BIOGAMI
BIOmolecular Grammar for protein Aggregation Modulation and Intervention
What if we could detect and repair the earliest stages of protein dysfunction to eliminate neurodegenerative disease?
The Problem
- Proteins are tiny machines in our cells that need to fold into the right shape to work. Sometimes they get the wrong signals and fold the wrong way or stick together, forming clumps (aggregates) that damage cells. This damage can lead to Alzheimer’s disease, ALS, some cancers, and other chronic and degenerative conditions.
- Getting older, having certain genes, or being exposed to toxins can all cause proteins to misfold.
- We don’t have good tools to predict, stop, or undo these early misfolding and clumping events.
- Most treatments go after large protein clumps that show up late in disease, when much of the damage is already done. At that point, it is very hard to get cells working normally again. Many of the proteins involved are very flexible and hard for current drugs to target, so they are often called “undruggable.”
The Solution
- BIOGAMI focuses on the very earliest steps in the misfolding process, especially in the brain and other vulnerable tissues.
- The program will decode the “grammar” that guides how flexible, disordered proteins behave and create new ways to steer misfolded or clumped proteins back into healthy shapes.
- BIOGAMI will build tools to detect the earliest warning signs of protein misfolding and clumping.
- By acting this early, BIOGAMI aims to stop neurodegenerative and other chronic diseases before they fully develop, instead of only treating symptoms after serious damage has occurred.
Only ARPA-H can...
- break down research silos working to understand these flexible, disordered proteins,
- bring together experts in protein science, AI, and computing to rewrite this molecular grammar, and
- accelerate progress in the long fight against neurodegenerative diseases and chronic illnesses.
Solicitation
What ARPA-H needs to solve this problem
The BIOGAMI program aims to stop diseases like Alzheimer’s and other brain disorders by finding and fixing problems with proteins very early—before they clump together and damage cells. The program has two technical focus areas: (1) build next-generation artificial intelligence and experimental models for intrinsically disordered proteins (IDPs) and aggregation; and (2) leverage novel tools to develop novel therapeutic modalities that interfere with or prevent IDP misfolding and aggregation while preserving critical functions, and create novel detection capabilities that respond to early-stage IDP aggregation.
Notice ID: ARPA-H-SOL-26-149
ARPA-H invites interested parties to review the solicitation, which is posted and maintained on SAM.gov. The solicitation outlines the opportunity and its requirements, key dates and deadlines, submission documents and templates, evaluation criteria for submissions, and information on how to apply.
Key Dates:
- Hybrid Proposers’ Day: February 20, 2026 in Arlington VA
- Solution Summary Due: Wednesday, March 4, 2026, 12:00PM ET
A summary is required to submit a full proposal. - Full Proposal Due: Wednesday, April 15, 2026, 12:00PM ET
After submission of a solution summary, proposers will either be encouraged or discouraged from submission of a full proposal. It is strongly recommended that only proposers who are encouraged to submit a full proposal do so.
Reminder: Dates are estimates and subject to change. Please reference the solicitation for the most up-to-date information.
Ready to apply? To submit a Solution Summary, sign-in to the ARPA-H Solutions Portal.
Frequently Asked Questions
Review responses to common questions about this funding opportunity asked by others in the proposer community.
You can also ask a question.
Proposers' Day
This is an optional event for the proposer community to learn more about this opportunity, ask questions, and make connections. This event is not intended for patients, patient advocates, the media, or general interest audiences.
Event date: February 20, 2026
Event location: Hybrid in Arlington, VA
Details subject to change. For the most up-to-date information, reference the Special Notice (ARPA-H-SN-26-147) on SAM.gov.
Teaming
ARPA-H anticipates that teaming will be necessary to achieve the goals of BIOGAMI. Prospective proposers are encouraged to form teams with varied technical expertise to submit a research proposal.
To facilitate this process, we have created a teaming page where prospective proposers can share their profiles and learn more about other interested parties.
Program Manager
“Disordered proteins are like sentences without punctuation—multiple meanings can be implied depending on how the reader pauses or places emphasis. BIOGAMI intends to preserve the critical meaning of a protein’s sentence by applying punctuation and grammatical structure, essentially fixing protein misfolding before anything is published."
