Drug Discovery, Project Lead

Location: South San Francisco, CA

Department: DRUG DISCOVERY

Who We Are:

Calico (Calico Life Sciences LLC) is an Alphabet-founded research and development company whose mission is to harness advanced technologies and model systems to increase our understanding of the biology that controls human aging. Calico will use that knowledge to devise interventions that enable people to lead longer and healthier lives. Calico’s highly innovative technology labs, its commitment to curiosity-driven discovery science and, with academic and industry partners, its vibrant drug-development pipeline, together create an inspiring and exciting place to catalyze and enable medical breakthroughs.

Position Description: 

We are seeking a highly accomplished and motivated individual to step into the crucial role of Drug Discovery Project Lead within our Medicinal Chemistry team. This position is central to our mission of discovering new medicines. This leadership role requires taking full ownership of a drug discovery project, leading it from initial screening (hit identification) all the way through to successful preclinical candidate nomination. The ideal candidate will leverage deep and proven expertise in medicinal chemistry and project management to address challenging disease targets and deliver novel small-molecule therapeutics across Calico’s diverse therapeutic areas. 

Responsibilities: 

• Lead a multidisciplinary drug discovery project team (e.g., Medicinal Chemistry, Biology, DMPK, Safety) from the hit identification phase to preclinical candidate nomination, ensuring successful, timely, and data-driven execution 
• Utilize expert drug discovery knowledge to define the Target Candidate Profile (TCP) and formulate a comprehensive, efficient, and effective execution strategy with the project team to ensure delivery of the highest quality preclinical candidate 
• Independently lead and manage internal/external partners across all key drug discovery disciplines within the drug discovery team (e.g., synthetic chemistry, ADME, pharmacology) to ensure scientific excellence, high productivity, and agile prioritization
• Utilize expert knowledge in organic and medicinal chemistry to design and synthesize novel small molecules, driving the comprehensive strategy for identifying and optimizing potential drug candidates
• Proactively monitor and interpret biological testing, ADME characterization, and hit-to-lead/lead optimization profiling data to propose and execute innovative strategies for improving key drug attributes in a multi-parameter optimization fashion and identifying new target molecules 
• Effectively tackle, evaluate, and communicate research findings and project progress to chemistry, cross-functional teams, and senior leadership, enabling informed go/no-go decisions 
• Author and contribute to patent applications, study reports, and scientific publications 

Position Requirements: 

• Ph.D. or Postdoctoral experience in Organic or Medicinal Chemistry with 10+ years of progressive and impactful industrial experience in drug discovery
• Demonstrated and proven track record of successfully delivering small molecule candidates that have achieved preclinical candidate nomination and progressed into clinical development as the primary project leader
• Significant prior experience leading an integrated drug discovery project (hit identification to preclinical candidate nomination), demonstrating a proven ability to collaborate effectively with and lead a multidisciplinary project team 
• Leveraged senior expertise to successfully manage CRO chemistry and/or medicinal chemistry teams, driving high-quality execution and productivity leading directly to preclinical candidate nominations
• Extensive working knowledge and practical application of modern medicinal chemistry and drug discovery techniques (e.g., hit finding technologies, structure-based drug design (SBDD), computational chemistry, and advanced multi-parameter optimization of target and druglike attributes, physicochemical, and ADME properties)
• Expert-level knowledge in complex molecule synthesis, multi-step synthesis, and methods development, purification, and spectroscopic analysis techniques 
• Proven ability to effectively lead and manage cross-functional teams and related external partners
• Demonstrated success in mentoring and developing junior scientists and medicinal chemists within a project team, promoting efficient skill development and mindset for a successful preclinical candidate nomination 
• Strong publication and patent record in medicinal chemistry 
• Direct collaboration with Intellectual Property (IP) counsel to craft and implement patent strategies, ensuring robust protection of chemical matter and its key uses
• Self-motivated, enthusiastic, and highly adaptable with the ability to quickly identify core project challenges and pivot strategies in a fast-paced environment
• Exceptional oral communication and writing skills, with meticulous record-keeping and data organization skills
• Must be willing to work onsite 5 days a week 

Nice to Have: 

• Experience with covalent inhibitors, targeted protein degradation and proximity inducing agents 
• Experience with various hit identification technologies, including fragment-based drug design (FBDD), DNA-encoded library (DEL), high-throughput screening (HTS), virtual ligand screening (VLS), and de novo drug design 
• Familiarity with preclinical development areas (e.g. CMC, GLP toxicology)
• Experience implementing or leveraging AI/ML tools for hit identification, lead optimization, retrosynthesis planning, or predictive ADME/Tox modeling

The estimated base salary range for this role is $213,000 - $258,000. Actual pay will be based on a number of factors including experience and qualifications. This position is also eligible for two annual cash bonuses.