ARPA-H - BIOGAMI: Biomolecular Grammar for Protein Aggregation Modulation and Intervention

Below is a brief summary. Please check the full solicitation before applying (link in resources section).

Executive Summary:

ARPA-H’s BIOGAMI program is funding teams to predict, detect, and control protein misfolding before disease begins. The program targets intrinsically disordered proteins (IDPs) and regions (IDRs), which are implicated in neurodegeneration, cancer, diabetes, and other chronic diseases and are largely considered “undruggable.”

Solution Summary Due: March 4, 2026 (12:00 PM ET)

Funding & Structure

1. Awards: Multiple OT awards anticipated

2. Program Length: Up to 48 months

3. Phases:

   • Phase 1 (0–24 months): Model IDR behavior and demonstrate early modulation and sensing

   • Phase 2 (25–48 months): Translate to preventative therapeutics and early detection tools

4. Down-selection occurs after Phase 1 based on quantitative technical metrics.

What ARPA-H Is Trying to Build

BIOGAMI aims to create a generalizable, reusable platform that can:

• Predict IDR structure, dynamics, aggregation, and interactions from sequence

• Modulate protein folding to prevent or reverse aggregation

• Identify early indicators of misfolding—before symptoms appear

• Enable new therapeutic classes for currently undruggable targets

The program emphasizes root-cause intervention, not symptomatic treatment.

Technical Scope (Both Required)

Technical Area 1 (TA1): Molecular Grammar of IDRs

TA1 teams must establish foundational models that explain how IDR sequences and environments drive protein behavior.

Key requirements include:

• Integrated AI/ML + experimental approaches

• High-throughput in vitro, cell-based, and in vivo systems

• Prediction of structure, aggregation, condensate formation, and interactomes

• Validation across diverse sequences, conditions, and post-translational modifications

• Open-source sharing of TA1 models and datasets

By Phase 2, models must predict and validate IDR properties within 60 days of receiving a sequence.

Technical Area 2 (TA2): Modulate IDPs to Detect and Control Folding

TA2 focuses on therapeutic and diagnostic translation.

Teams must:

• Prevent or reverse aggregation and restore protein function

• Develop early, clinically translatable indicators of misfolding

• Target two diseases:

  • One rare disease (<1 in 100,000)

  • One non-rare disease
    (across neurodegenerative and non-neurodegenerative categories)

By Phase 2, teams must:

• Demonstrate in vivo efficacy

• Preserve or restore >90% of critical protein function

• Validate ≥1 novel biomarker and prepare for FDA Biomarker Qualification engagement

Eligible Applicants

• Startups and large companies

• Universities and nonprofits

• Multi-party teams required (not prime/sub)

• Not eligible:

• FFRDCs and government entities as performers

• Entities from covered foreign countries or foreign entities of concern

• Work is prioritized to be performed in the United States.

Evaluation Criteria (In Order)

Scientific and technical merit

1. Team capability and experience

2. Relevance to ARPA-H mission and health impact

3. Cost realism and value

Commercialization Expectations

1. 5-year and 10-year commercialization plans required

2. Translation Advisory Board required

3. Active or planned commercial partnerships strongly encouraged

4. TA2 outputs expected to be positioned for pre-clinical development

How can BW&CO help?

BW&CO helps biotech and deep-tech teams quickly determine whether BIOGAMI is the right opportunity and, if so, how to pursue it with a credible, ARPA-H–ready strategy by translating dense solicitation language into clear founder-level guidance, pressure-testing technical and team fit against TA1/TA2 requirements and metrics, shaping a compelling program narrative that aligns AI, biology, and validation, designing compliant multi-party teaming structures, aligning commercialization and open-source expectations, and proactively flagging proposal risks—so teams can move confidently toward a competitive submission or make an informed decision to walk away.

How much would BW&CO Charge?

With a flat rate of $4000, you’d work with our grant writing team to put the solution summary together and submit before the March 4th deadline.

Additional Resources

Review the solicitation here.