Direct Biologics LLC

AUSTIN, Texas--(BUSINESS WIRE)-- Direct Biologics LLC, a late-stage biotechnology company leveraging its regenerative medicine platform using extracellular vesicles (EVs) secreted from bone marrow-derived mesenchymal stem cells (BM-MSCs) to address multiple disease indications, announces favorable safety data and significant efficacy results from its Phase 2 clinical trial (NCT04493242) of ExoFlo™ in hospitalized adult COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS). These results were published in the June 2023 edition of the peer-reviewed medical journal CHEST in a paper titled “Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicle Infusion for the Treatment of Respiratory Failure from COVID-19: A Randomized Placebo Controlled Dosing Clinical Trial” by lead author Amy L. Lightner, M.D., Chief Medical Officer of Direct Biologics. “This prospective, double-blind, randomized, placebo-controlled Phase 2 trial is the first clinical study to show BM-MSC EVs are safe and exhibit potential for efficacy based on post-hoc subgroup analyses in the treatment of respiratory failure or ARDS related to COVID-19,” said Joe Schmidt, President and co-founder of Direct Biologics. “A critical finding of this study was the safety pro ExoFlo. There was a lack of adverse or serious adverse events in this very sick patient population. This overwhelming safety pro highly encouraging for our future development pathway in patients with ARDS.” This prospective Phase 2 multicenter, double-blind, randomized, placebo-controlled trial was conducted at five sites across the U.S. with infusions of placebo, 10 mL of ExoFlo or 15 mL of ExoFlo on Day 1 and Day 4. A total of 102 patients with COVID-19 associated moderate-to-severe ARDS were enrolled and randomized. Adverse events were documented throughout the trial period. The primary outcome measure was all-cause 60-day mortality rate. Secondary outcomes included time to death (overall mortality), the incidence of treatment-emergent serious adverse events, proportion of discharged patients at Day 7, Day 30 and Day 60, time to hospital discharge and ventilator-free days (VFDs). Over the duration of the clinical trial, no treatment-related adverse events were reported. The overall mortality rate among all subjects was 61.0%. For the post-hoc subgroup analyses, those with respiratory failure had a 60-day mortality of 50.0% in the placebo group and 19.2% in the ExoFlo-15 group, representing an absolute risk reduction of 30.8% and a relative risk of 0.385 (95%CI=0.159,0.931, p=0.0340). For those aged 18-65 years who met modified Berlin criteria for moderate-to-severe ARDS, the 60-day mortality was 72.7% in the placebo group and 30.8% in the ExoFlo-15 group, yielding an absolute risk reduction of 41.9% and a relative risk of 0.423 (95%CI=0.173,1.032, p=0.0588). For the 18-65 year age group, the number of VFDs in the ExoFlo-15 group was improved compared with placebo (47.6 days versus 30.3 days, respectively). In addition, a trend in dose response was observed for VFDs in both moderate and severe ARDS in this age group. Based on preliminary results previously demonstrated from ExoFlo, the FDA issued a regenerative medicine advanced therapeutic (RMAT) designation and also authorized proceeding with a double-blind, placebo-controlled Phase 3 clinical trial of ExoFlo for the treatment of all-cause ARDS. “Given the limited number of approved therapeutics with a proven mortality benefit, expedient results of our ongoing Phase 3 trial will be critical to the treatment of ARDS patients,” said Mark Adams, Chief Executive Officer and co-founder of Direct Biologics. “It is truly exciting to see a novel regenerative medicine platform technology with this safety record and potential to treat a patient population comprising 15% of all ICU patients, as well as any future pandemic where ARDS is a leading cause of mortality.” About Direct Biologics Direct Biologics is a late-stage biotechnology company leveraging a regenerative medicine platform which uses extracellular vesicles (EVs) secreted from bone marrow-derived mesenchymal stem cells to address multiple disease indications. Direct Biologics’ mission is to be the global leader in regenerative medicine through discovery, innovation, advancement of science, and treatment of patients in a safe and effective manner. Our therapeutic product candidate, ExoFlo, is designed to be a scalable, reproducible, and effective next-generation biologic that leverages our proprietary EV platform technology designed to reduce inflammation, modulate the immune system, and restore tissue through cellular regeneration. Direct Biologics is 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). In addition, the Company has initiated Phase 1 clinical trials with ExoFlo for the treatment of ulcerative colitis and Crohn’s disease, and expanded access trials in solid abdominal organ transplantation and severe ARDS patients. Direct Biologics intends to pursue additional clinical applications including a Phase 1b/2a clinical trial in medically refractory perianal fistulizing Crohn’s disease as well as in necrotizing enterocolitis. Headquartered in Austin, Texas, Direct Biologics also has an R&D facility in San Diego, California and an operations and order-fulfillment center in San Antonio, Texas. For more information, please visit and follow us on Twitter @directbiologics.

ExoFlo is the first extracellular vesicle therapeutic candidate to be evaluated in this indication AUSTIN, Texas--(BUSINESS WIRE)-- Direct Biologics LLC, a late-stage biotechnology company leveraging its regenerative medicine platform using extracellular vesicles (EVs) secreted from bone marrow-derived mesenchymal stem cells (MSCs) to address multiple disease indications, announces U.S. Food and Drug Administration (FDA) clearance of the Company’s investigational new drug (IND) application for a Phase 1b/2a clinical trial to evaluate the safety and efficacy of ExoFlo™ for the treatment of medically refractory perianal fistulizing Crohn’s disease (CD). “The expansion of our inflammatory bowel disease clinical program into perianal fistulizing Crohn’s disease underscores our commitment to providing treatment options to a patient population that suffers from chronic inflammatory disease,” said Mark Adams, Chief Executive Officer of Direct Biologics. “We look forward to the results of our Phase 1b/2a study given that ExoFlo is the first EV product candidate to be evaluated in this patient population.” The multicenter, single-blind, randomized, placebo-controlled trial is expected to enroll 36 patients with medically refractory perianal fistulizing CD. The trial will have three treatment arms with cohorts receiving escalating doses of ExoFlo. Patients will be monitored for safety and evaluated for efficacy using a combination of clinical examination and radiographic evaluation with pelvic MRI. The Phase 1b/2a clinical trial is designed to be a safety study with exploratory assessments of efficacy. The primary endpoint of the study is to evaluate the number of adverse events and serious adverse events of one 15 mL or 30 mL treatment or two treatments of 30 mL ExoFlo. The secondary endpoints include clinical and radiographic improvement, and the tertiary/exploratory endpoints are patient reported disease outcomes. The secondary endpoint of combined clinical and radiographic complete healing was selected based on previous clinical trials of MSCs in this phenotype of CD. The trial will also evaluate the efficacy of ExoFlo in fistulizing subtypes, including patients with proctitis and numerous fistula tracts. “FDA clearance to initiate this randomized trial of ExoFlo in perianal fistulizing Crohn’s disease marks a defining moment for patients suffering from this devastating phenotype that greatly diminishes quality of life. We believe ExoFlo to be a promising therapeutic candidate for fistulizing Crohn’s disease since it is designed as an off-the-shelf, cell-derived product with anti-inflammatory, immunomodulatory and tissue restoring properties,” said Amy Lightner, M.D., Chief Medical Officer of Direct Biologics. “We look forward to the prospect of providing a regenerative product used in everyday clinical practice for this critical unmet need.” About Perianal Fistulizing Crohn’s disease The prevalence of Crohn’s disease in the United States is approximately 200 per 100,000 adults and 46 per 100,000 children aged 2-17 years. One of the most severe manifestations of CD is fistulizing disease, developing in up to 50% of patients, particularly those with colonic and rectal involvement. These patients experience significant morbidity due to pain, persistent drainage, recurrent perianal sepsis and ongoing need to access medical care resulting in increased costs and impaired quality of life. Perianal fistulizing CD is notoriously difficult to cure with 37% of patients experiencing refractory disease and >90% undergoing multiple surgical interventions, putting them at risk of incontinence. The limited efficacy with available medical and surgical interventions is underscored by 20% of patients still undergoing a proctectomy with a permanent stoma. These results have spurred significant interest in identifying improved treatment options. About Direct Biologics Direct Biologics is a late-stage biotechnology company leveraging a regenerative medicine platform which uses extracellular vesicles (EVs) secreted from bone marrow-derived mesenchymal stem cells to address multiple disease indications. Direct Biologics’ mission is to be the global leader in regenerative medicine through discovery, innovation, advancement of science, and treatment of patients in a safe and effective manner. Our therapeutic product candidate, ExoFlo, is designed to be a scalable, reproducible, and effective next-generation biologic that leverages our proprietary EV platform technology designed to reduce inflammation, modulate the immune system, and restore tissue through cellular regeneration. Direct Biologics is 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). In addition, the Company has initiated Phase 1 clinical trials with ExoFlo for the treatment of ulcerative colitis and Crohn’s disease, and expanded access trials in solid abdominal organ transplantation and severe ARDS patients. Direct Biologics intends to pursue 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. For more information, please visit and follow us on Twitter @directbiologics.

Company’s Phase 3 EXTINGUISH ARDS trial is enrolling hospitalized patients with moderate-to-severe ARDS regardless of underlying etiology AUSTIN, Texas--(BUSINESS WIRE)-- Direct Biologics LLC, a late-stage biotechnology company leveraging its regenerative medicine platform using extracellular vesicles (EVs) secreted from bone marrow-derived mesenchymal stem cells to address multiple disease indications, announces favorable safety and efficacy data from its ExoFlo™ expanded access program in hospitalized adult COVID-19 patients with moderate-to-severe acute respiratory distress syndrome (ARDS). “We are pleased to report compelling findings from more than 100 patients with respiratory failure due to COVID-19 who were treated with ExoFlo as part of our expanded access program. 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,” said Mark Adams, Chief Executive Officer of Direct Biologics. “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 initiated a multicenter expanded access program in the United States of intravenous ExoFlo in hospitalized COVID-19 patients with moderate-to-severe ARDS, including patients with respiratory failure who were not eligible to participate in the Company’s Phase 2 or Phase 3 clinical trial. To date, 103 patients have been enrolled and treated in the program. Patients received 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, patients received simultaneous standard-of-care treatment for severe-to-critical COVID-19. All 103 enrolled subjects were evaluated as of February 2023. Upon review by an independent data safety monitoring board, no adverse events or serious adverse events were determined to be related to ExoFlo. No infusion reactions were observed, supporting the favorable safety pro this investigational product. The overall 60-day mortality rate was lower in patients younger than 65 years old compared with those 65-85 years old (22% and 42%, respectively). Further, patients younger than 65 were discharged from the hospital earlier and had more ventilator-free days than patients 65-85. “It is exciting to see the safety results in over 100 patients who typically were too sick to enroll in our Phase 2 or Phase 3 randomized control trials. I am encouraged by the potential ExoFlo holds as we eagerly await the results from our ongoing Phase 3 trial and look forward to the potential to save more lives afflicted with ARDS,” said Amy Lightner, M.D., Chief Medical Officer of Direct Biologics. Phase 3 EXTINGUISH ARDS trial The global multicenter randomized, double-blinded, placebo-controlled pivotal Phase 3 EXTINGUISH ARDS trial (NCT05354141) is designed to evaluate the safety and efficacy of ExoFlo for the treatment of hospitalized patients with moderate-to-severe ARDS from any underlying etiology. The trial is expected to enroll 320 patients ages 18-65. The trial will have two treatment arms with half of the enrolled patients receiving a placebo and half receiving up to three intravenous doses of ExoFlo-15 mL. All patients in both arms will receive standard of care. The primary endpoint of 60-day all-cause mortality was selected based on the significant survival benefit observed in the completed randomized Phase 2 clinical trial of ExoFlo. Secondary endpoints include ventilator-free days, oxygen-free days and ICU-free days, along with additional exploratory endpoints. In addition, the trial will evaluate the efficacy of ExoFlo in ARDS subtypes to better understand the disease process. In March 2022, ExoFlo received Regenerative Medicine Advanced Therapy (RMAT) designation from the U.S. Food and Drug Administration (FDA) for the treatment of severe or critical COVID-19, which provides opportunities to expedite ExoFlo’s clinical development for moderate-to-severe ARDS. About Direct Biologics Direct Biologics is a late-stage biotechnology company leveraging a regenerative medicine platform which uses extracellular vesicles (EVs) secreted from mesenchymal stem cells to address multiple disease indications. Direct Biologics’ mission is to be the global leader in regenerative medicine through discovery, innovation, advancement of science, and treatment of patients in a safe and effective manner. Our therapeutic product candidate, ExoFlo, is designed to be a scalable, reproducible, and effective next-generation biologic that leverages our proprietary EV platform technology designed to reduce inflammation, modulate the immune system, and restore tissue through cellular regeneration. Direct Biologics is 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). In addition, the Company has initiated Phase 1 clinical trials with ExoFlo for the treatment of ulcerative colitis and Crohn’s disease, and expanded access trials in solid abdominal organ transplantation and severe ARDS patients. Direct Biologics intends to pursue 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. For more information, please visit and follow us on Twitter @directbiologics.