KEY TAKEAWAYS
- The interventional phase 1 study aimed to optimize SIRPa-fusion for potent, safe multi-tumor efficacy.
- The result demonstrates that HCB101 excels in diverse tumors, promising efficacy and safety in ongoing clinical trials.
Macrophages function through the SIRPa receptor, interacting with CD47 on cells. Cancer cells often increase CD47 to avoid immune detection. Blocking SIRPa-CD47 interaction seems promising for controlling tumor growth. However, due to side effects or insufficient effectiveness, anti-CD47 antibodies faced challenges in clinical progress. To address this, ZONG SEAN JUO and a team of researchers developed a SIRPa-fusion protein with enhanced efficacy across various tumors and maintained good safety profiles.
Through precise protein engineering based on structural guidance, researchers identified a SIRPa mutant demonstrating significant tumor phagocytosis while preserving safety in normal cells. Evaluating its efficacy, they tested the molecule in diverse mouse models, comparing it with other biologics in clinical trials. Additionally, they conducted quantitative RNA transcriptional analysis to assess gene expression changes within tumors and their microenvironment.
In contrast to fellow clinical candidates, HCB101 induced potent phagocytic responses against tumor cells without affecting red blood cells. Across 14 human tumor xenograft models, HCB101 consistently demonstrated remarkable efficacy against hematological and solid tumors. The tumor growth inhibition index ranged from 60-100% at doses of 0.5-10 mg/kg compared to a placebo. Post-HCB101 treatment, an increased M1/M2 macrophage ratio correlated with observed anti-tumor effects.
Quantitative RNA transcriptional analysis revealed significant gene expression changes, suggesting a distinctive mechanism of action contributing to HCB101’s superior efficacy.
Notably, toxicology studies showed no apparent adverse reactions, affirming a favorable safety profile.
The study concluded that relative to pertinent clinical counterparts, HCB101 demonstrates heightened efficacy across 14 diverse CDX models encompassing hematological and solid tumors, concurrently upholding commendable safety profiles. It is a potent biologic with robust effectiveness in monotherapy and combination settings, as substantiated by an ongoing clinical trial. This study is sponsored by FBD Biologics Limited.
Clinical Trial: https://clinicaltrials.gov/study/NCT05892718
Juo ZS. et al.” An Engineered Ligand-Trap Biologic Targeting the CD47 Signaling Pathway for Cancer Treatment with Superb Efficacy and Safety Profiles”. Presented at ESMO IO 2023. (Abstract: 145P).
