Director, In Vivo Pharmacology and Disease Biology

We are seeking an experienced scientific leader to build and direct our In Vivo Pharmacology and Disease Biology function. In this newly created role, you will set the strategic direction for in vivo pharmacology across the portfolio, lead / manage a network of CRO partnerships with an opportunity, over time, to build an internal team.  As a member of the Preclinical Leadership Team, you will serve as a senior scientific voice shaping program strategy, resourcing and go/no-go decisions alongside the Chief Scientific Officer and other functional leaders.

You will design and validate disease-relevant animal models in mice, rats and non-human primates (NHPs) to test, rank, and characterize innovative sustained release therapies.  You will demonstrate the efficacy across full monthly or quarterly dosing intervals, define the exposure-response relationships to enable human dose projections and ascertain the impact on the molecular disease pathobiology of the indications being studied.  The candidate will assess the impact of our novel and differentiated therapies on disease comorbidities and biomarkers; and, has demonstrated experience in rigorous data analysis, interpreting and writing pharmacology reports and authoring the preclinical / pharmacology sections of IND submissions and other regulatory documents as programs move from lead selection through candidate nomination and into the clinic.

• Set / communicate in vivo pharmacology strategy across portfolio, aligning study design with deliverables and milestones ensuring the advance of demonstrably differentiated therapies.
• Define data-driven go/no-go criteria and make recommendations to support progression through preclinical and clinical stages.
• Contribute biological and disease-area insight to new program ideas, including combination and pharmacokinetically matched approaches.

• Research, establish and validate disease-relevant models of obesity / metabolic disease, (DIO mice and rats, genetic models (for example ob/ob, db/db and ZDF rats) and models of related conditions such as MASH, diabetes, or other indications.
• Develop / optimize in vivo models to determine how our sustained-release molecules behave across pharmacokinetics, pharmacodynamics and efficacy parameters.
• Design NHP studies for translational efficacy, tolerability and PD, in line with 3Rs.
• Design long-duration studies to test efficacy (single injection or multidose) including durability.
• Apply body-composition (DEXA, qNMR or MRI), food intake, energy expenditure, glucose and insulin tolerance and muscle function endpoints as programs require.

• Plan, oversee, analyze, and interpret studies, own CRO governance vendor relationships
• Collaborate with Preclinical functions to understand conjugate and release-linker properties and design the right in vivo models for each candidate.
• Analyze and troubleshoot data using sound statistical design (power, randomization, blinding), and continuously optimize models and protocols based on results.
• Evaluate tolerability of hydrogel microsphere formulations together with Safety and Toxicology.

 

• Build or help build exposure-response and PK/PD models that link drug exposure to efficacy and PD biomarkers and endpoints.
• Translate animal data into human dose and dosing-interval projections.
• Identify and validate translational biomarkers for preclinical and clinical use.

• Author / review study reports, pharmacology summaries, and the nonclinical pharmacology sections of INDs, Investigator's Brochures and other regulatory filings.
• Build the business case for internal capabilities, potentially hire, mentor and develop scientific staff as function grows.

• PhD/DVM pharmacology, physiology, endocrinology, metabolism, biology or related discipline.
• At least 10 years of experience (12+ preferred) in biotech / pharmaceutical industry, including demonstrated leadership skills directing in vivo pharmacology function or running programs.
• Hands-on experience designing/interpreting models of obesity, diabetes or metabolic disease.
• Designed and overseen NHP studies and understand species-specific study designs / biology.
• Proven track record managing in vivo studies at CROs, including protocols, budgets, vendor governance and data review and interpretation.
• Extensive knowledge of pharmacokinetics / pharmacodynamics, exposure-response analysis.
• You have set scientific strategy, influenced programs, and helped make portfolio level decisions at a leadership level – shown functional or program leadership.
• Authored nonclinical pharmacology study reports and pharmacology sections for INDs, etc…
• Strong statistical skills for in vivo study design and analysis, and can integrate complex data sets to inform drug development strategy.

• Experience with long-acting, depot, peptide/conjugate-based therapeutics, or complex PK/PD.
• Experience with incretin (GLP-1, GIP, glucagon) or amylin-based therapies strongly preferred.
• Hands-on experience with PK/PD or exposure-response modeling (for example Phoenix WinNonlin, NONMEM, Monolix or R) and calculation of human dose projection.
• Experience in body composition, energy balance, and lean-mass preservation studies.
• Translational biomarkers development for clinic and experience in metabolic pharmacology.

• Articulate and clear communication style, and comfortable presenting to executive leadership.
• Data focused, still review raw data, protocols and CRO reports yourself to help set direction.
• Help make decisions with incomplete/imperfect data sets and explain the risks clearly.
• Collaborate on multidisciplinary teams, track record of scientific rigor and creativity in research.
• Thrive in a fast-changing, largely outsourced environment and enjoy building something new.

• The chance to build a new function and see programs move from the lab into the clinic.
• Opportunity to work with an innovative platform designed to make obesity medicines better tolerated with monthly to quarterly dosing.
• Base salary range: $220,000 to $250,000, plus annual bonus and equity. Final pay depends on experience and qualifications.
• Comprehensive medical, dental and vision benefits, a 401(k) plan and paid time off.