Senior Scientist/Principal Scientist - Biotherapeutic Engineering

Associate Director/Director, Digital Innovation Alchemist

Xilio Therapeutics is a clinical-stage biotechnology company discovering and developing tumor-activated immuno-oncology (I-O) therapies with the goal of significantly improving outcomes for people living with cancer without the systemic side effects of current I-O treatments. The company is using its proprietary platform to advance a pipeline of novel, tumor-activated clinical and preclinical I-O molecules that are designed to optimize the therapeutic index by localizing anti-tumor activity within the tumor microenvironment. Learn more by visiting www.xiliotx.com and follow us on LinkedIn (Xilio Therapeutics, Inc.).

SUMMARY:

We are seeking a highly skilled and experienced Sr. Scientist/Principal Scientist in Biotherapeutics Engineering to design and optimize complex biologics including multi-specific formats, incorporating rational design, generative AI/ML approaches, in silico computational methods, and structure-function analysis of experimental data generated by cross-functional teams. The successful candidate will have a strong background in structural biology and protein engineering with demonstrated experience applying advanced computational design tools including AlphaFold, Rosetta, and machine learning-driven protein design platforms. A background in applying machine learning techniques and molecular modeling to improve the biophysical and biological properties of biotherapeutics is desired. The candidate is expected to participate in cross-functional teams, manage external research collaborations, analyze key data, and communicate analyses and recommendations to discovery project teams.

Job Responsibilities:

• Design and generate complex biologics and various multi-specific formats for preclinical therapeutic validation using both traditional rational design and cutting-edge generative AI approaches.
• Analyze protein structures to rationally design biologics, focusing on structural determinants of binding affinity, selectivity, and therapeutic function.
• Leverage AI/ML-driven protein design tools (AlphaFold, RFDiffusion, Rosetta, ProteinMPNN, ESMFold, etc.) to predict protein structures, design novel sequences, and optimize biotherapeutic properties.
• Apply molecular modeling techniques and state-of-the-art in silico biotherapeutic engineering tools to predict molecular behavior, understand interactions, and design and optimize biologics-based drugs.
• Develop and implement computational workflows that integrate structure prediction, sequence design, and property optimization for biotherapeutic engineering.
• Identify relevant protein sequences from public literature and databases, utilizing analysis to inform therapeutic design and engineering decisions.
• Apply machine learning approaches to analyze large datasets of protein sequences, structures, and functional data to identify design principles and optimize therapeutic candidates.
• Collaborate with data-generating scientists to provide analytical expertise on protein therapeutics, utilizing knowledge of engineering design rationale and tested hypotheses to elucidate structure-function relationships.
• Represent functional group at cross-functional project team meetings.
• Manage contract research organization (CRO) relationships from initiation through completion, including project initiation, monitoring project progress, and ensuring timely delivery of contractual deliverables.
• Capture detailed experimental information in electronic lab notebook (ELN) entries.

Skills, Qualifications, and Requirements:

• BS/MS or PhD in Biochemistry, Structural Biology, Chemical and Biomolecular Engineering, Computational Biology, Bioinformatics, or a related field with 8-12 years (BS/MS) or 3-7 years (PhD) of relevant post-graduate experience in industry setting.
• Strong expertise in biotherapeutics design and protein engineering is required.
• Hands-on experience with AI/ML protein design tools (AlphaFold, Rosetta, ProteinMPNN, ESMFold, ChimeraX AlphaFold) and computational structure prediction platforms is desired.
• Strong analytical and problem-solving skills for computational analysis of protein sequences and structures are required.
• Experience with scientific literature review and protein sequence databases (e.g., UniProt, PDB) is preferred.
• Experience with biotherapeutic engineering tools (i.e. CCG-MOE, etc.) is highly preferred.
• Familiarity with electronic lab notebooks (such as Benchling) is desired.
• Experience with cloud computing platforms (AWS, Google Cloud) for running computationally intensive protein design workflows is preferred.
• Experience with CRO project management is highly preferred.
• Excellent communication skills to effectively collaborate with key intra- and inter-departmental stakeholders are required.
• Excellent organizational skills, with the ability to multi-task in a fast-paced environment with changing priorities.

Equal Opportunity and Inclusion

Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and developing our existing and additional employees. We are committed to equal opportunity and inclusion across all aspects of our organization, including in our recruitment, advancement and development practices. We conduct annual performance and development reviews for each of our employees to discuss the individual's strengths and development opportunities, career development goals and performance goals. We also regularly survey employees to assess employee engagement and satisfaction. In addition, each regular full-time employee is provided an allowance and time to attend appropriate job-related trainings and other professional development courses, seminars, meetings, and similar sessions. If you are an individual with a disability who requires an accommodation with the hiring process, please reach out to ....

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