The Bill & Melinda Gates Foundation is seeking applications for the Grand Challenge on “Accelerating Discovery for Non-Hormonal Contraceptives”.
The Bill & Melinda Gates Foundation is committed to a long-term vision of expanding contraceptive options for the most vulnerable women in low-resource settings through development of new methods that better align with women’s preferences. Contraceptive product innovation will be required to achieve this goal. Specifically, the emphasis for this work is on developing safe and effective non-hormonal contraceptive agents with both improved overall tolerability and a side effect profile differentiated from hormonal methods. This emphasis is based on an understanding that overall tolerability of and side effects from hormonal methods present real and meaningful barriers to women realizing their reproductive intentions.
This vision demands establishment of a strong research foundation upon which to build a robust pipeline of product candidates, recognizing that the attrition rate of products in preclinical and clinical development will likely be substantial due to the high bar for safety and efficacy. In order to establish a set of critical reproductive biology and early stage discovery capabilities, in-source novel ideas from other areas of science, and improve the knowledge base needed to support such an effort, the foundation is launching the “Accelerating Discovery for Non-Hormonal Contraceptives” Grand Challenge in 2020. The goal of this Grand Challenge is to identify new approaches and concepts directed at the characterization of novel contraceptive drug targets, the identification of active contraceptive compounds useful for target validation and proof-of-principle studies, and the development of novel and impactful research tools with the potential to revolutionize the field of contraceptive R&D.
The ultimate outcome driving the foundation’s investment in this area is the discovery new drug candidates that:
- provide safe and effective contraception,
- do not rely on systemic administration of reproductive steroid hormones or act through perturbation of sex steroid pathways, and
- are suitable and appropriate for deployment in a low resource setting.
The focus of this Grand Challenge is on broadly enhancing the research ecosystem for contraceptive discovery and advancing novel and bold ideas that can accelerate drug discovery in this field.
Funding Focus Areas
- Biological Assay Development: Many aspects of female reproduction remain challenging to replicate or model in a tractable, physiologically relevant, and highly reproducible fashion, but such tools and models will be fundamentally important to identifying and profiling contraceptive drug targets and contraceptive compounds. A better toolset of in vitro assays is needed that can recapitulate oocyte and follicle development, follicle selection, follicular rupture/ovulation, corpus luteum formation, cumulus-oocyte complex dynamics, and fertilization, including peri-fertilization events. New models should focus on assay tractability as well as establishing physiological relevance and modeling closely relevant features of the in vivo environment. Applicants seeking to develop such systems should clearly describe the planned approach and how this would improve upon existing methods. Including approaches to validate with human samples or human genetics/genomic information would be viewed favorably. Proposals should include a discussion on how assays will be standardized, validated, and scaled, including where possible the use of genetic or chemical probes as positive controls to demonstrate biologically relevant outcomes following assay perturbation.
- Drug Target Identification and Validation: In the past two decades, target-based drug discovery approaches have become increasingly sophisticated and powerful, but further and complementary approaches are needed to sustain a pipeline of potential drug targets and enhance the understanding of target biology. Emphasis will be placed on unbiased approaches to identify potential contraceptive drug targets. These may include (but are not limited to):
- RNAi- or CRISPR-based methods utilizing a robust and relevant biological assay,
- chemical genomics or proteomics linking probe compound activity to specific drug targets or pathways,
- analyses of human infertility as a pathway to identify relevant drug targets, or
- artificial intelligence-enabled approaches to target identification.
- Chemical genomics, probe generation, pilot screening: The availability of active compounds that interfere with key steps in fertility would open up many avenues for further biological exploration and target validation, but methods for screening small compound libraries for chemical probe discovery are currently limited. Applications will be considered that propose small pilot-scale screening in complex systems for the purposes of identifying active compounds interfering with key reproductive functions. Applicants must detail how screening systems will be developed, tested, and validated in a format suitable for testing compounds, and should detail the type and source of chemical libraries that would be utilized. Biologically-informed hypotheses may be proposed to select mechanism- or target class-focused libraries as a starting point.
- Contraceptive Antibodies: While the cost and practicality of antibody-based therapeutics has historically been a challenge, particularly for application in a low resource setting, new advances in antibody half-life extension and cost-effective production open up the possibility that antibodies may be a more tractable option in the future, particularly if used in an “on demand” contraceptive modality. Moreover, this may allow consideration of targets that would otherwise not be amenable to small molecule inhibitors and may provide an enhanced safety window. Applications focused on contraceptive antibodies should clearly articulate the data supporting the validation of the proposed antigen target, the methods to be used for antibody identification, and the assays to be used relevant to determination of antibody function.
- Translational Science/Preclinical Evaluation Tools: In addition to target and hit discovery activities, downstream aspects of drug and product development require early consideration to ensure the appropriate tools and data are in place once advanced leads and candidates are identified. They would consider funding for projects aimed at the following issues:
- Identifying candidate biomarkers of efficacy for non-hormonal contraceptive mechanisms-of-action, including biochemical or imaging markers, that can be applied to preclinical in vivo models and, ideally, that could be applicable for validation in human clinical studies.
- Improving the understanding and prediction of reproductive tract and reproductive tissue pharmacokinetics to assist in building PK/PD models and enable early dose selection and safety risk evaluation.
- Improved and tractable in vivo models for contraceptive efficacy that overcome limitations of existing rodent and primate models.
- Innovative methods for early assessment of safety, toxicity, and side effect risk, with particular emphasis on the potential for endocrine disruption and bleeding side effects.
This Grand Challenges request for proposals intends to fund individual awards of up to USD $2 million and for up to 3 years, based on the scope of the proposed project. The proposed budget must realistically reflect the technical work and project deliverables within a 3-year time frame; in some cases, a smaller budget may be justified to establish initial proof-of-concept. Budgets and scope may be negotiated with applicants as part of the review process to ensure the foundation’s ability to fund a robust and balanced portfolio with existing available budget.
The Foundation is looking for proposals that:
- Engage scientists across a variety of disciplines, including those new to the field of contraceptive R&D;
- Demonstrate innovative thinking by applying or incorporating concepts, methods or technologies not currently being used for contraceptive discovery;
- Present concepts and strategies that are “off the beaten track”, significantly radical in conception, and daring in premise;
The Foundation will NOT consider funding for:
- Proposals focused on development of male contraceptives, including work on sperm-based approaches that could only feasibly be applied as vaginal methods;
- Proposals targeting the endometrium for the prevention on embryo implantation;
- Proposals on novel drug delivery systems for contraception;
- Discovery of adjunct or complementary molecules intended for co-delivery with hormonal contraceptive regimens;
- Basic studies of human reproductive biology without a clear connection to enabling non-hormonal contraceptive discovery;
- Pre-clinical or clinical development of advanced leads and candidates;
- Social science, marketing, or acceptability studies related to contraceptive use and uptake.
- Grand Challenges is open to both foreign and domestic organizations, including non-profit organizations, for-profit companies, international organizations, government agencies and academic institutions. Individuals and organizations classified as individuals for U.S. tax purposes are not eligible to receive an award from the foundation as part of the Grand Challenges initiative.
- Upon registration, applicants must provide information about the tax status of their organization as different terms and conditions may apply. You should confirm your organization’s tax status with the appropriate advisor or entity within your organization such as your grants or contracts department, finance, or office of sponsored research. The foundation may request additional information regarding your tax status.
How to Apply
Interested applicants can apply via given website.
For more information, visit Bill & Melinda Gates Foundation.