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.
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—Aegle Therapeutics, Exopharm Ltd, United Therapeutics, Avalon Globocare (NASDAQ: AVCO), and Direct Biologics—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). Most recently, Aegle began dosing patients in its Phase 1/2a trial that is administering AGLE-102 for the treatment of severe second-degree burns.
On 28th January 2020, Melbourne-based Exopharm announced the 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 has 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.
Direct Biologics was also granted approval by the U.S. FDA to conduct a clinical trial under an Investigational New Drug (IND) application for use of its ExoFlo™ product in the treatment of COVID-19 induced ARDS. In July 2021, Direct Biologics announced it would facilitate its ARDS Phase I/II trial in late 2021, as well as to two other recently approved IND applications for “post-acute COVID-19 syndrome” and “chronic post-COVID-19”. Direct Biologics states that it is the only exosome company with INDs approved for the full range of COVID-19 indications, including ARDS.
In May 2023, Kimera® Labs, a leading company that is focused on MSC-derived exosomes, announced that the FDA had approved an IND for its Phase I/IIa clinical trial. This trial is assessing the safety and efficacy of a single IV dose of its placental cell line derived, MSC extracellular vesicles (EVs) for the treatment of COVID-19 symptoms in adults with mild to moderate illness.
Finally, Organicell has received 18 eINDs (Emergency INDs) from the U.S. FDA for Zofin™, an exosome therapeutic derived from perinatal sources. The U.S. FDA has also approved Organicell for four Phase I/II randomized, placebo-controlled trials investigating the therapeutic potential of Zofin™ for chronic obstructive pulmonary disease (COPD), osteoarthritis (OA), COVID-19, and COVID Long Haulers, as well as an Expanded Access trial which was completed and published late last year for Mild to Moderate COVID-19.
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.
AGS Therapeutics, Avalon, Aegle Therapeutics, ExoCoBio, AgeX Therapeutics, Kimera Labs, and United Therapeutics are examples of companies focusing on “naïve” exosomes.
Exopharm, Aruna Bio, and Avalon are involved with both the types of exosomes. For example, although Aruna Bio is working on payload loading, its lead candidate (“AB126”) is a naïve exosome. The company is on track to file its first IND in late Q2 of this year to take “AB126” into the clinic for treating various CNS conditions, starting with ischemic stroke.
Capricor, Evox, Ilias, Carmine Therapeutics, ReNeuron, Anjarium, Adipomics, Brainstorm Cell Therapeutics, Exocure Biosciences, and TriArm Therapeutics are dealing with “engineered” exosomes.
Just behind Aegle, Exopharm, United Therapeutics, and Organicell are two other firms which had planned to start clinical trials, but were impacted by the COVID-19 pandemic: Codiak Biosciences and Avalon Globocare. Codiak’s aim is was use an engineered exosome called exoSTING, which contains a therapeutic payload to combat cancer. Unfortunately, Codiak BioSciences filed for bankruptcy in March 2023 and is in the process of selling off its assets. 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. Although Capricor’s focus is on its lead asset CAP-1002, cardiosphere-derived cells (CDCs), it is also developing CAP-2003. CAP-2003 are exosomes derived from CDCs, which are being investigated 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.
To learn more about this rapidly expanding market, view the “The Global Exosome Market – Market Size, Forecast, Trials and Trends.”
