Innovent Biologics, Inc. ("Innovent") (HKEX: 01801), a biopharmaceutical company dedicated to the discovery, development, manufacturing, and commercialization of innovative medicines for the treatment of oncology, autoimmune, cardiovascular and metabolic, ophthalmology, and other major diseases, announced updated Phase 1 clinical data for IBI3003, a novel trispecific antibody targeting GPRC5D, BCMA, and CD3, in patients with relapsed or refractory multiple myeloma (R/R MM) in an oral presentation at the 23rd International Myeloma Society (IMS) Annual Meeting 2026. Based on the results of the Phase 1 dose optimization study, the recommended Phase 2 dose (RP2D) of IBI3003 was determined to be 360 μg/kg. At the RP2D, IBI3003 demonstrated rapid, deep, and durable response signals, particularly in heavily pretreated, high-risk patients with extramedullary disease.

IBI3003 is a novel trispecific antibody targeting G protein-coupled receptor C5D (GPRC5D), B-cell maturation antigen (BCMA), and CD3. Its dual-targeting design against BCMA and GPRC5D is intended to overcome tumor escape caused by the loss or downregulation of a single tumor antigen. In preclinical mouse models, IBI3003 demonstrated superior in vivo anti-tumor activity compared with marketed benchmark bispecific antibodies targeting GPRC5D/CD3 or BCMA/CD3, with particularly prominent tumor-killing activity in in vitro cell models with low expression of BCMA and GPRC5D. Currently, Innovent is conducting Phase 1/2 clinical trials of IBI3003 in China, Australia, and the United States (NCT06083207 and NCT07336472) to evaluate its safety, tolerability, and preliminary efficacy in patients with R/R MM. In parallel, Innovent has advanced the Phase 3 TriadicMM-1 study (NCT07623798) in China for IBI3003 in patients with R/R MM who have received 1 to 4 prior lines of therapy. ‌ In addition, the Phase II study of IBI3003 combined with CD38 monoclonal antibody for frontline MM is also ongoing (NCT07764861).

The updated data were from the Phase 1 clinical study NCT06083207, which enrolled eligible patients with R/R MM who had failed at least two prior lines of therapy, including at least one proteasome inhibitor (PI), one immunomodulatory drug (IMiD), and one anti-CD38-based therapy, and who had relapsed or were refractory to their last anti-myeloma regimen. Patients with prior BCMA- and/or GPRC5D-targeted therapy were also eligible for enrollment. IBI3003 was administered subcutaneously once weekly (QW). Patients who received continuous treatment for ≥6 months and achieved a partial response (PR) or better for ≥2 months could switch to once-every-two-weeks (Q2W) dosing for maintenance. To reduce the risk of cytokine release syndrome (CRS), 1 to 3 priming doses were incorporated into the study design.

A total of 102 patients were enrolled in this phase of the study in China and Australia, with doses ranging from 0.1 μg/kg to 800 μg/kg. The median patient age was 62 years (range: 40-88), 37.1% of patients were classified as high risk according to mSMART criteria, and 53.9% had ≥1 site of extramedullary disease (EMD). The median number of prior lines of therapy was 4 (range: 2-12). All patients had received at least three classes of therapy, including a PI, an IMiD, and an anti-CD38 antibody. Among them, 55.9% had received at least five classes of therapy, including at least two PIs, two IMiDs, and one anti-CD38 antibody; 33.3% had previously received anti-BCMA and/or anti-GPRC5D therapies; and 88.2% were refractory to their last treatment. As of the data cutoff date of June 30, 2026, the median follow-up duration was 6.65 months (range: 0.8-15.2).

Rapid, Deep, and Durable Responses Observed with IBI3003 at 360 μg/kg

Based on an integrated analysis of the efficacy, safety, and pharmacokinetic/pharmacodynamic (PK/PD) data from dose optimization cohorts receiving IBI3003 at 120, 360, and 540 μg/kg in the Phase 1 study, the RP2D was determined to be 360 μg/kg.

A total of 26 patients received IBI3003 at 360 μg/kg, with a median follow-up duration of 7.57 months. mPFS was not reached yet.

• The overall response rate (ORR) was 84.6%, including 11 cases of stringent complete response (sCR), 4 cases of very good partial response (VGPR), and 7 cases of partial response (PR). The ORR was 94.7% among 19 patients who had received 2 to 4 prior lines of therapy, 87.5% among 8 patients with non-bone-related EMD, and 92.3% among 13 patients without EMD.
• The median time to first response was 0.99 months (range: 0.9-8.3 months), the median time to first response of ≥VGPR was 1.87 months (range: 0.9-4.6 months), and the median time to first response of ≥CR was 2.79 months (range: 0.9-9.2 months).
• Among patients who achieved CR or better as assessed by central laboratory next-generation sequencing (NGS) testing, the minimal residual disease (MRD) negativity rate was 100% (n=8). Three patients achieved MRD negativity after receiving only one treatment cycle.

Manageable Safety Profile of IBI3003 in Patients with R/R MM

• Hematologic toxicities were the most common Grade ≥3 treatment-related adverse events (TRAEs), occurring primarily during the dose-escalation phase and being manageable and reversible.
• The incidences of CRS and immune effector cell-associated neurotoxicity syndrome (ICANS) were 52% and 3.9%, respectively. All events were Grade 1-2 and resolved with treatment. Prophylactic use of tocilizumab may reduce the risk of CRS.
• The incidence of infections was 42.2%, with Grade ≥3 infections reported in 26.5% of patients.
• For GPRC5D target-related TEAEs involving the oral cavity, skin, and nails, no Grade ≥3 oral TEAEs were observed. Most skin and nail TEAEs were Grade 1-2, with only two patients experiencing Grade 3 rash.

Potent and Sustained Pharmacodynamic Responses Observed with IBI3003 in Patients with R/R MM

• Biomarker analyses showed a significant and sustained decline in serum soluble BCMA (sBCMA) levels across the IBI3003 120 μg/kg, 360 μg/kg, and 540 μg/kg dose groups.
• Deep and durable reductions in sBCMA levels were observed across all dose groups. After three treatment cycles, the median reduction from baseline in sBCMA levels was 98.38% in the IBI3003 360 μg/kg group.

IBI3003 continued to demonstrate encouraging and durable responses, together with a manageable safety profile, in heavily pretreated patients with R/R MM. These efficacy and safety data support further evaluation of the clinical value of IBI3003 in the ongoing Phase 3 clinical study.

Professor Peng Liu of Zhongshan Hospital Affiliated to Fudan University stated, "Patients with R/R MM have a poor prognosis after failing treatments including PIs, IMiDs, and anti-CD38-based therapies, with an ORR of only 29.8%, a median progression-free survival of 4.6 months, and a median overall survival of 12.4 months^[1]. Although bispecific antibodies are reshaping the treatment landscape of R/R MM, trispecific antibodies targeting two antigens simultaneously may help overcome treatment resistance caused by intra-tumor and inter-tumor heterogeneity, as well as treatment-induced antigen escape. A substantial unmet clinical need remains in R/R MM, particularly among heavily pretreated and high-risk patients.

The dual-target coverage of BCMA and GPRC5D by IBI3003 addresses antigen expression heterogeneity and treatment resistance associated with single-target therapies, thereby reducing tumor escape. Its optimized CD3 affinity enables precise T-cell activation and tumor killing while improving safety. In the Phase 1 results presented at this meeting, IBI3003 demonstrated a manageable safety profile and impressive efficacy at the 360 μg/kg dose, with an ORR of 84.6%. Significant efficacy was also observed in patients with EMD or other high-risk features, fully demonstrating the potential of IBI3003 to overcome treatment resistance. The ORR reached 94.7% among patients who had received 2 to 4 prior lines of therapy. We look forward to the results of the ongoing Phase 3 clinical study of IBI3003."