Hanmi Pharmaceutical's HM16390 Shows Dual Mechanism for Enhanced Cancer Immunotherapy Safety and Efficacy
Key Insights
Hanmi Pharmaceutical presented four posters at SITC demonstrating HM16390's novel IL-2 analog design that optimizes both alpha and beta receptor binding for improved therapeutic outcomes.
The drug selectively increases regulatory T cells in blood rather than tumors to reduce systemic toxicity while significantly boosting tumor-specific CD8+ T cells for enhanced antitumor efficacy.
Collaborative research with KAIST (search) identified IL-2-related immune signaling pathways as predictive biomarkers for immunotherapy response across 5,000 patients and nine cancer (search) types.
Hanmi Pharmaceutical has unveiled promising preclinical data for its next-generation immunotherapy HM16390, demonstrating a differentiated approach to IL-2-based cancer (search) treatment that addresses both efficacy and safety challenges that have plagued previous IL-2 therapies. The company presented four research posters at the Society for Immunotherapy of Cancer (SITC) conference held November 5-9 in National Harbor, Maryland, showcasing the drug's novel dual-receptor optimization strategy.
Novel IL-2 Design Addresses Historical Limitations
HM16390 represents a strategic departure from previous IL-2 development approaches. While currently approved recombinant IL-2 therapies face limited clinical use due to serious side effects including vascular leak syndrome (search) and cytokine release syndrome (search), and previous IL-2 candidates that focused solely on minimizing systemic toxicity failed to demonstrate sufficient efficacy, HM16390 pursues what Hanmi describes as a strategy to "capture both rabbits."
The drug leverages Hanmi's proprietary LAPScovery platform technology to create a long-acting formulation requiring only once-per-cycle subcutaneous administration. The key innovation lies in its optimized binding affinity for both IL-2 alpha and beta receptors, designed to maximize therapeutic efficacy through enhanced beta receptor binding while ensuring safety through optimized alpha receptor binding.
Mechanistic Evidence for Dual Benefits
Hanmi's research directly demonstrated HM16390's differentiated mechanism in knockout models. The drug temporarily and selectively increases regulatory T cells (Treg) only in the bloodstream rather than in tumors, thereby alleviating excessive immune responses and reducing systemic toxic reactions. This selective action represents a significant advancement in managing IL-2's notorious safety profile.
In comparative studies, HM16390 showed superior antitumor activity when compared to variants lacking IL-2 alpha receptor (search) binding affinity. Only HM16390 significantly increased tumor-specific CD8+ T cells (TST), with most expressing PD-1 (search) on their surface in an activated state. This provides evidence that the IL-2 alpha receptor binding property contributes not only to safety but also to antitumor efficacy, strengthening the drug's mechanistic differentiation.
Biomarker Discovery for Personalized Treatment
In collaboration with Professor Choi Jungkyun from KAIST (search)'s Department of Bio and Brain Engineering, Hanmi conducted extensive biomarker research ahead of planned combination trials with MSD's Keytruda (pembrolizumab). The team integrated and analyzed large-scale transcriptome data from blood and tumor tissues of approximately 5,000 patients across nine cancer (search) types who received immunotherapy, along with single-cell transcriptome data from about 600 patients across five cancer types.
The analysis revealed that IL-2-related immune signaling pathways and T cell characteristics are associated with response to immune checkpoint inhibitor therapy. These findings suggest that statistical multivariate predictive model analysis based on large-scale patient transcriptome data could enable response prediction and establish patient selection criteria for personalized treatment strategies.
Clinical Development Progress
HM16390 is currently advancing through global Phase 1 trials, with the dose-escalation portion of the monotherapy cohort underway. Hanmi plans to expand to combination studies with Keytruda in the first half of next year, leveraging the biomarker insights to optimize patient selection and treatment strategies.
"HM16390 is a next-generation immunomodulatory anticancer drug designed to secure both antitumor efficacy and safety," said Choi In-young, head of Hanmi Pharmaceutical's R&D Center. "We are reviewing broad applicability across various cancer (search) types, and it is a promising candidate that induces a strong immune response while minimizing side effects."
The comprehensive approach combining mechanistic innovation, biomarker-driven patient selection, and strategic combination therapy positioning represents Hanmi's effort to overcome the historical challenges that have limited IL-2's clinical utility in cancer (search) immunotherapy.