Exosomes are extracellular vesicles (EVs) of endosomal origin that range in size between 30 and 150 nanometers. Exosomes are secreted by a wide range of cells, since virtually all living cells utilize exosome-mediated communication. Exosomes carry cell-specific cargos of proteins, lipids, and nucleic acids that are selectively taken up by recipient cells.
Although exosomes were discovered more than 30 years ago, it was not until recently that the scientific community began to give credit to exosomes for a range of promising traits. Today, there are an astounding 18,000+ articles published about exosomes on PubMed.gov, of which an astounding three-quarters (74%) were released in the past five years.
The Therapeutic Potential of Exosomes
In recent years, several universities and research hospitals have performed small-scale Phase I clinical trials using exosomes. So far, only a few companies have reached the pivotal point and transitioned into human clinical trials. Testing a new therapeutic in human subjects for the first time is a major step in the translation of any novel treatment from the laboratory bench to clinical use. While the development of exosome therapeutics represents a paradigm shift, reaching this milestone is even more important.
On May 11, 2018, Aegle Therapeutics announced the FDA had cleared its first IND application to initiate an exosome clinical trial in severe second degree burn patients. The company launched a Phase 1/2a clinical trial of its lead product AGLE-102 in late 2018. This made it the first extracellular vesicle (EV) company cleared by the FDA to enter clinical trials in humans. Aegle has two products under development, AGLE-102 for burn treatment and AGLE-103 for the management of epidermolysis bullosa (EB).
On 28th January 2020, Melbourne-based Exopharm announced the first dosing under its first human clinical trial, becoming the first company to test the therapeutic capacity of exosomes for wound healing. The Phase I study is testing Exopharm’s Plexaris product, a cell-free formulation of exosomes from platelets, which in preclinical animal studies have shown a regenerative effect, improving wound closure and reducing scarring.
On 26th June 2019, United Therapeutics announced approval for a Phase I trial of an exosome-based therapy against bronchopulmonary dysplasia (BDP), a condition common in preterm infants that receive assisted ventilation and supplemental oxygen. Recruitment has commenced but dosing has not been announced. BDP is characterized by arrested lung growth and development, with health implications that can persist into adulthood.
Naïve Exosomes versus Engineered Exosomes
Companies participating in exosome sector are of two types: companies using “naïve” exosomes and companies using “engineered” exosomes. Naïve exosomes are the exosomes naturally released by cells, while “engineered” exosomes are those loaded with additional biomolecules in the laboratory.
Avalon, Aegle Therapeutics, ExoCoBio, Capricor, AgeX Therapeutics, and United Therapeutics are examples of companies focusing on “naïve” exosomes. Exopharm and Avalon are involved with both the types of exosomes. Codiak, Evox, Ilias, Carmine Therapeutics, Aruna Bio, ReNeuron, Anjarium, Adipomics, Brainstorm Cell Therapeutics, Exocure Biosciences, and TriArm Therapeutics are dealing with “engineered” exosomes.
Just behind Aegle, Exopharm, and United Therapeutics, are two other firms which had planned to start clinical trials by the end of 2020, but were impacted by the COVID-19 pandemic: Codiak Biosciences and Avalon Globocare. Codiak’s aim is to use an engineered exosome called exoSTING, which contains a therapeutic payload to combat cancer. Avalon GloboCare’s AVA-201 is also an engineered exosome that is enriched with RNA miR-185 to suppress proliferation of cancer cells.
Preclinical Stage Exosome Therapeutics
Of course, numerous companies are involved with the preclinical stage of exosome therapeutics. The UK-based company Evox Therapeutics is in the process of developing an engineered exosome carrying a protein therapeutic cargo to target a lysosomal storage disorder called Niemann-Pick Disease type C. The South Korea-based Ilias Biologics is developing engineered exosomes carrying protein therapeutics to treat sepsis, preterm labor, and Gaucher’s disease.
ExoCoBio is focused on developing an engineered exosome for the treatment of atopic dermatitis. Carmine Therapeutics plans to develop exosomes for the treatment of hematological, oncological, and immunological disorders. Aruna Bio is developing neural exosomes that can cross the blood-brain barrier. ReNeuron, which has been evaluating its CTX stem cells for post-stroke rehabilitation, is studying the drug and gene delivery potential of exosomes obtained from its CTX stem cells.
Anjarium is developing an exosome to deliver therapeutic RNA cargo. Capricor is focused on developing its CAP-2003 for the treatment of inflammatory diseases such as Duchenne muscular dystrophy (DMD). Within the academic realm, the UC Davis Stem Cell Program is exploring the use of stem cell exosome therapeutics to address wound healing, diabetic retinopathy, and neurological diseases.
The Evolution of Exosome Therapeutics
Today, exosomes therapeutics are being developed by dozens of companies who are entering clinical trials with both naïve and engineered exosome products. Unsurprisingly, a number of cell therapy companies are also expanding into the exosome space.
The next few years will undoubtedly see dynamic change, growing numbers of strategic partnerships, and eventually, product commercialization. What other companies are commercializing novel exosome therapeutics? Mention them in the comments below.