December 18, 2020
Company Name: AnGes Inc.
Presentative: Ei Yamada, President & CEO

Initiation of the First-in-Human Clinical Trial of a Potential Vascular Normalization
COVID-19 Treatment
First subjects have been dosed in Phase 1 study of AV-001,
a novel first-in-class therapeutic
Should the Phase 1 results show AV-001 is safe and well-tolerated, AnGes andVasomune will initiate a Phase 2 proof-of-concept study to assess efficacy in patientswith moderate-to-severe COVID-19 disease
December 18, 2020 – AnGes and Vasomune Therapeutics, a clinical-stage biopharmaceuticalcompany, announced today the first subjects have been dosed in a Phase 1 study of AV-001 in
healthy subjects. AV-001 is a first-in-class therapeutic that targets the Tie2 tyrosine kinase
receptor, a key regulatory protein in the vasculature responsible for maintaining normal vascularfunction. Should the benefit demonstrated in animal studies translate to the clinic, AV-001 has
the potential to improve survival and shorten the duration of hospitalization for patients
hospitalized with COVID-19.
“Emerging evidence suggests serious SARS-CoV-2 infection impairs vascular function in thelungs and throughout the body, which explaains why patients with pre-existing vascular
dysfunction (elderly, hypertension, diabetes and obesity) are at higher risk. Our therapeuticstrategy focuses on normalizing the vasculature, which we believe could improve patient
survival and shorten recovery time which, in turn, would reduce the strain on health careresources, including medical personnel, ICU beds and ventilators.” said Douglas Hamilton,President and CEO of Vasomune.
The Phase 1 randomized, double-blind, placebo-controlled single and multiple ascending dosetrial of AV-001 is currently enrolling healthy subjects. This study is a first-in-human design toassess the safety, tolerability and pharmacokinetics of daily administration of single and multiple
doses of AV-001. Vasomune Therapeutics, Inc. plans to seek Emergency Use Authorization(EUA) from the US Food and Drug Administration (FDA) pending successful clinical trials for thetreatment of patients with moderate-to-severe COVID-19 disease.
About AV-001
Originally discovered and designed at Sunnybrook Hospital in Toronto, AV-001 is being
developed by Vasomune Therapeutics, Inc. under a co-development agreement with AnGes,
Inc. [TYO: 4563]. AV-001 is a novel investigational medicine that targets the Tie2 receptor, atransmembrane protein target most highly expressed on the surface of endothelial cells in thevasculature. AV-001 activates the Tie2-Angiopoietin pathway and restores normal vascularfunction and endothelial stability. Vascular dysfunction contributes to the underlying disease
pathophysiology in patients with COVID-19 and acute respiratory distress syndrome (ARDS),

especially in patients with pre-existing vascular comorbidities, such as hypertension, diabetes
and obesity. Emerging evidence suggests SARS-CoV-2 infects pulmonary endothelial cells andcauses microvascular leaks, contributing to the initiation and propagation of respiratory distressand ARDS in COVID-19 patients by altering blood vessel barrier integrity, promoting a
coagulated state and inducing vascular inflammation (endotheliitis). In preclinical studies
involving a lethal RNA virus infection animal model of influenza/ARDS, AV-001 has been shownto stabilize the vasculature by enhancing endothelial cell stability, restoring normal barrier
defense and blocking vascular leak. Importantly, AV-001 monotherapy significantly improved
survival and lung function compared to untreated controls and showed the benefit of enhanced
recovery in combination with antiviral therapy. AV-001 is being developed for the treatment ofmoderate to-severe COVID-19 and ARDS.
About Vasomune Therapeutics, Inc.
Vasomune Therapeutics, Inc. is a private clinical-stage biopharmaceutical company developing
the next generation of medicines to harness the body’s ability to defend against illness.
Originally founded in 2014, Vasomune discovers and develops drugs using a novel therapeutic
approach focused on vascular normalization strategies. Vascular dysfunction is associated withthe pathology of several disease states, including COVID-19, influenza-associated ARDS, acutelung injury, acute kidney injury, hemorrhagic shock, sepsis and stroke. Vasomune’s corporate
headquarters and laboratory is located in Toronto, Canada with US offices in San Mateo, CA.
For more information about the company and its product candidates, please visit
www.vasomune.com
About AnGes, Inc.
AnGes, Inc., a biopharmaceutical company founded in December 1999 focuses on thedevelopment of gene-based medicines. In March 2019, AnGes obtained conditional and timelimited approval for its lead product, Collategene® (Hepatocyte Growth Factor, HGF, plasmidgene therapy), for the treatment of Lower Limb Ischemic Ulcers. In September 2019, AnGes
commenced the commercialization in Japan of Collategene®. Collategene® is the world’s firstmarketed drug using Plasmid DNA. AnGes is currently focusing on the development of DNA
vaccines for COVID-19 and Hypertension, Tie2 tyrosine kinase receptor agonist for COVID-19treatment, and NF-κB decoy oligonucleotide for Chronic Discogenic Lumbar Back Pain.
Furthermore, AnGes acquired EmendoBio to expand its capabilities in Genome EditingTechnologies in December 2020. For more information, visit www.anges.co.jp/en/.
AnGes, Inc.
Public Relations & Investor Relations GroupTEL: +81-3-5730-2641, FAX: +81-3-5730-2635
https://www.anges.co.jp/en/