Job Function: Discovery & Pre-Clinical/Clinical Development
Job Sub Function: Biotherapeutics R&D
Job Category:Scientific/Technology
All Job Posting Locations:Spring House, Pennsylvania, United States of America
Job Description:We are searching for the best talent for Principal Scientist, Biologics Optimization in Spring House, PAPurpose: The Biologics Optimization team within Biologics Discovery is responsible for the design and optimization of lead biologic variants across multiple therapeutic modalities to achieve differentiated functional outcomes aligned with desired therapeutic mechanism of action (MoA). In this position, the Principal Scientist will serve as a scientific leader and subject matter expert in biologics optimization, driving and dissecting protein engineering strategies that translate molecular design into improved biological function across diverse therapeutic modalities. This role requires deep expertise in antibody and protein engineering, computational and AI/ML-enabled design approaches, and mechanism-driven biologics discovery expertise. The Principal Scientist will provide scientific leadership in function-based biologics optimization, translating therapeutic mechanisms of action and molecular design insights into differentiated functional outcomes across diverse therapeutic modalities. This role will drive the design and delivery of fit-for-purpose optimized protein sequences and evaluate critical attributes-including biological function, potency, selectivity, production, and developability-using display technologies, structure- and modeling-guided design, and emerging computational and AI/ML approaches. The successful candidate will partner closely with Therapeutic Area scientists, computational scientists, protein engineers, and drug discovery teams to develop and implement optimization strategies that enhance potency, selectivity, efficacy, and overall therapeutic performance. This role offers an exciting opportunity to not only engage in the discovery and molecular engineering of biotherapeutics, but to develop new processes and technologies in collaboration with other functional group with the opportunity to lead project teams and interact with world-class Therapeutic Area scientists.
You will be responsible for:- Lead biologics optimization efforts across multiple therapeutic programs, translating target biology and desired mechanisms of action into rational protein engineering strategies.
- Serve as a subject matter expert in function-driven optimization: develop and champion novel development efforts aimed at fulfilling strategic long-term antibody design/optimization initiatives and validation.
- Develop optimization strategies that integrate antibody sequence, structure, developability, and biological function to achieve program objectives.
- Develop and champion novel display-based platform development efforts aimed at fulfilling strategic long-term antibody design/optimization initiatives and validation.
- Lead/participate on project teams to advance discovery portfolio projects. Act as a point of accountability for optimization engineering asks and manage project timelines independently.
- Partner with teams across TD/TA to define critical functional hypotheses and establish screening cascades that enable MoA-driven decision making.
- Apply computational, AI/ML, and data-driven approaches to guide variant design, library construction, sequence prioritization, and hit selection.
- Evaluate emerging technologies and develop innovative approaches to accelerate biologics optimization workflows and therapeutic discovery.
- Independently present/defend scientific findings in multi-functional project teams/initiatives.
- Independently plan, analyze and interpret experimental results and draft patent applications, manuscripts, protocols, SOPs, technical reports, etc.
Qualifications / Requirements:- Education: A minimum of a MS Degree in in Molecular Biology, Biochemistry, Biotechnology, Biomedical Engineering, structural biology or related field is required. PhD is highly preferred.
Skills/ExperienceRequired:•
- A minimum of 3 years of relevant industry experience in biologics discovery, protein engineering, or therapeutic optimization is required.
- Demonstrated scientific leadership and expertise in biologics optimization with a strong focus on improving functional outcomes aligned with therapeutic mechanisms of action.
- Deep understanding of antibody structure-function relationships, including variable region architecture, framework and CDR design, sequence liabilities, affinity maturation, specificity engineering, and developability considerations.
- In-depth knowledge and demonstrated experience in yeast display, including relevant molecular biology/library preparation and hands on experience in cell-based (FACS Aria/iQue) systems for screening protein domains. Demonstrate examples in applying state of the art display technologies to advance therapeutic programs beyond discovery.
- Proven ability to evaluate therapeutic mechanisms of action and design optimization strategies that improve biological activity, efficacy, selectivity, or target engagement.
- Strong understanding of biophysical and biochemical methods used for antibody and protein characterization, including techniques such as SPR, ELISA, flow cytometry, thermal stability analysis, aggregation assessment, and other developability metrics.
- Experience leveraging AI/ML, computational biology, protein modeling, or data science approaches to support biologics optimization and engineering workflows.
- Zeal for addressing complex scientific questions and solving novel challenges with creativity and a collaborative spirit. Demonstration of successful implementation of new ideas with calculated risk taking. Abilities to lead by influence and communicate across teams with diverse backgrounds is required.
- Demonstration of clear, concise, and timely communication skills, exemplified by peer-reviewed publications is required.
Preferred:- Candidates with a Master's degree: 6 years of industry experience is preferred
- Candidates with a PhD: 3 years of industry experience is preferred
- Expertise in scientific computing (e.g. Python) and experience with in silico protein structure and sequence modeling using AI/ML methods to facilitate collaboration with computational and AI/ML functional teams•
- Expertise in protein structure modeling and visualization tools such as Schrödinger, MOE, PyMOL, Chimera, or AlphaFold-based workflows.
- Experience with cell-based functional assays across oncology or immunology areas (e.g. T-cell redirection, immune modulation)
- Experience/strong understanding of high-throughput binding assays and screening technologies, including ELISA, SPR, MSD, flow cytometry, or related platforms.
- Strong understanding of mammalian protein expression systems, including transient expression and recombinant protein production workflows.
- Experience integrating large-scale experimental datasets with computational and AI/ML approaches to accelerate optimization decisions.
- Demonstrated ability to establish new scientific capabilities, influence strategy, and mentor scientists within a matrixed research environment.
Required Skills: Preferred Skills: 
