Jianhui Ma

• Lead early discovery Degrader Antibody-Drug Conjugates (DAC) program, designing studies to support candidate selection, evaluate target engagement and selectivity, characterize toxicities (in vitro and in vivo), and define mechanism of action (MOA) and pharmacodynamic/biomarker profiles. • Act as translational biology representative in program strategy and business development discussions, contributing to new target nominations, indication and line-of-therapy prioritization, and niche market identification

Exceled as translational lead (preclinical and clinical biomarker) and drove efforts for several clinical-stage programs, including drugs targeting cell cycle, DNA damage repair pathway, estrogen receptor (SERD), EGFR and BCL-2/BCL-xL, overseeing multiple trials in solid tumors and AML. • Supervised a team of Ph.D. scientists to develop translational models and design studies (efficacy, PK/PD) to inform dose optimization, patient selection, biomarker discovery and combination strategies, resulting in multiple publications, issued patents, and industry collaborations. • Predicted human efficacious exposure and dosing regimens using preclinical models whish has been applied in clinical trials • Identified Cyclin E1 as a predictive biomarker for WEE1 inhibition, led biomarker assay (IHC) development with CROs, and collaborated with computational biology to establish clinical cutoff criteria for patient stratification • Drove biomarker strategy and execution, collaborating with clinical operations, CROs, and clinical scientists to ensure timely biomarker testing, novel platform assessment and data analysis. • Led combination strategy development with chemotherapies, antibody drug conjugates (ADCs) and radioligand drugs, triggered partnerships with large pharmas and clinical trials • Authored and reviewed key regulatory documents, including IND documents, pharmacology reports, clinical protocols, investigator brochures (IB), FDA meeting packages, orphan drug designation, and fast-track applications. • Established and managed collaborations with academic institutions and industry partners, overseeing multiple investigator-initiated studies. • Delivered strategic presentations to senior management, communicating key findings and recommendations to inform decision-making processes • Maintained up-to-date knowledge of emerging therapies, literature, competitive landscape, and clinical data to inform and guide translational and biomarker strategies

Thrived as translational lead of several clinical stage programs: designed and executed preclinical studies to evaluate efficacy, PK/PD, MOA, and biomarker hypotheses. Validated an ERα-mediated transcription gene signature as pharmacodynamic biomarker, later adopted as clinical biomarker assay for patient samples. • Coordinated outsourcing of clinical assays to CROs, collaborate with clinical operations to ensure clinical sample collection for biomarker analysis. • Development and implementation of translational biomarkers in clinical programs for the establishment of proof of mechanism and biological activity for oncology drug candidates. • Worked with bioinformaticians to analyze clinical biomarker data; explore correlations between biomarkers, drug exposure and tumor response, interpret and present data and contribute to publications. • Wrote pharmacology and biology sections for IND documents, patents, investigator’s brochure (IB). Review and write biomarker section of clinical protocols. Biology lead for early discovery programs: Selective Estrogen Receptor Degrader (SERD) and PROTAC project • Established screen cascade; designed, optimized and executed biochemical assays for target validation, MOA and on-target / off-target toxicity. • Designed in vitro, in vivo studies, PK/PD studies to evaluate lead candidates • Interpreted results and made scientific presentations at company meetings • Supervised & trained research associate in design, analysis & execution of cellular & molecular studies

• Identified a critical role of the well-known tumor suppressor, PTEN, in mediating radiation resistance in GBM through regulating DNA damage and repair and validated that the PTEN-DNA repair cascade could be targeted for therapy in pre-clinical GBM mice models • Designed, evaluated and validated the efficacy of small molecular FGFR inhibitors in pre-clinical glioblastoma (GBM) mouse models. Achieved promising results that promotes collaboration with pharmaceutical companies • Utilized the AOM/DSS colon cancer model to investigate the function of PTEN phosphorylation. • Lead collaborations with Dr. Joe Costello (University of California, San Francisco) and Dr. Nam (Samsung Medical Center, South Korea) analyzing the role of PTEN in clinical GBM patients’ samples • Supervised junior postdocs in designing, conducting and optimizing in vitro and in vivo experiments

• Identified a signaling mechanism that regulates sustained inflammatory response and proved that inhibition of the late-phase inflammation reduced TNF-α production and benefited mice with inflammatory diseases (sepsis) • Used LPS and CLP-induced sepsis mice models to investigate the function of a small protein GABARAP in the development of inflammatory diseases and the mechanism of TNFα induced cross-tolerance to endotoxin

• Identified the receptor tyrosine kinase (RTK)-PI3K-AKT- mTOR- STAT3/p63-Notch signaling cascade as a regulator of cell differentiation and tumorigenesis • Demonstrated that avian influenza A virus H5N1 causes autophagy-dependent cell death through suppression of mTOR signaling • Conceived the idea of testing the role of mTOR pathway in cancer metabolism and found this oncogenic signaling regulated glycolysis in cancer cells through PKM2, a critical kinase for aerobic glycolysis • Supervised undergraduate students in conducting cellular and molecular biology experiments