Simcere and its subsidiary Xianxiang have initiated the phase 1 study (NCT06375044) of SIM0500, an anti-GPRC5D×BCMA×CD3 tri-specific antibody in China. The first-in-human trial is estimated to enroll 130 patients to evaluate the safety, tolerability, efficacy, and pharmacokinetics of SIM0500.
SIM0500
The US FDA has recently approved several anti-GPRC5D×CD3 and anti-BCMA×CD3 bispecific antibodies for patients with multiple myeloma (MM). Up to now, no tri-specific antibody has been approved for MM.
Previously, we reported the submission of the IND application for the phase 1 trial of SIM0500. The preclinical study showed the binding and efficacy data compared to teclistamab (特立妥单抗, JNJ 7957) and talquetamab (塔奎妥单抗, JNJ 7564).
 |
| Preclinical results of SIM0500 |
The phase 1 study for SIM0500 is focused on patients with refractory or relapsed multiple myeloma (rrMM) who have not responded to conventional standard-of-care treatments. Since no anti-GPRC5D×CD3 and anti-BCMA×CD3 bispecific antibodies have been approved in China previously, their exclusion from consideration is still uncertain.
Anti-GPRC5D×BCMA×CD3 tri-specific antibody
Recently, several tri-specific antibodies targeting anti-GPRC5D×BCMA×CD3 have entered the clinical stage, such as JNJ-79635322 by Janssen, IBI3003 by Innovent, and MBS314 by Mabworks/KyinnoBio. Currently, there have been no clinical data reports for these tri-specific antibodies.
JNJ-79635322
JNJ-79635322 is a tri-specific antibody designed to target both B-cell maturation antigen (BCMA) and G-Protein-coupled receptor class 5 member D (GPRC5D). By leveraging dual antigen recognition on plasma cells, this tri-specific antibody, which includes a CD3 arm for T-cell engagement, aims to increase tumor binding through avidity. This approach has the potential to effectively deplete malignant clonal populations and mitigate tumor antigen loss, thereby addressing resistance issues. In vivo, JNJ-79635322 demonstrated significant antitumor efficacy compared to both the vehicle and antibody controls in a murine multiple myeloma (MM) xenograft prevention model using single-target expressing clonal H929 cells. Additionally, it showed substantial tumor regression in two tumor regression models using RPMI 8226 and MM.1S cells.
 |
| JNJ-79635322 is a potential first-in-class trispecific antibody targeting BCMA and GPRC5D |
Janssen initiated the first-in-human study (NCT05652335) in patients with relapsed or refractory multiple myeloma or amyloid light-chain (AL) amyloidosis in December 2022. The trial is anticipated to enroll a total of 170 participants across both the dose escalation and dose expansion stages.
IBI3003
IBI3003 is a tri-specific antibody targeting GPRC5D, BCMA, and CD3 developed by Innovent, and it initiated phase 1 clinical trials specifically targeting patients with relapsed or refractory multiple myeloma in October 2023. The study aims to enroll a total of 116 patients.
MBS314
MBS314 is a humanized tri-specific antibody against GPRC5D, BCMA, and CD3 for r/r MM treatment co-developed by Mabworks and KyinnoBio. MBS314 exhibits weaker binding to CD3 with a KD of 181 nM, in contrast to talquetamab with a KD of 25.6 nM and CC-93269 with a KD of 41.0 nM. However, MBS314 shows high affinities for GPRC5D (KD=3.5 nM) and BCMA (KD=0.22 nM), which are comparable to talquetamab (KD=4.21 nM for GPRC5D) and CC-93269 (KD=1.0 nM for BCMA).
Mabworks/KyinnoBio launched the phase 1 clinical trial for multiple myeloma in China in February 2024, with a total enrollment target of 154 patients.
Comments