Apollina Goel

- Translational Biomarker Lead for HER3-DXd portfolio - Translational Science and Biomarker analysis of T-DXd studies

• Translational Medicine Lead for two clinical-stage oncology assets: - Implemented biomarker-driven strategy for clinical trials - Delivered clinic-ready diagnostic and fit-for-purpose biomarker assays - Maintained a cross-functional role with Clinical Operations, Translational Immunology, and Quality - Integrated exploratory biomarker readouts with clinical dataset and PK/PD modeling - Prepared regulatory and clinical documents including IND filing and Investigator's Brochures - Participated in FDA meetings to obtain feedback on dose selection, pivotal Phase 3 study design, and IVD development program • Advanced preclinical pipeline in autoimmune diseases: - Participated in cross-functional project meetings and reviewed studies assessing PK/tolerability and in vivo PD/efficacy readouts - Contributed to preclinical research design to advance joint external collaborations

• Led discovery research for different platforms i.e., biologics, gene- and cell-based therapies, RNA therapeutics, and small molecules. • Performed multimodal studies for biomarker development and PoC preclinical studies across therapeutic areas i.e., oncology, immuno-oncology, autoimmune and inflammatory diseases. • Strong background in conducting in vivo imaging (nuclear and optical) to assess biodistribution, PK/PD, efficacy, target engagement/receptor occupancy, toxicity/safety and tissue cross reactivity. • Extensive experience in biomarker discovery (spatial transcriptomics, proteomics) and digital pathology.

Cancer Research, Inflammation, and Redox Metabolism 1. Established role of altered oxidative redox metabolism in intrinsic and acquired chemotherapy resistance in myeloma. o Identified molecular druggable targets; performed mechanistic and preclinical validation of novel redox-based antioxidant (Ridaura, Antabuse) and prooxidant (TPP+ derivatives, Glucophage, 2-deoxyglucose) strategies. o Discovered the role of reactive oxygen species (ROS) production by tumor microenvironment-induced IL-6 in NF-κB activation and downstream antioxidant homeostasis, cancer survival, and drug resistance. o Revealed altered redox status of clonogenic stem cell-like myeloma cells. Designed and evaluated redox-based therapy to selectively induce cytotoxicity in these putative cancer stem cells. 2. Conducted focused screening of antioxidant gene network, demonstrating the scavenger receptor class A member 3 gene as predictor of myeloma progression and therapeutic response. o Performed animal imaging using 18F-FDG-PET, 18F-DOPA-PET, and 99mTc-SPECT combined with μCT. o Conducted miR expression array profiling, validation, and pathway analysis studies to identify disease biomarkers. o Co-discovered that clinical EGFR inhibitors increase pro-inflammatory cytokines in HNSCC in vitro and in vivo, thereby promoting immune/ inflammatory responses, angiogenesis, metastasis and tumor progression. 3. Contributed to validation of novel targets modulating endothelial cell surface molecules (LFA-1, GPCRs, selectins) that regulate leukocyte and lymphocyte adhesion and infiltration during acute/ chronic vascular inflammation. 4. Co-identified and validated targets (SNARE protein syntaxin 6, class l myosin family member Myo1C) involved in the modulation of angiogenesis, vascular inflammation, glucose uptake by regulating cell surface levels of VEGFR2, cell adhesion receptors (integrins), and GLUT-4 transporter.

Identified Bortezomib (BTZ) as a potent radiosensitizer in multiple myeloma. o Combined BTZ (Velcade) with Quadramet (153Sm-EDTMP) in a syngeneic mouse model. o Acquired planar gamma camera images to show skeletal targeting with Quadramet in mice. o Determined hematopoietic toxicity in vitro (CFC assays) and in vivo (complete blood cell analysis). o Analyzed serum cancer proteins and DEXA bone mineral density scans as surrogate readouts. o Designed and conducted prospective clinical trial research for efficacy biomarker analysis. Demonstrated imaging and radiovirotherapy of multiple myeloma. o Generated and characterized recombinant vesicular stomatitis virus (VSV) encoding for human sodium iodide symporter (NIS) gene. o Showed specific in vitro oncolytic activity and 125I accumulation in cell lines and primary human tumor cells. o Utilized xenograft and syngeneic models for imaging (123I-SPECT) and therapy (131I) with VSV-NIS. o Determined virus biodistribution, %ID, and absorbed radiation dose in tumors.

Conducted research on assembly of regulatory machineries and post-translational modifications of DNA-binding transcription factor (ER81) function in normal development and breast cancer. o Identified novel interaction partners (i.e. P/ CAF, ACTR and GRIP-1). o Mapped specific lysine residues that are acetylated by distinct HATs. o Determined role of acetylation/ phosphorylation on DNA binding, transactivation, and protein stability. o Identified regulatory pathways in cancer (Her2/ Neu, estrogen receptor activity by RNA helicases). Attained perspective on drug discovery and development of transcription factor inhibitors for cancer therapy.

Characterized divalent and multivalent single-chain antibody fragments (scFvs) of TAG-72 antibody (CC49). o Performed vector construction, humanization, expression (yeast), and protein purification. o Conducted surface plasmon resonance (SPR) studies using BIAcore. o Performed scFv radiolabeling (131I, 99mTc), characterization (HPLC, radioimmunoassay), and stability studies. Comprehensive understanding on dual-labeled protein biodistribution and pharmacokinetics studies in mice. o Compared tumor targeting (%ID) of scFvs with a range of IgG formats, like F(ab)2 and Fab. o Measured blood pool clearance and determined α and β-phase T1/2 values. Utilized 99mTc-labeled divalent and tetravalent scFv for tumor imaging by macro-autoradiography. Compared therapeutic potential of single vs. fractionated RIT. o Determined xenograft size, radiation absorbed dose in tumor vs. liver and kidney, median survival time.