LONGBIO-B(01779): Topline Data from the China Phase II Clinical Trial of LP-005 for the Treatment of PNH

LONGBIO-B(01779) announces that the topline data from the Phase II clinical trial (Phase II clinical trial) of LP-005 (a bifunctional antibody fusion protein independently developed by the Group, targeting C5 and C3b complement and used for the treatment of paroxysmal nocturnal hemoglobinuria (PNH)) conducted in China has been read out. These topline data show that LP-005 has significant efficacy and favorable safety and tolerability profiles. LP-005 is the first product from the Group's bifunctional antibody development platform and is a bifunctional antibody fusion protein targeting C5 and C3b complement. As a multi-target complement inhibitor, LP-005 acts simultaneously on multiple key nodes of the complement cascade and comprehensively inhibits all three complement signaling pathways (i.e., the classical pathway, the alternative pathway, and the lectin pathway). Compared with single-target inhibitors, it is expected to more comprehensively block the complex disease pathological mechanisms. The potential indications of LP-005 include complement-mediated autoimmune diseases such as PNH, complement-mediated kidney diseases, and periodontitis. PNH is a rare acquired clonal hematopoietic stem cell disease, mainly characterized by chronic intravascular hemolysis, thrombosis, and bone marrow failure. Patients typically present with symptoms such as fatigue, hemoglobinuria, abdominal pain, dyspnea, and anemia, and may experience major adverse vascular events. Existing complement inhibitor therapies have improved patient clinical outcomes to some extent. LP-005 is a novel bifunctional fusion protein that can simultaneously inhibit the proximal and terminal complement pathways and has a longer half-life. The Phase II clinical trial is a multicenter, randomized, open-label Phase II clinical study conducted in China (registration number: CTR20242478), aimed at evaluating the efficacy, safety, and pharmacokinetic characteristics of LP-005 injection in the treatment of PNH patients. The trial includes three dose cohorts of 900 mg, 1,200 mg, and 1,500 mg, with subjects receiving intravenous infusion once every four weeks (Q4W), with a total treatment period of 48 weeks. The primary endpoints of the Phase II clinical trial include: (i) the change from baseline in serum lactate dehydrogenase (LDH) levels at Week 12 after dosing; and (ii) the proportion of patients with a hemoglobin (Hb) increase of 2 g/dL from baseline without the need for transfusion at Week 24 after dosing. A total of 30 PNH patients were enrolled in the Phase II clinical trial, of whom 27 patients completed 24 weeks of treatment. At Week 12, LDH levels decreased significantly from baseline. The hemolysis control rate (LDH below 1.5 upper limit of normal (ULN)) reached 100% in both the 1,200 mg and 1,500 mg dose groups. All three dose groups achieved a 100% transfusion avoidance rate, and no breakthrough hemolysis (BTH) was observed. At Week 24, 85.7% (6/7) of patients in the 1,500 mg group achieved a hemoglobin increase of 2 g/dL without the need for transfusion, and 71.4% (5/7) of patients had hemoglobin 120 g/L. The transfusion avoidance rate was 100% (7/7), and no BTH was observed. LP-005 demonstrated potent hemolysis control and Hb improvement effects. In terms of safety, no treatment-related serious adverse events (SAEs) were reported. LP-005 overall demonstrated favorable safety and tolerability profiles. The Board believes that the topline data from the Phase II clinical trial confirm that LP-005, as a dual-target complement inhibitor, has competitive advantages in terms of efficacy, along with favorable safety and tolerability profiles, and the Q4W dosing interval reflects the long-acting advantage of LP-005. These results support further advancement of the clinical development of LP-005.