BioBuzz by Workforce Genetics

BioFactura Receives BARDA Funding for Smallpox Antibody

For more than 40 years, smallpox has not been a viral concern for the world. No cases have naturally occurred since 1977. Despite that, government agencies are worried that smallpox could become a biological weapon in the hands of terrorists and rogue states and are making preparations for such a scenario by stockpiling old medications that have been successful, as well as new, experimental therapies.

One of those experimental therapies is an antibody being developed by Frederick, Maryland-based BioFactura. Recently, the company announced the activation of a $16 million option from the Biomedical Advanced Research and Development Authority (BARDA) to support development and filing of an Investigational New Drug Application for the antibody cocktail, which targets both the variola virus—the virus that causes smallpox, as well as monkeypox, which has recently been reported in several states as well as in multiple countries. This latest option is part of BioFactura’s prime contract awarded in 2019 and valued at up to $68.2 million for the advanced development of a smallpox biodefense therapeutic.

Darryl Sampey, BioFactura President and CEO

Smallpox is a contagious disease caused by the variola virus. It is estimated to have killed millions of people over the centuries it has been around. The last known natural case occurred in Somalia in 1977. In 1980 WHO declared smallpox eradicated, and it has remained the only infectious disease to achieve this designation. However, for years, there have been concerns that the virus can be used as a biological weapon. It’s this fear that prompted the government and BioFactura to work on developing effective countermeasures.

Currently there are a handful of drugs used to combat smallpox, including Tpoxx (tecovirimat), which is effective against wild-type smallpox virus. Approved in 2018, Tpoxx was the first drug specifically indicated for smallpox. Tembexa (brincidofovir) has also been approved for treatment of smallpox. There are also vaccines authorized to prevent smallpox infections; however, these medications have some safety concerns. While these drugs have been approved, it is possible that bioterrorists could engineer a smallpox virus to be resistant to these medications. And that’s why additional measures such as BioFactura’s antibody-based therapeutic are so necessary.

Dr. Darryl Sampey, President and Chief Executive Officer of BioFactura, said the funds from the grant will support animal tests with the monkeypox virus in non-human primates, the gold standard model for human smallpox. Animals that are infected with the virus will be given doses of increasing strengths in order to determine an effective dose. Other activities include scaled-up manufacturing of the product and toxicology studies. Once dosing and safety are understood, a first-in-humans Phase I study can be conducted. Such a study is expected to be initiated in 2024.

BioBuzz Emily Whitehead Foundation

Sampey explained that under the U.S. Food and Drug Administration’s Animal Rule, monkeypox is relied upon as a surrogate disease for smallpox in humans. The regulatory rule allows for the approval of drugs and licensure of biological products when human efficacy studies are not ethical, such as infecting humans with a deadly virus like smallpox that has a 30% fatality rate. Tembexa and Tpoxx were approved under the Animal Rule.

Dr. Jeffrey Hausfeld, Chief Medical Officer and Chairman of the BioFactura Board of Directors, added that the protocols of the Phase 1 trial will allow for the comparing of data to the monkey studies in order to extrapolate efficacy in humans. At the end of the Phase 1 study, the pharmacokinetics and pharmacodynamics will be compared to the animal study in order to properly gauge the efficacy of the antibody cocktail in humans who could become infected with smallpox should an outbreak or attack occur. If the studies achieve the desired endpoints, BioFactura will be positioned to sell the product to the U.S. government to be included in the stockpile of essential medications.

“To be fully approved as a therapeutic for smallpox, the product has to go through standard clinical phases. But there is another path with Emergency Use Authorization,” Sampey said. He noted that a sale to the government is allowed to happen under a pre-Emergency Use Authorization model that is often used in biodefense. “This is a significant milestone for us to have actual procurement and purchasing of the product.”

“BARDA has been an excellent partner on this journey,” Hausfeld said. “We have worked with them in a collaborative and scientific manner that has moved the program forward to the IND-enabling phase.”

While the antibody product is being developed as a countermeasure to a potential outbreak of smallpox from biological attack, because of its significant efficacy signs against monkeypox, the drug could become an important tool to combat the recent outbreaks.

“Because of its unique characteristics and ability to treat monkeypox, this will also be of interest to allied countries around the globe who want to have this in their stockpiles,” Sampey said.