Turnobi (L-citrulline intravenous) / Asklepion Pharma - LARVOL DELTA

A Study of Intravenous L-Citrulline in Patients Aged 6-21 Years Old With Sickle Cell Disease Presenting to Emergency Departments in Acute Vaso-Occlusive Crisis (clinicaltrials.gov) - P3 | N=120 | Not yet recruiting | Sponsor: Asklepion Pharmaceuticals, LLC

New P3 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Study Evaluating the Efficacy and Safety of IV L-Citrulline for the Prevention of Clinical Sequelae of Acute Lung Injury Induced by Cardiopulmonary Bypass in Pediatric Patients Undergoing Surgery for Congenital Heart Defects (clinicaltrials.gov) - P3 | N=64 | Terminated | Sponsor: Asklepion Pharmaceuticals, LLC | N=97 ➔ 64 | Trial completion date: Feb 2024 ➔ May 2024 | Recruiting ➔ Terminated | Trial primary completion date: Dec 2023 ➔ May 2024; Interim Analysis triggered futility

Enrollment change • Surgery • Trial completion date • Trial primary completion date • Trial termination • Acute Lung Injury • Pediatrics • Respiratory Diseases

L-citrulline Injection in Patients Aged 6-21 Years Old with Sickle Cell Disease Presenting with Vaso-Occlusive Crisis (VOC) (clinicaltrials.gov) - P1/2 | N=30 | Terminated | Sponsor: Asklepion Pharmaceuticals, LLC | N=120 ➔ 30 | Trial completion date: Jul 2024 ➔ Feb 2024 | Recruiting ➔ Terminated | Trial primary completion date: Jun 2024 ➔ Feb 2024; Impacted by viraemia resulting in higher than expected admissions

Enrollment change • Trial completion date • Trial primary completion date • Trial termination • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

L-citrulline Injection in Patients Aged 6-21 Years Old With Sickle Cell Disease Presenting With Vaso-Occlusive Crisis (VOC) (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: Asklepion Pharmaceuticals, LLC | Trial completion date: Jul 2023 ➔ Jul 2024 | Trial primary completion date: Jun 2023 ➔ Jun 2024

Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Study Evaluating the Efficacy and Safety of IV L-Citrulline for the Prevention of Clinical Sequelae of Acute Lung Injury Induced by Cardiopulmonary Bypass in Pediatric Patients Undergoing Surgery for Congenital Heart Defects (clinicaltrials.gov) - P3 | N=97 | Recruiting | Sponsor: Asklepion Pharmaceuticals, LLC | Trial completion date: Aug 2023 ➔ Feb 2024

Trial completion date • Acute Lung Injury • Pediatrics • Respiratory Diseases

Design of an adaptive randomized clinical trial of intravenous citrulline for sickle cell pain crisis in the emergency department. (PubMed, Contemp Clin Trials Commun) - "Part 2 of the trial is a double-blind, placebo-controlled adaptive "pick-the-winner" design to evaluate the efficacy and tolerability of IV l-citrulline in patients with SCD while receiving standard of care therapy for VOC. This ED based sickle cell adaptive trial will determine the optimal dose for IV citrulline and whether the intervention improves outcome as a potential novel therapy for VOC in SCD."

Clinical • Journal • Genetic Disorders • Hematological Disorders • Pain • Sickle Cell Disease

L-citrulline Injection in Patients Aged 6-21 Years Old With Sickle Cell Disease Presenting With Vaso-Occlusive Crisis (VOC) (clinicaltrials.gov) - P1/2 | N=120 | Recruiting | Sponsor: Asklepion Pharmaceuticals, LLC | Trial completion date: Jul 2022 ➔ Jul 2023 | Trial primary completion date: Jun 2022 ➔ Jun 2023

Trial completion date • Trial primary completion date • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

A Study Evaluating the Efficacy and Safety of IV L-Citrulline for the Prevention of Clinical Sequelae of Acute Lung Injury Induced by Cardiopulmonary Bypass in Pediatric Patients Undergoing Surgery for Congenital Heart Defects (clinicaltrials.gov) - P3 | N=97 | Recruiting | Sponsor: Asklepion Pharmaceuticals, LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Acute Lung Injury • Pediatrics • Respiratory Diseases

A Study Evaluating the Efficacy and Safety of IV L-Citrulline for the Prevention of Clinical Sequelae of Acute Lung Injury Induced by Cardiopulmonary Bypass in Pediatric Patients Undergoing Surgery for Congenital Heart Defects (clinicaltrials.gov) - P3 | N=97 | Not yet recruiting | Sponsor: Asklepion Pharmaceuticals, LLC | Trial completion date: Jan 2023 ➔ Aug 2023 | Trial primary completion date: Dec 2022 ➔ Jun 2023

Trial completion date • Trial primary completion date • Acute Lung Injury • Pediatrics • Respiratory Diseases

A Study Evaluating the Efficacy and Safety of IV L-Citrulline for the Prevention of Clinical Sequelae of Acute Lung Injury Induced by Cardiopulmonary Bypass in Pediatric Patients Undergoing Surgery for Congenital Heart Defects (clinicaltrials.gov) - P3 | N=104 | Not yet recruiting | Sponsor: Asklepion Pharmaceuticals, LLC

New P3 trial • Acute Lung Injury • Pediatrics • Respiratory Diseases

Intravenous L-Citrulline to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients With COVID-19 (SARS-CoV-2) Illness (clinicaltrials.gov) - P2; N=65; Completed; Sponsor: Asklepion Pharmaceuticals, LLC; Recruiting ➔ Completed

Trial completion • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Folic acid, either solely or combined with L-citrulline, improves NO signaling and ameliorates chronic hypoxia-induced pulmonary hypertension in newborn pigs. (PubMed, Physiol Rep) - "Nonetheless, treatment with folic acid, either singly or when combined with L-citrulline, increases NO production and inhibits PH in chronically hypoxic newborn piglets. Folic acid merits consideration as a therapy for PH in human infants with chronic heart and lung conditions that are associated with chronic hypoxia."

Journal • Hypertension • Pulmonary Arterial Hypertension • Pulmonary Disease • Respiratory Diseases

Gut Microbiome Features Associated with Liver Fibrosis in Hispanics, a Population at High Risk for Fatty Liver Disease. (PubMed, Hepatology) - "Hispanics with liver fibrosis display microbiome profiles and associated functional changes that may promote oxidative stress and a pro-inflammatory environment. These microbiome signatures, together with NCK2 polymorphisms, may have utility in risk modeling and disease prevention in this high-risk population."

Clinical • Journal • Fibrosis • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Immunology • Liver Cirrhosis • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Oncology • Solid Tumor

L-citrulline Injection in Patients Aged 6-21 Years Old With Sickle Cell Disease Presenting With Vaso-Occlusive Crisis (VOC) (clinicaltrials.gov) - P1/2; N=120; Recruiting; Sponsor: Asklepion Pharmaceuticals, LLC; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

L-citrulline Injection in Patients Aged 6-21 Years Old With Sickle Cell Disease Presenting With Vaso-Occlusive Crisis (VOC) (clinicaltrials.gov) - P1/2; N=120; Not yet recruiting; Sponsor: Asklepion Pharmaceuticals, LLC

New P1/2 trial • Genetic Disorders • Hematological Disorders • Sickle Cell Disease

Intravenous L-Citrulline to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients With COVID-19 (SARS-CoV-2) Illness (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Asklepion Pharmaceuticals, LLC; Not yet recruiting ➔ Recruiting

Enrollment open • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases

Intravenous L-Citrulline to Delay and Potentially Prevent the Need for Invasive Mechanical Ventilation for Acute Hypoxemic Respiratory Failure in Patients With COVID-19 (SARS-CoV-2) Illness (clinicaltrials.gov) - P2; N=60; Not yet recruiting; Sponsor: Asklepion Pharmaceuticals, LLC

Clinical • New P2 trial • Infectious Disease • Novel Coronavirus Disease • Respiratory Diseases