Evidence library

Manufacturing Therapeutic Exosomes: from Bench to Industry

Ahn SH et al. (2022). Manufacturing Therapeutic Exosomes: from Bench to Industry

Discusses cell line development, upstream culture, downstream purification, formulation, and GMP challenges for clinical-grade exosome therapeutics.

Supports claims: ev_manufacturing_not_plug_and_play

Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

Gimona M et al. (2017). Manufacturing of Human Extracellular Vesicle-Based Therapeutics for Clinical Use

Requirements for manufacturing, safety, and efficacy testing of EV therapeutics from laboratory to patient; MSC-EV translational strategies.

Supports claims: potency_assay_ambiguity, ev_manufacturing_not_plug_and_play, local_topical_more_practical

Toward Exosome-Based Therapeutics: Isolation, Heterogeneity, and Fit-for-Purpose Potency

Willis GR et al. (2017). Toward Exosome-Based Therapeutics: Isolation, Heterogeneity, and Fit-for-Purpose Potency

Isolation variability, EV heterogeneity, and need for fit-for-purpose potency assays in MSC-exosome therapeutics.

Supports claims: potency_assay_ambiguity, isolation_defines_product

Minimal information for studies of extracellular vesicles (MISEV2023)

Welsh JA et al. (2024). Minimal information for studies of extracellular vesicles (MISEV2023)

Updated ISEV guidance on EV nomenclature, separation, characterization, functional studies, and reporting rigor.

Supports claims: potency_assay_ambiguity

Minimal information for studies of extracellular vesicles 2018 (MISEV2018)

Théry C et al. (2018). Minimal information for studies of extracellular vesicles 2018 (MISEV2018)

ISEV position on EV isolation, characterization, and functional analysis standards.

Supports claims: potency_assay_ambiguity

Applying extracellular vesicles based therapeutics in clinical trials: an ISEV position paper

Lötvall J et al. (2015). Applying extracellular vesicles based therapeutics in clinical trials: an ISEV position paper

Regulatory categorization of EV therapeutics, manufacturing QC, and cooperation with competent authorities for clinical translation.

Advancing translational potential of EVs through ISEV-TRA

Falcon-Perez JM et al. (2025). Advancing translational potential of EVs through ISEV-TRA

ISEV Translation, Regulation and Advocacy Committee addresses regulatory uncertainty and manufacturing barriers to EV commercialization.

Supports claims: ev_manufacturing_not_plug_and_play

ISEV Task Force on Regulatory Affairs and Clinical Use of EV-based Therapeutics

ISEV (2024). ISEV Task Force on Regulatory Affairs and Clinical Use of EV-based Therapeutics

Focus on IND pathways, potency measurement, and reporting standards for modified EV therapeutics.

Supports claims: potency_assay_ambiguity

Public Safety Notification on Exosome Products

U.S. FDA (2019). Public Safety Notification on Exosome Products

No FDA-approved exosome products; exosomes for disease treatment are regulated as drugs/biologics requiring premarket approval.

Supports claims: exosome_clinic_regulatory_risk

Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes

U.S. FDA (2020). Consumer Alert on Regenerative Medicine Products Including Stem Cells and Exosomes

FDA authority over exosome products; warns against illegally marketed products with unsubstantiated claims.

Supports claims: exosome_clinic_regulatory_risk

Public Safety Alert: Marketing of Unapproved Stem Cell and Exosome Products

U.S. FDA (2019). Public Safety Alert: Marketing of Unapproved Stem Cell and Exosome Products

Serious adverse events linked to unapproved exosome products; clinics may misrepresent regulatory status.

Supports claims: exosome_clinic_regulatory_risk

Stem Cell and Exosome Products (CDC HAI)

U.S. CDC (2019). Stem Cell and Exosome Products (CDC HAI)

CDC collaboration with FDA on serious adverse events from unapproved exosome products in Nebraska.

Supports claims: exosome_clinic_regulatory_risk

Codiak BioSciences Chapter 11 Filing (8-K)

Codiak BioSciences (2023). Codiak BioSciences Chapter 11 Filing (8-K)

Voluntary Chapter 11 filed March 27, 2023; company to pursue asset sale of engEx exosome platform programs.

Codiak to Pursue Asset Sale through Chapter 11

Codiak BioSciences (2023). Codiak to Pursue Asset Sale through Chapter 11

Engineered exosome platform did not sustain financing for ongoing clinical operations.

Codiak files for bankruptcy after financial needs unmet

Fierce Biotech (2023). Codiak files for bankruptcy after financial needs unmet

Layoffs and pause of phase 2 exoSTING/exoIL-12 programs preceded Chapter 11 filing.

Capricor initiates rolling BLA submission for deramiocel

Capricor Therapeutics (2024). Capricor initiates rolling BLA submission for deramiocel

Deramiocel (CDC) acts via secreted exosomes; exosome-based candidates not approved for clinical investigation.

Capricor receives CRL on deramiocel BLA

Capricor Therapeutics (2025). Capricor receives CRL on deramiocel BLA

FDA issued Complete Response Letter on DMD cardiomyopathy BLA; illustrates conventional CMC/regulatory review risk.

Aegle first patient dosed in AGLE-102 DEB trial

Aegle Therapeutics (2024). Aegle first patient dosed in AGLE-102 DEB trial

Topical allogeneic MSC-derived EV product for local wound treatment in dystrophic epidermolysis bullosa.

Supports claims: local_topical_more_practical

MSC EVs in Dystrophic Epidermolysis Bullosa (NCT04173650)

Aegle Therapeutics (2024). MSC EVs in Dystrophic Epidermolysis Bullosa (NCT04173650)

Phase 1/2A topical AGLE-102 for RDEB wounds with intra-subject controls.

Supports claims: local_topical_more_practical

Evox progress on DeliverEX and ExoEdit platforms

Evox Therapeutics (2023). Evox progress on DeliverEX and ExoEdit platforms

Engineered exosome delivery for mRNA, RNAi, and gene editing; company claims vs LNP at equal dose in preclinical work.

Supports claims: engineered_ev_vs_lnp

Robust mRNA loading and delivery by engineered extracellular vesicles

Smith et al. (2023). Robust mRNA loading and delivery by engineered extracellular vesicles

Preclinical comparison of EV vs LNP mRNA delivery; not peer-reviewed—verify independently.

Supports claims: engineered_ev_vs_lnp

EXTINGUISH ARDS: ExoFlo Phase 3 (NCT05354141)

Direct Biologics (2024). EXTINGUISH ARDS: ExoFlo Phase 3 (NCT05354141)

Phase 3 IV bone marrow MSC-derived EVs (ExoFlo) vs placebo in moderate-to-severe ARDS.

MSC Exosomes Nebulizer for ARDS (NCT04602104)

Ruijin Hospital (2023). MSC Exosomes Nebulizer for ARDS (NCT04602104)

Completed phase 1/2 study of inhaled hMSC-Exos for ARDS with dose escalation.

Direct Biologics Phase 3 EXTINGUISH ARDS trial of ExoFlo

Direct Biologics (2024). Direct Biologics Phase 3 EXTINGUISH ARDS trial of ExoFlo

FDA expanded Phase 3 ExoFlo study to all-cause moderate-to-severe ARDS; MSC-derived EV administered IV with standard of care.

Supports claims: potency_assay_ambiguity, ev_manufacturing_not_plug_and_play

Aruna Bio FDA clearance of IND for AB126 neural exosome

Aruna Bio (2024). Aruna Bio FDA clearance of IND for AB126 neural exosome

First exosome IND cleared for neurological indication; AB126 is unmodified neural-derived EV for acute ischemic stroke with in-house cGMP manufacturing.

Aruna Bio AB126 platform overview

Aruna Bio (2024). Aruna Bio AB126 platform overview

Neural exosome CNS specificity, anti-inflammatory effects in stroke models, and in-house cGMP scale-up for clinical material.

RION completes enrollment in Phase 2 PEP diabetic foot ulcer trial

RION (2025). RION completes enrollment in Phase 2 PEP diabetic foot ulcer trial

Platelet-derived lyophilized Purified Exosome Product (PEP) for topical DFU; path toward Phase 3 and BLA.

Supports claims: local_topical_more_practical

PEP on skin graft donor site wound (NCT04664738)

Rion Inc. (2024). PEP on skin graft donor site wound (NCT04664738)

Phase 1b safety study of platelet-derived PEP exosomes on skin graft donor wounds.

Supports claims: local_topical_more_practical

PEP-TISSEEL for diabetic foot ulcers (NCT06319287)

Rion Inc. (2024). PEP-TISSEEL for diabetic foot ulcers (NCT06319287)

Phase 2a randomized study of topical PEP-TISSEEL plus standard of care vs SOC alone for DFU.

Supports claims: local_topical_more_practical

Efficient RNA drug delivery using red blood cell extracellular vesicles

Usman WM et al. (2018). Efficient RNA drug delivery using red blood cell extracellular vesicles

RBCEV platform for scalable RNA delivery without horizontal gene transfer risk from nucleated cell sources.

Supports claims: engineered_ev_vs_lnp

Carmine Therapeutics and Takeda collaborate on RBCEV gene therapies

Carmine Therapeutics (2020). Carmine Therapeutics and Takeda collaborate on RBCEV gene therapies

REGENT platform uses red blood cell EVs for non-viral gene therapy with large payload and repeat-dosing potential vs AAV.

Supports claims: engineered_ev_vs_lnp

Anjarium Series A for Hybridosome non-viral gene therapies

Anjarium Biosciences (2021). Anjarium Series A for Hybridosome non-viral gene therapies

Hybridosome technology fuses extracellular vesicle delivery modules with synthetic drug encapsulation for tissue-targeted gene therapies.

Supports claims: engineered_ev_vs_lnp

Evox acquires Codiak engEx-AAV platform and IP

Evox Therapeutics (2023). Evox acquires Codiak engEx-AAV platform and IP

Post-Chapter 11, Evox purchased Codiak engEx-AAV technology following Codiak asset sale process.

Supports claims: ev_manufacturing_not_plug_and_play

Capricor FDA resumes deramiocel BLA review; PDUFA Aug 2026

Capricor Therapeutics (2026). Capricor FDA resumes deramiocel BLA review; PDUFA Aug 2026

CRL lifted; BLA resubmission under review for DMD cardiomyopathy. Product acts via secreted exosomes from cardiosphere-derived cells.