Createrna Announces Phase II Clinical Results of MY008211A in Treatment-Naïve PNH Patients at ASH 2024

Wuhan, China — Wuhan Createrna Science and Technology Development Co., Ltd. (“Createrna”) today announced results from a Phase II clinical study of its novel complement factor B (CFB) inhibitor, MY008211A, as monotherapy in patients with paroxysmal nocturnal hemoglobinuria (PNH) who have not previously received complement inhibitor therapy. The data will be presented at the 2024 American Society of Hematology (ASH) Annual Meeting, to be held December 7–10 in San Diego, California.

Key Finding: 100% of patients (34/34) across all dose groups achieved the primary endpoint of ≥20 g/L increase in hemoglobin from baseline at Day 84, with no transfusion requirements.

MY008211A is a first-in-class oral complement factor B (CFB) inhibitor independently developed by Createrna. CFB is a positive regulator of the complement alternative pathway (AP). MY008211A specifically binds to factor B, inhibiting its activity within the alternative pathway and suppressing the positive feedback amplification loop, thereby blocking the formation of C3 and C5 convertases. This dual mechanism of action ameliorates intravascular hemolysis while eliminating the risk of extravascular hemolysis.

Two Phase III clinical studies of MY008211A monotherapy are currently ongoing: one enrolling PNH patients without prior complement inhibitor therapy and another enrolling PNH patients previously treated with complement inhibitors. In addition, a Phase II clinical study of MY008211A Tablet for the treatment of IgA nephropathy has been initiated and is actively enrolling patients. Further indications in development include primary membranous nephropathy, atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), and immune complex membranoproliferative glomerulonephritis (IC-MPGN).

The data presented pertain to a multicenter, open-label, dose-exploratory Phase II clinical study (NCT06050226) evaluating the efficacy and safety of MY008211A Tablet as monotherapy in PNH patients without prior complement inhibitor therapy. Eligible patients were enrolled into three dose cohorts: 400 mg BID, 600 mg BID, and 800 mg QD. The primary endpoint was the proportion of subjects achieving an increase in hemoglobin (Hb) concentration of ≥20 g/L from baseline at Day 84. Change in Hb concentration from baseline served as a secondary endpoint.

From August 2023 to April 2024, a total of 34 PNH patients were enrolled: 15 patients in the 400 mg BID cohort, 9 in the 600 mg BID cohort, and 10 in the 800 mg QD cohort. The mean age was 39.5 years, with 19 female patients (55.9%). All 34 patients were included in both the efficacy and safety analyses.

In the absence of blood transfusions, all 34 subjects (100%) across all dose groups achieved the primary endpoint of an increase in Hb concentration of ≥20 g/L from baseline at Day 84. Hemoglobin levels increased markedly from baseline in the 400 mg BID, 600 mg BID, and 800 mg QD groups, with mean increases of 44.7 g/L, 43.6 g/L, and 42.4 g/L, respectively. Lactate dehydrogenase (LDH) levels decreased substantially from baseline across the three cohorts, with reductions of 87%, 87%, and 81% at Day 84, respectively.

All patients required no blood transfusions following MY008211A Tablet treatment.

No deaths, treatment-related serious adverse events (SAEs), or premature discontinuations occurred during the study. The most common adverse event was headache, the majority of which were mild in severity.

In this multicenter, open-label Phase II study, MY008211A demonstrated a favorable safety and tolerability profile. After 12 weeks of treatment across all three dose cohorts, all patients achieved an Hb increase of ≥20 g/L from baseline. Improvements in secondary endpoints, including the FACIT-Fatigue score, were comparable across the different dose groups.

Iptacopan hydrochloride, a drug in the same class, was approved in China in April of this year for the treatment of adult patients with PNH who have not previously received complement inhibitor therapy.

Based on the data currently disclosed, Createrna's MY008211A Tablet achieved the primary endpoint of an increase in hemoglobin (Hb) concentration of ≥20 g/L from baseline at 12 weeks in all patients, with early data suggesting efficacy superior to that of iptacopan hydrochloride (92.2%). Further results from the two ongoing Phase III studies of MY008211A in PNH are eagerly anticipated.

Forward-Looking Statements

This press release contains forward-looking statements regarding Createrna's clinical development programs and the potential of MY008211A. Actual results may differ materially from those indicated by these forward-looking statements due to various factors, including risks inherent in clinical development.