smallpox, the earliest written accounts come from China in the 6th Century CE which spread to Africa and then Europe in the 18th century. In 1796, an English doctor by the name of Edward Jenner noticed that milkmaid previously infected with cowpox were immune to smallpox. As any good doctor without federal oversight, he experimented by injecting cowpox into the 9 year old son of his gardener to see if he would become immune to smallpox. It worked! and in 1801 the famous doctor went on to publish the original manuscript on vaccination called "On the Origin of the Vaccine Inoculation.” Since then, the cowpox was replaced with another pox virus that was more easily reproduced called Vaccinia virus as the ingredient of the smallpox vaccine.

Why produce an antibody for Smallpox? Smallpox was successfully eradicated or more accurately declared eradicated by the World Health Organization in 1980 but a foreshadowing twist of events led to two locations officially storing and handling variola virus for research purposes

1. Centers for Disease Control and Prevention in Atlanta, Georgia, and

2. State Research Center of Virology and Biotechnology (VECTOR Institute) in Koltsovo, Russia

So it was no surprise that if the virus still exists, the risk of bioterrorism will always be there. With funding from BARDA, Siga Technologies recieved FDA approval in 2018 for TPOXX (Tecovirimat), a smallpox treatment. The efficacy was tested on animals and that was sufficent under the FDA's Animal Rule (when the it's unethical to test efficacy on humans) and safety was evaluated in 359 healthy human volunteers. Tecovirimat is an antiviral against the orthopox family of viruses that works by blocking transmission of the virus to other cells. The US already has 1.7 million doses in stockpile and actively increasing that amount.

The funding to BioFactura is to manufacture a complementary therapeutic to fight against drug resistance of the Variola Virus (VARV) by giving patients a boost of antibodies.

**This project has been funded in whole or in part with federal funds from the Department of Health and Human Services; Office of the Assistant Secretary for Preparedness and Response; Biomedical Advanced Research and Development Authority, under Contract No. 75A50119C00054.