NExT R&D Activities
The NExT pipeline is arbitrarily divided into six discovery stages. Projects can enter at any stage based on specific need.
Example of Activities that Support NExT Discovery Stages
| Target Validation |
Exploratory Screen Development |
Screening/ Hit-to-Lead |
Lead Development |
Candidate Selection |
Preclinical Evaluation |
|---|---|---|---|---|---|
|
Evaluate and define Is the target associated with disease pathology? Identify causal/driver variant(s)/patient populations with |
Conduct a technology overview Develop a screening strategy Identify potential biomarkers (efficacy/surrogate) Develop a strategy for “clinical readiness” Prepare medical needs assessment Prepare project operational plan |
Run screen(s) Assess mechanism of action for link to disease Determine desirable potency Determine evidence of structure–activity relationship Evaluate functional activity in vitro Determine selectivity for target Evaluate physicochemistry (Rule-of-Five compliance)/in silico modeling Evaluate PK and PD using best available tools Assess amenability to synthesis Evaluate stability |
Establish laboratory objectives for clinical efficacy Resolve IP issues Evaluate activity in validated disease models Evaluate physicochemistry Differentiate leads from competitors and current therapies Evaluate preliminary safety issues Develop PD and toxicology biomarker assays(s) Assess achievability of human PK/PD profile Assess feasibility of scale-up and bulk synthesis |
Evaluate synthesis and proposed clinical formulation Evaluate biopharmaceutical properties (absorption in rodents and non-rodents, clearance, and bioavailability) Assess potency against clinical efficacy Evaluate biodistribution Evaluate clinical readiness of PK/PD assay(s) and specimen handling SOPs Assess amenability to imaging Evaluate safety issues (most sensitive species) in range-finding toxicology studies Prepare clinical development plan |
Manufacture GMP-grade bulk drug/active pharmaceutical ingredient (API) Conduct IND-directed toxicology studies including toxicokinetics Determine preclinical MTD, DLTs, and starting dose Validate PK/PD assay(s) and specimen handling SOPs Develop and validate product characterization and release assays Characterize clinical product Prepare CMC package and toxicology summary report Prepare and review clinical protocol at each participating site Prepare and file IND |