Signet Therapeutics Secures RMB 60 Million in Oversubscribed Angel Round to Advance Novel Cancer Targeted Therapies

VCBeat has learned that Signet Therapeutics, a company dedicated to the development of innovative cancer-targeted drugs based on disease models, recently announced the oversubscription of its angel financing round, raising approximately RMB 60 million. The round was led by Tiantu Investment, with participation from Lihhe Capital, XtalPi, and Yunjiu Capital, among other investors. According to reports, the funds will be used to expand the R&D team, accelerate the progression of existing pipelines into clinical stages, and simultaneously conduct lead compound screening for new targets.

Founded in late 2020, SIGNET was established by a founding team from the Dana-Farber Cancer Institute at Harvard University. The Institute is a world-leading research hospital integrating "basic translational research, clinical trials, and cancer treatment," with approximately 1,100 ongoing clinical trials. Leveraging the genomic profiles of cancer patients, the SIGNET team developed a proprietary disease model and made the first global discovery of a potent target for diffuse gastric cancer. In deep strategic collaboration with the AI-driven drug discovery company XtalPi, SIGNET advanced this independently developed targeted therapy to the Preclinical Candidate (PCC) stage within just over six months. Additionally, SIGNET has multiple other pipelines in parallel development.

Dr. Zhang Haisheng, Founder and CEO of SIGNET, stated, “We believe that a deep understanding of specific diseases and their underlying biology, serving as the foundation for new drug development, will play a crucial role in innovative pharmaceutical R&D. Furthermore, we consider differentiation to be the most critical attribute of a technology-driven innovation company. In traditional drug development, the responses of cell lines used in in vitro experiments often differ significantly from those observed in actual human patients. Therefore, building on our years of extensive research in gastric cancer, we have established disease-specific models and platforms based on the genuine genomic alterations found in cancer patients. These platforms are utilized for drug screening, evaluation, and optimization, ensuring that drug responses more closely mirror real patient reactions—akin to ‘tailored medicine’ or the philosophy of ‘from the disease, back to the disease.’ During the clinical trial phase, we employ our proprietary biomarkers to screen target patients, thereby ensuring high predictability of their response to the drug. The core differentiated advantage of our team lies in addressing challenges traditionally encountered during the clinical stage at the preclinical stage. This approach not only saves substantial human and financial resources but also allows for iterative optimization. We are confident that this will become a major trend in new drug development.”

Wei Guoxing, Partner at Tiantu Investment, stated, “We highly recognize SIGNET’s position as a global leader in gastric cancer research. Its profound understanding of biology and disease is crucial for later-stage clinical trials. XtalPi holds unique advantages in small-molecule drug development. The collaboration between SIGNET and XtalPi integrates XtalPi’s strengths at the molecular level with SIGNET’s proprietary platform advantages in functional biology, which will significantly accelerate the efficiency of new drug development and improve clinical response rates. SIGNET Therapeutics is highly differentiated from existing new drug development companies, positioning it to rapidly grow into a leader in this niche sector.”

Fu Ying, Investment Director at Lihhe Venture Capital, stated, “SIGNET’s first-in-class targeted therapy for diffuse gastric cancer has the potential to rapidly fill a significant gap in the market. This is particularly meaningful for China, a country with a high burden of gastric cancer, as SIGNET’s deep commitment to this field will not only improve patient survival but also significantly promote pharmaceutical innovation across China. Furthermore, SIGNET will leverage the distinct advantages offered by this indication in both China and the United States—gastric cancer is classified as a rare disease in the U.S., qualifying for FDA fast-track pathways, while the large patient population in China enables rapid clinical trial advancement—to accelerate clinical development and capture market share. In addition to its core pipeline, SIGNET’s R&D team possesses expertise in PROTAC technology. We believe these diversified pipelines will help SIGNET evolve into an international innovative pharmaceutical company.”

Wen Shuhao, Chairman of XtalPi, expressed great pleasure at the rapid progress in SIGNET’s R&D pipeline facilitated by XtalPi. “From the early stages, we at XtalPi have highly valued SIGNET’s team and technology. The swift advancement of SIGNET’s pipeline not only demonstrates their strengths in biology but also indirectly validates that AI-driven drug discovery is not only significantly enhancing R&D efficiency but is also likely to be a game changer. It enables drug discovery to break free from the constraints of existing small-molecule libraries, yielding entirely novel (de novo) drug molecules, which holds profound significance for current pharmaceutical R&D practices. Our collaboration with SIGNET will deepen further. Beyond the current flagship pipeline, the data accumulated by SIGNET on its functional biology platform—such as organoids, patient-derived organoids (PDOs), and patient-derived xenografts (PDXs)—will substantially improve the accuracy of XtalPi’s machine learning models in predicting drug functionality at the stage ‘post-molecular design but pre-IND,’ thereby greatly expanding the operational scope of XtalPi’s AI capabilities.”

Cao Darong, Founding Partner of Yunjiu Capital, stated, “We are delighted to witness the rapid progress SIGNET is making in its pipeline R&D. SIGNET’s unique advantages in disease models and platforms not only help accelerate drug development but also significantly reduce risks associated with its R&D pipeline. Dr. Zhang is a leading scholar in the field of diffuse gastric cancer research in China, having assembled a team at the forefront of the industry. The team members possess solid backgrounds and complementary expertise, supported by abundant technical R&D resources. We believe that SIGNET holds immense promise in collaborative drug development and precision medicine.”

Before founding SIGNET, Haisheng Zhang was a postdoctoral fellow in the research team led by Adam Bass at the Dana-Farber Cancer Institute. The team’s work on gastric cancer as part of The Cancer Genome Atlas (TCGA) classified this malignancy—the third leading cause of cancer-related deaths worldwide—into four distinct molecular subtypes. These findings, published in Nature, have become a landmark achievement in the molecular classification of gastric cancer.

Diffuse gastric cancer, which accounts for approximately one-third of all gastric cancer cases, is classified as a genomically stable subtype. This implies that conventional targeted therapies directed at common targets such as HER2 and EGFR are not suitable for the treatment of patients with diffuse gastric cancer. Furthermore, these patients often exhibit poor sensitivity to traditional modalities like chemotherapy and radiotherapy, highlighting an urgent clinical need for effective targeted therapeutics specifically for diffuse gastric cancer.

Globally, nearly 780,000 people die from gastric cancer each year, with China accounting for nearly half of all prevalent and newly diagnosed cases. Due to the relatively low incidence of gastric cancer in Western countries, research and development of therapeutic agents have progressed relatively slowly. Addressing this substantial unmet clinical need, Dr. Zhang Haisheng and his team, who have dedicated years to this field, identified robust therapeutic targets for this cancer by establishing organoid models and transgenic mouse models. Their related research was published in late 2019 in Cancer Discovery, a premier journal in oncology research.

Zhang Haisheng stated, “Our research findings fill a gap in this field. By elucidating the mechanisms of such cancers and identifying potential therapeutic targets, we hope to attract and encourage more scholars and experts, particularly Chinese researchers, to engage in this area of study. Our ultimate goal is to ensure that patients benefit from these advances in the near future, thereby addressing the current challenge of having no available treatment options.”

Following target identification, SIGNET entered into a deep strategic collaboration with XtalPi, fully leveraging XtalPi’s advantages in AI-driven drug discovery and integrating traditional medicinal chemistry to rapidly design and synthesize a library of highly potent candidate molecules. Subsequently, through screening and evaluation on SIGNET’s disease model-based platform, and iterative optimization by XtalPi using an “enzyme activity–disease model function–enzyme activity” feedback loop, a preclinical candidate compound with independent intellectual property rights was obtained within just over six months.

If clinical trials succeed, SIGNET’s targeted therapy for diffuse gastric cancer will rapidly fill the market void for targeted treatments in this indication and could be extended to targeted therapies for other malignant cancers, such as ovarian, breast, and pancreatic cancers. Furthermore, combining this therapy with chemotherapy and immunotherapy agents may significantly improve patient survival. Zhang Haisheng told VCBeat that SIGNET will continue to apply its “from disease, to disease” R&D philosophy to other pipeline developments, early disease screening, and adjunctive diagnostics, among other clinical applications.

Signet Therapeutics is an innovative company dedicated to the development of targeted cancer therapies based on disease models. Founded in late 2020 and originating from Harvard University, Signet’s core team comprises distinguished talents from academia—including Harvard University, the Massachusetts Institute of Technology (MIT), and the Chinese Academy of Sciences—as well as from the pharmaceutical industry. Headquartered in Shenzhen with a branch in Boston, USA, the company’s Chinese name “Xige” (希格) is not only a phonetic translation of “Signet,” but also embodies its vision of “harboring hope and pursuing knowledge through rigorous investigation.” Through the team’s professionalism, cutting-edge expertise, and relentless pursuit of excellence, Signet aims to instill hope in patients with currently untreatable cancers and is committed to transforming highly lethal malignant cancers into manageable chronic diseases through precision targeted therapy.

The Tiantu VC team was established in 2016. Prior to this, it had managed three venture capital funds and one angel fund, with a cumulative assets under management (AUM) exceeding RMB 3 billion. After four years of practice, the team has developed a relatively mature investment decision-making system and has invested in more than 60 early-stage projects.

Shenzhen Lehe Venture Capital Co., Ltd. is a wholly-owned subsidiary of Lehe Sci-Tech Innovation Group. Its venture capital operations commenced in 1999, serving as a key pillar of the Group’s technology services. The company is responsible for investing in and incubating the Group’s technology enterprises, working in close synergy with its applied R&D, talent training, and innovation base services. Distinguished by its focus on the commercialization of scientific and technological achievements, it is one of China’s earliest venture capital and incubation institutions dedicated to investing in high-tech enterprises. It has established a full-chain investment business model that spans from the investment and incubation of early-stage hard technology projects to ongoing investment services for portfolio companies. To date, Lehe Sci-Tech Innovation Group has incubated and served over 2,500 enterprises, nurturing 30 listed companies, more than 50 companies listed on the National Equities Exchange and Quotations (NEEQ), over 300 national high-tech enterprises, and numerous star technology projects.

XtalPi is an AI-driven drug discovery technology company powered by digitalization and intelligence. Leveraging quantum physics, quantum chemistry, artificial intelligence, and cloud computing, XtalPi provides intelligent drug R&D services to innovative pharmaceutical companies worldwide. By enhancing the efficiency and success rate of critical stages in drug development and reducing R&D costs, we aim to help our partners deliver more high-quality medicines to patients. Founded on the campus of the Massachusetts Institute of Technology (MIT), XtalPi’s core team comprises top talents from academia, the IT and internet sectors, and the pharmaceutical industry. Headquartered in Shenzhen, the company has established branches in Beijing, Shanghai, and Boston. Since its inception, XtalPi has successfully provided drug R&D services to over 70 pioneering pharmaceutical companies across the United States, Europe, China, and Japan.

Yunjiu Capital, established in 2016, is a venture capital fund. The team comprises senior technology experts, successful entrepreneurs, and investors, with a primary focus on internet platforms, hard technology, enterprise services, and the consumer and general health sectors. With years of deep engagement in China’s venture capital landscape, the Yunjiu team is committed to growing alongside the world’s largest innovation market, exploring the unknown, and co-creating the future.

Writing Reference

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