Huadong Medicine Announces Positive Preliminary Results from a Phase Ⅰ study of HDM2005, a ROR1-Targeting ADC

HANGZHOU, China, Sept. 5, 2025 /PRNewswire/ -- Huadong Medicine Co., Ltd. (hereinafter referred to as "Huadong Medicine") today announced positive preliminary results from a Phase I study of HDM2005, an independently developed Class 1 innovative antibody–drug conjugate (ADC) targeting receptor tyrosine kinase-like orphan receptor 1 (ROR1), in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) or classical Hodgkin lymphoma (cHL). The results showed that HDM2005 demonstrated promising efficacy with a favorable safety and tolerability profile in B-NHL and cHL, which will support the clinical development moving forward.

ROR1 is a transmembrane protein overexpressed in various cancers, including lymphomas. HDM2005 is composed of a humanized IgG1 monoclonal antibody, a proteolytically cleavable linker, and the cytotoxic payload monomethyl auristatin E (MMAE). In preclinical studies, HDM2005 demonstrated potent anti-tumor activity across multiple lymphoma and solid tumor models. This first-in-human Phase I study (NCT06615193) enrolled patients with relapsed or refractory B-NHL or cHL. The primary objectives were to evaluate safety and tolerability, determine the maximum tolerated dose (MTD) and the recommended Phase Ⅱ doses (RP2Ds) and perform a preliminary evaluation of antitumor efficacy in lymphoma.

As of July 4, 2025, a total of 29 patients were enrolled (n=1, 4, 10, 11 and 3 in the 0.3, 1.0, 1.8. 2.5 and 2.75 mg/kg dose cohorts), including 17 patients with mantle cell lymphoma (MCL), 8 patients with diffuse large B-cell lymphoma (DLBCL), and 4 patients with cHL. Most patients (21, 72.4%) had received ≥3 prior lines of anti-tumor therapy. No patient permanently discontinued treatment due to treatment related adverse events (TRAEs). In the 1.8 mg/kg and 2.5 mg/kg cohorts, 38.1% of patients (8/21) experienced Grade ≥3 TRAEs, the most common (≥5%) being neutrophil count decrease (4 patients, 19.0%). No Grade ≥3 gastrointestinal adverse reactions or peripheral neuropathy were reported. Peripheral neuropathy occurred in 4 patients (13.8%), all of which were Grade 1 or 2.

In the 1.8 mg/kg and 2.5 mg/kg cohorts, the objective response rate (ORR) was 50% (6/12) in MCL patients, including 1 complete response (CR) and 5 partial responses (PR). The ORR was 100% (2/2) in cHL patients with CRs.

The preliminary results of this Phase I clinical trial show that HDM2005 was well-tolerated and demonstrated promising anti-tumor activity in patients with relapsed/refractory B-NHL or cHL. Huadong Medicine will commit to its "science-driven, patient-centered" mission, advance HDM2005 through clinical development and registration, and strive to bring more treatment options to patients.

About HDM2005

HDM2005 Injection is a Class 1 innovative biologic drug targeting ROR1. It is an ADC independently developed by Hangzhou Zhongmei Huadong Pharmaceutical Co., Ltd., a wholly-owned subsidiary of Huadong Medicine, which holds global intellectual property rights. The clinical trials for HDM2005 were approved in June 2024 by the National Medical Products Administration (NMPA) and the U.S. Food and Drug Administration (FDA) respectively, for the treatment of advanced malignant tumors. In February 2025, HDM2005 received Orphan Drug Designation from the U.S. FDA for the treatment of mantle cell lymphoma (MCL). In April 2025, its Investigational New Drug (IND) application for use in combination with rituximab, cyclophosphamide, doxorubicin (or epirubicin), and prednisone (R-CHP) for previously untreated diffuse large B-cell lymphoma (DLBCL) was approved by the NMPA.

The project is currently advancing at the first tier of the global clinical R&D landscape for ROR1 ADC. The following 3 clinical trials are currently ongoing in China:

• A Phase I trial of HDM2005 monotherapy for advanced hematologic malignancies (MCL, DLBCL, cHL): four dose-escalation cohorts have been completed, the fifth cohorts is ongoing, with expansion phases initiated at two dose levels.
• A Phase I trial of HDM2005 monotherapy for advanced solid tumors: the first patient was dosed in May 2025, and the trial is currently in dose-escalation.
• A Phase I b/Ⅱ trial of HDM2005 combination therapy for DLBCL patients: the leading site has been activated.