Document EbKM5jZ8mjQyn9DvV8k9meBN

# ?: r 7.! therapeutics, inc. "eva thgrapeuticsi inc. April 2023 Executive Summary Unmet medical needs For severe hypoxemia, the mechanical ventilator and extracorporeal membrane oxygenation (ECMO) are commonly utilized at ICU, while invasiveness, labor and cost are problem Recent pandemic caused supply imbalance, endangering numerous patients' lives at risk Core Technology First-in-history "organ" repurposing therapy: enteral ventilation to enable gas exchange EVA101 (first pipeline): A simple enema of liquid oxygen (perfluorocarbon) to prevent or treat the acute deterioration of severe hypoxemia R&D strategy EVA101 (device): Japan IND Submission completed in 2022 4Q conducting a clinical trial EVA102 (drug): Initiate pre-oxygenated perfluorocarbon development and US clinical development in 2023 4Q EVA101/102 Market Opportunity Japan: USD 100-200 million US&EU5: USD 1-2 billion 2 Corporate Leadership Combination of Young Creative Researchers and Experienced Industry Senior Experts Hiromu Ozaki : Chief Executive Officer Ex-CEO of Astellas Pharma Canada, Biogen Japan and Sosei Japan Hirofumi Nagai: Chief Technology Officer Ex Head of Takeda Safety Research, Expert in Pharmacology and Toxicology Yukinori Kanekawa: Chief Regulatory Officer Ex PMDA Lead of Medical Device Evaluation Chihiro Yokota: Chief Development Officer Ex SVP of Development of Astellas 3 Corporate Philosophy VISION Unlock New Potential of the Gut MISSION Deliver Enteral Ventilation (EVA) Therapeutics PASSION Help People, Care for Patients, Cure Diseases 4 Loaches evolved intestinal gas exchange mechanism under extensive hypoxia Accessory breathing mechanisms in fishes Esophagus breathers (Crawford, 1971) Stomach breathers (Carter & Beadle,1931) Foregut breathers (Nelson et al., 2007) Intestinal breathers (Yadav & Singh, 1980) Hindgut breathers (McMahon& Burggren, 1987) Journal of Fish Biology (2014) 84, 554-576 doi:10.1111/jfb.12323. Breaking wind to survive: fishes that breathe air with their gut Translating "gut breathing" mechanism in mammalian 5 Our Inspiration: "Perfluorocarbon (Liquid Oxygen)" primes the gut for ventilation SpO2 (%) SpO2 (%) The use of perfluorocarbon (liquid oxygen) 120 100 Inspired by Evangelion 80 The Entry Plug of an Eva Unit, containing its cockpit, is completely flooded with LCL, and, because it is oxygenated, upon being sub6m0 erged Eva pilots can "breathe" the liquid (similar to real-life experiments involving liquid breathing). 40 A Hypoxia (10% O2) 120 Hypoxia (10% O2) + l-EVA 100 80 60 40 I-EVA 20 Sham 0 -5 0 5 10 15 20 25 30 35 40 45 50 55 60 Time after administration (min) Enteral ventilation allows for oxygen normalization more than an hour in rode6nt. Proof of Concept of Enteral Ventilation Due to the proven safety of perfluorochemicals in clinics, EVA potentially provides an adjunctive means of oxygenation for patients under respiratory distress conditions. Okabe, et al. Med, 2019 The exploitation of intestinal breathing phenomenon in mammalian pre-clinical models. Offering an additional route of O2 administration to patients who are in critical need of immediate respiratory support. 7 EVA A therapy Oxygen bubbling (5-10min) enabled O2 increase / CO2 Hypoxic gas (N2/O2) ventilation Vital monitoring SpO2 -80% decrease in large-animal model Fujii, et al. iScience, 2023 B 800 O2 bubbling into PFD O2 retention PFD 800 600 600 400 400 pO2 of PFD (mmHg) pO2 of PFD (mmHg) 200 200 0 0 5 10 15 Time after O2 bubbling (min) 0 01234567 Day after bubbling PFD (Purity>99%) Continuous rocuronium i.v. O2-PFD 20ml/kg Swan-Ganz catheter PaO2 SaO2SivcO SpO2 2 SvO2SpvO2 C Arterial gas analysis in pig (n=12) 10 Injected EVA treatment rieved Ret 5 PaO2 0 Partial pressure in arterial blood (mmHg) Infusion time* 250ml/min Rectal catheter (PFD was collected at 30min)* -5 PaCO2 0 5 10 15 20 25 30 35 40 Time after O2-PFD administration (min) Our first product EVA101 offers a window to bridge to advanced care EVA-101 Kit (Medical Device) A) Injection bag B) PFD(perfluorodecalin) C) Other components GMP grade Bubbling cannula, Filter, Needle, etc D) Instruction Materials Bubbling, Collection and Disposal protocols Oxygen bubbling Drug O2 gas After bubbling, O2 conc can be sustained over 6months at least Bolus Intended scenario Bridge to advanced medical care during medical transport Intubation difficulty or denial cases to provide temporal support Preparation to NPPV, MV and ECMO EVA101&102 will bridge emergency patients to advanced care Midium Mild Target : 3 million Acute Respiratory Failure cases a year in US Emergency Transport EVA 102 In-patient Acute Respiratory Failure O2 Inhalation EVA101 NPPV Non-invasive positive pressure ventilation EVA101 Mechanical ventilator EVA101 ECMO Urgency EVA101 Up to 200K case EVA102 2-3 million case Severity 10 Severe EVA Therapeutics, Inc. Pipeline Bridge use (medical device) Bridge use (medical drug) Continued use Hypercapnia GI disease 11 EVA Clinical Development Timeline Single Use Enema Medical Device EVA 1.0 EVA101 Pharmaceutical EVA102 EVA 1.5 2022 2023 2024 2025 2026 2027 2028 2029 IND Preclinical Ph1 Ph2 (Confirmatory) Submission Launch O2 Pre-loaded EVA CMC Development IND Phase IIb/III Treatment of Hypoxia Submission Launch US Presence EVA USA US Capital Raise 12 EVA Technology - Clinical Narrative Stage 1 EVA101 Single Use EVA 1.0 for Japan Stage 2 EVA102 O2 pre-loaded Ready to Use Enema EVA 1.5 global Bridge to advanced medical care during medical transport Stage 3 EVA201 Continuous Use EVA 2.0 global Bolus TMDU Cincinnati Children's Translational research Organoid research Drug development Our Scientific Team Street Medical research T-CiRA YCU-CDC THANK YOU!