SEED Therapeutics Initiates First-in-Human Trial of ST-01156, Novel Molecular Glue Degrader Targeting RBM39
核心洞察
SEED Therapeutics (搜索) has dosed the first patient in a Phase 1a dose-escalation study of ST-01156, an oral molecular glue degrader targeting RBM39 (搜索) in patients with advanced solid tumors (搜索).
ST-01156 demonstrated complete tumor regression in preclinical animal models of Ewing sarcoma (搜索) and KRAS-mutant colorectal cancer (搜索), with robust target engagement and favorable safety profile.
The drug has received FDA Orphan Drug Designation and Rare Pediatric Disease Designation for Ewing sarcoma (搜索), where no new therapeutic agent has been approved in 30 years.
SEED Therapeutics (搜索) has achieved a significant milestone by dosing the first patient in its Phase 1a dose-escalation study of ST-01156, an oral molecular glue degrader targeting RBM39 (搜索) in patients with advanced solid tumors (搜索). The clinical-stage biotechnology company announced this development on January 9, 2026, marking the transition of their novel therapeutic approach from preclinical research to human testing.
Novel Mechanism Targets Undruggable Protein
ST-01156 represents an innovative approach to cancer treatment as an orally administered, brain-penetrant molecular glue degrader designed to selectively degrade RBM39 (搜索), a key regulator of RNA splicing and transcription required for the survival of several cancer types. The drug's mechanism of action addresses what has traditionally been considered an undruggable target, potentially opening new therapeutic avenues for difficult-to-treat cancers.
The initial component of the clinical trial allows enrollment of patients with any form of advanced solid tumor malignancy while enriching for cancer types with strong preclinical evidence of RBM39 (搜索)-dependency, including Ewing sarcoma (搜索), KRAS-mutant cancers (搜索), and hepatocellular carcinoma (搜索).
Promising Preclinical Results Drive Clinical Translation
In preclinical studies, ST-01156 demonstrated robust target engagement, anti-tumor activity, and a favorable safety profile, including complete tumor regression in animal models of Ewing sarcoma (搜索) and KRAS-mutant colorectal cancer (搜索). These compelling preclinical results provided the foundation for advancing the compound into human clinical trials.
The drug has received significant regulatory recognition, obtaining U.S. FDA Orphan Drug Designation and Rare Pediatric Disease Designation for the treatment of Ewing sarcoma (搜索), where no new therapeutic agent has been approved in the last 30 years. This regulatory support underscores the urgent medical need and potential therapeutic value of ST-01156.
Trial Design and Objectives
The Phase 1a study employs a carefully structured dosing regimen, with ST-01156 administered orally once daily for 5 days every 7 days, for 28 consecutive days. The primary objective of the open-label, first-in-human trial is to evaluate the safety, tolerability, and adverse event profile of ST-01156, as well as to identify the recommended dose level for subsequent clinical development.
Secondary objectives include the characterization of pharmacokinetics and preliminary evidence of anticancer activity. Exploratory objectives include the demonstration of target engagement in circulating cells in blood. The trial is registered on ClinicalTrials.gov (NCT07197554) and includes participation from leading cancer centers: Dana-Farber Cancer Institute, Memorial Sloan Kettering Cancer Center, MD Anderson Cancer Center, Mass General Hospital, City of Hope, and Hoag Cancer Center.
Leadership Perspective on Clinical Milestone
"Dosing the first patient with ST-01156 marks an important milestone for SEED and for patients with cancers that urgently need new therapeutic options," said Dr. Lan Huang, PhD, Co-Founder, Chair, and Chief Executive Officer of SEED Therapeutics (搜索). "We believe RBM39 (搜索) degradation represents a powerful and differentiated therapeutic strategy, and we look forward to advancing this program through clinical development."
George Demetri, MD, Professor of Medicine at Harvard Medical School and Dana-Farber Cancer Institute, and Chair of SEED Scientific Advisory Board, emphasized the trial's comprehensive approach: "This trial is thoughtfully designed to build on the powerful preclinical signals of safety and efficacy while integrating PK, PD, and biomarker learning from the outset, with the goal of learning from each patient to optimize therapeutic development. The initiation of clinical dosing brings us one step closer to translating the novel mechanism of ST-01156 action into meaningful benefit for patients."
Company Foundation and Platform
SEED Therapeutics (搜索) was co-founded by four scientific leaders, including Nobel Laureate Prof. Avram Hershko, discoverer of the ubiquitin-proteasome system, and other prominent researchers in the field of protein degradation. The company's proprietary RITE3™ platform enables targeted protein degradation with small-molecule precision, supporting a pipeline of six molecular glue programs across oncology, neurodegeneration, immunology, and virology.
Eli Lilly and Co. (搜索) and Eisai Co., Ltd., serve as cornerstone investors and research collaborators, supporting SEED's mission to unlock undruggable disease targets through their innovative molecular glue degrader approach.