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Focus Grants: Targeted Protein Degradation

Male Contraceptive Initiative

Purpose: Nearly half of all pregnancies worldwide are unintended. Furthermore, male contraceptives are limited to condoms and vasectomy, which do not provide adequate variety in characteristics to meet the needs of all users.

Male Contraceptive Initiative (MCI), a US-based 501(c)3 nonprofit, is a funding agency and advocate for safe, effective, and reversible contraceptive solutions for sperm-producing people.

Background: MCI's Focus Grants are designed as a strategic signal-setting mechanism to create deliberate incentives in areas where progress is unlikely without targeted support. Many of the most important advances in non-hormonal male contraception will not occur organically, particularly given the predominantly academic landscape and limited pharmaceutical engagement. Focus Grants concentrate resources where strategic investment can create disproportionate impact.

Focus Area: Targeted Protein Degradation

Proteolysis targeting chimeras (PROTACs) and related targeted protein degradation approaches (e.g, molecular glues) represent a promising but underexplored modality for male contraception. These molecules are typically bifunctional: one region binds the target protein, while a second region connected by a linker serves as an E3 ubiquitin ligase recruiting element (E3RE) that binds to an E3 ligase, thereby initiating the degradative process.

Contraceptives leveraging this mechanism of action have the potential to be both fast-acting and possess a long duration of action, addressing key unmet needs in the male contraceptive product landscape, and offering a potential solution to the problem of ‘washout’ in the female reproductive tract for inhibitors targeting mature sperm function. However, targeted degradation remains an emerging field even in common therapeutic areas. Knowledge of the distribution, localization, and functional relevance of testis- and sperm-expressed E3 ligases is limited, and there is a major unmet need for new E3RE chemotypes beyond commonly used ligands (e.g., cereblon-based systems), particularly in contraceptive applications where selectivity, safety, and tolerability are paramount.

Award Budget

$150,000 - $300,000 of total costs allowed depending on project scope.

AI Based Application Success Predictor

🧬 1. Strong Focus on Male Contraception (Non-Negotiable)

Projects must directly address:
- Male contraceptive development
Especially:
- Non-hormonal
- Reversible methods

👉 Off-topic reproductive or general fertility research → low success probability

🔄 2. Translational Pathway Toward Real Products (Top Predictor)

MCI funding is designed to:
- Move discoveries toward usable contraceptives
Includes:
- Target validation
- Preclinical → clinical development

👉 Key question:
“Will this lead to a viable male contraceptive method?”

MCI actively funds projects progressing toward market-ready solutions

🚀 3. Innovation in Non-Hormonal & Reversible Methods (Critical)

Core strategic focus:
- Non-hormonal contraception
Examples:
- Sperm function inhibition
- Reversible vas-occlusive methods

👉 Innovation must be practical and scalable

🎯 4. Addressing a Major Unmet Need (High Impact Factor)

There are currently:
- Very limited male contraceptive options (condoms, vasectomy)
Strong demand exists for:
- New, user-friendly methods

👉 Proposals that clearly address this gap score highly

🧪 5. Feasible, Milestone-Driven Research Plan

Funding often supports:
- Early-stage or pilot projects
Must include:
- Clear milestones
- Achievable outputs

👉 Overly ambitious or vague proposals are commonly rejected

👩‍🔬 6. Early-Career Researcher Development (Major Priority)

MCI strongly supports:
- Graduate students, postdocs, and trainees
Programs include:
- Fellowships
- Career development funding

👉 Evaluation includes:

Research potential
Career alignment with male contraception

🤝 7. Engagement with the Male Contraception Research Community

MCI encourages:
- Participation in:
  - Conferences
  - Collaborations
  - Networking

👉 Applicants engaged in the field have an advantage

🌍 8. Global & Public Health Relevance

Projects that:
- Improve reproductive autonomy and access globally
Particularly relevant for:
- Low-resource settings

👉 Broader impact strengthens applications

🧠 9. Interdisciplinary Approaches (Advantage)

Successful projects often combine:
- Biology + chemistry
- Reproductive science + engineering

👉 Cross-disciplinary innovation improves competitiveness

📈 10. Potential for Follow-On Funding & Development

MCI funding acts as:
- Catalytic/seed funding
Strong proposals:
- Lead to:
  - Clinical trials
  - Venture or institutional funding

👉 Clear next-step pathway is important

📊 Summary: Key Predictors (Ranked)

Highest impact factors:

Male contraception–specific focus
Translational pathway to product
Innovation (non-hormonal, reversible)

Moderate predictors:
4. Unmet need relevance
5. Feasibility
6. Early-career development

Supporting factors:
7. Community engagement
8. Interdisciplinary approach
9. Global health relevance

💡 Insider Insight

Compared to NIH or general reproductive funders:

Male Contraceptive Initiative is:
👉 highly niche (male contraception only)
👉 strongly product- and translation-driven

👉 Winning formula:
Non-hormonal idea + clear path to real contraceptive + feasible pilot study

✔️ What wins:

Novel reversible male contraceptive targets
Translational drug/device development
Early-stage, high-impact innovation

❌ What struggles:

General reproductive biology
Pure basic science without application
Lack of feasibility or development pathway

Specialties

Clinical Trials

Eligibility Requirements

This application is open to global academic institutions, for-profit organizations, and other entities. Any individual(s) with the skills, knowledge, and internal or external resources necessary to carry out the proposed research as a Principal Investigator (PI) is invited to submit an application through their institution.

Eligibility is explicitly limited to projects centered at the intersection of targeted protein degradation and male contraception. Applications must clearly address one or more of the three strategic areas outlined above.

Applicants may submit more than one application, provided that each application is scientifically distinct. Current MCI grantees are eligible to apply. MCI values representation and diversity in the scientific community. Applications from women, people of color, the LGBTQIA community, and other historically marginalized groups are encouraged.

Projects that are not responsive to this announcement include: General PROTAC chemistry or E3 ligase biology without clear application to male contraception. Projects focused on targets not relevant to male reproductive biology. Approaches developing contraceptives intended to be delivered to female users. Approaches that permanently inhibit fertility or cause sterility. Approaches involving administration of steroid hormones to manipulate the HPG axis. Approaches that induce active immunity. Applications focused on molecular targets for which there is no human ortholog. Projects that duplicate or highly overlap with other funded work.

Applicants should note that MCI also offers other grant programs geared towards larger development-focused projects, small exploratory projects, and fellowships for pre-doctoral and post-doctoral training. Proposals better suited to these mechanisms may be redirected during review. Applicants with questions regarding eligibility or appropriate mechanism are encouraged to contact MCI in advance of application submission.

Sponsor Details

Sponsor Institute/Organizations: Male Contraceptive Initiative

Sponsor Type: Corporate/Non-Profit

Address: 811 Ninth Street, Suite 120 #255, Durham, NC 27705

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