On September 21, 2022, Shanghai Escugen Biotechnology Co., Ltd. ("Escugen") successfully held the "Phase Ib/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ESG401 in Patients with Locally Advanced/Metastatic Solid Tumors (ESG401-101)" clinical investigator meeting online. Prominent clinical experts and their teams from 20 top-tier oncology clinical research institutions across the country participated in the meeting. The launch of the Phase Ib/II study was announced at the meeting.
ESG401 ADC Molecule
The ESG401 ADC molecule features a significantly differentiated "stable and degradable" linker structure and performance design, which greatly reduces off-target toxicity caused by the premature release of the cytotoxic payload SN38, significantly widening the safety window. Additionally, this molecular design significantly improves the blood exposure and tumor tissue distribution of the ADC drug, with marked enhancement in preclinical efficacy.
Clinical investigators reviewed the results achieved in the Phase Ia stage of ESG401 and concluded that ESG401 represents the "second generation" of Trop-2 ADCs. The clinical results clearly demonstrate its extremely significant safety advantages, which can greatly improve patients' quality of life and treatment experience. The current highest dose escalation of ESG401 in clinical trials has far exceeded all other publicly available Trop-2 ADC products globally, and the maximum tolerated dose (MTD) has not yet been reached. The frequency and severity of hematologic toxicity (leukopenia and neutropenia, anemia) and gastrointestinal toxicity (severe diarrhea) have been significantly reduced. Under the "current best" treatment regimen, the incidence of Grade 3 or higher neutropenia and leukopenia is extremely low, with minimal occurrence of diarrhea, no anemia, and no observed side effects such as stomatitis, mucosal damage, or interstitial lung disease.
Very positive tumor response signals were observed in the Phase Ia stage of ESG401. In patients with advanced "triple-negative" breast cancer and hormone receptor-positive breast cancer who had progressed after multiple lines of treatment, high tumor response rates were observed across several dose groups, which could be maintained for a long time. The tumor response rate under the "current best" regimen is higher than that of other Trop-2 ADCs with publicly available data. More encouragingly, ESG401 was found to be effective in patients who had progressed after treatment with Enhertu and also showed efficacy in intracranial metastases.
The experts were very excited about the experimental results obtained. They shared their clinical experience from Phase Ia, discussed the Phase Ib/II protocol and future research strategies and directions. The investigators highly affirmed the significance of ESG401 as a Trop-2 ADC developed and led by Chinese enterprises and clinical researchers, which is suitable for Chinese clinical practice and has differentiated advantages. The investigators offered valuable suggestions on how to complete the subsequent trials with high quality and efficiency, to bring ESG401 to market as soon as possible and meet the urgent clinical needs for cancer treatment in China, demonstrating their strong sense of responsibility, mission, and professional capabilities.
The successful convening of the ESG401 Phase Ib/II clinical trial initiation meeting is another milestone event for Escugen. The official launch of the Phase Ib/II stage marks that Escugen will enter a new clinical development phase with a deeper scientific understanding and greater confidence in its pipeline. The purpose of the Phase Ib/II study is to further evaluate the safety and efficacy of ESG401 in a larger patient population, laying a solid foundation for registration and market launch.
ESG401 has improved the linker to enhance the robustness of the manufacturing process, product yield, and stability, which significantly reduces manufacturing costs and brings competitive pricing advantages for the drug. Escugen will fully advance the clinical development and product launch of ESG401, making high-end biologics accessible and affordable for patients.
About Escugen Biotechnology
Founded in 2017 in Shanghai, Escugen Biotechnology is a clinical-stage biotechnology company. The company completed a Series A financing round of over 100 million yuan in September 2021. Escugen focuses on the development of new drugs based on monoclonal antibodies and innovative antibody-drug conjugates (ADCs). The company was founded by veteran returnees with decades of R&D experience in both international and domestic biopharmaceutical companies. The founding team has accumulated rich and successful R&D experience in leading biopharmaceutical companies both domestically and internationally, with capabilities covering antibody discovery, conjugation technology, process development and quality research, preclinical and clinical studies. The company continuously tracks new technologies, targets, and processes in the field of antibody drugs, explores innovative uses of new technologies, and has built a series of product pipelines with distinct competitive advantages targeting unmet clinical needs. ESG401 is a Trop-2 ADC with multiple competitive advantages in safety, efficacy, and process stability. ESG206 is the second pipeline from Escugen to enter the clinical stage, targeting new targets for the treatment of B-cell malignancies and autoimmune diseases, and has already initiated clinical trials in Australia. The company will continue to introduce multiple innovative product pipelines into clinical trials.
