A dose-escalation and safety study of CID-103 followed by a randomized, open-label, parallel-arm multi-dose study evaluating the efficacy and tolerability of CID-103 in adults with persistent or chronic immune thrombocytopenia Free

Introduction: Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by a decreased platelet count due to accelerated destruction and impaired production n of platelets by the immune system. Anti-CD38 antibodies have recently been evaluated for treatment of autoimmune diseases by depleting long-lived plasma cells which produce pathological autoantibodies. CID-103, a novel anti-CD38 antibody, recognizes a unique epitope on CD38 and pre-clinical studies demonstrate good efficacy and possibly improved safety compared to other anti-CD38 antibodies by virtue of an equal or higher Antibody-Dependent Cell-mediated Cytotoxicity (ADCC) and lesser Complement-Dependent Cytotoxicity (CDC). We report preliminary safety and efficacy results of CID-103 from an on-going study in Chinese patients with persistent or chronic ITP (NCT07017725).

Methods: In this multicenter, randomized, open-label, phase 1/2 study, adults between 18 and 65 with primary ITP who had received at least two previous lines of treatment and whose mean platelet count was ≤ 35 x 10⁹/L on at least two measurements at least one week apart were enrolled. Part A, dose escalation, incorporated both accelerated escalation and standard 3+3 design. Patients were assigned to sequential dose cohorts of CID-103 at 30 mg, 150 mg, 300 mg, 600 mg, and 900 mg, with a priming dose of CID-103, of either 30mg or 150 mg administered prior to the cohort dose. In Part B (not yet accruing), patients will be randomized into 3 CID-103 dose levels identified to be safe in Part A. CID-103 is administered once weekly for 5 weeks after the 1^st week priming dose, and then every two weeks for the subsequent 6 weeks, followed by once monthly treatments for up to 6 months. Safety follow-up visits two and four months after the last dose are included. The protocol allows intra-patient dose escalation if a cohort of patients had completed and tolerated the higher dose.

The primary safety endpoint is to evaluate dose-limiting toxicities (DLT) and treatment-emergent adverse events (TEAEs) related to CID-103. The primary efficacy endpoint is the proportion of patients achieving a platelet response, which was defined as a platelet count ≥ 50 x 10⁹/L and ≥ 20 x 10⁹/L above baseline on at least two consecutive measurements at least seven days apart, and absence of bleeding requiring medical intervention/treatment within the first 12 weeks of treatment. The study also explores pharmacokinetics and pharmacodynamics of CID-103.

Results: As of August 2, 2025, 6 patients, two females, were enrolled, including 30mg/30mg (n=1), 30mg/150mg (n=1), 150mg/300mg (n=1), and 150mg/600mg (n=3). At data cut off, the median age was 32.5 years (range, 27-55); and median duration of ITP was 35.5 months (range, 14-96); the median baseline platelet count was 15 x10⁹/L. All patients had received corticosteroids, 67% TPO-RA and 33% immunosuppressants prior to the study. Dose escalation of CID-103 is ongoing with the maximum tolerated dose not yet reached.

At cut-off date, no DLT or serious adverse events have been reported. Four patients experienced a total of 19 TEAEs, 7 related to CID-103. One patient with a history of anemia experienced 2 episodes of grade 3 aggravated iron deficiency anemia which quickly responded to intravenous iron treatment. One patient experienced a Grade 2 infusion reaction.

Three patients are evaluable for efficacy. Two patients in the 30mg/30mg and 30mg/150mg cohorts achieved a platelet response on Days 6 and 57, respectively. The patient in 30mg/30mg cohort lost the response by Week 12. The patient in the 30mg/150mg cohort has maintained the response for over three months, during which the patient has undergone the intra-patient escalation to 150mg/300mg; and continues to benefit from study drug treatment.

Preliminary pharmacokinetics demonstrated increasing C_max with increasing dose. The preliminary t_1/2of ClD-103 is approximately 10 hours at a dose of 30 mg, and about 25 hours at doses of 150 mg and 300 mg. The AUC_tau increased with the dose.

Conclusions: These first CID-103 data obtained from patients with persistent or chronic ITP suggest that CID-103 may potentially have good efficacy and acceptable safety for treatment of patients with ITP. The study continues to progress through the dose cohorts and to collect safety and efficacy data.