Sigent Therapeutics Advances Two Innovative Oncology Pipelines with Lung Cancer Pioneer Professor Wu Yilong as Leading PI

Recently, Signet Therapeutics (hereinafter referred to as SIGNET) announced,Professor Wu Yilong, Chief Expert at Guangdong Provincial People's Hospital and a leading figure in precision lung cancer therapy in China, has officially been appointed as the Leading Principal Investigator (Leading PI) for the Phase I clinical trial of SIGX2649, SIGNET's first Pan-TEAD inhibitor candidate, as well as for the Phase I/II clinical trial of the world's first FAK/SRC dual-target inhibitor SIGX1094 in combination with a KRAS-G12C inhibitor.

This landmark collaboration marks the addition of a second world-renowned clinical expert to Signet Therapeutics’ solid tumor portfolio, fully underscoring the scientific merit and clinical development potential of its two innovative pipelines.

Professor Wu Yilong: Leading Expert in Lung Cancer Treatment in China

Professor Wu Yilong is “Leading Figure in Precision Medicine for Lung Cancer in China”. In 2015, he was awarded the "Distinguished Science Award" by the International Association for the Study of Lung Cancer (IASLC), marking the first time in the award's 40-year history that it was conferred upon a scientist of Chinese descent. He has been recognized as a Highly Cited Researcher in clinical medicine for six consecutive years, and has consistently ranked first in academic influence among lung cancer experts for many years. In the 2026 "Global Top 100,000 Scientists Academic Competitiveness Ranking," he ranked first among mainland Chinese scholars in the field of oncology. With nearly four decades of dedication to research in precision therapy for lung cancer, he serves as Chief Expert at Guangdong Provincial People's Hospital, Honorary Director of the Guangdong Lung Cancer Institute, and Chairman of the Chinese Thoracic Oncology Group (CTONG). Under his leadership, multiple targeted therapies have been approved for market launch both domestically and internationally, fundamentally transforming the global landscape of precision lung cancer treatment. As the pioneer of the world's first "drug holiday" model, he was the first to demonstrate that certain advanced-stage patients can safely discontinue treatment after achieving a deep response. The related findings were published in the top-tier international journal JAMA Oncology.

Professor Wu Yilong has published nearly 400 high-impact academic papers as the first (co-) or corresponding author, including 5 in *The New England Journal of Medicine*. He has also, as the principal investigator, obtained...One Second Prize of the National Science and Technology Progress Award, three First Prizes of the Provincial/Ministerial Science and Technology Progress Awards.

Pipeline 1: TEAD Inhibitor SIGX2649—A Potential First-in-Class Targeting "Undruggable" Targets

TEAD inhibitors target the Hippo signaling pathway—an oncogenic driver pathway on par with P53, Myc, and RAS that has long been recognized as an "undruggable" target. SIGX2649 is a global first-in-class pan-TEAD inhibitor. Preclinical data demonstrate its effective inhibition of all four TEAD isoforms and its ability to promote the binding of the transcriptional repressor VGLL4 to TEAD, achieving a "dual-blockade" mechanism. This confers differentiated advantages, including enhanced antitumor activity and reduced nephrotoxicity. TEAD inhibitors are expected to demonstrate superior efficacy in patients with advanced solid tumors such as mesothelioma, small cell lung cancer, and hepatocellular carcinoma.

Currently,SIGX2649 has received IND approval from the U.S. FDA., relevant core data were selected for presentation at the 2026 American Association for Cancer Research (AACR) Annual Meeting.

Pipeline 2: Phase I/II Clinical Trial of SIGX1094 in Combination with a KRAS G12C Inhibitor —— Overcoming Drug Resistance in Lung Cancer

KRAS G12C mutations account for approximately 30% of non-small cell lung cancer mutations, a field that has faced the "targetable but undruggable" dilemma for the past four decades. Dabert® (fulzeresib tablets), the first KRAS G12C inhibitor approved in China, has Professor Wu Yilong as the principal investigator for its monotherapy clinical studies in China.

However, drug resistance inevitably develops with KRAS inhibitor monotherapy. SIGX1094 from Signet Therapeutics is the world’s first FAK/SRC dual-target inhibitor to enter clinical development. It has been granted Orphan Drug Designation and Fast Track Designation by the U.S. FDA and is currently undergoing a Phase I clinical trial at Peking University Cancer Hospital. Studies have demonstrated that the combination of FAK inhibitors and KRAS-G12C inhibitors yields a significant synergistic anti-tumor effect, offering a novel strategy to overcome resistance to KRAS inhibitors.

SIGNET is a pioneer in the global "organoid + AI"-empowered R&D model for innovative targeted therapies, recognized as a National High-Tech Enterprise and a Specialized, Refined, Differential, and Innovative (SRDI) Enterprise. The founding team comprises outstanding researchers from premier institutions such as Harvard University, MIT, and the Chinese Academy of Sciences. Having published over 20 breakthrough studies in oncology—particularly focusing on gastric and esophageal cancers—as first or corresponding authors in journals with impact factors exceeding 20, including Nature, Nature Medicine, and Cancer Cell, the company has established itself as a global leader in gastric and esophageal cancer research. Since its establishment in Shenzhen in late 2020, SIGNET has secured nearly RMB 300 million in financing and project grants, and currently holds over 40 core intellectual property rights.

The company currently maintains a portfolio of multiple first-in-class drug pipelines and an organoid service platform. Among them, the core pipeline SIGX1094, as the world's first targeted therapy for diffuse gastric cancer, has sequentially secured IND approvals from the U.S. FDA and China's NMPA, along with U.S. FDA Orphan Drug Designation (ODD) and Fast Track Designation (FTD). In August 2025, the drug was nominated for the Galien Prize, widely recognized as the "Nobel Prize of the pharmaceutical industry." It is currently undergoing a Phase I clinical trial at Peking University Cancer Hospital & Institute, with a Phase II trial poised to commence shortly. Notably, this pipeline is the first globally to be advanced to the clinical stage via an "organoid + AI" technology platform. The second pipeline, SIGX2649, is a pan-TEAD inhibitor that targets key downstream effectors of the Hippo signaling pathway. To date, no marketed drugs exist for this target, and the candidate has already obtained an IND approval from the U.S. FDA. The organoid service platform not only supports the company’s internal pipelines but also actively empowers major pharmaceutical enterprises in novel drug R&D. Collaborative partners include Shenzhen Second People's Hospital, The University of Hong Kong, The Hong Kong University of Science and Technology, Shenzhen Bioray Pharmaceuticals, and ZhenShi Biopharma, among others, collectively fostering the development of more innovative therapeutics.

Since its establishment in late 2020, the Company’s forward-looking strategic deployment of an “organoid + AI” technology platform empowering the R&D of innovative targeted cancer drugs has received authoritative international recognition. It was featured on the homepage of the globally renowned biotech media Fierce Biotech and hailed as the “next-generation paradigm for cancer drug development (NEXT Generation).” In April 2025, the U.S. FDA officially issued a statement explicitly endorsing the gradual replacement of traditional animal testing with organoid and AI technologies, fully validating the foresight and scientific rigor of the Company’s technological strategy formulated four years prior.