licancopan fumarate (HRS-5965) / Jiangsu Hengrui Pharma - LARVOL DELTA

Hengrui's licancopan wins China PNH approval after outperforming eculizumab in Phase III (AllSci Corp) - "Licancopan fumarate (HRS-5965) capsules are approved at a 25 mg strength as a prescription drug....The approval was supported by a randomized Phase III trial in 78 complement inhibitor-naïve PNH patients comparing oral licancopan with intravenous eculizumab over 24 weeks."

China approval • Paroxysmal Nocturnal Hemoglobinuria

A Trial of HRS-5965 Tablets in Primary IgA Nephropathy (clinicaltrials.gov) - P2 | N=123 | Completed | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Active, not recruiting ➔ Completed | Trial primary completion date: Dec 2024 ➔ Oct 2025

Trial completion • Trial primary completion date • Glomerulonephritis • IgA Nephropathy • Renal Disease

A Trial to Evaluate the Long-term Safety and Tolerability of HRS-5965 in Patients With Primary IgA Nephropathy (clinicaltrials.gov) - P2 | N=380 | Recruiting | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Glomerulonephritis • IgA Nephropathy • Renal Disease

EFFICACY AND SAFETY OF HRS-5965 IN PAROXYSMAL NOCTURNAL HEMOGLOBINURIA PATIENTS WITH PERSISTENT ANEMIA DESPITE STABLE C5 INHIBITOR THERAPY: A MULTICENTER, SINGLE-ARM, OPEN-LABEL PHASE 3 STUDY (EHA 2026) - "Efficacy and Safety Outcomes HRS-5965 50mg bid (N = 39) Primary endpoints Hb ≥12 g/dL # , n (%) (95% CI) 27 (69.2; 52.4, 83.0) Secondary endpoints Hb increase ≥2 g/dL #, *, n (%) (95% CI) 36 (92.3; 79.1, 98.4) Transfusion avoidance (after Wk 2), n (%) (95% CI) 39 (100.0; 91.0-100.0) Mean Hb change from baseline (g/dL) # , LS Mean (SE) (95% CI) 4.95 (0.14) (4.66, 5.24) FACIT-Fatigue score improvement # , LS Mean (SE) (95% CI) 8.75 (0.26) (8.23, 9.26) Reticulocyte count change # , x10 ⁹ /L, LS Mean (SE) (95% CI) -170.18 (3.52) (-177.13, -163.23) Safety MAVEs, n (%) 0 Treatment-related AEs, n (%) 19 (48.7) Treatment-related serious AEs, n (%) 2 (5.1) # Assessed over Weeks 18-24 in the absence of RBC transfusions after Week 2. *Hb increase ≥2 g/dL was the key secondary endpoint."

Clinical • P3 data • Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Thrombocytopenia

EFFICACY AND SAFETY OF HRS-5965 VERSUS ECULIZUMAB IN PATIENTS WITH PAROXYSMAL NOCTURNAL HEMOGLOBINURIA: A MULTICENTER, RANDOMIZED, OPEN-LABEL, ACTIVE-CONTROLLED PHASE 3 TRIAL (EHA 2026) - "Efficacy and Safety Outcomes HRS-5965 (N=40) Eculizumab (N=36) Difference (95% CI) P value Primary endpoints Hb ≥12 g/dL # , n (%) 28 (70.0%) 4 (11.1%) 57.4% (39.6-75.2) <0.0001 Secondary endpoints Hb increase ≥2 g/dL #, *, n (%) 38 (95.0%) 20 (55.6%) 39.2% (20.9-57.4) <0.0001 Transfusion-free (after Wk 2), n (%) 40 (100%) 31 (86.1%) 13.7% (2.4-24.9) 0.0149 Mean Hb change from baseline # , g/dL, LS Mean (SE) 5.47 (0.31) 2.86 (0.32) 2.61 (1.72-3.49) <0.0001 FACIT-Fatigue score improvement # , LS Mean (SE) 8.62 (0.70) 4.43 (0.74) 4.19 (2.15-6.23) 0.0001 Reticulocyte count change from baseline # , x10 ⁹ /L, LS Mean (SE) -118.97 (9.41) 42.40 (9.93) -161.37 (-188.62, -134.13) <0.0001 Safety MAVEs, n (%) 0 0 — — TRAEs, n (%) 29 (72.5%) 20 (55.6%) — — Treatment-related serious AEs, n (%) 2 (5.0%) 0 — — # Assessed over Weeks 18-24 in the absence of RBC transfusions after Week 2. *Hb increase ≥2 g/dL was the key secondary endpoint."

Clinical • P3 data • Complement-mediated Rare Disorders • Hematological Disorders • Infectious Disease • Paroxysmal Nocturnal Hemoglobinuria • Pneumonia • Rare Diseases • Respiratory Diseases

A Trial to Evaluate the Long-term Safety and Tolerability of HRS-5965 in Patients With Primary IgA Nephropathy (clinicaltrials.gov) - P2 | N=380 | Not yet recruiting | Sponsor: Chengdu Suncadia Medicine Co., Ltd.

New P2 trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

HRS-5965-103: Investigation of Pharmacokinetics,Safety,and Pharmacodynamics of HRS-5965 in Subjects With Hepatic Impairment (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Recruiting ➔ Completed | Trial completion date: Mar 2025 ➔ Jan 2026 | Trial primary completion date: Mar 2025 ➔ Jan 2026

Trial completion • Trial completion date • Trial primary completion date • Hepatology • Renal Disease

Efficacy and Safety of HRS-5965 in Patients With PNH Who Are Still Anemia After Anti-C5 Antibody Treatment (clinicaltrials.gov) - P3 | N=39 | Completed | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Comparison of HRS-5965 Capsules and Tablets in Healthy Subjects (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease

HRS-5965-203: Long-term Safety and Tolerability of HRS-5965 in Patients With Paroxysmal Nocturnal Hemoglobinuria (clinicaltrials.gov) - P2 | N=132 | Active, not recruiting | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

Multicenter, Randomized Phase 2 Study Evaluating the Efficacy and Safety of HRS-5965 in Patients with Primary IgAN (KIDNEY WEEK 2025) - "Most common TEAEs (＞ 10%) in HRS-5965 groups were upper respiratory tract infection and hyperuricemia. Conclusion HRS-5965 showed proteinuria reduction in IgAN patients with acceptable safety and tolerability, which will further support the evaluation of HRS-5965 in phase 3 clinical trials."

Clinical • Late-breaking abstract • P2 data • Glomerulonephritis • IgA Nephropathy • Infectious Disease • Inflammation • Respiratory Diseases • CFB

Efficacy and Safety of HRS-5965 Monotherapy in Patients with Paroxysmal Nocturnal Hemoglobinuria Who Have Not Received Complement Inhibitors: A Proof-of-Concept, Multicenter, Randomized, Open-Label Study (ASH 2024) - P2 | "Both dosages were well-tolerated. This study provides evidence that HRS-5965 might represent a novel treatment option for this patient population."

Clinical • Monotherapy • Anemia • Aplastic Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • CFB

Efficacy and Safety of HRS-5965 in Patients With PNH Who Are Still Anemia After Anti-C5 Antibody Treatment (clinicaltrials.gov) - P3 | N=39 | Active, not recruiting | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Recruiting ➔ Active, not recruiting

Enrollment closed • Anemia • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

HRS-5965-301: A Study to Evaluate the Efficacy and Safety of Oral HRS-5965 in Adult Paroxysmal Nocturnal Hemoglobinuria (PNH) Patients Who Are Naive to Complement Inhibitor Therapy (clinicaltrials.gov) - P3 | N=76 | Completed | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Active, not recruiting ➔ Completed | Trial completion date: Dec 2025 ➔ Jul 2025 | Trial primary completion date: Dec 2025 ➔ Jul 2025

Trial completion • Trial completion date • Trial primary completion date • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases

A Trial of HRS-5965 Capsule in Primary IgA Nephropathy (clinicaltrials.gov) - P3 | N=378 | Recruiting | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Not yet recruiting ➔ Recruiting

Enrollment open • Glomerulonephritis • IgA Nephropathy • Renal Disease

Investigation of Drug-drug Interaction of HRS-5965 With Clopidogrel and Clarithromycin in Healthy Subjects (clinicaltrials.gov) - P1 | N=36 | Active, not recruiting | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Anemia • Hematological Disorders • Renal Disease

Investigation of Drug-drug Interaction of HRS-5965 With Clopidogrel and Clarithromycin in Healthy Subjects (clinicaltrials.gov) - P1 | N=36 | Completed | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Active, not recruiting ➔ Completed

Trial completion • Anemia • Hematological Disorders • Renal Disease

A Clinical Study to Evaluate the Effect of Food on the Pharmacokinetic Profiles of HRS-5965 Capsules in Healthy Subjects (clinicaltrials.gov) - P1 | N=16 | Completed | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Not yet recruiting ➔ Completed

Trial completion • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease

HRS-5965-106: A Safety, Tolerability, Pharmacokinetic/Pharmacodynamic Study, and QT Interval Study of HRS-5965 Capsules in Healthy Subjects (clinicaltrials.gov) - P1 | N=32 | Completed | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | Recruiting ➔ Completed

Trial completion • Anemia • Hematological Disorders

Efficacy and safety of HRS-5965 monotherapy in complement inhibitor-naïve patients with paroxysmal nocturnal haemoglobinuria. (PubMed, Br J Haematol) - "The most common treatment-related adverse events were mild lab abnormalities, including increased alkaline phosphatase and alanine aminotransferase. In conclusion, HRS-5965 monotherapy at either 50 or 75 mg BID resulted in substantial Hb improvements and reduced haemolysis with an acceptable safety profile, suggesting its potential as a promising oral therapy for complement inhibitor-naïve PNH patients."

Journal • Monotherapy • Cardiovascular • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Thrombosis • CFB

Investigation of Drug-drug Interaction of HRS-5965 With Clopidogrel and Clarithromycin in Healthy Subjects (clinicaltrials.gov) - P1 | N=36 | Not yet recruiting | Sponsor: Chengdu Suncadia Medicine Co., Ltd.

New P1 trial • Anemia • Hematological Disorders • Renal Disease

A Clinical Study to Evaluate the Effect of Food on the Pharmacokinetic Profiles of HRS-5965 Capsules in Healthy Subjects (clinicaltrials.gov) - P1 | N=16 | Not yet recruiting | Sponsor: Chengdu Suncadia Medicine Co., Ltd.

New P1 trial • Complement-mediated Rare Disorders • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases • Renal Disease

Efficacy And Safety Of Hrs-5965 In Patients With Primary Immunoglobulin A Nephropathy (Igan): A Randomized, Double-Blind, Parallel, Placebo-Controlled Phase 2 Trial (ERA 2025) - P1, P2 | "Consistent with its mechanism of action, HRS-5965 results in clinically meaningful proteinuria reduction with in IgAN patients at 12 weeks compared with placebo. This suggests that HRS- 5965 may reduce the risk of chronic kidney disease progression. These results reinforce the therapeutic rationale for selective AP inhibitors and further support the evaluation of HRS-5965 in phase 3 clinical trials for treating IgAN."

Clinical • P2 data • Anemia • Chronic Kidney Disease • Glomerulonephritis • Hematological Disorders • IgA Nephropathy • Infectious Disease • Inflammation • Renal Disease • Respiratory Diseases • CFB

A Trial of HRS-5965 Capsule in Primary IgA Nephropathy (clinicaltrials.gov) - P3 | N=378 | Not yet recruiting | Sponsor: Chengdu Suncadia Medicine Co., Ltd.

New P3 trial • Glomerulonephritis • IgA Nephropathy • Renal Disease

HRS-5965-203: Long-term Safety and Tolerability of HRS-5965 in Patients With Paroxysmal Nocturnal Hemoglobinuria (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Chengdu Suncadia Medicine Co., Ltd. | N=24 ➔ 120

Enrollment change • Complement-mediated Rare Disorders • Hematological Disorders • Paroxysmal Nocturnal Hemoglobinuria • Rare Diseases