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U.S. National Institutes of Health
Last Updated: 10/28/10

NExT STAGE GATES

Critical to the success of NExT governance is the NExT Stage Gate evaluation process modeled after biotech/pharma benchmarks. The Stage Gate evaluation process will guide project progress decisions based on a defined set of guidelines and milestones to support transition of a project from one stage to the next.

NExT Stage Gates
Discovery Definitions: Development Definitions:

ESD = Exploratory Screen Development
SDS = Screening/Designed Synthesis
LD = Lead Development
CS = Candidate Seeking

CAN = Clinical Candidate
P0 = Phase 0
PI = Phase I
PII = Phase II

The drug discovery and development evaluation process is divided into 4 discovery and 4 development phases within the NExT Stage Gate guidelines. These guidelines are designed to ensure that all scientific objectives for nomination for clinical development are met. The table below outlines the guidelines for each stage. Applied consistently across projects, these guidelines are critical to NCI's ability to manage its portfolio by prioritizing projects and allocating resources.

Stage Gate Guidelines

Exploratory Screen Development Screening/Designed Synthesis Lead Development Candidate Seeking Clinical Candidate

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