BIOmolecular Grammar for protein Aggregation Modulation and Intervention (BIOGAMI)

Solicitation / RFP / RFQ

This solicitation, ARPA-H-SOL-26-149, titled "BIOGAMI" (BIOmolecular Grammar for protein Aggregation Modulation and Intervention), seeks innovative solutions to fundamentally transform therapeutic approaches to protein dysfunction in disease. The program aims to control protein folding and prevent aggregation, addressing the root cause of chronic and degenerative illnesses like neurodegenerative diseases, cancers, and diabetes. The goal is to develop novel therapeutics that prevent misfolding and aggregation, and to identify early detection methods for misfolded proteins.

• Technical Area 1 (TA1): Establish the "molecular grammar" of Intrinsically Disordered Regions (IDRs) by determining sequence, features, and environmental conditions that regulate IDR behavior. This includes developing computational and experimental methods to characterize IDR structural ensembles and biomolecular condensates.

• Technical Area 2 (TA2): Validate the foundational model from TA1 to develop potential detection and therapeutic applications. This involves creating methods to reverse protein aggregation, restore protein function, and validate clinical indicators for early detection of protein misfolding. Solutions should target one rare and one non-rare disease.

• Enabling Technologies: Performers may leverage advanced biophysics, imaging techniques, molecular dynamics simulations, AI/ML, and high-throughput assays.

• Data Management: Open sharing of deidentified/sanitized data acquired through TA1 activities is required.

• Anticipated Awards: Multiple Other Transaction (OT) Agreements.

• Period of Performance: Two phases, Phase 1 (0-24 months) and Phase 2 (25-48 months).

• Submission Process: Two steps: 1) Solution Summary (required), 2) Full Proposal (optional, based on encouragement from Solution Summary review).

• Key Deadlines:

  • Solution Summaries due: March 4, 2026
  • Questions & Answers due: March 11, 2026
  • Full Proposals due: April 15, 2026

• Evaluation Criteria:

  1. Overall Scientific and Technical Merit
  2. Proposer's Capabilities and/or Related Experience
  3. Potential Contribution to ARPA-H Mission and User Experience
  4. Assessment of Proposed Cost/Price

• All responsible sources are eligible, including universities, non-profit organizations, small businesses, and other than small businesses.

• Federally Funded Research and Development Centers (FFRDCs) and Government entities are generally not permitted to respond as part of a performer team, with specific exceptions.

• Proposers must have an active registration in SAM.gov.

• A Proposers' Day will be held on February 20, 2026.

• Commercialization plans (5-year and 10-year) are required prior to award.

• Specific requirements regarding Dangerous Gain of Function research, Intellectual Property, Human Subjects Research, and Animal Subjects Research are detailed.

Form / Attachment / Pricing Sheet

This document, "APPENDIX G ADMIN NATIONAL POLICY (Other Transaction) - BIOGAMI.docx", is a required attachment for Volume III of the proposal submission. It details the administrative and national policy requirements that must be addressed by all proposers. The document must be completed in full and should not have any portions deleted.

• Formatting Requirements: 8-1/2 by 11-inch paper, 1-inch margins, sans-serif font (11pt minimum, 8-10pt for figures/tables/charts). No page limit.
• Submission Format: .pdf, .doc, or .docx; must be in English.
• Cover Page: Requires Proposal Title, Proposer Organization, Technical Point of Contact (TPOC), Administrative POC (APOC), Date of Submission, and Proposal Validity Period.
• Team Member Identification: Table to list all organizations/institutions involved, their status (U.S./non-U.S.), and role (prime, sub-awardee, contractor, vendor).
• Senior/Key Personnel: Table to list personnel, their organization, and confirmation of attached Common Forms (Biographical Sketch, Current & Pending Support).
• FFRDC Participation: Disclosure and justification if an FFRDC is included.
• Organizational Conflict of Interest (OCI): Disclosures and mitigation plans for potential conflicts, including specific questions about Internal Support Contractors (ISC)/Systems Engineering Technical Assistance (SETA) and prior ARPA-H support.
• Research Security Disclosure: Questions regarding participation in foreign talent recruitment programs (FTRPs), ownership by foreign entities, and research conducted in Foreign Countries of Concern (FCOCs).
• Novelty of Proposed Work: Disclosure if the work has been submitted to other government solicitations or received prior funding.
• Intellectual Property (IP): Table to identify background IP or restricted data, its role, basis for assertion, associated government rights (Unlimited, Government Purpose, Limited, Specially Negotiated/Other), and asserting entity. Specific instructions for patents and IP developed with government funding are provided.
• Human Subjects Research (HSR): Disclosure and documentation plan for IRB review and Federal-wide Assurance if HSR is involved.
• Animal Subjects Research (ASR): Disclosure and documentation plan for IACUC review, Vertebrate Animal Section (VAS) worksheet, and Animal Welfare Assurance if ASR is involved.
• Representations: Declarations regarding unpaid delinquent tax liability or recent felony convictions.
• Cybersecurity: Description of the organization's cybersecurity program, standards, incident response capabilities, and experience managing Controlled Unclassified Information (CUI).
• Biosecurity: Disclosure regarding dangerous gain-of-function research and procurement of synthetic nucleic acids or benchtop nucleic acid synthesis equipment.

This document is critical for bidders to understand the administrative, policy, and compliance requirements of the proposal. It outlines mandatory information and disclosures related to personnel, organizational conflicts, intellectual property, research security, and ethical considerations. Failure to complete and submit this appendix accurately may impact proposal evaluation and award.

Form / Attachment / Pricing Sheet

This document, "APPENDIX A SOLUTION SUMMARY FORMAT AND INSTRUCTIONS - BIOGAMI.docx," provides the required template and instructions for bidders to submit a Solution Summary for the ARPA-H-SOL-26-149, BIOGAMI opportunity. It outlines the specific sections and content required for the submission.

• Cover Letter: Includes space for organization logo and title.
• Solution Summary Title: To be filled in by the bidder.
• Team Lead Organization: Identification of the primary organization.
• Organization Type: Selection from predefined categories (Large Business, Small Disadvantaged Business, etc.).
• SAM.gov Universal Entity Identifier (UEI): Required identifier.
• Points of Contact (POC): Technical and Administrative POC details (Name, Address, Telephone, Email).
• Total Basis of Estimate (BOE): Overall estimated cost.
• Place(s) of Performance: Location(s) where work will be performed.
• Other Team Members: Details on team members or subawardees/consultants.
• Concept Summary: Description of the proposed solution and its technical areas.
• Innovation and Impact: Explanation of the innovation, potential impact, and quantitative metrics.
• Proposed Work: Details on deliverables, milestones, technical approach, risks, and challenges.
• Team Organization and Capabilities: Roles, responsibilities, and qualifications of key personnel.
• Basis of Estimate (BOE) Table: Breakdown of costs (Direct Labor, Subcontracts, Materials, etc.) and requested federal funds.

Formatting Requirements:

• Submissions must be in English.
• Font size must be 12-point or larger (smaller for figures/tables).
• Formatting instructions must be deleted before submission.
• Solution summaries are limited to five (5) pages (citations and Key Personnel Table excluded).

This template is critical for bidders to understand the required structure, content, and formatting for their Solution Summary. Adhering to these instructions is essential for a compliant and competitive proposal. Bidders must carefully populate each section with detailed information regarding their proposed solution, team, technical approach, and cost estimates.

Form / Attachment / Pricing Sheet

This document, Appendix B, provides detailed instructions and formatting requirements for submitting a full proposal in response to the solicitation. It outlines the structure and content expected for each of the three proposal volumes.

Proposal Structure: Proposals must be organized into three volumes:

• Volume I: Technical and Management Proposal (Max 30 pages, excluding specific appendices)
  • Cover Page
  • Executive Summary
  • Solution Fit with BIOGAMI
  • Technical Plan
  • Management Plan
  • Capabilities
  • Commercialization Plan
  • Task Description Document (TDD) (See Appendix C)
  • Schedule and Milestones – GANTT Chart (See Appendix D)
  • Data Management and Sharing Plan (DMSP) (See Appendix E)
  • References Volume II: Cost Proposal
  • Cost Proposal Spreadsheet(s) (See Appendix F)
  • Cost and Pricing Data Support documents, including a Cost Narrative Volume III: Administrative and Policy Requirements Submission
  • Team Member Identification and associated Common Forms (See Appendix G)
  • FFRDC Participation
  • OCI Affirmations and Disclosure
  • Research Security Disclosure
  • Novelty of Proposed Work
  • Intellectual Property (IP)
  • Human Subjects Research
  • Animal Subjects Research
  • Representations Regarding Unpaid Delinquent Tax Liability or a Felony Conviction Under any Federal Law
  • Cybersecurity
  • Biosecurity
  • Security Attestation Form (See Appendix H)
  • Dangerous Gain of Function Assessment (See Appendix I)
  • Draft OT Response (See Appendix J)

Formatting Requirements:

• 8-1/2 by 11-inch paper with 1-inch margins.
• Font size no less than 11 point (Arial or non-serif).
• Page numbers at the bottom.
• Clear labeling with ISO number, proposer organization, and proposal title.

This document is critical for bidders as it dictates the exact format, content, and page limitations for proposal submissions. Adherence to these instructions is mandatory for a conforming proposal. It details the specific information required in each section of the technical, cost, and administrative volumes, including required appendices and supporting documentation.

Form / Attachment / Pricing Sheet

This document is a template for a Task Description Document (TDD) that bidders are strongly encouraged to use when preparing their proposals. It outlines the required structure and content for detailing proposed tasks and subtasks.

• Task Breakdown: Requires a detailed breakdown of tasks and subtasks, including:
  • General objective of each task/subtask.
  • Detailed description of the approach.
  • Identification of human subjects or animal research.
  • Identification of work performed on a university campus.
  • Primary organization responsible for execution.
  • Measurable milestones.
  • Deliverables (with IP assertions if applicable).
• Instructional Text: The template includes instructional text in blue font, which may be deleted in the final submission.

Bidders must use this template to structure their technical proposals, ensuring all required elements for task and subtask descriptions are included. It guides the level of detail expected for the approach, responsibilities, deliverables, and research components, directly impacting proposal completeness and evaluation.

Form / Attachment / Pricing Sheet

This document, "APPENDIX D ARPA-H GANTT Chart Sample - BIOGAMI.xlsx", appears to be a sample Gantt chart provided as an appendix. It serves as a template or example to illustrate project scheduling and milestone tracking, likely for a project related to ARPA-H (Advanced Research Projects Agency for Health).

• Project Schedule: Outlines tasks and milestones with Work Breakdown Structure (WBS) identifiers.
• Task/Milestone Title: Names of specific project activities or achievements.
• G/N Indicator: A "Go/No-Go" indicator, suggesting decision points within the project timeline.
• Start and End Dates: Specifies the planned commencement and completion dates for tasks and milestones.
• Quarterly Breakdown: Visual representation of task/milestone duration across multiple quarters (labeled 1 through 24+).

Bidders should review this sample Gantt chart to understand the expected level of detail and format for project scheduling and reporting that may be required if they are awarded a contract. It provides insight into how ARPA-H or the contracting agency visualizes and manages project timelines, key milestones, and potential go/no-go decision points. This can help in developing realistic project plans and understanding reporting expectations.

Form / Attachment / Pricing Sheet

This document outlines the requirements for a Data Management and Sharing Plan (DMS Plan) as mandated by NIH policy for research applications that generate scientific data. It serves as a template and guide for bidders to detail how they will manage and share data resulting from funded research.

• Element 1: Data Type: Specifies the types and amounts of scientific data to be generated, preserved, and shared, along with the rationale and associated metadata.
• Element 2: Related Tools, Software and/or Code: Details any specialized tools or software required for accessing or manipulating shared data.
• Element 3: Standards: Outlines the common data standards to be applied to ensure interoperability.
• Element 4: Data Preservation, Access, and Associated Timelines: Describes the repository for archiving data, how it will be findable and identifiable, and the timeline for its availability.
• Element 5: Access, Distribution, or Reuse Considerations: Addresses factors affecting data access, distribution, or reuse, including informed consent, privacy, confidentiality, and any limitations.
• Element 6: Oversight of Data Management and Sharing: Details the plan for monitoring and managing compliance with the DMS Plan.

Bidders must understand and address these requirements in their proposals if their research involves generating scientific data. This plan is crucial for demonstrating compliance with NIH data sharing policies and ensuring responsible data stewardship. Failure to submit an adequate DMS Plan may impact proposal evaluation and funding.

Form / Attachment / Pricing Sheet

This document is an Excel spreadsheet template designed for bidders to submit detailed cost proposals for ARPA-H opportunities that do not involve a Resource Sharing agreement. It outlines the structure for calculating direct labor, indirect costs, and other direct costs across multiple fiscal years and project phases.

• General Information: Proposer details, solicitation number, proposal ID.
• Proposer Constants: Business type selection (Large Business, Small Business, etc.), small business size estimate, and fiscal year definitions.
• Labor Rates: Detailed breakdown of labor categories, ARPA-H labor groups, burdened labor rates, and escalation rates.
• Phase Costs (Phases 1-6): Sheets for detailing direct labor, subproposer costs, consultant costs, other direct costs (ODCs), material handling, G&A, FCCM, and profit/fee per phase.
• Task Costs (Phases 1-6): Sheets to break down costs by specific tasks within each phase.
• Summary Cost Table & Total Amount: Consolidates costs from all phases and categories.
• Supporting Schedules: Tabs for Subproposers, Consultants, Travel, Materials/Supplies, Equipment, ODC Details, and Expenditures by Month provide detailed breakdowns.
• Animal/Human Use: Checklists for animal and human subject research involvement.

This spreadsheet is critical for bidders to accurately develop and present their cost proposals. It dictates the format for all cost-related submissions, including labor, overhead, materials, and other direct expenses. Adherence to the structure and instructions within this template is essential for a compliant and evaluable cost proposal.

Form / Attachment / Pricing Sheet

This document is Appendix H, the ARPA-H Security Attestation Form. It requires the prime organization and the covered individual to make certifications regarding the individual's non-involvement in Malign Foreign Talent Recruitment Programs (MFTRP).

• Prime Organization Certifications: Asserts the covered individual is not party to an MFTRP and commits to reporting new covered individuals or changes to conflict of commitment disclosures within 10 days of discovery.
• Covered Individual Certifications: Certifies they are not a party to an MFTRP and acknowledges annual recertification will be provided to ARPA-H.
• Acknowledgement of New Personnel: States that newly nominated covered personnel cannot begin work until a Research Security Assessment is completed by ARPA-H.
• Signatures: Requires signatures from the covered individual and an official responsible for the transaction, along with typed names, titles, organization, and dates.

Bidders must complete and submit this form as part of the application process. It is crucial for demonstrating compliance with ARPA-H's research security requirements, specifically concerning foreign talent recruitment programs. Failure to properly complete and submit this attestation may impact eligibility or the ability for personnel to commence work on the project.

Form / Attachment / Pricing Sheet

This document is Appendix I, a "Dangerous Gain of Function Assessment" form. Its purpose is to assist the BIOGAMI Proposal Review team in conducting an initial review of proposed initiatives to determine the risks of potentially dangerous gain of function research, in accordance with U.S. Government Executive Order 14292.

• Program Details: BIOGAMI Program Title, Proposal Title, Principal Investigator, Proposal Description.
• Scope: Questions regarding research activities involving prions or prion-like agents, and specific outcomes defined by E.O. 14292.
• Societal Consequences: Assessment of potential threats to public health, safety, economic, or national security.
• Foreign Involvement: Inquiry into whether research will be conducted by foreign entities in foreign countries.
• Risk Assessment: Evaluation of the overall risk for dangerous gain of function research.
• Mitigation Plan: A plan to avoid dangerous gain of function risk and mitigate other biosafety and biosecurity risks.

Bidders proposing research under the BIOGAMI program must complete this form as part of their proposal submission. It requires a detailed assessment of potential risks related to gain-of-function research, societal consequences, and foreign involvement, along with plans for risk mitigation. This document is critical for understanding compliance requirements and demonstrating responsible research practices.

Other / Unclassified

This document is a sample template for an Other Transaction Agreement (OTA) between the Advanced Research Projects Agency for Health (ARPA-H) and a performer. It outlines the standard articles, definitions, and attachments typically included in such agreements. The template includes placeholders for specific project details, performer information, and financial terms. It also highlights sections that may require input from the performer (turquoise) or the government (yellow).

This document serves as a template and provides insight into the contractual framework ARPA-H uses for Other Transactions. Potential bidders can use this to understand:

• Agreement Structure: The general terms and conditions, including scope, term, management, payment, disputes, intellectual property rights, and property disposition.
• Key Definitions: Understanding terms like "Subject Invention," "Government Purpose Rights," and "Limited Rights" is crucial for intellectual property considerations.
• Deliverables and Reporting: Outlines requirements for Task Description Documents (TDD), report submissions (technical status, milestone, final reports), and property reporting.
• Intellectual Property (IP) Rights: Details how IP developed under the agreement will be handled, including disclosure, election of title, and protection methods (patent vs. trade secret).
• Foreign Access and Restrictions: Specifies controls on transferring intellectual property to foreign entities.
• Payment Structure: Explains the milestone-based payment system.
• Points of Contact: Identifies key government and performer representatives.

While this is a sample, it offers a preview of the contractual obligations and expectations for performers engaging with ARPA-H through an OTA.