Group Leader, Antibody-Oligonucleotide Conjugates; Extrahepatic Delivery

Position Overview

We seek a highly innovative and results-driven Group Leader to build and lead an interdisciplinary team developing antibody-oligonucleotide conjugates (AOCs) for extrahepatic delivery. This role will integrate antibody discovery and engineering with linker chemistry, oligonucleotide conjugation, and fit-for-purpose bioanalytical and functional validation to enable asset generation beyond established hepatic indications. The successful candidate will own the scientific strategy and execution for the AOC platform, build an efficient group, establish platform capabilities (e.g., automation, conjugation, analytics, in vitro assays), and partner closely with oligonucleotide chemistry, DMPK, and bioanalytics teams.

• Scientific Leadership & Program Ownership
• Define AOC design principles for extrahepatic delivery (i.e., target selection, tissue/cell specificity, internalization, trafficking, endosomal escape strategies, payload selection, etc.).
• Drive program strategy, milestones, and decision-making frameworks (e.g., experimental plan, MOA validation, translation plan, develop ability risk).
• Lead multi-disciplinary project teams and represent AOC programs in governance forums and senior leadership reviews.
• Antibody Discovery, Engineering & Develop ability
• Guide antigen and epitope strategy for extrahepatic tissue targeting (e.g., muscle, adipose tissue, immune cells).
• Oversee generation, screening, and prioritization of antibodies via different display technologies (e.g., phage/yeast display, hybridoma, or computational design) using a balanced combination of internal capability and external CROs
• Engineer antibodies for:
• Affinity/avidity optimization, cross-reactivity, and species selection
• Internalization/trafficking (recycling vs. degradative pathways)
• Biophysical stability (aggregation, viscosity), PTMs, and manufacturability
• Establish develop ability workflows (e.g., expression, purification, stability, aggregation, poly-specificity, immunogenicity risk screening) using a balanced combination of internal capability and external CROs
• Linker Chemistry & Oligo Conjugation Platform
• Own the bioconjugation strategy (site‑specific vs. stochastic; cysteine/lysine conjugation, enzymatic conjugation, non‑natural amino acids, glycan remodeling, click chemistry, etc.).
• Partner with oligo chemists to define oligo formats (siRNA, ASO, splice‑switching oligos, etc.), chemical modifications, and conjugation handles.
• Design and optimize linkers for:
• Stability in systemic circulation
• Controlled release (if/as applicable)
• Compatibility with antibody and oligo chemistry
• Scalability and CMC readiness
• Establish analytical methods to quantify DAR, positional heterogeneity, purity, and stability (e.g., LC‑MS, SEC, CE‑SDS, HIC, UV/fluorescence, ion exchange, oligo integrity assays) plus hands‑on experience with multiscale purification and analytical characterization instruments.
• Functional Validation Readouts
• Develop and oversee in vitro assays to confirm:
• Binding and internalization (e.g., flow cytometry, microscopy, ligand competition)
• Intracellular trafficking/endosomal escape proxies
• Oligo activity (e.g., knockdown/splice modulation/qPCR/NGS readouts)
• Drive in vivo PK/PD and biodistribution studies in relevant models in close partnership with pharmacology team
• Cross‑Functional Partnering
• Collaborate with DMPK to establish AOC‑specific ADME understanding (e.g., deconjugation, metabolite profiling, clearance mechanisms)
• Partner with Bioanalytics to set up assays for intact conjugate, total antibody, free oligo, and catabolites.
• Work with CMC/process development for scale‑up readiness, control strategy, and quality attributes (CQAs) relevant to AOCs
• People Leadership & Capability Building
• Recruit, mentor,…