LYC001, a high-affinity hierarchical assembly for lymph node-targeted IL-2 immunotherapy: Preclinical validation of potent antitumor immunity and preliminary safety from the first-in-human phase Ia study
Presenter: Wenfeng Zeng, PhD Session: Phase 0 and First-in-Human Phase I Clinical Trials Time: 4/20/2026 2:00:00 PM → 4/20/2026 5:00:00 PM
Authors
Shuhang Wang 1 , Dongyan Liu 1 , Yanjie Han 1 , Mingzhen Li 2 , Wenfeng Zeng 2 , Wei Liang 2 , Ning Li 1 1 Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China, 2 LiangYuan Bioscience, LLC, Beijing, China
Abstract
High-dose systemic interleukin-2 (IL-2) has demonstrated efficacy in metastatic renal cell carcinoma and melanoma but is severely limited by vascular leak syndrome (VLS) and a short half-life. Current engineering strategies often compromise efficacy for safety. LYC001 is a novel IL-2 formulation engineered via a High-Affinity Hierarchical-Assembly Platform (H 2 P), utilizing PEG 2000 -DSPE to form a stable, non-covalent complex (Kd ≈ 10⁻⁸ M). Leveraging a hydrodynamic diameter of ~15 nm, LYC001 is designed for preferential lymphatic uptake following subcutaneous (SC) administration. This “lymph-targeting” strategy, combined with a “masking effect,” aims to bias immune activation towards lymph-resident CD8 + T cells while minimizing systemic toxicity and Treg stimulation. In preclinical studies, LYC001 monotherapy demonstrated robust antitumor activity with tumor growth inhibition (TGI) rates >70% in multiple syngeneic murine tumor models (B16F10, CT26, Renca & AB1). Mechanism studies revealed a superior immune profile of LYC001 with an approximate 10-fold increase in the CD8 + T cell to Treg ratio vs untreated control in murine models. Pharmacodynamic (PD) analysis in non-human primates (NHP) focused on lymphocyte expansion >300%, a historic predictor of survival benefit in IL-2 responders. LYC001 outperformed the marketed control, with 60% of high-dose (400,000 IU/kg) subjects exceeding this efficacy threshold (mean increase 315%) compared to only 20% in the control group. Pharmacokinetics (PK) analysis in NHPs confirmed that SC administration of 200,000 IU/kg LYC001 resulted in a longer T 1/2 (5.71 ± 0.51 h vs 2.27 ± 0.54 h), higher C max (255 ± 60 IU/mL vs 123 ± 33 IU/mL), and greater AUC 0-34h (1283 ± 209 h·IU/mL vs. 841 ± 322 h·IU/mL) compared to marketed products. By minimizing non-target tissue exposure, toxicology studies showed no evidence of VLS, cardiovascular toxicity, injection site reactions, or ADA, validating the safety of LYC001. LYC001-I-01 (CTR20254113) is an ongoing Phase Ia, open-label, single-center dose-escalation study in patients with advanced solid tumors, utilizing an accelerated titration followed by a 3+3 design (12,000 IU/kg to 540,000 IU/kg). Objectives are to evaluate safety, MTD determination, PK, immunogenicity, and preliminary efficacy. The first patient (12,000 IU/kg) was successfully dosed and completed the DLT observation period. The drug was well-tolerated with no dose-limiting toxicities (DLTs) or signs of VLS. Enrollment is ongoing, and updated dose-escalation data will be presented.
Disclosure
S. Wang, None.. D. Liu, None.. Y. Han, None. M. Li, LiangYuan Bioscience, LLC Employment. W. Zeng, LiangYuan Bioscience, LLC Employment. W. Liang, LiangYuan Bioscience, LLC Employment. N. Li, None.
Cited in
Control: 9780 · Presentation Id: 12040 · Meeting 21436