The Advanced Research Projects Agency for Health (ARPA-H) has released a new Innovative Solutions Opening (ISO) for the BIOmolecular Grammar for protein Aggregation Modulation and Intervention (BIOGAMI) program. Announced under ARPA-H-SOL-26-149, BIOGAMI reflects ARPA-H’s mission to pursue high-risk, high-reward research that can fundamentally transform health outcomes. The program is focused on addressing the root causes of disease driven by protein misfolding and aggregation, an underlying mechanism shared across neurodegenerative diseases, cancer, diabetes, and other chronic and rare conditions.
Rather than treating symptoms after damage has occurred, BIOGAMI seeks to intervene upstream by predicting, detecting, and controlling protein folding itself. By unlocking the molecular grammar governing intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs), ARPA-H aims to enable entirely new classes of therapeutics and early diagnostic tools for targets long considered undruggable.
BIOGAMI Program Overview and Objectives
Protein misfolding and aggregation play a central role in a wide range of diseases, including Alzheimer’s disease, Parkinson’s disease, Amyotrophic Lateral Sclerosis (ALS), Huntington’s disease, multiple cancers, and metabolic disorders. According to the ISO, approximately 70 percent of the human proteome contains intrinsically disordered regions, protein segments that do not adopt a single stable structure and are highly sensitive to cellular context. While this flexibility is essential for normal biology, it also increases susceptibility to pathological aggregation.
BIOGAMI is designed to close critical gaps that currently limit the development of effective therapeutics for these conditions. The program emphasizes the integration of artificial intelligence (AI) driven computational models with experimental validation to predict protein folding behavior, identify early indicators of misfolding, and develop interventions that prevent or reverse aggregation. Importantly, BIOGAMI is structured to move beyond disease silos, targeting shared mechanisms across both rare and prevalent diseases.
Program Structure and Technical Areas
BIOGAMI is organized as a 48 month program consisting of two sequential phases, each lasting 24 months, and includes two required Technical Areas (TAs). Proposers must address both TAs within a single, integrated research program.
Technical Area 1 (TA1): Establish the Molecular Grammar of IDRs
TA1 focuses on developing foundational computational and experimental models that define how IDR sequence features, environmental conditions, and molecular interactions influence protein folding, aggregation, and biomolecular condensate formation. Performers are expected to build high throughput screening platforms, validate predictive models, and contribute to an open source data and model ecosystem.
Technical Area 2 (TA2): Modulate IDPs to Detect and Control Protein Folding
TA2 translates the TA1 foundation into therapeutic and diagnostic applications. Teams will identify and refine candidate molecules capable of preventing or reversing aggregation and develop clinically translatable indicators or biomarkers for early detection. Proposers must address one rare disease and one non rare disease, including at least one neurodegenerative indication, and demonstrate in vivo efficacy by Phase II.
Progression from Phase I to Phase II is contingent upon meeting rigorous, metric driven technical milestones, with formal down selection conducted by ARPA-H.
Key Dates and Submission Milestones
ARPA-H has established the following critical dates for the BIOGAMI ISO. All times are Eastern.
- Proposers’ Day: Friday, February 20, 2026
ARPA-H will host a virtual Proposers’ Day to provide program details, answer questions, and encourage teaming. - Solution Summaries Due: Wednesday, March 4, 2026, at 12:00 PM ET
Submission of a Solution Summary is strongly encouraged prior to submitting a full proposal. - Questions and Answers Deadline: Wednesday, March 11, 2026, at 12:00 PM ET
Final opportunity to submit written questions to ARPA-H. - Full Proposals Due: Wednesday, April 15, 2026, at 12:00 PM ET
Full proposals may be submitted regardless of encouragement status following Solution Summary review.
Funding and Award Information
ARPA-H anticipates making multiple awards under BIOGAMI using Other Transaction (OT) agreements. While individual award sizes are not specified in the solicitation, performers should plan for a multiyear effort spanning up to 48 months, with funding structured by phase and milestone achievement. Teams are strongly encouraged to demonstrate early and credible commercialization pathways, including partnerships with industry, to support eventual translation beyond the program.
Why BIOGAMI Matters for Human Health
BIOGAMI represents a fundamental shift in how protein driven diseases may be treated and detected. By targeting the earliest stages of protein misfolding, before irreversible damage occurs, the program has the potential to enable preventative therapies, earlier diagnosis, and more durable clinical outcomes across a wide range of devastating diseases. If successful, BIOGAMI could unlock therapeutic opportunities for conditions that have resisted traditional drug development approaches for decades.
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