ExoFlo™ Expanded Access Program Exceeds 100 Subjects: Compelling Data Emerges in Hospitalized COVID-19 Patients with Moderate-to-Severe ARDS

Direct Biologics LLC, a late-stage biotechnology company utilizing its regenerative medicine platform with extracellular vesicles (EVs) secreted from bone marrow-derived mesenchymal stem cells, is pleased to announce the successful results of its ExoFlo™ expanded access program in treating hospitalized adult COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS). The data showed favorable safety and efficacy outcomes, demonstrating the potential of EVs to treat this serious condition.

Direct Biologics is thrilled to announce remarkable results from its expanded access program, in which over 100 critically-ill COVID-19 patients with respiratory failure were treated with ExoFlo, the first regenerative medicine product candidate to demonstrate this level of tolerability. This breakthrough could be a major step towards combating the disease and its associated pulmonary complications.

Mark Adams, Chief Executive Officer of Direct Biologics, said, “We believe ExoFlo is the first regenerative medicine product candidate to demonstrate this level of tolerability in patients who are critically ill with COVID-19 associated ARDS. The potential for ExoFlo to treat critically ill patients with COVID-19 associated pulmonary complications represents a powerful advancement in our efforts to combat this disease.”

In January 2021, Direct Biologics launched a multi-center Expanded Access Program in the United States, offering intravenous ExoFlo to hospitalized COVID-19 patients with moderate-to-severe ARDS and respiratory failure, who otherwise could not participate in the Company’s Phase 2 or Phase 3 clinical trials. The program has already seen great success, with 103 patients receiving a 60-minute infusion of ExoFlo-15 mL diluted to 100 mL in normal saline up to three times over the course of one week, in addition to standard-of-care treatment.

ExoFlo, an investigational product, appears to be safe and effective for all 103 enrolled subjects evaluated as of February 2023. An independent data safety monitoring board confirmed that no adverse events or serious adverse events were related to ExoFlo, with no infusion reactions reported.

Notably, the mortality rate for patients younger than 65 years old was significantly lower than those 65-85 at 22% and 42%, respectively. Moreover, patients younger than 65 were able to leave the hospital sooner and had more ventilator-free days. These findings suggest that ExoFlo could be a promising treatment option for older adults.

The potential of ExoFlo to save lives afflicted with ARDS is truly inspiring. With over 100 patients already showing promising safety results, we are eagerly awaiting the results of our ongoing Phase 3 trial. As Chief Medical Officer of Direct Biologics, I am encouraged by the potential of ExoFlo to make a difference and am looking forward to the potential to save even more lives.


The EXTINGUISH ARDS trial (NCT05354141), an innovative, multicenter, randomized, double-blinded, placebo-controlled Phase 3 trial, is set to investigate the safety and efficacy of ExoFlo for the treatment of moderate-to-severe ARDS in hospitalized patients of all ages and backgrounds.

This ground-breaking trial will enroll 320 patients, with half receiving a placebo and the other half receiving up to three intravenous doses of ExoFlo-15 mL, along with standard of care. With the potential to improve the lives of those affected by ARDS, this pivotal trial is an exciting step in the right direction.

In March 2022, ExoFlo received the prestigious Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA) for the treatment of severe or critical COVID-19. This opens up opportunities to accelerate the clinical development of ExoFlo for moderate-to-severe ARDS.

The primary endpoint of the completed randomized Phase 2 clinical trial of ExoFlo was 60-day all-cause mortality due to its significant survival benefit. Secondary endpoints included ventilator-free days, oxygen-free days and ICU-free days, along with additional exploratory endpoints. Moreover, the trial will assess the impact of ExoFlo on ARDS subtypes in order to gain a better understanding of the disease process.

About Direct Biologics

Direct Biologics is revolutionizing regenerative medicine with a cutting-edge platform that utilizes extracellular vesicles (EVs) secreted from mesenchymal stem cells. Our therapeutic product candidate, ExoFlo, is designed to reduce inflammation, modulate the immune system, and restore tissue through cellular regeneration.

We are currently conducting the global Phase 3 EXTINGUISH ARDS clinical trial of ExoFlo for the treatment of hospitalized adults with moderate-to-severe acute respiratory distress syndrome (ARDS). We are also exploring a range of additional clinical applications, including perianal fistulizing Crohn’s disease and necrotizing enterocolitis.

Headquartered in Austin, Texas, Direct Biologics also has an R&D facility at the Center for Novel Therapeutics on the campus of University of California at San Diego, and operations and order-fulfillment center in San Antonio, Texas. We are striving to be the world leader in regenerative medicine, discovering, innovating, and advancing science to safely and effectively treat patients.

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