Genexine’s GX-BP1 (SOX2 bioPROTAC) Suppresses Tumor Regrowth despite Osimertinib and Dato-DXd Combination and Achieves 6/6 Complete Responses in Triple Combination

SOX2 degradation enhances durability of response with osimertinib and Dato-DXd and shows potent activity in an ADC-resistant lung cancer model

SEOUL, South Korea--(BUSINESS WIRE)--Genexine, Inc. (KOSDAQ: 095700) announced that Jaehyun Choi, Ph.D., CEO and Head of R&D, presented new preclinical data for GX-BP1, the company’s SOX2-targeting bioPROTAC, at the 2026 World Conference on Lung Cancer (WCLC) in Seoul on September 13.

The mini oral presentation, titled ‘Lung-Targeted mRNA-LNP Delivery of SOX2 bioPROTAC: A Comprehensive Strategy for LUAD, LUSC, and SCLC in Monotherapy and Combination Settings’ highlighted the potential of GX-BP1 to overcome treatment resistance and suppress tumor regrowth when combined with standard lung cancer therapies, including the EGFR-targeted therapy osimertinib and the TROP2 antibody-drug conjugate datopotamab deruxtecan (Dato-DXd).

In an HCC827 EGFR-mutant lung cancer xenograft model, osimertinib initially produced strong tumor control, but tumors began to regrow after treatment ended at day 20. The combination of osimertinib and Dato-DXd delayed regrowth, but tumors eventually progressed from day 40 and showed significant volume after day 70.

In contrast, osimertinib plus GX-BP1 combination therapy maintained durable tumor control for more than 100 days, with no substantial tumor regrowth observed during the study period. Most notably, the triple combination of GX-BP1, osimertinib and Dato-DXd achieved complete responses in all six animals (6/6 CR) with no regrowth observed.

Genexine also presented data from a Dato-DXd-resistant tumor model. GX-BP1 alone achieved 92.3% tumor growth inhibition (TGI), while the combination of GX-BP1 and Dato-DXd achieved 115.3% TGI, indicating tumor regression from baseline despite resistance to the ADC.

Targeting SOX2 to Address Recurrence and Drug Resistance

Genexine believes the antitumor activity of GX-BP1 is driven by degradation of SOX2, a transcription factor associated with cancer stemness, treatment resistance, recurrence and metastasis.

In EGFR-mutant lung cancer cells, treatment with osimertinib increased SOX2 expression in a dose-dependent manner. Similar increases were observed following treatment with other EGFR-targeted therapies, including lazertinib and amivantamab.

Osimertinib treatment also increased the expression of genes associated with drug efflux pumps, a resistance mechanism that reduces intracellular drug exposure by transporting therapeutic agents or cytotoxic compounds out of cancer cells. Such mechanisms may also reduce intracellular exposure to cytotoxic payloads delivered by ADCs.

By degrading SOX2, GX-BP1 is designed to target cancer stem cells and drug-persistent cancer cells while reducing mechanisms associated with treatment resistance.

“Our goal with GX-BP1 is to develop it as a combination backbone molecule with any standard therapies for lung cancer as an anti-resistant anti-cancer therapy” said Dr. Choi. “The WCLC data support the potential of GX-BP1 to improve the durability of response when combined with EGFR-targeted therapies and ADCs.”

Dr. Choi added, “The observed effect on drug-efflux mechanisms generated significant interest during our WCLC presentation. We plan to further develop GX-BP1 in combination with established lung cancer therapies and actively pursue global licensing opportunities with companies developing EGFR-targeted agents and ADCs.”

About Genexine

Genexine is one of the first-generation biotechnology companies in South Korea, dedicated to developing innovative biologics to address unmet medical needs in patients with serious diseases. The company leverages its proprietary technology platforms, including the long-acting hyFc® platform, DNA vaccine technology, and the next-generation bioPROTAC platform, to develop novel therapeutics.

In particular, Genexine is advancing a pipeline of global first-in-class drug candidates based on its bioPROTAC platform, including GX-BP1 for lung cancer and GX-BP2 for atopic dermatitis. In addition, the company is progressing late-stage bio-better assets toward commercialization. Efesa® (GX-E4), a long-acting treatment for anemia in chronic kidney disease, is currently under regulatory review in Korea and other global markets for non-dialysis patients. GX-H9, a long-acting growth hormone, is also preparing for regulatory approval in China.

About EPDeg™ bioPROTAC

EPDeg™ bioPROTAC is a next-generation targeted protein degradation (TPD) technology that directly fuses a synthetic nanobody-based target-binding moiety with an E3 ligase. This design overcomes key limitations of conventional small molecule-based PROTAC approaches, enabling improved development efficiency and enhanced tissue specificity. By selectively degrading disease-causing proteins, EPDeg™ bioPROTAC offers a novel therapeutic strategy with the potential to address previously undruggable targets.