I recently had the opportunity to attend the Proposers’ Day for Advanced Research Projects Agency for Health (ARPA-H)’s BIOmolecular Grammar for protein Aggregation Modulation and Intervention (BIOGAMI) program. BIOGAMI focuses on Intrinsically disordered proteins (IDPs) — systems that are dynamic and context-dependent rather than fixed in structure. The “origami” reference captures the core goal: understanding how proteins fold, misfold, and shift states, and learning to intervene in ways that impact diseases driven by IDP misregulation.
“I expected a deep dive into protein biophysics, particularly the structural challenges of intrinsically disordered proteins (IDPs). But the real story wasn’t just the science. It was how ARPA-H thinks, operates, and engages with proposers.”
Here’s what I learned:
Being in the Room Matters More Than You Think
If you are serious about applying to ARPA-H, attend Proposers’ Day in person. In the room, you pick up tone, emphasis, and energy around certain ideas. You hear side conversations and see which questions spark enthusiasm versus skepticism. That context shapes how you interpret the written solicitation.
Virtual attendance delivers content. In-person attendance delivers nuance—and with ARPA-H, nuance matters.
Do your Homework Before You Show Up
The strongest teams had clearly:
- Studied the solicitation carefully
- Identified partners through Teaming Profiles
- Initiated conversations in advance
- Understood ARPA-H contracting mechanics
BIOGAMI, like many ARPA-H programs, requires tightly integrated, multi-partner teams. Collaboration is foundational. Working with organizations experienced in ARPA-H contracting and compliance provides a strategic advantage, especially given aggressive timelines.
This Is a Program Manager–Driven Mission
ARPA-H programs are deeply driven by the Program Manager (PM).
Proposers’ Day is your only official opportunity to understand why the problem was selected and what success looks like through the PM’s lens. Assume the PM will be your toughest critic—and your most important internal advocate. You are executing their vision.
Strong science is essential, but alignment with intent is what makes a proposal compelling.
If You’re on the Fence, Apply Anyway
If your technology plausibly maps to the problem, submit a Solution Summary.
ARPA-H rarely reissues near-duplicate programs. Waiting for a “perfect fit” can mean missing the window. A well-aligned, ambitious submission—even if imperfect—can generate feedback and sharpen your strategy.
When drafting your Solution Summary, search the solicitation for phrases like “Proposers must” and “Proposers should.” Treat them as non-negotiable guideposts. If you have a scientific rationale to deviate from the guidelines, justify it clearly.
BIOGAMI-Specific Observations
Key themes for this program:
- Tight AI and experimental collaboration is essential
- The goal is a radically new IDP modeling framework and not just incremental improvement
- Early binders should mature toward clinically relevant assets
- Commercialization and translation must be considered from day one
- Timelines are aggressive: Solution Summary feedback expected by March 13, 2026; contracting targeted for July/August 2026
- General models and data (TA1) must be public; disease-specific applications (TA2) may be IP-protected
- Gain-of-function considerations must be addressed at the Solution Summary stage
- Modifying the target protein sequence is out of scope; biophysical and structural modulation without sequence changes is allowed
- Multiple submissions may require an Associate Contractor Agreement to prevent overlap
The Bigger BIOGAMI Message
BIOGAMI makes clear that incremental advances are not the objective. ARPA-H is seeking mission-driven teams willing to tackle hard biological problems and pursue paradigm shifts. For BIOGAMI, that means building new frameworks to understand and intervene in IDP-driven disease—frameworks that translate into real clinical assets, not just improved models.
Bottom Line
As George H. Heilmeier, the first DARPA director who helped codify what we now call the Heilmeier Catechism, implicitly taught future innovators: “What are you trying to do… and why will it matter?” Those deceptively simple questions force innovators to clarify their technology’s impact before embarking on the path of ARPA-H and other funding.
In the spirit of innovation: ARPA-H encourages us to build something audacious, bring others along, and don’t be afraid to rewrite what’s “possible.” ARPA-H gives us the runway – now it’s our job to take off.