SigNet Therapeutics to Present Preclinical Data of SIGX2649, a First-in-Class Pan-TEAD Inhibitor Targeting Hippo-YAP/TAZ Pathway, at AACR Annual Meeting 2026

Signet Therapeutics announced today that the preclinical study of its self-developed potential first-in-class/best-in-class targeted drug SIGX2649, a pan-TEAD inhibitor that suppresses solid tumor growth by blocking the Hippo-YAP/TAZ signaling pathway (A pan-TEAD inhibitor, SIGX2649, blocks Hippo-YAP/TAZ signaling pathway and suppresses solid tumor growth in preclinical trials), will be presented at the prestigious academic platform in the field of oncology—the AACR Annual Meeting 2026. The conference committee will decide by February 3 whether it will be presented as an oral report or a poster presentation.

SIGX2649 is the second novel drug pipeline developed based on SIGNET's world-first "organoid + AI" drug discovery platform, and also the second novel drug pipeline co-discovered by Signet Therapeutics and XtalPi (2228.HK), the first company in the "AI + robotics" sector to go public.. As a pan-TEAD inhibitor, it targets the key downstream effector of the Hippo signaling pathway, the dysregulation of which is closely related to the occurrence and development of various solid tumors.

SIGX2649 can block the palmitoylation of TEAD proteins, disrupt the formation of the YAP/TAZ-TEAD complex, and thereby inhibit the transcription of oncogenes. Currently, there are no marketed drugs targeting this pathway, and the globally fastest-progressing Tead inhibitor is in Phase I clinical trials. Preclinical research data from Signet Therapeutics shows that, compared with similar drugs, SIGX2649 effectively inhibits all four proteins of the TEAD family, achieving optimal efficacy. Moreover, SIGX2649 can more effectively promote the binding of the transcriptional repressor VGLL4 to TEAD, achieving a dual effect. Due to its unique activity and differentiated mechanism, SIGX2649 has the potential to become a first-in-class/best-in-class targeted drug in the HIPPO pathway. This targeted drug will soon be submitted for IND approval simultaneously in China and the United States.

In preclinical studies, SIGX2649 demonstrated efficacy in various in vitro tumor models (including YAP-activatedLiver Cancer OrganoidsAnd in mesothelioma cells carrying LATS mutations/NF2 deletions, etc.) it has demonstrated excellent anti-proliferative activity. In in vivo models, it exhibits strong anti-tumor efficacy, favorable pharmacokinetic properties, and compared to other TEAD inhibitors, shows reduced renal targeting toxicity. Moreover, when combined with RAS pathway inhibitors, SIGX2649 triggered significant synergistic effects in KRAS-mutant solid tumors.

SIGNET is a pioneer in the global "organoid + AI"-powered innovative targeted drug R&D model, as well as a national high-tech enterprise and a specialized and innovative enterprise. The company’s founding team consists of top talents from prestigious institutions such as Harvard University, MIT, and the Chinese Academy of Sciences. As first or corresponding authors, they have published over 20 groundbreaking research papers on gastric cancer and esophageal cancer in journals with impact factors exceeding 20, including Nature, Nature Medicine, and Cancer Cell, establishing themselves as global leaders in the field of gastric and esophageal cancer research. Since its establishment in Shenzhen at the end of 2020, the company has secured nearly 220 million yuan in financing and project funding, and holds more than 40 core intellectual property rights.

The company currently has four first-in-class drug pipelines and one organoid platform in its portfolio. Its core pipeline, SIGX1094, is the world's first targeted drug for diffuse gastric cancer. It has successively received IND approvals from the U.S. FDA and China's NMPA, and has been granted Orphan Drug Designation (ODD) and Fast Track Designation (FTD) by the U.S. FDA. In August 2025, the drug was nominated for the Galien Award, known as the "Nobel Prize of the pharmaceutical industry." It is currently undergoing Phase I clinical trials at the Peking University Cancer Hospital. This pipeline is also the world’s first drug to be advanced to the clinical stage via an "organoid + AI" technology platform.

Since its establishment at the end of 2020, the company's forward-looking strategic layout of an "Organoid + AI"-powered technology system for innovative targeted cancer drug development has gained international authoritative 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 research and development. In April 2025, the U.S. FDA officially issued a statement explicitly supporting the gradual replacement of traditional animal experiments with organoid and AI technologies, fully validating the foresight and scientific rigor of the company’s technical layout from four years prior.