Oral, Selective RBM39 Degrader Under Evaluation in Phase 1 Trial; Preclinical Data Support Expansion Potential Across Ewing Sarcoma, Hepatocellular Carcinoma, KRAS-Mutant Cancers, Neuroblastoma, and Other RBM39-Dependent Tumors
KING OF PRUSSIA, Pa., June 02, 2026 (GLOBE NEWSWIRE) -- SEED Therapeutics, Inc. (“SEED”), a clinical-stage biotechnology company pioneering rationally designed molecular glue degraders, today announced the presentation of a trial-in-progress poster at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting highlighting the first-in-human Phase 1 study of ST-01156, SEED’s oral, selective RBM39 molecular glue degrader. The presentation underscores SEED’s transition from platform validation to clinical execution, with ST-01156 advancing across multiple RBM39-dependent cancers, with development informed by mechanism-based preclinical data and real-time pharmacokinetic and pharmacodynamic assessments.
ST-01156 is designed to degrade RNA-binding motif protein 39 (RBM39), a regulator of RNA splicing programs that govern oncogenes essential for tumor survival. The ASCO poster outlines the scientific rationale, Phase 1 dose-escalation design, and planned expansion strategy for ST-01156which is currently being evaluated in a first-in-human Phase 1 dose-escalation study (NCT07197554) in patients with advanced solid malignancies.
Highlights At A Glance
- Clinical-stage lead asset: ST-01156 is currently being evaluated in an open-label Phase 1 study in patients with advanced solid malignancies.
- Oral, brain-penetrant molecular glue degrader: ST-01156 was rationally optimized for selective RBM39 degradation, potency, metabolic stability, and drug-like properties.
- Integrated biomarker and dose-selection strategy: The study incorporates real-time RBM39 target engagement in peripheral blood mononuclear cells (PBMCs), together with safety and pharmacokinetics, to support recommended Phase 2 dose (RP2D) selection.
- Broad oncology expansion potential: Planned expansion cohorts include Ewing sarcoma, advanced hepatocellular carcinoma, KRAS-mutant cancers, and other RBM39-dependent tumors, including biliary tract carcinoma, endometrial carcinoma, and DNA damage repair–aberrant cancers.
- Preclinical proof-of-concept across multiple models: SEED has demonstrated preclinical antitumor activity in response to RBM39 degradation, including tumor regression, with complete regression observed in Ewing sarcoma, neuroblastoma, and KRAS-mutant colorectal cancer models.
Together, these findings support SEED’s strategy to advance ST-01156 from dose escalation into patient-enriched expansion cohorts where emerging RBM39 biology informs indication selection and clinical proof-of-concept.
Scientific Rationale and ASCO Poster Takeaways
RBM39 is an RNA-binding protein that regulates cancer-relevant RNA splicing programs, including pathways involved in tumor proliferation, survival, DNA damage response, and oncogenic fusion proteins. ST-01156 is designed to act as a molecular glue degrader by recruiting RBM39 to DCAF15, an E3 ligase adapter, leading to RBM39 degradation through the ubiquitin-proteasome system. By eliminating RBM39, ST-01156 has the potential to disrupt multiple cancer-driving pathways that are difficult to address with conventional targeted therapies.
The ASCO poster highlights preclinical and clinical-development findings supporting SEED’s strategy:
- Ewing sarcoma rationale: ST-01156 demonstrated tumor regression in an A673 Ewing sarcoma xenograft model, with complete regression at higher dose levels. Separately, treatment with ST-00937, a non-deuterated precursor of ST-01156, showed complete elimination of RBM39 and the EWS-FLI1 fusion protein in tumor lysates.
- Neuroblastoma and KRAS-mutant cancer activity: ST-01156 produced complete tumor regression in an SH-SY5Y neuroblastoma xenograft model, while ST-00937 demonstrated complete regression in an HCT-116 KRAS G13D-mutant colorectal cancer xenograft model.
- Mechanism-based expansion strategy: The clinical development plan includes expansion cohorts in Ewing sarcoma, advanced hepatocellular carcinoma, KRAS-mutant cancers, and other RBM39-dependent tumors, including biliary tract carcinoma, endometrial carcinoma, and tumors with DNA damage repair aberrations.
- Integrated dose-selection approach: The Phase 1 study is designed to determine the optimal dose and recommended Phase 2 dose using safety, pharmacokinetic, and pharmacodynamic data, including real-time measurement of RBM39 target engagement in PBMCs.
“ST-01156 is designed to address a biologically important and difficult-to-drug target through selective RBM39 degradation. The ASCO presentation highlights a disciplined clinical strategy that integrates safety, pharmacokinetics, and real-time target engagement to guide dose selection and expansion into cancers with strong mechanistic rationale. We believe this approach positions ST-01156 to generate early meaningful clinical proof-of-concept across multiple RBM39-dependent tumor types,” said Dr. James Tonra, PhD, President, and Chief Scientific Officer of SEED.
“The advancement of ST-01156 into first-in-human clinical evaluation is an important milestone for SEED and a validation of our RITE3™ technology. Our goal is not only to discover molecular glues, but to rationally design degraders with clear target biology, translational biomarkers, and a defined clinical development path. ST-01156 reflects that strategy and represents a meaningful step toward unlocking disease drivers that have historically been considered undruggable,” said Dr. Lan Huang, PhD, Co-Founder, Chairman, and Chief Executive Officer of SEED.
Clinical Development Status
ST-01156 is being evaluated in an ongoing, open-label Phase 1 multiple ascending dose (MAD) study in patients with advanced solid malignancies. The study is designed to enroll approximately 30 to 50 patients, with ST-01156 administered orally once daily for five days every seven days, with the option to adapt to a continuous once-daily schedule based on emerging data.
The primary objectives are to characterize safety and tolerability and determine the optimal dose and recommended Phase 2 dose. Secondary objectives include pharmacokinetics, RBM39 target engagement in PBMCs, and preliminary antitumor activity. Per protocol, SEED plans to evaluate ST-01156 in mechanism-based back-fill cohorts within this MAD study, including Ewing sarcoma, advanced hepatocellular carcinoma, KRAS-mutant cancers, and other RBM39-dependent tumors. Data from these cohorts are intended to inform the design of the protocol’s subsequent Phase 1 expansion phase.
ASCO 2026 Poster Presentation Details:
- Title: First-in-Human Clinical Evaluation of ST-01156, an Optimized and Selective Degrader of RNA-Binding Motif 39 (RBM39): A Phase 1 Study in Advanced Solid Malignancies with a Focus on RBM39-Dependent Cancers
- Presenter/Authors: Eric K. Rowinsky, Gregory M. Cote, George D. Demetri, Robert G. Maki, Suzanne George, Daneng Li, Alain C. Mita, Monica M. Mita, Jordi Rodon Ahnert, Dan Lu, Dong Liu, Lan Huang, James Tonra
- Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology
- Abstract Number: TPS3164
About SEED Therapeutics
SEED Therapeutics is a clinical-stage biotechnology company developing rationally designed molecular glue degraders to treat diseases driven by proteins previously considered undruggable. Its proprietary RITE3™ technology enables selective targeted protein degradation with a defined therapeutic window, supporting a pipeline of six molecular glue programs across oncology, neurodegeneration, and immunology.
SEED was co-founded by four preeminent scientists:
- Nobel Laureate Prof. Avram Hershko, co-discoverer of the ubiquitin-proteasome system, the cellular machinery that SEED’s molecular glue degraders harness to eliminate disease-causing proteins.
- Dr. Lan Huang, a pioneering structural biochemist who determined the first high-resolution structure of an E3 ligase substrate-binding domain, providing foundational insight into how targeted protein degradation can be rationally designed.
- Prof. Ning Zheng (University of Washington, HHMI Investigator), structural biologist and pioneer of RING-finger E3 ligase mechanisms, and the scientist who coined the term “molecular glue” to describe small molecules that redirect E3 ligases to degrade neo-substrates.
- Prof. Michele Pagano (NYU Grossman School of Medicine, HHMI Investigator), one of the world’s foremost authorities on ubiquitin-mediated proteolysis and its role in cell cycle control and cancer, whose work has defined how E3 ligase dysregulation drives tumor development.
Additional information is available at www.seedtherapeutics.com.
Forward-Looking Statements
This press release contains forward-looking statements regarding SEED Therapeutics, including statements about the design and progress of its clinical and preclinical programs. Actual results may differ materially due to various risks, including those inherent to drug development. SEED undertakes no obligation to update these statements except as required by law.
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