Biomarker Research to Support Fertility Regulation Development by Small Business (R43 Clinical Trial Optional)

Purpose The purpose of this Funding Opportunity Announcement (FOA) is to invite SBIR applications to support and facilitate the development of new and/or improved clinical biomarkers and companion biomarker diagnostics (e.g., point of care and/or direct-to-consumer tests, DTC) to support the clinical development of non-hormonal contraceptive product(s) for men and women. Background Nearly half of all pregnancies in the United States are unintended. Pursuant to the critical need for new non-hormonal contraceptives for men and women, including those that incorporate an anti-infective property, is the development of biomarkers that demonstrate the contraceptive product's efficacy (e.g., pharmacodynamic, pharmacokinetic, drug-target interaction) in a clinical setting. This FOA supports the NICHD in its mission to develop novel, safe and effective non-hormonal contraceptive products for men and women. Research Objectives and Scope Projects must be focused on the development of new and/or improved clinical biomarker(s), and/or companion biomarker diagnostic device(s) (e.g., point-of-care and/or direct-to-consumer testing) that support the non-hormonal contraceptive product(s) being advanced. Alternatively, projects can be focused on the development of novel assay biomarker platforms that can be used in a point-of-care setting. Projects focused on biomarkers, or related companion biomarker devices/diagnostics, should be impactful for clinical trial(s)/investigations, responsive to the target being modulated resulting in infertility, and can beused as a surrogate readout to the final contraceptive product. Any proposed companion biomarker diagnostic must have characteristics consistent with the development of a safe and effective product that would be satisfactory to men or women and an improvement on existing technology, where and when applicable. Contraceptive biomarker product development programs of high priority are: Biomarker development (e.g., pharmacodynamic, pharmacokinetic, drug-target interaction) informative to a planned clinical trial (e.g., Phase 0 or 1) Biomarker development (pharmacokinetic, pharmacodynamic, or drug-target interaction) informative to a late stage preclinical contraceptive target or modulator of that contraceptive target Biomarker development informative to a companion diagnostic device (e.g., point-of-care and/or direct-to-consumer testing device) Applications that include the following are not responsive to this FOA: Applications not focused on the development of a contraceptive biomarker Applications focused on clinical biomarkers that are not related to the non-hormonal contraceptive target being modulated Biomarkers (clinical or otherwise) and related devices that only evaluate: Sperm count Sperm concentration Biomarker applications that utilize contraceptive agents that: May act post-fertilization May act via the oviduct or uterus Are based on intrauterine devices/intrauterine system(s) Act via steroid receptors Require the administration of one or more exogenous steroidal molecules that act via nuclear steroid receptors Acts by physical obstruction of any region/segment of the male or female reproductive tract Applications focused on male or female condom development Applications focused on biomarker development of an active pharmaceutical ingredient (e.g., small molecule) whereby the target is not known Applications focused on biomarker development of an active pharmaceutical ingredient (e.g., small molecules) that modulates multiple targets (e.g., a pan-antagonist or pan-agonist) Applications focused on biomarker development of an active pharmaceutical ingredient (e.g. small molecule) that modulates its target irreversibly (e.g., alkylation, Michael acceptor, conjugate addition) Applications focused on biomarker development of multiple inhibitors modulating a single, or multiple, target(s) Applications focused of biomarker development of multiple active pharmaceutical ingredients (e.g. small molecules) that utilize, or require, an additive or synergistic effect affording infertility Applications for biomarker development of the following molecules and/or their chemical derivatives. Gamendazole H2-Gamendazole Adjudin Gossypol alpha-chlorohydrin Applications focused on biomarker development of type I-II kinase inhibitors Application focused on biomarker development of molecules or devices that disrupt/perturb the blood-testis and/or blood-epididymal barriers Applications focused on biomarkers for molecular targets for which there is no human ortholog Validation This FOA requires that applications include data demonstrating that the mechanism proposed for development is validated. Validation, as defined in this RFA, is the demonstration in a mammalian species whereby the modulation proposed in the application to achieve a contraceptive effect, whether specific (e.g. antagonism or agonism of a single specific enzyme) or non-specific (e.g., sperm motility inhibition by exposure to a high molecular weight polymer) results in infertility. Subfertility is not sufficient to constitute validation. Subfertility, as defined in this RFA, is the generation of live animals from in vivo mating trials and/or an in vivo or in vitro fertilization rate greater than zero.