GLB-002, A Novel Molecular Glue Degrader, Approved for Clinical Trials
October 08, 2023San Diego, California, Oct 7, 2023 - GluBio Therapeutics Inc., a clinical-stage, Molecular glue degrader (MGD)-focused biotech company, announced that it has received drug clinical trial approval from the National Medical Products Administration (NMPA) of China to initiate clinical trials for its novel molecular glue degrader, GLB-002. The trials will evaluate GLB-002 in patients with hematologic malignancies including Non-Hodgkin Lymphoma (NHL) and Multiple Myeloma (MM).
About GLB-002
GLB-002 is a novel CRBN E3 Ligase Modulator (CELMoDs) with a completely new chemical core structure. By binding to the CRL4CRBN E3 ligase CRBN, it promotes the ubiquitination of the transcription factors IKZF1 (Ikaros) and IKZF3 (Aiolos), which are subsequently degraded by the proteasome, activating multiple downstream anti-tumor pathways, ultimately exerting a therapeutic effect on hematologic malignancies such as NHL and MM.
As a next-generation molecular glue degrader, GLB-002 demonstrates significant advantages over the currently clinical-stage IMiDs-based agents Iberdomide (CC-220, third-generation), Golcadomide (CC-99282) and Mezigdomide (CC-92480) (both fourth-generation). Proteomics show that GLB-002 achieves highly selective protein degradation, significantly degrades only IKZF1/3 proteins without affecting other novel substrates. Results from preclinical toxicology studies indicated that the excellent pharmacokinetic profile and high selectivity of GLB-002 greatly enhance its therapeutic window. Furthermore, the in vitro anti-tumor proliferative activity of GLB-002 in drug-resistant NHL and MM cell lines is significantly higher than that of Iberdomide (>100-fold), Golcadomide (>10-fold), and Mezigdomide (>2-3 fold). Collectively, GLB-002 is expected to address the issues of poor selectivity, off-target toxicity, and drug resistance associated with the non-specific degradation of IKZF1/3 by approved immunomodulatory drugs (IMiDs). Compared to the fourth-generation CELMoDs Golcadomide or Mezigdomide currently in clinical trials, GLB-002 shows significantly increased binding affinity for CRBN and enhanced degradation selectivity for new substrate proteins, making it a highly promising potential therapy for hematologic malignancies such as NHL and MM.
“GLB-002 is the second internally developed molecular glue degrader from GluBio to enter clinical trials. As a next-generation, highly selective IKZF1/3 molecular glue degrader, it follows in the footsteps of Iberdomide, Golcadomide, and Mezigdomide." said Gang Lu, Ph.D., Founder, President and CEO of GluBio Therapeutics. “Preclinical studies have shown that GLB-002 offers potent degradation activity, high selectivity, more complete protein degradation, and the ability to overcome acquired resistance to immunomodulatory drugs. We believe GLB-002 has the potential to deliver superior clinical efficacy across various types of hematologic tumors. We look forward to it becoming a best-in-class therapy that better meets the clinical needs of patients with blood cancers such as NHL and MM.”