Many in vitro and in silico approaches encouraged in new funding opportunity from the Bill & Melinda Gates Foundation – Proposals due November 9
Grant Opportunity title: Develop Novel Platforms to Accelerate Contraceptive Drug Discovery (Round 18)
Deadline: 9 Nov 2016 – 11:30am PST
While access to a range of appropriate and desirable contraceptive methods can have a broad beneficial impact on the lives of women, men and their families, this goal is currently not being achieved. As part of a comprehensive approach to addressing the unmet need for contraception, we believe that innovative new methods, particularly those that address shortcomings of existing methods, have the potential to dramatically improve access, method uptake, use, and satisfaction. Given the relative lack of attention and funding this area historically has received, the tools and assays that would enable significant progress in this area remain underdeveloped. This call is seeking new approaches that can address these technical barriers and accelerate contraceptive drug discovery. A number of options exist (see below), but applications should focus on developing and validating tools and platforms that would enable drug discovery and how those may be broadly applicable, rather than on discovering and characterizing specific compounds, as the latter would be outside the scope of this GCE call.
What we are looking for:
This call is soliciting concepts for contraceptive discovery platforms that can contribute to development of new methods suitable for women or men living in limited resource settings. Such platforms will be essential to support the foundation’s efforts to develop new methods that would be safe and effective for long-term regular use, in the form of injectables, implants, or regular oral contraception. We are not looking for new injectable formulations or implants using existing agents, nor are we looking for methods that could only practically lead to intermittent “on-demand” or pericoital use (e.g., vaginal gels). Proposed research plans should align with this goal. Importantly, research proposed for funding should not be focused on a particular experimental agent, but rather on development and validation of a set of tools and technologies to address technical limitations in this field and that could be subsequently applied to a broader drug discovery and development program. While research related to a specific drug target or target class may be warranted if justification is provided, applications with a broader scope will be viewed favorably.
A few of the many potential examples to be considered include:
- Development of in vitro phenotypic screening methods that recapitulate key female or male reproductive processes (e.g. ovulation, follicular maturation, sperm maturation).These need not be immediately suitable for a high-throughput format, but should be focused on assays that would minimally enable screening of small compounds libraries;
- Scale up and/or automation of existing laboratory assays for medium- to high-throughput and validation on a well-characterized pilot compound set or biological probe compounds;
- Development of low-throughput in vivo screening methods using native or modified (transgenic, knockout) model organisms (e.g. zebrafish, C. elegans) to interrogate compound activity against key reproductive processes;
- Development and validation of biochemical or other target-based assays, based on a clear explanation of why the proposed female or male target(s) would be viable and high value for contraceptive discovery;
- Development of PK/PD approaches, including small animal models and in silico modeling, to enable rational medicinal chemistry;
- Identification of methods to identify adjuvant compounds that could be co-formulated with existing hormones to mitigate undesirable side effects;
- Development of preclinical in vitro or in vivo models to predict side effects (e.g., endometrial bleeding, testicular toxicity) associated with contraceptive agents
- Development of tractable and relevant in vitro and small animal models of spermatogenesis and epididymal function