A Study to Investigate Safety and Effectiveness of Porcine Pancreatic Cells (OPF-310) in Patients With Type 1 Diabetes Mellitus

This study is First In Human study for Encapsulated Porcine Islet Cells for Xenotransplantation (OPF-310). The purpose of this study to assess the safety, tolerability, and efficacy of OPF-310 transplantation and to define the recommended Phase 2 dose (RP2D) in adult subjects with unstable Type 1 Diabetes Mellitus (T1DM) and a level 3 (severe) hypoglycemic episode at least three times within the 1 year prior to enrollment despite treatment with a closed loop system (CLS) for at least 6 months.

Inclusion Criteria: 1. Subject must be aged 35 to 70 years of age inclusive, at the time of signing the informed consent. 2. Subject has an established diagnosis of type 1 diabetes mellitus (T1DM) (in accordance with the American Diabetes Association's criteria), with a minimum duration since diagnosis of 5 years. 3. If one of the following criteria (either a or b) applies: 1. Subject has unstable T1DM, not achieving adequate control after receiving CLS (CGM:Dexcom G6, insulin pump: Omnipod® 5 or t:slim X2) under care of a qualified diabetes team for at least 6 months prior to enrollment. 2. Subject has unstable T1DM, not achieving adequate control after receiving CLS (CGM:Dexcom G7, insulin pump: Omnipod® 5, t:slim X2, iLet Bionic Pancreas or The Tandem Mobi System) under care of a qualified diabetes team for at least 6 months prior to enrollment. 4. If one of the following criteria (either a, b or c) applies: 1. Subject has had a Level 3 (severe) hypoglycemic episode (defined as having cognitive impairment requiring external assistance for recovery) at least three times within the 1 year prior to enrollment recorded in the medical record or patient log. 2. Subject has had a Level 3 (severe) hypoglycemic episode at least once within the 1 year prior to enrollment and demonstrates a Clarke Score ≥4, assessed by trained study personnel. The SHE(s) and Clarke Score must be recorded in the medical record or patient log. 3. Subject has had TBR \>1% at glucose levels below 70mg/dL and demonstrates a Clarke Score≥4, assessed by trained study personnel. TBR data used for screening and Clarke score must be recorded in the medical record or patient log. 5. Subject has C-peptide \ 300 mg albumin/gm creatinine). 5. Estimated glomerular filtration rate (eGFR) cut-off of \< 30 ml/min for all per Kidney Disease Improving Global Outcomes (KDOQI) and Kidney Disease Outcomes Quality Initiative (KDIGO) consensus. 9. Use of warfarin or other anticoagulant therapy (except aspirin), or prothrombin time and international normalized ratio (PT-INR) \> 1.5 10. Adrenal insufficiency being treated with corticosteroids 11. Previous pan-peritonitis 12. Previous cardiovascular or cerebrovascular disease. NOTE: For the purposes of this exclusion criterion, "previous cardiovascular disease" is defined as the presence of co-existing cardiac disease, characterized by any of the following conditions: 1. Recent myocardial infarction (within past one year), or 2. Angiographic evidence of non-correctable coronary artery disease, or 3. Evidence of ischemia on functional cardiac exam (with a stress echo test recommended for subjects with a history of ischemic disease), or 4. Heart failure \> NYHAII For subjects aged 65 to \ 80 %. 24. Active drug, substance or alcohol addiction. 25. Body mass index (BMI) \>27 kg/m2. 26. Any other condition that, in the opinion of the Investigator, may interfere with adherence to the study protocol, including dementia, psychiatric disorder, medical condition, or a history of non-adherence to appointments or treatments