NIH Complement-ARIE NAMs Reduction-to-Practice Challenge: Phase 2 Milestone 1 (2026-2027)

NIH Complement-ARIE NAMs Reduction-to-Practice Challenge: Phase 2 Milestone 1 (2026-2027)

The NIH Common Fund’s Complement Animal Research in Experimentation (Complement-ARIE) Reduction-to-Practice Challenge is currently in Phase 2 Milestone 1. This is an active stage of a multi-phase prize competition, not a newly opened competition for anyone who missed the first round. The official NIH challenge page says that Phase 2 Milestone 1 is open from 2026-07-20 through 2027-03-22 and that only Phase 1 winners may register. HeroX, the challenge platform named by NIH, describes the overall challenge as closed to new competitors while Phase 2 work continues for the selected teams.

The program is intended for integrated, human-relevant new approach methodologies (NAMs). A combinatorial NAM can combine in vitro cell, tissue, or organoid work with in silico modeling, in chemico analysis, or other complementary methods. The point is not simply to present a promising assay. Teams must show how their combined platform can be built, scaled, tested, and used for a defined human-health or regulatory decision.

Current opportunity at a glance

The deadline in the front matter is therefore the Phase 2 Milestone 1 registration and submission deadline, not the old Phase 1 date. The first phase closed on 2026-03-01. That earlier date remains useful historical context, but it is not the live deadline for the current stage.

What Phase 2 Milestone 1 is designed to fund

Phase 2 moves the selected solutions from an early feasibility result toward a usable prototype. NIH describes two required outcomes for Milestone 1. First, the team must successfully construct and scale its combinatorial NAM platform according to fit-for-purpose industry guidance. Second, it must provide quantifiable progress toward initial performance and testing requirements in a specific context of use.

The award is tied to successful completion of the milestone. It is not a general-purpose research grant, an unrestricted operating award, or a payment for submitting an interesting concept. Up to 10 winning teams can receive $150,000 each. Phase 2 Milestone 2 is a separate stage with a separate window and award: up to seven teams may receive $200,000 each after demonstrating progress toward internal validation, reproducibility, data standards, and a documented path for assessment by the Complement-ARIE Validation and Qualification Network (VQN).

The broader prize structure also includes the completed Phase 1 awards of $80,000 per winner for up to 20 winners, three Phase 3 runner-up awards of $500,000, and one Phase 3 grand prize of $1,000,000. A solver that wins the applicable awards through the challenge can receive as much as $1,430,000 cumulatively. Those later amounts should not be read as guaranteed funding for a Phase 2 applicant. Each phase has its own deliverables and review.

Who can use the current window

The most important eligibility condition is advancement from Phase 1. The NIH page states plainly that only Phase 1 winners are eligible to register for Phase 2 Milestone 1. A team that did not submit in Phase 1, or submitted but was not selected as a Phase 1 winner, cannot use this deadline to make a new entry. The Phase 1 winners were publicly announced by NIH on 2026-07-20.

Phase 2 participants must continue as a Team or an Entity. A Team must identify one Team Leader who registers and submits for the members and handles communications with the sponsors. To receive a cash prize, that Team Leader must be a U.S. citizen or permanent resident. Members who are not U.S. citizens or permanent residents may participate in an otherwise eligible team, but they cannot receive prize money.

An Entity must identify a Point of Contact who registers and submits for the organization. The Entity must be incorporated in the United States and maintain its primary place of business in the United States to receive a cash prize. If federal grant, cooperative agreement, or other transaction award funds will be used in developing the submission, the participant must register as an Entity on behalf of the awardee institution or organization and comply with the underlying award terms. Federal entities, federal employees acting within the scope of employment, and HHS employees acting in a personal capacity are excluded under the official rules; other federal employees should consult their agency ethics officials.

Participants must be at least 18 years old at the time of submission and must register under NIH’s challenge rules. Everyone on the submission should be listed with the required name, affiliation, and contact information. Phase 2 solutions must be based on the respective team or entity’s Phase 1 submission, so this is a continuation route rather than an opportunity to replace the original scientific direction with an unrelated proposal.

How an eligible Phase 1 winner applies

The registration and submission process is administered through the official HeroX challenge page linked from NIH. An eligible winner should use this sequence:

1. Confirm that the team or entity is one of the Phase 1 winners and decide whether the existing participant structure will continue as a Team or Entity.
2. Identify the Team Leader or Entity Point of Contact who will register, submit, communicate with NIH, and manage the submission record.
3. Register on the HeroX Complement-ARIE RTP page before 2027-03-22. The registrant must provide the names, affiliations, and contact information for all participating individuals and acknowledge whether federal funding is involved.
4. Complete the Phase 2 Eligibility Review Form and certify that the participant accepts the official eligibility, participation, and submission rules.
5. Upload the responsive Phase 2 proposal and supporting files through the designated challenge page. NIH allows PDF or MP4 files for this stage, with written material in English and no handwritten material.
6. Check the submission for the restrictions on government seals, logos, and claims of federal endorsement. The official page also says that generative AI must not be used to develop the writing, imagery, or data of a submission outside dedicated performance within the proposed NAM platform.

The current Phase 2 Milestone 1 package has four parts. The technical package may be up to 15 pages. It should explain what was built from the Phase 1 solution, how the integrated platform operates, how it is being refined, and how its initial performance will be measured. The Regulatory/Industry Report may be up to 5 pages, with attachments for references; it should connect the platform to fit-for-purpose needs, industry expectations, and a concrete decision context. The Development Plan may be up to 5 pages and may include one attachment such as a spreadsheet Gantt timeline. Finally, the submission may include one solution-demonstration video of up to 15 minutes.

What a competitive Milestone 1 package needs to show

The current judging structure gives the team a useful preparation checklist. Construction and model refinement account for 60 points, covering successful construction, the decision context, refinement, the development plan, and evidence of industry or regulatory guidance. Quantifiable performance measurements account for 40 points, including progression against testing requirements, a reproducibility gate, a human-based application, tested results, tolerance, and predictive capacity. Scaling can add bonus points.

That structure favors evidence that a real platform exists and is becoming more reliable. A good technical package should identify each component of the combinatorial system, explain the interface between those components, and distinguish measured results from planned work. It should say what the platform is meant to predict or support, what reference data or standards will be used, what counts as an acceptable result, and how failures or out-of-range behavior will be handled.

The development plan should connect activities to owners, dates, dependencies, and measurable gates. It should make clear how the team will move from the Phase 1 concept into a prototype that can be scaled for its intended use. A list of experiments without a decision rule is weaker than a shorter plan that explains what result permits the next refinement, what result triggers a change, and what evidence will be retained.

The Regulatory/Industry Report is also substantive. It should document the intended user or decision maker, the relevant workflow, the requirements the platform must meet, and any engagement or feedback that shaped the design. Teams should avoid presenting validation or regulatory acceptance as already achieved unless the evidence actually supports that claim. The challenge points toward VQN assessment and future qualification support; it does not itself make the platform a regulator-approved method.

Timeline beyond the current deadline

Phase 2 Milestone 2 is listed by NIH as open from 2027-05-18 through 2027-10-19. It will require progress toward internal validation and within-laboratory reproducibility against reference standards or their equivalent, data that meets the Complement-ARIE NAMs Data Hub and Coordination Center requirements, and documentation of interactions with the VQN for a possible use case. Phase 3, Prototype Delivery for Validation and Qualification, is listed as opening on 2028-01-31. Its deliverables include documentation and any materials needed to transfer the comprehensive NAM platform to the VQN, plus operating instructions for one or more solver-defined workflows.

These later windows are planning information, not alternate entry routes for teams that are not Phase 1 winners. The current actionable route is limited to eligible Phase 1 winners, who should use the NIH page and HeroX page for the authoritative registration interface and any updates to the package requirements.

Bottom line

This page should be treated as an active, restricted Phase 2 opportunity. The prior Phase 1 deadline has passed, but the challenge itself has not ended. A Phase 1 winner with a functioning integrated NAM, a defined context of use, initial performance evidence, and a credible development plan can apply for the current Milestone 1 review by 2027-03-22. New competitors cannot enter this stage. Teams should verify their participant status, assemble the four-part Phase 2 package, and submit through HeroX after reviewing the official NIH rules.

Official links

• NIH Complement-ARIE NAMs Reduction-to-Practice Challenge
• HeroX Complement-ARIE NAMs Reduction-to-Practice Challenge
• NIH Phase 1 winners announcement
• Official NIH challenge announcement PDF