AND017 / Hangzhou Andao Pharma - LARVOL DELTA

Clostridioides (Clostridium) difficile in hospitalised children in Cambodia. (PubMed, Anaerobe) - "A high prevalence of C. difficile was found in hospitalised children, with a high proportion of non-toxigenic and novel strains. Larger studies are required with whole genome sequencing necessary for characterising novel strains and advancing molecular epidemiological research in Asia."

Journal • Infectious Disease • Pain • Pediatrics

Pharmacological Evaluation of a First-in-Class Hemoglobin Elevating Agent (HbEA) AND017 in a Hbbd3th β-Thalassemia Mouse Model (ASH 2024) - "Treatments include blood transfusion plus iron chelation, hematopoietic stem cell transplantation, and recently FDA approved luspatercept, a "ligand trap" for various members of the TGF-β superfamily, and gene therapies; however, none of them can be widely applicable due to social-economical limitations. The increases in body weights and morphology improvements in red blood cells indicated AND017 could be a safe and effective oral treatment for β-thalassemia patients. Future clinical trials for AND017 in treating thalassemia are warranted."

Preclinical • Anemia • Beta-Thalassemia • Bone Marrow Transplantation • Chronic Kidney Disease • Gene Therapies • Genetic Disorders • Hematological Disorders • Sickle Cell Disease • MYC • TGFB1

Pharmacological Evaluation of a First-in-Class Hemoglobin Elevating Agent (HbEA) AND017 in Sprague Dawley Rats (ASH 2024) - "BackgroundInhibiting hypoxia-inducible factor prolyl hydroxylase (HIF-PH) by oral small molecules has been intensively pursued in treating chronic kidney disease (CKD) anemia during the past 20 years, leading to approval of daprodustat and vadadustat by FDA in treating dialysis-dependent (DD) CKD anemia in US while both plus roxadustat failed in getting approval by FDA in treating non-dialysis dependent (NDD) CKD anemia in US due to safety concerns. The hematocrits (%) for group 1 to 4 were between 38.7 and 39.1 on day 1, were 41.7±1.5, 44.0±2.0, 48.6±2.5**, and 57.9±2.7** respectively on day 28, and were 42.5±1.4, 41.7±1.5, 43.6±1.5, and 41.9±0.9 respectively on day 56. (Significance analysis was compared to group 1,* p<0.05,** p<0.01)ConclusionRBC, HGB, and HCT in normal SD male rats were significantly increased after dosing AND017 at 2.5 and 5 mg/kg PO QD for 4 weeks and gradually recovered to background levels after..."

Preclinical • Anemia • Beta-Thalassemia • Cardiovascular • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Renal Disease • Sickle Cell Disease • MYC

Pharmacological Evaluation of a First-in-Class Hemoglobin Elevating Agent (HbEA) AND017 in a Rat 5/6 Nephrectomy Model (ASH 2024) - "BackgroundTwo hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHI), daprodustat and vadadustat, have been approved by FDA to treat dialysis dependent (DD) chronic kidney disease (CKD) anemia patients in US while all HIF-PHIs failed in getting approval by FDA in treating non-dialysis dependent (NDD) CKD anemia in US due to safety concerns. The hematocrits (%) for 5 groups were between 38.2±1.5 and 39.4±2.0 on day 1, were 41.6±1.6**, 36.3±1.9, 36.3±1.4, 37.2±1.2, and 36.3±1.7 respectively on day 35, were 41.8±1.3**, 36.8±2.4, 39.4±1.9*, 43.9±1.4**, and 51.4±2.8** respectively on day 49, and were 41.0±1.2**, 35.2±2.3, 39.0±3.6*, 45.7±3.1**, and 59.1±3.7** respectively on day 63. (Significance analysis was compared to group 2,* p<0.05,** p < 0.01)ConclusionThe rat 5/6 nephrectomy CKD anemia model was successfully established; on day 63, RBC, HGB, and HCT for rats in three..."

Preclinical • Anemia • Beta-Thalassemia • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Renal Disease • Sickle Cell Disease • MYC

KIND Presents Preclinical Results of AND017 in Animal Models of…Myelodysplastic Syndromes (MDS), and β-Thalassemia at the 66th American Society of Hematology Meeting… (PRNewswire) - "In an inducible mutant c-Myc knock-in MDS mouse model, AND017 showed dramatic effects in improving hemoglobin level, red blood cell count, and hematocrit, while high-dose epoetin (EPO) had very little efficacy...In the Hbbd3th β-thalassemia mouse model, AND017 (15 mg/kg, PO, QD, 42 days), when compared to vehicle, increased Hb level by 22%, increased RBC numbers by 14%, and increased HCT by 21%. AND017 also improved morphology of RBCs."

Preclinical • Beta-Thalassemia • Myelodysplastic Syndrome

Pharmacological Evaluation of a First-in-Class Hemoglobin Elevating Agent (HbEA) AND017 in Townes SCD Mouse Model (ASH 2024) - "The current standard-of-care, a once daily oral hydroxyurea (HU), could increases expression of HbF and the magnitude of response (9-24% HbF) correlates with a reduction in anemia, pain crises and other complications in patients. These results indicate that AND017 has the potential to be a safe, efficacious and convenient oral drug for SCD patients. Future clinical trials for AND017 in SCD are warranted."

Preclinical • Anemia • Beta-Thalassemia • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Nephrology • Pain • Renal Disease • Sickle Cell Disease • HBG1 • HBG2

Pharmacological Evaluation of a First-in-Class Hemoglobin Elevating Agent (HbEA) AND017 in a Mouse MDS Model of an Inducible Mutant c-Myc Knock-in (ASH 2024) - "To mimic low c-Myc-driven MDS-like phenotypes in mice, we generated a knock-in (KI) mouse model by introducing a doxycycline-inducible double mutations c-Myc (T58A/S62E) expression cassette at Collagen 1A1 (Col1a1) locus. These results indicate that AND017 has the potential to be a safe, efficacious and convenient treatment for MDS patients in the future. Future clinical trials for AND017 in MDS are warranted."

Preclinical • Anemia • Beta-Thalassemia • Chronic Kidney Disease • Genetic Disorders • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Nephrology • Oncology • Renal Disease • Sickle Cell Disease • COL1A1 • MYC • VAV1

KIND Presents Preclinical Results of AND017 in Animal Models of Sickle Cell Disease (SCD)…at the 66th American Society of Hematology Meeting and Exposition and Announces FDA Authorization of Investigational New Drug (IND) Application for AND017 for Clinical Trial in Sickle Cell Disease (SCD) (PRNewswire) - "Kind Pharmaceutical...today announced that preclinical results from its leading program AND017 in Townes Sickle Cell Disease (SCD) mouse model...Concurrently, the U.S. Food and Drug Administration (FDA) approved the investigational new drug application for AND017 for the clinical trial in treating SCD patients. In the Townes SCD mouse model, AND017 was shown to elevate several important parameters related to anemia, including hemoglobin (Hb), red blood cells (RBC), and hematocrit (HCT), and significantly reduce mitochondrial retention in reticulocytes and mature RBCs in mice of the Townes SCD model...'In the Townes mouse model, beyond the erythropoiesis mechanism previously proposed for the treatment of CKD anemia with HIF-PH inhibitors, we found that AND017 could reduce red blood cell sickling and hemolysis by significantly improving their abnormal mitochondrial retention and reactive oxygen species (ROS) in SCD mice'..."

IND • Preclinical • Hematological Disorders • Sickle Cell Disease

Efficacy and Safety of AND017 for Treatment of Anemia in Dialysis-Dependent CKD (KIDNEY WEEK 2024) - P2 | "AND017 was safe and well tolerated in patients with ESKD on stable dialysis. At both TIW and QW dosing frequencies, AND017 effectively maintained Hb levels within the target range after 20 weeks of treatment and demonstrated non-inferiority to ESA treatment."

Clinical • Late-breaking abstract • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology

First-in-Human Study of Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (HIF-PHI) AND017 in Healthy Participants (KIDNEY WEEK 2024) - P1 | "AND017 appeared to be safe and well tolerated when administered to healthy adult subjects at oral doses ranging from 1 mg up to 50 mg in the SAD part and 4 mg up to 30 mg in the MAD part."

Clinical • P1 data • Fatigue • Pain

Effect of Food on the Pharmacokinetics of AND017 in a Phase I Study (KIDNEY WEEK 2024) - P1 | "In summary, a single dose of AND017 at 10 mg administered alone or in combination with food was generally safe and well-tolerated in healthy non-elderly volunteers. The study supports the safe use of AND017 under fed or fasted conditions."

P1 data • PK/PD data • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Safety and Efficacy of AND017, a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (HIF-PHI), in Patients with Nondialysis-Dependent CKD (NDD-CKD) (KIDNEY WEEK 2024) - P2 | "AND017 was safe and well tolerated in patients with NDD-CKD and anemia. AND017 effectively increased Hb level in a dose-dependent manner starting at 8 mg TIW within the first 5-week Fixed-dose period and maintained Hb within 10.0-11.0 g/dL at both TIW and QW dosing frequency in the following 8-week Titration period."

Clinical • Anemia • Chronic Kidney Disease • Hematological Disorders

KIND Announces Late-Breaking Abstract Accepted for Presentation on AND017 Clinical Trials to Treat Anemia in Chronic Kidney Disease (CKD) at ASN - Kidney Week 2024 (PRNewswire) - "Kind Pharmaceutical...announced that the late-breaking abstract on the AND017 Phase 2 clinical trial for treatment of anemia in dialysis-dependent chronic kidney disease (DD-CKD) was accepted to present at the annual meeting of American Society of Nephrology (ASN) Kidney Week in San Diego on October 24-27, 2024. Three other posters about the results of AND017 Phase 1 in healthy volunteers and Phase 2 for treatment of anemia in non-dialysis dependent chronic kidney disease (NDD-CKD) were also accepted to present previously."

Clinical data • Anemia • Chronic Kidney Disease • Hematological Disorders

A Study of AND017 to Treat Anemia in Chronic Kidney Disease Patients on Dialysis (clinicaltrials.gov) - P2 | N=175 | Completed | Sponsor: Kind Pharmaceuticals LLC | Active, not recruiting ➔ Completed | N=120 ➔ 175

Enrollment change • Trial completion • Anemia • Chronic Kidney Disease • Hematological Disorders • Myelodysplastic Syndrome • Nephrology • Renal Disease

A Study of Safety and Efficiency of AND017 in Patients With β-thalassemia (clinicaltrials.gov) - P2 | N=64 | Recruiting | Sponsor: Kind Pharmaceuticals LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Beta-Thalassemia • Genetic Disorders

ANALYSIS OF INPATIENT ADMISSIONS AND MORTALITY RATE OF AUTOIMMUNE HEPATITIS (AIH), PRIMARY BILIARY CIRRHOSIS (PBC), AND PRIMARY SCLEROSING CHOLANGITIS (PSC): A UNITED STATES NATIONWIDE STUDY. (DDW 2024) - "All subjects admitted between 011 and 017 with a diagnosis of AiLD (AIH PBC PSC) were identified using the International Classification of Diseases (ICD-9) and (ICD-10) codes...AiLD-related admissions appeared to have a signfinciant decline over the studied years with a decrease in length of stay. However we observed a significanti increase in financial burden on healthcare with increasing in-hospital costs with the majority of patients affected by Acute renal failure."

Clinical • Acute Kidney Injury • Autoimmune Hepatitis • Fibrosis • Gastrointestinal Cancer • Hepatocellular Cancer • Hepatology • Immunology • Inflammation • Oncology • Primary Biliary Cholangitis • Renal Disease • Solid Tumor

LONG-TERM RISK OF HEART FAILURE IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A NATIONWIDE POPULATION-BASED, SIBLING-CONTROLLED COHORT STUDY (DDW 2024) - " In this Swedish nationwide cohort patients with biopsy-confirmed IBD were identified between 1969 and 017 [n=81 749 Crohn's disease (CD n= 4 303) ulcerative colitis (UC n=45 709) and IBD-unclassified (IBD-U n=11 737)]... Patients with overall IBD had a moderately higher risk of developing HF for ≥ 0 years after IBD diagnosis."

Clinical • Cardiovascular • Congestive Heart Failure • Crohn's disease • Gastroenterology • Gastrointestinal Disorder • Heart Failure • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis

HEPATITIS B VERSUS HEPATITIS B DELTA CO-INFECTION AND RISK OF HEPATOCELLULAR CARCINOMA IN NON-CIRRHOTIC LIVER (DDW 2024) - "Method We conducted a nationwide review from 016 and 017 using the National Inpatient Sample (NIS)...The molecular profile of HCC-HDV is unique and distinct from that of HBV-HCC and has an enrichment of upregulated genes involved in cell-cycle/DNA replication DNA damage and repair which point to genome instability as an important mechanism of HDV hepatocarcinogenesis. Further studies are required to elucidate the carcinogenetic nature of HDV."

Fibrosis • Gastrointestinal Cancer • Hepatitis B • Hepatitis C • Hepatocellular Cancer • Hepatology • Immunology • Infectious Disease • Liver Failure • Oncology • Solid Tumor • KEAP1

EFFECT OF HELICOBACTER PYLORI TREATMENT ON RECURRENCE OF UPPER GASTROINTESTINAL BLEEDING IN ATRIAL FIBRILLATION PATIENTS WITH ANTITHROMBOTIC AGENTS (DDW 2024) - "While previous studies have reported the effect of HP eradication on GIB in participants taking aspirin and non-steroidal anti-inflammatory drugs (NSAIDs) its effect on GIB in AF patients taking anticoagulants is not well established...Based on the nationwide claims and health database we identified all AF patients newly diagnosed with upper GIB between 010 and 017. Patients were divided into three cohorts according to the anti-thrombotic use after AF diagnosis: warfarin NOAC and anti- platelets... AF patients with GIB were not significantly associated with a lower risk for recurrent GIB after HP treatment irrespective of the kinds of anti-thrombotic taken. However for AF patients on anti-platelet HP treatment reduced the risk of all-cause mortality during 5-years follow-up."

Clinical • Atrial Fibrillation • Cardiovascular • Gastroenterology • Gastrointestinal Disorder • Infectious Disease

HELICOBACTER PYLORI INFECTION AND INCREASED RISK OF NEW-ONSET PRIMARY SJOGREN’S SYNDROME: A POPULATION-BASED COHORT STUDY (DDW 2024) - " This population-based cohort study included patients diagnosed with H. pylori infections or peptic ulcer disease undergoing H. pylori eradication therapies between 000 and 017...Conclusion : Patients with H. pylori infections presented with an increased risk of SS especially in younger females and elderly males. Rheumatology referrals are needed for patients with H. pylori present who had symptoms indicative of SS."

Clinical • Gastroenterology • Gastrointestinal Disorder • Immunology • Infectious Disease • Oncology • Peptic Ulcer • Rheumatology • Sjogren's Syndrome

A Study of AND017 to Treat Anemia in Chronic Kidney Disease Patients on Dialysis (clinicaltrials.gov) - P2 | N=120 | Active, not recruiting | Sponsor: Kind Pharmaceuticals LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • Anemia • Chronic Kidney Disease • Hematological Disorders • Myelodysplastic Syndrome • Nephrology • Renal Disease

A Study of AND017 in Cancer Related Anemic Patients Receiving Chemotherapy (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Kind Pharmaceuticals LLC | Trial completion date: May 2025 ➔ May 2026 | Initiation date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2024 ➔ Dec 2025

Trial completion date • Trial initiation date • Trial primary completion date • Anemia • Chemotherapy-Induced Anemia • Hematological Disorders • Oncology

A Study of AND017 to Treat Cancer Related Anemia in Patients Not Receiving Chemotherapy (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Kind Pharmaceuticals LLC | Trial completion date: Aug 2025 ➔ Aug 2027 | Initiation date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Jan 2025 ➔ Jan 2026

Trial completion date • Trial initiation date • Trial primary completion date • Anemia • Hematological Disorders • Oncology

A Study of AND017 to Treat Anemia in Chronic Kidney Disease Patients on Dialysis (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Kind Pharmaceuticals LLC | Not yet recruiting ➔ Recruiting | Trial primary completion date: Jun 2024 ➔ Mar 2024

Enrollment open • Trial primary completion date • Anemia • Chronic Kidney Disease • Hematological Disorders • Myelodysplastic Syndrome • Nephrology • Renal Disease

A Study of AND017 to Treat Anemia in Non-dialysis-Dependent Chronic Kidney Disease (NDD-CKD) Patients (clinicaltrials.gov) - P2 | N=113 | Completed | Sponsor: Kind Pharmaceuticals LLC | Active, not recruiting ➔ Completed

Trial completion • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease