Project Designation: Tailoring EXosomes for Autoimmune Diseases

Acronym: TEXAD

Call: H2020INNOSUP201902

Type of Action: CSA

Number: 861869

Duration: 12 months

Start Date: 30 Dec 2019

Estimated Project Cost: €115,000.00

Requested EU Contribution: €54,195.58 €



Summary of the context and overall objectives of the project

Autoimmune diseases (AD) are among the most prevalent group of diseases, with 23 million patients only in US. These diseases are chronic and often lifethreatening, and according to AARDA (American Autoimmune Related Diseases Association), they are one of the top 10 leading causes of death in female children and women in all age groups up to 64 years of age. Current available treatments comprise chemicalbased drugs such as immunosuppressant, corticosteroids and NSAIDs. Although these products are effective in controlling AD symptoms, they significantly increase the risk of getting severe infections, or developing cancer, due to the constant artificial shut down of the immune system. The longterm consequences of their use are yet to be fully understood. Exogenus is a spinout company dedicated to the development of new therapeutic tools based in exosomes for diseases of high unmet needs. Our proprietary therapeutic tool are exosomes secreted by Umbilical Cord Blood (UCB) cells, secreted and purified in optimized conditions. Our vesicles have anti-inflammatory and immunomodulatory properties and can act as natural modulators of the immune system towards an immunotolerant state. While there are more than 80 different ADs, and limited solutions in the market with acceptable secondary effects, Exogenus’ vesicles can be a gamechanger, because they naturally rebalance theimmune system and increase its tolerability in the context of an AD crisis and can be tailored for specific ADs. It is urgent for Exogenus to identify the right target diseases and define the development path, and TEXAD project was designed to address these specific aims: a) decide which ADs to pursue as potential new markets and therapeutic areas; b) implementing meaningful ProofofConcept (POC) studies to demonstrate the products’ therapeutic potential for the target ADs; c) develop strong Target Product Profiles (TPP), meeting the needs of the new markets; d) define the roadmap for future development of up to three products for ADs; and e) design a new Innovation Project to achieve the POC in humans for one selected AD.

Work performed

Tailoring EXosomes for Autoimmune Diseases (TEXAD) was a oneyear project intended to advance the field of extracellular vesicles as a therapeutic alternative for autoimmune diseases with high unmet needs. Exogenus developed a product (Exo101), based on vesicles released by mononuclear cells from umbilical cord blood, which shows promise for regenerative medicine (namely healing of chronic wounds) and inflammatory diseases. The aim of this project was to study the latter in greater detail, by determining which disease or set of diseases would be most likely to benefit from Exo101 treatment, and conduct preclinical proofofconcept (POC) assays to support the drug’s development into clinical stage. An Innovation Associate (IA), with previous work in the field of autoimmune diseases, was hired to help guide and conduct this process. Due to the SARSCoV2 pandemic, Exogenus was faced with many challenges to implement the project, especially the difficulty to implement the POC studies on a timely manner. Faced with these limitations, and acknowledging the health threat imposed by the pandemic, Exogenus decided to explore the potential of Exo101 for the treatment of lung inflammation, leveraging on the data demonstrating its antiinflammatory and proregenerative effects. As such, the original plan suffered minor changes, to better fit with the new target disease. The IA hired under TEXAD was instrumental to the company during the past year, assisting in the redefinition of the Target Product Profile, and participating in fundraising, which in turn allowed Exogenus Therapeutics to retain her as an employee.

The IA contributed to the preparation of three scientific publications, one of the papers was recently published in Stem Cells Translational Medicine (Cardoso RMS andRodrigues SC et al, 2021), and the other two are about to be submitted. During the course of the TEXAD project, participation in scientific and industryled events was instrumental to position the company in the field of inflammatory diseases.

Progress beyond the state of the art

TEXAD was thought to be impactful in two ways: 1) by potentially providing a therapeutic alternative to patients with autoimmune conditions, who often lack effective and safe treatments (including longterm treatments); and 2) by introducing to the medical community and to the market a new class of therapeutics that, if proven effective and safe, can fundamentally change how therapies are perceived from managing symptoms to reestablishing balance in the organism, and from targeting single molecules and pathways to using a cocktail of biologic messengers to deal with complex disease mechanisms.

Due to the limitations imposed by Covid19 pandemic to the TEXAD project and to the society, and in light ofthe antiinflammatory and immunomodulatory properties of Exo101, Exogenus decided to explore its application todiseases with lung inflammation(focusing first in ARDS Acute Respiratory Distress Syndrome, a common hallmark of Covid19 and many other infectious and noninfectiousdiseases). The impactsof this alternative application are huge: the high rates of infection seen with SARSCoV2 mean that a large portion of the world’s population will be affected by the virus, a phenomenon that is expected to contribute to an increasein chronic lung illness. While the priority is to stop the spreading of the virus, namely with the development of vaccines and adoption of social measures,there is a high need for treatments that prevent disease progression to ARDS, and thus prevent lungdamage and death.Having already attracted governmental funds to explore the application of Exo101 to ARDS, the company is preparing to reach clinical studies in 2022.