Clinical Trials at American Society of Nephrology (ASN) – Kidney Week 2024

SAN FRANCISCO,Oct. 29,2024 -- Kind Pharmaceutical ("Hangzhou Andao Pharmaceutical Ltd. and Kind Pharmaceuticals LLC"),a clinical-stage biopharmaceutical company focused on developing innovative medicines to treat hematological diseases and cancers,today announced that positive results of four clinical trials from its leading program AND017 to treat anemia in non-dialysis dependent chronic kidney disease (NDD-CKD) and dialysis-dependent chronic kidney disease (DD-CKD) were presented at annual meeting of American Society of Nephrology (ASN) Kidney Week in San Diego. The four clinical trials are first-in-human trial in healthy subjects in Austria (clinical trial "AU-001",NCT04751539),food effects on pharmacokinetics (PK) in China (clinical trial "CN-101",NCT04712500),phase 2 trial in anemia in NDD CKD in both US and China (clinical trial "MN-201",NCT05035641),and phase 2 trial in anemia in DD CKD in both US and China (clinical trial "MN-202",NCT05265325).

In the AU-001 double-blinded,placebo-controlled,first-in-human clinical trial in healthy subjects in Australia,AND017 demonstrated favorable linear oral pharmacokinetics (PK) with T1/2 (elimination half-life) between 11.9 h and 19.7 h for the SAD part of trial (dosed from 1 mg to 50 mg) and T1/2 between 10.1 h and 19.4 h for the MAD part of trial (dosed from 4 mg to 30 mg QD for 10 days). In this trial,preliminary PD markers (EPO,Hb) were observed. In AU-001 trial,AND017 was safe and well tolerated in all doses (1 mg to 50 mg in SAD and 4 mg to 30 mg in MAD trials).

In the CN-101 phase I,randomized,open-label,two-sequence,two-period,crossover,single dose (10 mg) trial,the effect of food on the PK of AND017 was studied in non-elderly healthy subjects in China. The Fed/Fasted ratio of geometric mean of Cmax was 79.61% with 90% CI (73.40,86.34) and the Fed/Fasted ratio of geometric mean of AUC0-inf was 99.93% with 90% CI (96.31,103,68). The CN-101 trial demonstrated that AND017 with the current formulation can be administered with or without food.

In the MN-201 phase II,double-blinded,dose ranging study in U.S. and China,a total of 113 NDD CKD patients were randomized at 1:1:1:1 ratio to one of the four treatment groups to receive AND017 at three different doses of 8 mg,12 mg,16 mg,or placebo three times weekly (TIW) (28,29,28,and 28 patients respectively) in the first 5-week fixed-dose period; at Week 6 the drug-treated patients were combined and re-randomized to two TIW and once weekly (QW) dosing regimens to enter the 8-week titration period. At Week 6,the end of the titration period,all AND017 dose groups had significantly higher hemoglobin level (Hb) rise rate from baseline compared to placebo group; the dose of AND017 and the rate of rise in Hb were linearly correlated. After switching from the TIW dosing in the fixed-dose period,the Hb levels in both the TIW and QW dosing regimens maintained in the targeted range in the 8-week dose titration period. For the safety assessment,treatment emergent adverse events (TEAEs) occurred in 59 patients (69.4%) in the pooled AND017 group and 18 patients (64.3%) in the placebo group; the treatment-related TEAEs occurred in 10 patients (11.8%) in the pooled AND017 group and 1 patient (3.6%) in the placebo group. A total of six patients,three in AND017 12 mg group and three in AND017 16 mg group,experienced serious AEs (SAEs),none of which were assessed as treatment related. The MN-201 anemia in NDD-CKD trial demonstrated that AND017 was safe and well tolerated in NDD-CKD patients with safety prolife similar to the placebo; the drug effectively increased the Hb level in a dose-dependent manner starting at 8 mg TIW within the first 5-week fixed-dose period. The Hb levels were maintained within the target range 10.0-11.0 g/dL at both TIW and QW dosing groups in the following 8-week titration period.

The MN-202 trial is a phase II,active-controlled study to treat anemia in patients with dialysis-dependent with end-stage kidney disease (ESKD) in both U.S. and China. Eligible patients were randomized at a ratio of 1:1:1 to AND017 10 mg TIW group (59 pts),AND017 16 mg QW group (56 pts),and the active comparator erythropoietin stimulating agents (ESA) group (59 pts) and patients were treated for a total of 20-week study treatment with doses of AND017 adjusted based on the study protocol and doses of ESA adjusted based on the local package insert or clinical practice to target Hb ranges within 11.0-11.0 g/dL in U.S. and 10.0-12.0 g/dL in China. In the primary efficacy analysis,both AND017 10 mg TIW and 16 mg QW groups showed non-inferiority to ESA in the maintaining Hb levels within the target range during the 20-week treatment. For the safety assessment,treatment emergent adverse events (TEAEs) occurred in 91 patients (78.4%) treated with AND017 and 39 patients (66.1%) treated with ESA. Among all frequently reported TREAEs,the only TEAE deemed treatment-related was hyperkalemia (1 patient,1.7% from the AND017 10 mg TIW group); other treatment-related TEAEs were all <5% and occurred in no more than 2 patients in the pooled AND017 or ESA groups. A total of 48 patients experienced SAEs,with 35 patients (30.2%) treated with AND017 and 13 patients (22.0%) treated with ESA; none were assessed as treatment related. Both TIW and QW dosing regimens of AND017 effectively maintained Hb levels after 20 weeks of treatment in ESA-treated dialysis-dependent ESKD patients and demonstrated non-inferiority to ESA treatment with a favorable safety profile.

"AND017 demonstrated adequate safety and effectively increased and maintained hemoglobin levels in the 10.0-11.0 g/dL range in two Phase II studies involving both NDD and DD CKD patient populations. Efficacy and safety will be further assessed in Phase III trials," said Pablo E. Pergola,MD,Ph.D.,an expert in nephrology and the director of the Clinical Advancement Center,PLLC,a wholly-owned subsidiary of Renal Associates.

"We are excited about the overall PK,efficacy and safety profiles of our compound; our results provided a once weekly,longer interval dosing option in the same class of drugs," Qi Zhu,the CMO of Kind Pharmaceutical. "The longer interval dosing could be one of the keys to mitigate MACE issue,which plagued the previous clinical trials for anemia in NDD CKD. We are willing to tackle this tough problem in phase III trials."

The summary of the results from the four clinical trials presented at ANS is shown below; for more detail,please read the posters from Kind's website.

Last week FDA granted Orphan Drug Designation to this investigation drug in Sickle Cell Disease (SCD) treatment.

About Anemia in Chronic Kidney Disease

Chronic kidney disease (CKD) is very common in general population; the prevalence for CKD in the United States is about 14% in adults and that in China is about 8%. Anemia is a common complication in chronic kidney disease. There are about half million dialysis-dependent CKD anemia patients and about five million non-dialysis-dependent CKD anemia patients in US; it is estimated there are about 700K DD CKD anemia patients and about 50 million NDD CKD anemia patients in China. Anemia in CKD can increase the risk of cardiovascular complications,such as heart failure and stroke,and increase morbidity and mortality.

About AND017

AND017 is a first-in-class hemoglobin elevating agent (HbEA) that targets multiple stages of the red blood cell (RBC) life cycle and is being developed to treat anemia associated with dialysis-dependent chronic kidney disease (DD-CKD),non-dialysis dependent chronic kidney disease (NDD-CKD),cancer-related anemia (CRA),myelodysplastic syndromes (MDS) anemia,sickle cell disease (SCD),and β-thalassemia.

About Kind Pharmaceutical ("Hangzhou Andao Pharmaceutical Ltd. and Kind Pharmaceuticals LLC")

KIND is a clinical-stage biopharmaceutical company focused on developing innovative medicines to treat hematological diseases and cancers. The company's mission,"kind to human,humble to science,good to patients",drives its commitment to advancing current science to meet unmet medical need. KIND's lead clinical candidate,AND017,first-in-class hemoglobin elevating agent (HbEA),is being developed for treating anemia of various disorders,including dialysis dependent chronic kidney disease (DD-CKD) associated anemia,non-dialysis dependent (NDD) CKD associated anemia,cancer related anemia (CRA),and β-thalassemia. KIND's second clinical candidate,AND019,an orally available brain penetrant selective estrogen receptor degrader (SERD),is being developed to treat ER+/Her2- breast cancer. KIND is also developing promising disruptive next generation ADC technologies. For details,please visit http://en.kindpharmaceutical.com.

Contact:

Dong Liu,PhD,Chairman and CEO of Kind Pharmaceutical

Email: liudong@kindpharmaceutical.com

Tel: 650-315 6151