Upstream Principal Scientist, Vector Biology

Legend Biotech is a global biotechnology company dedicated to treating and, one day, curing life-threatening diseases. Headquartered in Bridgewater, New Jersey, we are advancing the next generation of cell therapy through a portfolio of innovative technologies, including autologous, allogeneic, and in vivo cell therapy approaches. Our research spans chimeric antigen receptor T-cell (CAR-T), T-cell receptor (TCR-T), natural killer (NK) cell-based therapies, and other emerging platforms designed to transform the treatment of serious diseases. From our global network of research and development sites, we are committed to discovering and developing safe, effective, and cutting-edge therapies for patients worldwide.

Legend Biotech entered into a global collaboration agreement with Johnson & Johnson to jointly develop and commercialize CARVYKTI® (ciltacabtagene autoleucel; cilta-cel). Through this strategic partnership, we combine complementary expertise and capabilities to advance innovative immunotherapies for patients living with multiple myeloma.

Legend Biotech is seeking an Upstream Principal Scientist, Vector Biology as part of the Vector Biology Upstream team based in Philadelphia, PA .

Role Overview

Legend Biotech seeks a highly experienced and scientifically driven Principal Scientist to join the Vector Biology Upstream team in Philadelphia, with a strategic focus on early process development and the establishment of a manufacturable lentiviral vector (LVV) platform in support of in-vivo CAR-T programs. This senior individual contributor role will serve as a scientific cornerstone within R&D, leading the early-stage definition, interrogation, and optimization of upstream LVV processes from molecular construct design through scalable bioreactor manufacturing with the deliberate intent of building a robust, developable process foundation that can be advanced into late-stage development and commercialization. The Principal Scientist will bring a rare combination of molecular biology depth and bioprocess engineering breadth, functioning as a key technical authority who bridges construct-level design decisions with upstream process outcomes, while closely interfacing with Downstream, Analytical, and Technical Development partners to ensure end-to-end process coherence and readiness for technology transfer.

Key Responsibilities

• Establish and optimize early-stage seed train strategies from shake flask through bench-scale bioreactor, defining the foundational process parameters, cell culture conditions, and operational ranges that will underpin a scalable and manufacturable LVV platform.
• Apply molecular biology expertise to evaluate LVV constructs encompassing plasmid architecture, packaging system selection, promoter and transgene configuration, and transfer vector optimization to establish high-performing, platform-compatible vectors that meet manufacturability and potency requirements for in-vivo CAR-T applications.
• Design and optimize LVV production workflows, including transient transfection systems and emerging stable producer cell line platforms, to systematically improve vector yield, product quality attributes, and process robustness as part of an integrated early process development strategy.
• Conduct systematic media optimization, feeding strategy evaluation, and bioreactor process control development to define process setpoints, identify critical process parameters (CPPs), and establish the mechanistic understanding needed to support scale-up to 40-L and beyond.
• Partner closely with Downstream colleagues to understand purification process constraints and integrate upstream design decisions including harvest conditions, clarification approaches, and vector quality attributes that enable a cohesive, end-to-end manufacturable process.
• Design and execute fit-for-purpose early process development studies to generate the foundational data packages required for process lock, comparability assessments, and downstream regulatory filings; apply structured Design of Experiments (DoE) and risk-based approaches to maximize information yield.
• Serve as the upstream scientific lead within Vector Biology, providing authoritative technical input to cross-functional forums on construct-process relationships, early development strategy, and the stage-appropriate advancement of research findings into formal process development programs aligned with IND-enabling timelines.
• Exercise a high degree of scientific independence in designing and executing complex experiments; proactively identify technical risks, generate mechanistic hypotheses, and implement data-driven solutions with minimal oversight to keep early development programs on track.
• Synthesize complex experimental datasets into clear, structured data packages and deliver evidence-based technical recommendations that drive go/no-go decisions, inform process development strategy, and support program progression within Vector Biology and across R&D functional teams.
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