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Development and Validation of Non-Mouse Reagents to Enable Preclinical Development of Novel Therapeutics


Fast-Track proposals will be accepted. Number of anticipated awards: 3-5 Budget (total costs, per award):
Phase I: up to $300,000 for up to 9 months
Phase II: up to $2,000,000 for up to 2 years
The preclinical development of cancer therapeutics, including the recent trend and focus on cancer immunotherapies, is evolving from the traditional use of mouse models to the use of other animal models including canine, rat, and minipig. Each of these non-mouse models carries its own advantages and abilities to increase the clinical relevance of the model as compared to mouse models. Yet, the wide use of these models for preclinical validation of novel therapeutics is limited by multiple factors including the availability of analytically validated reagents, such as antibodies, and aptamers, for each model system.
While this topic is not limited to the development of canine reagents, canine reagents are of particular interest. Canine models may be particularly useful for the development of novel therapeutics, as canines have intact immune systems that can be used to study the interactions of therapeutics with the immune system. Canine models include companion dogs with spontaneous cancer. It has been shown that canines metabolize drugs similarly to humans (unlike mice), are amenable to serial biologic sample collections, and have comparable tumor biology. Importantly, canines have been shown to respond to human cancer therapeutics. Canine models would be especially valuable for the testing of immunotherapies, as the availability of fully immune competent mouse models is quite limited. While canines are more expensive than mice, canine trials are not nearly as expensive as human trials as the trials can be completed much faster due to shorter progression-free intervals and overall survival times.
A commercial supplier of reagents resulting from this topic is advantageous, as it could provide both the analytical validation for each reagent and a long-term source, as compared to academic labs that may produce reagents for each set of studies. The need for animal model-specific, analytically validated reagents includes a wide range of reagents and antibodies that would enhance the ability to test therapeutics within that animal model. For example, analytically validated canine reagents demonstrated to be both renewable and reproducible would both expand the suite of validated assays amenable to canine studies and provide a long-term commercial source of reagents for follow-up studies. This topic is in line with the Cancer
Moonshot Blue Ribbon Panel’s Recommendation to support a Cancer Immunotherapy Translational Science Network.
Project Goals
The development and ultimate commercialization of analytically validated, non-mouse reagents will facilitate more robust preclinical evaluation of novel therapeutics. Currently, there are several hundred active combination clinical trials involving at least one immunotherapeutic, which is partially a result of the lack of clinically predictive model systems. Reagents developed under this topic are likely to facilitate the use of additional clinically relevant animal models. Thus, a short-term goal of this topic is the creation of a set of reagents that will enable additional preclinical testing of novel therapeutics. In addition, the development of reagents for clinical testing in companion animals (such as canines) will facilitate additional market opportunities and impact of newly developed therapeutics. Thus, the long-term goal of this contract topic is to enable better demonstration of the utility of novel therapeutics for administration in both humans and companion animals. While reagents that enable the use of models for the testing of immunotherapeutics are of particular interest, proposals to develop reagents for the testing of other therapeutic approaches, such as chemotherapy and radiation approaches, will be considered if a strong rationale is provided for the need of such reagents.
Materials developed under this topic may include, but are not limited to, reagents for a wide variety of preclinical assays for target validation, characterization of immune response, mass cytometry, and pharmacodynamic assays. Potential offerors should demonstrate the current need and potential utility of newly developed reagents. The targets and applications of newly developed reagents must be targets and applications that have relevance to the potential clinical efficacy, toxicity, or mechanism of action of newly developed therapeutics. Reagents that will enable immune-relevant assays in non-mouse models, which are not currently possible and/or predictive in mouse models, are of particular interest.

The offerors should provide all relevant controls, reference standards, protocols, and SOPs. In the Phase I, the offerors should develop and validate an appropriate number of reagents and should provide justification for the choice of the number developed (e.g., novelty, utility, and complexity). Analytical validation and characterization of the reagent(s) should include, as appropriate, but not limited to: purity, concentration, storage conditions, reference standards, specificity, linearity, and limits of detection (LOD).
Proposals should demonstrate the broad utility of the developed reagents and assays, as the reagents’ utilities should extend
beyond one specific researcher/research project. Proposals should identify the potential utility of the assay(s) and how it addresses an unmet need. Demonstration of potential utility should include a description of which therapeutics would be the focus of the reagents/assays developed through this topic. Quantitative milestones that can be used to evaluate the utility of the reagents should be clearly defined and justified.
Phase I Activities and Deliverables
 Analytically validate and characterize the reagent(s) for a number of parameters including, as appropriate, but not
limited to: purity, concentration, storage conditions, reference standards, specificity, linearity, limits of detection
(LOD), range, accuracy, and precision.
 Develop pertinent controls and reference standards.
 Conduct tests to characterize the developed reagents to ensure rigor and reproducibility:
Reagents designed for in vitro assays: Proposals should demonstrate likelihood of obtaining pertinent non-mouse samples, and projects must include feasibility testing of the characterization test. Veterinary schools are a potential source of canine tumor/matched normal tissue samples.
Reagents designed for in vivo assays: Proposals should demonstrate the rationale for feasibility testing in vivo, and projects should include sufficient characterization to suggest proof of concept. In Phase I, it is not required to conduct in vivo studies.
 Provide a proof-of-concept SOP for the reagents and assays. The SOP should include necessary information on the required equipment, operating parameters, sample preparation, standards control solution preparation, procedure, system suitability, calculations, data reporting, and statistics.
 Demonstrate renewability and reproducibility of the developed reagents.
Phase II Activities and Deliverables
 Scale-up production of the reagents to produce sufficient quantities for proof of concept studies.
 Refine the assays to CLIA-grade, as appropriate.
 Establish quality control measures and carryout critical reagent supply chain audits.
 Demonstrate proof-of-concept and compare to currently available assays as a means of validating the proposed
 Provide a complete and final SOP based on the studies conducted in Phase II.

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