Development Activities in DTP

The Developmental Therapeutics Program (DTP) has supported the development of hundreds of new agents since its inception in 1955. DTP has the resources and capabilities to support a broad range of early drug development activities including preclinical animal modeling, preclinical drug production and current Good Manufacturing Practices (cGMP) bulk drug production, and preclinical toxicity and pharmacology studies. DTP resources reside in the Biological Resources Branch, Biological Testing Branch, Pharmaceutical Resources Branch, Drug Synthesis and Chemistry Branch, and Toxicology and Pharmacology Branch.

Drug Development Consultation: Receive a consultation with NCI staff on development of small molecules, biologics, and imaging products intended for cancer patients.

Biological Testing Branch

The Biological Testing Branch (BTB) provides animal models to support the preclinical screening and evaluation of new agents in the NExT development pipeline. More than 70 distinct, quality-controlled xenograft and allograft models (including subcutaneous and orthotopic implants) as well as the hollow fiber-based screening model are used to assess activity, confirm efficacy, and provide samples for assessing drug effect on a molecular target. Information from these models can be used to aid in the validation of the “clinical readiness” of pharmacodynamic assays.

Biological Resources Branch

The Biological Resources Branch (BRB) supports preclinical and early clinical studies of biological response modifiers by maintaining a preclinical repository of biological reagents, managing a cGMP facility, conducting analytical and formulation development, and managing grants and contracts. BRB studies focus on assessing the effects of novel biological agents and exploring the relationships between biological responses and antitumor activity. BRB supports the NCI Preclinical Repository which distributes selected agents for peer-reviewed preclinical studies performed by both extramural and intramural investigators. Program staff also oversees a multiproduct current cGMP facility known as the Biopharmaceutical Development Program (BDP) at the Frederick National Laboratory for Cancer Research (FNLCR). BDP produces a variety of cGMP-grade biopharmaceuticals for clinical trials and advanced preclinical animal testing.

Pharmaceutical Resources Branch

The Pharmaceutical Resources Branch (PRB) specializes in synthetic chemistry and drug formulation and provides high-quality, well-characterized chemical substances and drug products to support DTP drug development activities. PRB establishes purification methods to deliver materials for IND-directed toxicology and future clinical trials, and performs studies to elucidate the molecular structure of compounds using state-of-the-art techniques and instruments. PRB also characterizes the basic physicochemical properties of compounds and develops compound-specific methods to assess compound potency and impurity and monitor drug production and stability.

Drug Synthesis and Chemistry Branch

The Drug Synthesis and Chemistry Branch (DSCB) in collaboration with the Laboratory of Synthetic Chemistry (LSC) at FNLCR provides chemistry support to DTP’s drug discovery and development efforts. In the context of the NExT Program, DSCB and LSC interact with various DCTD centers, programs within the NCI, and outside contract laboratories to identify hits and potential leads fordevelopment as drug candidates.

Toxicology and Pharmacology Branch

Preclinical toxicology and pharmacology are required for informed decision making throughout the drug discovery and development process and for preparing an IND filing to support clinical trials. Toxicological and pharmacological data can inform clinical trial design in aspects of dosing, drug administration regimen, and biomarker studies.

The resources and expertise of the Toxicology and Pharmacology Branch (TPB) can support several steps in the NExT Stage Gate process:

Exploratory Screen Development	Screening/ Hit-to-Lead	Lead Development	Candidate Selection	Preclinical Evaluation
Prepare project operational plan	Evaluate PK and PD using best available tools Determine acute toxicity profile in vitro	Determine safety issues Develop PD and toxicology biomarker assays Assess achievability of human PK/PD profile	Evaluate biopharmaceutical properties (absorption in rodents and non-rodents, clearance, and bioavailability) Evaluate biodistribution Evaluate clinical readiness of PK/PD assay(s) and specimen handling SOPs Evaluate safety issues (most sensitive species) in range-finding toxicology studies	Conduct IND-directed toxicology studies including toxicokinetics Determine preclinical MTD, DLTs, and clinical starting dose Validate PK/PD assay(s) and specimen handling SOPs Prepare and file IND