DARPA BTO: Protean

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

Executive Summary:

DARPA’s Biological Technologies Office has released DARPARA2601: Protean, a high-impact research announcement focused on developing next-generation medical countermeasures that protect critical human proteins from chemical threat agents. This program aims to create prophylactics (and optionally therapeutics) that protect protein function against chemical threat challenges over 10,000x LD50s . Abstracts are due March 12th, 2026 at 4:00pm ET.

How much funding would I receive?

  • Award instruments: Cooperative Agreements or Research Other Transactions (OTs)

  • Period of performance: 33 months total

    • Phase 1 (Base): 18 months

    • Phase 2 (Option): 15 months

  • Funding levels will depend on proposal quality and availability of funds.

What could I use the funding for?

Funding must support work aligned with Protean’s objective: restoring or protecting protein function against chemical threat agents at the mechanistic level .

Focus Areas (You must propose both phases)

You may propose in one or more of the following:

  1. Nerve agents

  2. Synthetic opioids

  3. Ion channel toxins

Work must target DoD-relevant proteins such as:

  • Acetylcholinesterase

  • Mu Opioid Receptor

  • Ion channels

Phase 1 – Non-Classical Protection (18 months)

Funding may support:

  • Discovery of novel regulatory points in protein conformational landscapes

  • Identification of distal regulatory sites (>1 required by Month 6 milestone)

  • Structural biology and computational modeling of bound/unbound conformations

  • Experimental validation of novel conformational states

  • Mechanistic characterization of intoxication pathways

  • In vitro demonstration of functional rescue or protection

  • Demonstrating:

    • 10-fold decrease in threat simulant binding affinity (Month 12)

    • 10x increase in ED50 of >3 threat surrogates (Month 16)

End of Phase 1 requires in vitro evaluation by a government Test & Evaluation (T&E) partner .

Phase 2 – Countermeasure Design (15 months)

Funding may support:

  • Structure-based or ligand-based drug design

  • Optimization of non-competitive chemical matter

  • In vitro and in vivo efficacy improvements

  • Pharmacokinetics and pharmacodynamics studies

  • ADME validation

  • Safety and acute toxicity screening

  • In vivo rodent validation against real CWAs

Key metrics include:

  • 1,000x increase in ED50 in vitro (Month 24)

  • LD50 with intervention >1000x baseline (Month 24, rodent model)

  • 10,000x increase in ED50 in vitro (Month 30)

  • LD50 with intervention >10,000x baseline exposure (Month 33, rodent model)

Are there any additional benefits I would receive?

  • Access to government Test & Evaluation (T&E) partners for real chemical warfare agent testing

  • Potential use of flexible Other Transaction (OT) authority

  • Early technical feedback via invitation-only pre-award sessions (if selected after Gate 1)

  • Opportunity for DoD transition and chemical/biological defense positioning

What is the timeline to apply and when would I receive funding?

Key Dates:

  • Posting Date: February 11th, 2026

  • Protean Virtual Proposers Day: February 20th, 2026

  • Question Submittal Closed: March 9th, 2026 by 4:00 PM ET

  • Gate 1 Due Date (Abstract): March 12th, 2026 by 4:00 PM ET

  • Gate 2 Due Date (Full Proposal): May 7th, 2026 by 4:00 PM ET

Gate 1 selection is required to submit a full proposal.

The program period of performance is 33 months .

Where does this funding come from?

Funding comes from the Defense Advanced Research Projects Agency (DARPA), Biological Technologies Office (BTO) .

Funding Opportunity Number: DARPARA2601
NAICS Code: 541714

Who is eligible to apply?

All responsible sources capable of satisfying the Government's needs, including U.S. and non-U.S. sources, may submit proposals .

  • Historically Black Colleges and Universities, small businesses, small-disadvantaged businesses, and minority institutions are encouraged to apply .

  • Proposers must be registered in SAM and have a valid Unique Entity ID .

  • Proposals must be UNCLASSIFIED or CUI .

  • FFRDCs, UARCs, and Government entities must contact the agency POC prior to submission to discuss eligibility , competitive proposals will:

  • Present highly innovative, non-classical mechanistic approaches

  • Identify >1 novel distal regulatory site by Month 6

  • Demonstrate feasibility across both Phase 1 and Phase 2 metrics

  • Provide experimentally validated structural insights (not purely computational)

  • Show credible in vivo translation plans

  • Demonstrate strong relevance to DoD chemical and biological defense

Proposals that fail to address both phases will be deemed non-conforming .

Are there any restrictions I should know about?

Key restrictions include:

  • Must propose to both Phases

  • Must comply with Controlled Unclassified Information (CUI) handling requirements (NIST 800-171 compliant systems)

  • IP ownership or licensing must be clearly documented

  • Potential publication restrictions for non-fundamental research

  • Organizational Conflict of Interest disclosures required

  • No classified submissions allowed at Gate 1

How long will it take me to prepare an application?

Gate 1 is intentionally streamlined:

  • 10-minute Video Abstract (max 5 slides)

  • 5-page Abbreviated Technical Volume

  • Rough Order of Magnitude cost estimate

Most well-prepared teams should expect 3–6 weeks to develop a competitive Gate 1 submission, depending on technical maturity and team alignment.

Gate 2 preparation will require significantly more effort if invited.

How can BW&CO help?

We help founders and research teams:

  • Reverse-engineer DARPA evaluation criteria

  • Position non-classical mechanisms to align with milestone language

  • Translate structural biology and modeling approaches into milestone-driven narratives

  • Architect Phase 1 → Phase 2 transition logic

  • Draft Gate 1 materials that maximize selection probability

  • Build credible in vivo translation pathways

Our role is to make sure your science aligns exactly with DARPA’s stated metrics and exclusion criteria.

How much would BW&CO Charge?

We charge a flat $4,000 fee to submit the pre-proposal for Gate 1. We also have an hourly rate to strategize, review, and edit applications of $250.

Additional Resources

Review the solicitation here.

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