GS24-B047, a potential best-in-class DLL3-targeting T-cell engager with integrated costimulatory signal, for the treatment of small cell lung cancer
Presenter: Fu Li, PhD Session: Immunomodulatory Agents and Interventions Time: 4/22/2026 9:00:00 AM → 4/22/2026 12:00:00 PM
Authors
Zeng Qi 1 , Fu Li 1 , Zhiyu Cui 1 , Hongmei Xie 1 , Sijia Liu 1 , Dechen Cao 1 , Liang Xu 1 , Yihui Lin 1 , Lishan Kang 1 , Siqin Wang 1 , Lei Jin 2 , John L. Xu 2 1 Changchun GeneScience Pharmaceutical Co., Ltd., Shanghai, China, 2 Changchun GeneScience Pharmaceutical Co., Ltd, Shanghai, China
Abstract
Background: Small cell lung cancer (SCLC) remains an aggressive malignancy with limited therapeutic options and poor prognosis, particularly in the relapsed/refractory settings. DLL3, a tumor-associated antigen highly expressed on SCLC cells with minimal expression in normal tissues, represents a promising therapeutic target. While T-cell engagers (TCEs) targeting DLL3 and CD3, such as Tarlatamab, have demonstrated clinical activity, maintaining T-cell function in the tumor microenvironment remains challenging, and improvements in progression-free survival (PFS) have been limited. GS24-B047 is a novel DLL3-targeting TCE that incorporates a proprietary costimulatory signal designed to enhance T cell activation and persistence, with the potential to improve clinical efficacy in SCLC patients. Methods: Binding activity and specificity of GS24-B047 to DLL3, CD3, and the costimulatory target were characterized by surface plasmon resonance (SPR), Octet biosensor, and flow cytometry. In vitro functional activity was assessed in co-culture assays with human PBMCs and DLL3-expressing SCLC cell lines, measuring T cell activation, cytokine release, and cytotoxicity. In vivo anti-tumor efficacy was evaluated in SCLC cell-derived xenograft (CDX) models with human immune system reconstitution. Results: GS24-B047 bound to DLL3 with sub-nanomolar affinity, recognizing a distinct, more membrane-proximal epitope as compared to Tarlatamab, and effectively mediated simultaneous engagement of DLL3 on tumor cells and CD3 on T cells. In vitro , GS24-B047 induced T cell activation, proliferation, and cytokine secretion, and exhibited potent cytotoxicity against DLL3-expressing SCLC cell lines (with EC 50 values in the picomolar range). GS24-B047 demonstrated a favorable therapeutic index with a high ratio of tumor cell killing to IL-6 release. The integrated costimulatory signal reduced markers of T-cell exhaustion as compared to a benchmark DLL3xCD3 TCE, supporting a more sustained T-cell response. In vivo , GS24-B047 treatment resulted in significant and durable tumor regression in multiple CDX models of SCLC, showing enhanced anti-tumor activity when compared to clinical benchmarks. Conclusion: GS24-B047 is a novel DLL3-targeting TCE with integrated costimulation that promotes potent and sustained anti-tumor immunity in preclinical SCLC models. Collectively, our data support GS24-B047 as a potential therapeutic candidate for SCLC and warrant further evaluation in IND-enabling studies.
Disclosure
Z. Qi, Changchun GeneScience Pharmaceutical Co., Ltd. Employment. F. Li, Changchun GeneScience Pharmaceutical Co., Ltd. Employment. Z. Cui, Changchun GeneScience Pharmaceutical Co., Ltd. Employment. H. Xie, Changchun GeneScience Pharmaceutical Co., Ltd. Employment. S. Liu, Changchun GeneScience Pharmaceutical Co., Ltd. Employment. D. Cao, Changchun GeneScience Pharmaceutical Co., Ltd. Employment. L. Xu, Changchun GeneScience Pharmaceutical Co., Ltd. Employment. Y. Lin, Changchun GeneScience Pharmaceutical Co., Ltd. Employment. L. Kang, Changchun GeneScience Pharmaceutical Co., Ltd. Employment. S. Wang, Changchun GeneScience Pharmaceutical Co., Ltd. Employment. L. Jin, Changchun GeneScience Pharmaceutical Co., Ltd Employment. J. Xu, Changchun GeneScience Pharmaceutical Co., Ltd Employment.
Cited in
Control: 3406 · Presentation Id: 9591 · Meeting 21436