ExoFlo (bone marrow-derived extracellular vesicle and exosomes) / Direct Biologics - LARVOL DELTA

Study of ExoFlo for the Treatment of Medically Refractory Crohn's Disease (clinicaltrials.gov) - P1 | N=3 | Terminated | Sponsor: Direct Biologics, LLC | N=10 ➔ 3 | Active, not recruiting ➔ Terminated; Enrollment challenges.

Enrollment change • Trial termination • Colon Cancer • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammation • Inflammatory Bowel Disease

Study of ExoFlo for the Treatment of Perianal Fistulas (clinicaltrials.gov) - P1/2 | N=5 | Terminated | Sponsor: Direct Biologics, LLC | N=36 ➔ 5 | Active, not recruiting ➔ Terminated; Enrollment challenges.

Enrollment change • Trial termination • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

Study of ExoFlo for the Treatment of Medically Refractory Ulcerative Colitis (clinicaltrials.gov) - P1 | N=4 | Terminated | Sponsor: Direct Biologics, LLC | N=10 ➔ 4 | Active, not recruiting ➔ Terminated; Enrollment challenges.

Enrollment change • Trial termination • Colon Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

ExoFlo™ Infusion for Post-Acute COVID-19 and Chronic Post-COVID-19 Syndrome (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Direct Biologics, LLC | N=60 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • CRP

Unlocking the promise of mesenchymal stem cells and extracorporeal photopheresis to address rejection and graft failure in intestinal transplant recipients. (PubMed, Hum Immunol) - "Both ECP and EVs present novel opportunities to address graft rejection and inflammation in bowel transplant recipients. More work will be needed to define the optimal therapeutic parameters for each treatment modality."

Journal • Inflammation • Pediatrics • Transplant Rejection • Transplantation • CRP

Study of ExoFlo for the Treatment of Perianal Fistulas (clinicaltrials.gov) - P1/2 | N=36 | Active, not recruiting | Sponsor: Direct Biologics, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

Study of ExoFlo for the Treatment of Medically Refractory Crohn's Disease (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Direct Biologics, LLC | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Jul 2024 ➔ Dec 2024

Enrollment closed • Trial completion date • Trial primary completion date • Colon Cancer • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Immunology • Inflammation • Inflammatory Bowel Disease

EXIT-ARDS: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for ARDS (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Direct Biologics, LLC | N=81 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Study of ExoFlo for the Treatment of Medically Refractory Ulcerative Colitis (clinicaltrials.gov) - P1 | N=10 | Active, not recruiting | Sponsor: Direct Biologics, LLC | Recruiting ➔ Active, not recruiting | Trial completion date: Sep 2024 ➔ Dec 2024 | Trial primary completion date: Jul 2024 ➔ Dec 2024

Enrollment closed • Trial completion date • Trial primary completion date • Colon Cancer • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

ExoFlo™ Infusion for Post-Acute COVID-19 and Chronic Post-COVID-19 Syndrome (clinicaltrials.gov) - P1/2 | N=60 | Not yet recruiting | Sponsor: Direct Biologics, LLC | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Nov 2023 ➔ Nov 2024

Trial completion date • Trial primary completion date • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • CRP

Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS) (clinicaltrials.gov) - P3 | N=970 | Recruiting | Sponsor: Direct Biologics, LLC | Trial completion date: Aug 2024 ➔ Aug 2025 | Trial primary completion date: Mar 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Safety and Efficacy of Intravenous ExoFlo in the Treatment of Complex Regional Pain Syndrome. (PubMed, Pain Physician) - "IV delivery of ExoFlo appears safe in patients with CRPS. In addition, ExoFlo exhibited efficacy in addressing CRPS symptoms. Given the lack of effective and safe treatments available to CRPS patients, these results suggest that further studies are warranted to explore and validate this potential treatment for CRPS."

Journal • Inflammation • Musculoskeletal Pain • Pain

Treatment of idiopathic facial paralysis (Bell's Palsy) and secondary facial paralysis with extracellular vesicles: a pilot safety study. (PubMed, BMC Neurol) - "All seven patients enrolled in the study improved with this treatment protocol. After the second week of treatment, we saw a progression of independent motion of the affected eyelid, brow motion, and commissure. Although all patients began at different House-Brackman starting points, almost all ended at the same endpoint on the scale over the same period of time - four weeks. No adverse effects were encountered. Clearly, the duration of the treatment protocol needs to be longer than one month. The pathomechanism is still unknown. But it appears that the mechanism is reversible. At last, these patients can have hope."

Journal • CNS Disorders • Pain

Study of ExoFlo for the Treatment of Perianal Fistulas (clinicaltrials.gov) - P1/2 | N=36 | Recruiting | Sponsor: Direct Biologics, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

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. (PubMed, Chest) - "ExoFlo (15 mL dose) is safe in patients with severe or critical COVID-19 respiratory failure. In participants aged 18 to 65, the risk reduction in 60-day mortality was further improved from all aged subjects in the ITT population after two doses of 15 mL of ExoFlo as compared to placebo."

Journal • Acute Respiratory Distress Syndrome • Immune Modulation • Infectious Disease • Novel Coronavirus Disease • Pulmonary Disease • Respiratory Diseases

Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (EXTINGUISH ARDS) (clinicaltrials.gov) - P3 | N=970 | Recruiting | Sponsor: Direct Biologics, LLC | N=320 ➔ 970

Enrollment change • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

EXIT-ARDS: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for ARDS (clinicaltrials.gov) - P1/2 | N=81 | Not yet recruiting | Sponsor: Direct Biologics, LLC | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Sep 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Study of ExoFlo for the Treatment of Perianal Fistulas (clinicaltrials.gov) - P1/2 | N=36 | Not yet recruiting | Sponsor: Direct Biologics, LLC

New P1/2 trial • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Immunology • Inflammatory Bowel Disease

Direct Biologics Receives FDA Clearance to Initiate Phase 1b/2a Clinical Trial of ExoFlo in Patients with Medically Refractory Perianal Fistulizing Crohn’s Disease (Businesswire) - "Direct Biologics, LLC...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 multicenter, single-blind, randomized, placebo-controlled trial is expected to enroll 36 patients with medically refractory perianal fistulizing CD."

IND • Crohn's disease • Immunology • Inflammatory Bowel Disease

EXIT-ARDS: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for ARDS (clinicaltrials.gov) - P1/2 | N=81 | Not yet recruiting | Sponsor: Direct Biologics, LLC | Trial completion date: Jun 2023 ➔ Dec 2023 | Trial primary completion date: May 2023 ➔ Sep 2023

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

EXIT-ARDS: Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicles Infusion Treatment for ARDS (clinicaltrials.gov) - P1/2 | N=81 | Not yet recruiting | Sponsor: Direct Biologics, LLC | Trial completion date: Jan 2023 ➔ Jun 2023 | Trial primary completion date: Jan 2023 ➔ May 2023

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Bone Marrow Mesenchymal Stem Cell Derived Extracellular Vesicle Treatment for Acute Respiratory Distress Syndrome (ARDS) (clinicaltrials.gov) - P3 | N=320 | Recruiting | Sponsor: Direct Biologics, LLC | Trial completion date: Jul 2023 ➔ Aug 2024 | Trial primary completion date: Apr 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Acute Respiratory Distress Syndrome • Pulmonary Disease • Respiratory Diseases

Direct Biologics Announces First Patient Dosed with ExoFlo in a Phase 1 Clinical Trial for Medically Refractory Ulcerative Colitis (Businesswire) - "Direct Biologics, LLC...announces that the first patient has been dosed in its Phase 1 clinical trial evaluating ExoFlo™ for the treatment of patients with medically refractory ulcerative colitis (UC)....This open-label Phase 1 study (NCT05176366) is designed to evaluate the safety and efficacy of ExoFlo for the treatment of medically refractory UC. The trial is expected to enroll 10 patients, aged 18-75 years, who have had a diagnosis of medically refractory UC of at least six months duration and have failed at least one monoclonal antibody therapy."

Trial status • Immunology • Inflammatory Bowel Disease • Ulcerative Colitis

Direct Biologics Announces Initiation of Phase 1 Clinical Trial for Medically Refractory Crohn’s Disease (Businesswire) - "Direct Biologics, LLC...announced it has dosed the first patient in its Phase 1 clinical trial evaluating ExoFlo™ for the treatment of patients with medically refractory Crohn’s disease....The trial is expected to enroll 10 patients between the ages of 18 and 75 who have been diagnosed with medically refractory moderate-to-severe Crohn’s disease of at least six months duration and have failed at least one monoclonal antibody therapy."

Trial status • Crohn's disease • Immunology • Inflammatory Bowel Disease

Expanded Access for Use of ExoFlo in Abdominal Solid Organ Transplant Patients (clinicaltrials.gov) - P=N/A | N=N/A | Available | Sponsor: Direct Biologics, LLC | Phase classification: P1 ➔ P=N/A

Phase classification • Immunology • Solid Organ Transplantation • Transplant Rejection • Transplantation