Parameterizing a PBPK model for a novel route of administration.
Absco Therapeutics used Urchin to accelerate PBPK model parameterization and cross-species translation during its IND-enabling program.
Working with E9 was extremely helpful as we developed a PKPB model for a novel route of administration for sustained release into the cervix. The collaboration greatly accelerated our literature-based decisions for model design and GLP toxicology species selection.
Steve Linderman, Founder and CEO, Absco Therapeutics
27PBPK parametersEstimated with structured rationale, supporting evidence and a confidence assessment for each.
9Species comparedMice, rats, rabbits, pigs, sheep, hamsters, beagles, non-human primates and humans.
1Mechanistic questionResolved from evidence that would otherwise have required empirical experiments.
Source: engagement recordAbsco Therapeutics
Project overview
Context
Absco Therapeutics is developing a locally injectable hydrogel formulation designed to deliver imiquimod, a TLR7 agonist used in HPV-related disease, directly to the cervix to treat high-grade cervical precancers. By achieving sustained PK only on the target tissue, instead of the imprecise placement and burst PK with rapid clearance of the topical cream, Absco's approach aims to generate robust adaptive immune education without systemic toxicity.
As part of its IND-enabling program, Absco engaged specialist consultants to build a physiologically based pharmacokinetic (PBPK) model to predict the absorption, biodistribution, metabolism, and excretion of its therapeutic candidate. Developing the model required estimating dozens of physiological and pharmacological parameters spanning tissue architecture, drug transport, species-specific anatomy, and formulation behavior.
The challenge
PBPK parameterization is one of the most evidence-intensive stages of preclinical drug development. Many parameters cannot be measured directly and instead must be inferred from evidence scattered across decades of literature spanning pharmacology, anatomy, physiology, biomaterials, and comparative biology.
Because many of these quantities vary substantially across species, developing a robust model requires not only literature review, but careful biological reasoning about which evidence is applicable to a given experimental system.
What Urchin did
Urchin conducted a series of targeted analyses to support PBPK parameterization, working alongside Absco's modeling consultants across multiple stages of the engagement.
- Parameter estimation. Systematically identified, evaluated, and synthesized evidence to produce biologically grounded estimates for 27 PBPK parameters, covering tissue volumes, blood flows, drug transport, and formulation behavior, with structured rationale and confidence assessments for each.
- Comparative physiology. Evaluated translational differences across mice, rats, rabbits, pigs, sheep, hamsters, beagles, non-human primates, and humans to identify species-specific differences relevant to model translation.
- Mechanistic investigations. Answered specialized questions concerning cervical mucus composition, mucin turnover, tissue architecture, vaginal physiology, and local drug transport that informed parameter selection.
Each analysis produced a structured report documenting the biological rationale, supporting evidence, and confidence behind every parameter estimate. Together, these reports created an auditable record that supported PBPK model development and documentation. As new questions emerged during model development, Urchin was used iteratively to investigate increasingly specialized aspects of cervical physiology and cross-species translation.
Impact
Rather than spending weeks manually assembling evidence across disparate disciplines, Absco received a structured foundation for PBPK model parameterization.
The engagement clarified which preclinical species were viable translational models and which were not, identified which experimental measurements would most reduce uncertainty in the model, and resolved a mechanistic question about imiquimod absorption that would otherwise have required empirical experiments to answer.
The result was a faster, more defensible parameterization process and a stronger mechanistic foundation for the PBPK model as it advanced through IND-enabling studies.