Direct Biologics has received approval from FDA that it may proceed with a Phase II trial under an Investigational New Drug (IND) application for the use of ExoFlo?, a bone marrow-derived extracellular vesicle and exosome product, in the treatment of COVID-19 associated Acute Respiratory Distress Syndrome (ARDS). The ExoFlo Infusion Treatment for COVID-19 (EXIT COVID-19) Associated ARDS trial will be a multi-center, double-blind, randomized, placebo-controlled clinical trial.

Direct Biologics believes that this study is the first and only Phase II IND trial utilizing bone marrow-derived extracellular vesicles to treat SARS-CoV-2 (COVID-19) related ARDS. Extracellular vesicles are naturally occurring vesicles produced by most eukaryotic cells and are the primary mode of intercellular paracrine signaling. The population of extracellular vesicles secreted by bone marrow-derived mesenchymal stem cells (bmMSCs) have been studied extensively in preclinical studies for inflammation, and these studies suggest that they may have the ability to downregulate inflammation and upregulate tissue repair in humans.

"We are pleased the FDA has approved Direct Biologics to proceed with our study in the treatment of severe COVID-19 infections. In addition to its promise in treating COVID-19, the ongoing clinical and scientific research suggests that our proprietary advanced biotechnology platform has the potential to be part of a new class of medicine that may generate positive medical outcomes for patients," Mark Adams, Co-Founder and Chief Executive Officer of Direct Biologics, said. "We are also very grateful for the steadfast support of Congressman Michael McCaul, U.S. Representative for his congressional district in Texas. Through his leadership, vision, and support of Direct Biologics, Congressman McCaul has been and continues to be an integral part of the quest to bring a real solution for patients suffering from COVID-19."

"The study of bone marrow-derived stem cell extracellular vesicles as a treatment for acute lung disease has been a topic of great interest among the medical community for years," said Direct Biologics Co-Founder and President, Joe Schmidt. "We are excited to conduct this potentially ground-breaking study and hope the findings will help in the fight to defeat COVID-19. Furthermore, we are pleased with the collaborative spirit, diligence, and responsiveness of the FDA during the IND application process. We are grateful for the ability to proceed with EXIT COVID-19. Proceeding to a Phase II clinical trial reflects the significant efforts of Direct Biologics to develop a meaningful therapy for COVID-19 and to establish controls necessary for current Good Manufacturing Practice."

The EXIT COVID-19 study will enroll 60 COVID-19 patients with moderate-to-severe ARDS at three research sites across the U.S. The primary efficacy endpoints will be all-cause mortality and median days to recovery. Direct Biologics expects to commence patient enrollment in the next 30 days.

This Phase II investigational study will expand upon previous findings from a prospective, open-label safety and efficacy study of ExoFlo, which was led by New York City physician Vikram Sengupta, MD, in collaboration with Sascha Sengupta, MD, and Angel Lazo, Jr, MD. In that trial, 24 critically ill patients with moderate to severe ARDS caused by COVID-19, many of them entering or in the midst of the destructive inflammatory state known as cytokine storm, were treated with a single intravenous dose of ExoFlo. This initial COVID-19 study had promising safety and efficacy data, and it appeared to be well tolerated. It was published in a special issue of Stem Cells and Development this past June.

ExoFlo is an investigational new drug that has not been approved or licensed by FDA. It is an allograft extracellular vesicle product isolated from human bone marrow mesenchymal stem or stromal cells (MSCs). ExoFlo provides signaling proteins that have been shown to modulate inflammation and may stimulate bioactivity and direct cellular communication.