AND017 / Hangzhou Andao Pharma - LARVOL DELTA

A Study of AND017 to Evaluate Efficacy and Safety in Patients With Anemia Due to Non-Dialysis-Dependent Chronic Kidney Disease (NDD-CKD) (clinicaltrials.gov) - P3 | N=240 | Recruiting | Sponsor: Kind Pharmaceuticals LLC

New P3 trial • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

A Study of AND017 to Evaluate Efficacy and Safety in Dialysis-Dependent Chronic Kidney Disease (DD-CKD) Patients With Anemia (clinicaltrials.gov) - P3 | N=300 | Recruiting | Sponsor: Kind Pharmaceuticals LLC

New P3 trial • Anemia • Chronic Kidney Disease • Hematological Disorders • 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 2026 ➔ May 2028 | Trial primary completion date: Dec 2025 ➔ Dec 2027

Trial completion date • Trial primary completion date • Anemia • Chemotherapy-Induced Anemia • Oncology

A Study of Safety and Efficiency of AND017 in Patients With β-thalassemia (clinicaltrials.gov) - P2 | N=64 | Recruiting | Sponsor: Kind Pharmaceuticals LLC | Trial completion date: Jul 2026 ➔ Jul 2027 | Trial primary completion date: Dec 2025 ➔ Dec 2026

Trial completion date • Trial primary completion date • Beta-Thalassemia • Genetic Disorders

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 2027 ➔ Aug 2028 | Trial primary completion date: Jan 2026 ➔ May 2028

Trial completion date • Trial primary completion date • Anemia • Oncology

A Study of Efficacy and Safety of AND017 in Patients With Myelodysplastic Syndrome (clinicaltrials.gov) - P2 | N=63 | Recruiting | Sponsor: Kind Pharmaceuticals LLC | Not yet recruiting ➔ Recruiting

Enrollment open • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

The efficacy of hypoxia-inducible factor prolyl hydroxylase inhibitor AND017 in NUP98-HOXD13transgenic mouse (ASH 2025) - "In the bone marrowof AND017 group, the frequency of ErPs within megakaryocyte-erythroid progenitor cells was higher.Transcriptome sequencing of ErPs in the two groups exhibited that HIF-1, PI3K−Akt and apoptosissignaling pathway were significantly upregulated, while porphyrin metabolism, cell cyclep53 signalingpathways and ferroptosis were downregulated in the AND017 group.ConclusionsAND017 can significantly and sustainably improve anemia of NHD13 mice. It may play a certain role inregulating erythroid progenitors and can efficiently promote terminal erythroid differentiation in NHD13mice, while the specific mechanism needs to be study further."

Preclinical • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • CD34 • HIF1A • ITGA2B • KIT • NUP98 • TFRC

Pharmacological mechanism of action and therapeutic potential of a quantitative and qualitative RBC- and hemoglobin-elevating agent AND017 in the Townes SCD model (ASH 2025) - "Hydroxyurea (HU), a once-daily oral fetal hemoglobin (HbF) inducer andcurrent standard-of-care, exerts its therapeutic effect by achieving sufficient HbF induction to preventRBC sickling and hemolysis. Furthermore, AND017functions as a HIF-PHI, promoting mitophagy and shifting mitochondrial metabolism toward glycolysis,which collectively promotes erythroid maturation and reduces the Mito-ROS and oxidative stresses inRBCs. Overall, our results support the potential of AND017 as a safe, efficacious, and orally convenienttherapy for patients with SCD, warranting further clinical investigation."

Anemia • Chronic Kidney Disease • Gene Therapies • Genetic Disorders • Hematological Disorders • Nephrology • Renal Disease • Sickle Cell Disease • HIF1A

Quantitative Pharmacology of AND017, a Novel Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (HIF-PHI), to Support Phase 3 Dose Selection in Anemia Due to CKD (KIDNEY WEEK 2025) - "Conclusion Given the PK differences between NDD-CKD and DD-CKD patients, the starting doses of AND017 will be 8 mg TIW and 10 mg TIW, respectively. Once Hb levels reach the target range, dosing may be switched from TIW to QW at a slightly higher dose."

P3 data • Anemia • Chronic Kidney Disease • Hematological Disorders

Phase 3 Study of AND017, a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (HIF-PHI), in Patients with Anemia Due to Nondialysis-Dependent CKD (NDD-CKD) (KIDNEY WEEK 2025) - "The non-inferiority of AND017 to ESA treatment will be established if the lower bound of the 1-sided 95% CI in mean Hb is ≥-1.0 g/dL. This protocol has been reviewed with the China NMPA and is considered a pivotal Phase 3 trial of AND017 for the treatment of anemia in CKD in China."

Clinical • P3 data • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

Phase 3 Study of AND017, a Hypoxia-Inducible Factor-Prolyl Hydroxylase Inhibitor (HIF-PHI), in Anemic Patients with Dialysis-Dependent CKD (DD-CKD) (KIDNEY WEEK 2025) - "The non-inferiority of AND017 to ESA will be established if the lower bound of the 1-sided 95% CI in mean Hb is ≥-1.0 g/dL. This protocol has been reviewed with the China NMPA and is considered a pivotal Phase 3 trial of AND017 for the treatment of anemia in CKD in China."

Clinical • P3 data • Anemia • Chronic Kidney Disease • Hematological Disorders • Nephrology • Renal Disease

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 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

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 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 • 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

A single-center, open-label, single-arm Phase II clinical study of AND017 for the treatment of anemia in participants with IPSS-R low-risk myelodysplastic syndrome (MDS) (ChiCTR) - P2 | N=104 | Recruiting | Sponsor: Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences; Institute of Hematology & Blood Diseases Hospital, Chi

New P2 trial • Anemia • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology

THE EFFICACY OF HYPOXIA-INDUCIBLE FACTOR PROLYL HYDROXYLASE INHIBITOR AND017 IN NUP98-HOXD13 TRANSGENIC MOUSE (MDS 2025) - "In comparison with NHD13 mice in vehicle group, the percentage of basophilic erythroblasts in bone marrow significantly decreased while the percentage of orthochromatic and reticulocytes significantly increased in AND017 group after two-week administration of AND017(Figure 2). ConclusionsAND017 can significantly improve anemia of NHD13 mice continuously and efficiently promote terminal erythroid differentiation in bone marrow of NHD13 mice, while the specific mechanism needs to be study further."

Preclinical • Hematological Malignancies • NUP98 • TFRC

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

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

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