Prolastin-C (human alpha1-proteinase inhibitor IV) / Grifols, OrphanPacific - LARVOL DELTA

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Two Different Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% in Participants With Alpha1-Antitrypsin Deficiency (clinicaltrials.gov) - P1/2 | N=17 | Completed | Sponsor: Grifols Therapeutics LLC | Active, not recruiting ➔ Completed

Trial completion • Alpha-1 Antitrypsin Deficiency • Pulmonary Disease • Respiratory Diseases

Evaluating the Economic Burden: Lifetime Direct and Indirect Costs of Managing Alpha-1 Antitrypsin Deficiency for Patients With the PiZZ Genotype Receiving Augmentation Therapy in the United States (ATS 2025) - "Utilization and costs were calculated for hospitalizations, outpatient visits, augmentation therapy (Prolastin-C 1000 mg / 20 ml vials; highest U.S. market share), other medications, oxygen, lab tests, and scans... AATD (PiZZ) imposes a significant economic burden, including both direct and indirect costs."

Clinical • HEOR • Alpha-1 Antitrypsin Deficiency • Bronchiectasis • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Immunology • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Two Different Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% in Participants with Alpha1-Antitrypsin Deficiency (clinicaltrials.gov) - P1/2 | N=16 | Active, not recruiting | Sponsor: Grifols Therapeutics LLC | Trial completion date: Mar 2025 ➔ Jul 2025 | Trial primary completion date: Mar 2025 ➔ Jul 2025

Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Hepatology • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Two Different Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% in Participants With Alpha1-Antitrypsin Deficiency (clinicaltrials.gov) - P1/2 | N=16 | Active, not recruiting | Sponsor: Grifols Therapeutics LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Alpha-1 Antitrypsin Deficiency • Hepatology • Pulmonary Disease • Respiratory Diseases

BATMAN: Bronchiectasis Alpha-1 Augmentation Trial- Modulating Airway Neutrophil Function (clinicaltrials.gov) - P4 | N=20 | Completed | Sponsor: University of Dundee | Recruiting ➔ Completed

Trial completion • Bronchiectasis • Pulmonary Disease • Respiratory Diseases • ELANE

SPARTA: Efficacy and Safety of Alpha1-Proteinase Inhibitor (Human), Modified Process (Alpha-1 MP) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency (AATD) (clinicaltrials.gov) - P3 | N=345 | Active, not recruiting | Sponsor: Grifols Therapeutics LLC | Trial completion date: Aug 2026 ➔ Jan 2027

Trial completion date • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases

SPARTA-OLE: Long Term Safety of Alpha1-Proteinase Inhibitor in Subjects With Alpha1 Antitrypsin Deficiency (clinicaltrials.gov) - P3 | N=290 | Enrolling by invitation | Sponsor: Grifols Therapeutics LLC | Trial completion date: Jul 2028 ➔ Feb 2029

Trial completion date • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Two Different Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% in Participants With Alpha1-Antitrypsin Deficiency (clinicaltrials.gov) - P1/2 | N=16 | Recruiting | Sponsor: Grifols Therapeutics LLC | Trial completion date: Nov 2024 ➔ Mar 2025 | Trial primary completion date: Nov 2024 ➔ Mar 2025

Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Hepatology • Pulmonary Disease • Respiratory Diseases

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Two Different Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% in Participants With Alpha1-Antitrypsin Deficiency (clinicaltrials.gov) - P1/2 | N=16 | Recruiting | Sponsor: Grifols Therapeutics LLC | Trial completion date: Mar 2024 ➔ Nov 2024 | Trial primary completion date: Mar 2024 ➔ Nov 2024

Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Hepatology • Pulmonary Disease • Respiratory Diseases

SPARTA-OLE: Long Term Safety of Alpha1-Proteinase Inhibitor in Subjects With Alpha1 Antitrypsin Deficiency (clinicaltrials.gov) - P3 | N=250 | Enrolling by invitation | Sponsor: Grifols Therapeutics LLC | Trial completion date: Apr 2028 ➔ Jul 2028 | Trial primary completion date: Apr 2028 ➔ Jul 2028

Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases

SPARTA: Efficacy and Safety of Alpha1-Proteinase Inhibitor (Human), Modified Process (Alpha-1 MP) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency (AATD) (clinicaltrials.gov) - P3 | N=339 | Active, not recruiting | Sponsor: Grifols Therapeutics LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases

Alpha-1 Antitrypsin (AAT) Enhances Islet Autograft Survival in Patients With Chronic Pancreatitis (clinicaltrials.gov) - P1/2 | N=48 | Completed | Sponsor: Medical University of South Carolina | Active, not recruiting ➔ Completed

Trial completion • Pancreatitis

BATMAN: Bronchiectasis Alpha-1 Augmentation Trial- Modulating Airway Neutrophil Function (clinicaltrials.gov) - P4 | N=20 | Recruiting | Sponsor: University of Dundee | Trial completion date: Mar 2023 ➔ Oct 2024 | Trial primary completion date: Mar 2023 ➔ Oct 2024

Trial completion date • Trial primary completion date • Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CTSG • ELANE

BATMAN: Bronchiectasis Alpha-1 Augmentation Trial- Modulating Airway Neutrophil Function (clinicaltrials.gov) - P4 | N=20 | Recruiting | Sponsor: University of Dundee | Not yet recruiting ➔ Recruiting

Enrollment open • Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CTSG • ELANE

A Study to Evaluate Safety, Tolerability and Pharmacokinetics of Two Different Doses of Alpha1-Proteinase Inhibitor Subcutaneous (Human) 15% in Participants With Alpha1-Antitrypsin Deficiency (clinicaltrials.gov) - P1/2 | N=16 | Recruiting | Sponsor: Grifols Therapeutics LLC | Trial completion date: Feb 2023 ➔ Mar 2024 | Trial primary completion date: Feb 2023 ➔ Mar 2024

Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Hepatology • Pulmonary Disease • Respiratory Diseases

SPARTA-OLE: Long Term Safety of Alpha1-Proteinase Inhibitor in Subjects With Alpha1 Antitrypsin Deficiency (clinicaltrials.gov) - P3 | N=250 | Enrolling by invitation | Sponsor: Grifols Therapeutics LLC | N=192 ➔ 250

Enrollment change • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases

SPARTA-OLE: Long Term Safety of Alpha1-Proteinase Inhibitor in Subjects With Alpha1 Antitrypsin Deficiency (clinicaltrials.gov) - P3 | N=192 | Enrolling by invitation | Sponsor: Grifols Therapeutics LLC | Recruiting ➔ Enrolling by invitation | Trial completion date: Apr 2024 ➔ Apr 2028 | Trial primary completion date: Apr 2024 ➔ Apr 2028

Enrollment status • Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases

SPARTA: Efficacy and Safety of Alpha1-Proteinase Inhibitor (Human), Modified Process (Alpha-1 MP) in Subjects With Pulmonary Emphysema Due to Alpha1 Antitrypsin Deficiency (AATD) (clinicaltrials.gov) - P3 | N=339 | Recruiting | Sponsor: Grifols Therapeutics LLC | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases

BATMAN: Bronchiectasis Alpha-1 Augmentation Trial- Modulating Airway Neutrophil Function (clinicaltrials.gov) - P4 | N=20 | Not yet recruiting | Sponsor: University of Dundee

New P4 trial • Bronchiectasis • Non‐Cystic Fibrosis Bronchiectasis • Pulmonary Disease • Respiratory Diseases • CTSG • ELANE

SPARTA-OLE: Long Term Safety of Alpha1-Proteinase Inhibitor in Subjects With Alpha1 Antitrypsin Deficiency (clinicaltrials.gov) - P3 | N=192 | Recruiting | Sponsor: Grifols Therapeutics LLC | Active, not recruiting ➔ Recruiting

Enrollment open • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases

Long-term safety of Prolastin®-C, an alpha1-proteinase inhibitor, in Japanese patients with alpha1-antitrypsin deficiency. (PubMed, Respir Investig) - P1/2 | "Long-term weekly intravenous infusions of 60 mg/kg Alpha-1 MP are generally safe and well-tolerated in Japanese patients with AATD."

Journal • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Hepatology • Immunology • Pulmonary Disease • Respiratory Diseases

High-level production of wild-type and oxidation-resistant recombinant alpha-1-antitrypsin in glycoengineered CHO cells. (PubMed, Biotechnol Bioeng) - "Using the CR5 promoter, glycoengineered stable CHO pools were able to produce over 2.1 g/L and 2.8 g/L of wild-type and mutein forms of A1AT, respectively, with N-glycans analogous to the plasma-derived clinical product Prolastin-C...These purified recombinant A1AT proteins showed in vitro inhibitory activity equivalent to Prolastin-C and substitution of methionine residues 351 and 358 with valines rendered A1AT significantly more resistant to oxidation. The recombinant A1AT mutein bearing an improved oxidation-resistance described in this study could represent a viable biobetter drug, offering a safe and more stable alternative for augmentation therapy."

Journal • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Immunology • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases • ELANE • ST6GAL1

Study to Evaluate the Safety and Efficacy of Liquid Alpha1-Proteinase Inhibitor (Human) in Hospitalized Participants With Coronavirus Disease (COVID-19) (clinicaltrials.gov) - P2 | N=54 | Terminated | Sponsor: Grifols Therapeutics LLC | N=100 ➔ 54 | Recruiting ➔ Terminated; Study Stopped for Futility

Enrollment change • Trial termination • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases • CRP

SPARTA-OLE: Long Term Safety of Alpha1-Proteinase Inhibitor in Subjects With Alpha1 Antitrypsin Deficiency (clinicaltrials.gov) - P3 | N=192 | Active, not recruiting | Sponsor: Grifols Therapeutics LLC | Enrolling by invitation ➔ Active, not recruiting | Trial completion date: Jul 2027 ➔ Apr 2024 | Trial primary completion date: Jul 2027 ➔ Apr 2024

Enrollment closed • Trial completion date • Trial primary completion date • Alpha-1 Antitrypsin Deficiency • Chronic Obstructive Pulmonary Disease • Genetic Disorders • Hepatology • Pulmonary Disease • Pulmonary Emphysema • Respiratory Diseases

Alpha-1 Antitrypsin (AAT) Enhances Islet Autograft Survival in Patients With Chronic Pancreatitis (clinicaltrials.gov) - P1/2 | N=48 | Active, not recruiting | Sponsor: Medical University of South Carolina | Trial completion date: Dec 2021 ➔ Nov 2022

Trial completion date • Pancreatitis