A02-SOO 12-31-2025.docx

STATEMENT OF OBJECTIVES (SOO)

Title: Assessment of Host-targeted Nanobody Therapeutics

Requiring Activity/Agency Name: U.S. Army Medical Research of Infectious Diseases (USAMRIID) and all other Defense Health Agency (DHA) labs

1. PURPOSE

The Contractor shall provide all personnel, equipment, supplies, facilities, transportation, tools, materials, supervision, and other items and non-personal services necessary to evaluate host-targeted nanobody therapeutics using established in vitro porcine blood brain barrier (BBB) models and to develop novel in vitro BBB models useful for further characterization of nanobody therapies as defined in this SOO except for those items specified as government furnished property and services. The Contractor shall perform to the standards in this contract.

2. BACKGROUND

USAMRIID works closely with other U.S. Army Medical Research and Development Command (USAMRDC) organizations, Department of War (DoW), the Interagency (including Interagency Laboratories), and private companies to accomplish its mission of protecting the Warfighter from biological threats and being prepared to investigate disease outbreaks or threats to public health.

Defense Health Agency Contracting Activity (DHACA) and USAMRIID shall issue task orders against this proposed Indefinite Delivery/Indefinite Quantity (IDIQ). Each task order will define the deliverables for each task. Each task order shall represent a Firm-Fixed-Price response to a USAMRAA issued Assessment of Host-targeted Nanobody Therapeutic request to evaluate host-targeting nanobody therapies for their ability to bind to and traffic across in vitro BBB models, and potentially other tissue model systems, and shall represent all personnel and materials required to provide a turnkey solution to the Government’s requirement as defined in the SOO.

Numerous neurotropic viral families are considered high priority pathogens to the DoW, but therapeutic development is stymied by the difficulty of trafficking into the Central Nervous System (CNS). This is mediated primarily by BBB tight junctions that prevent large molecule entry into the parenchymal space. However, the CNS has significant physiological needs in the form of energy, oxygen and other molecular components. BBB transporters, receptors and ion channels regulate this via either non-specific transcytosis, specific carrier-mediated transport (CMT) or receptor-mediated transcytosis (RMT). As part of a Defense Threat Reduction Agency (DTRA) funded effort to address these challenges, we will target various transporters expressed on the luminal side of the BBB with host-targeting nanobodies to transport molecules on a blood-to-brain directional gradient for therapeutic payload delivery. To provide multiple shots on goal, we aim to develop nanobodies against a diverse set of BBB transporters with a range of species-specificities to identify the optimal targeting strategy in the context of neurotropic viral infections. Via this IDIQ, we will contract out the in vitro BBB modeling assessment of host-targeting nanobodies and refinement of in vitro and in vivo evaluation systems that will be leveraged in outyears to down-select optimal host-targeting nanobody candidates for continued development.

3. SCOPE OF EFFORT

The Government intends to award an IDIQ contract for the assessment of host-targeting nanobody therapies (to be provided to the performer by USAMRIID using in vitro BBB models. These services include but are not limited to the characterization of porcine BBB arenavirus infection models, determining the mechanism of nanobody transmigration across the BBB, and establishment and characterization of a marmoset BBB model. Each task order is unique in scope and will require flexibility in design, schedule, and execution, details of which will be specified for each task order.

· The Contractor shall refine in vitro BBB models for the assessment of nanobody therapeutic transmigration in the context of viral infection. The Contractor, as subject matter experts on the in vitro BBB model and virologic assessment, shall utilize applicable technical methods to assess in vitro BBB models following infection with a pathogen of interest to characterize BBB targets for prioritization. Contractor shall deliver a comprehensive report detailing the technical methods used and the targets identified.

· The Contractor shall utilize applicable technical methods to establish baseline transmigration efficiencies for non-targeted nanobody therapies. Contractor shall deliver a comprehensive report establishing baseline transmigration efficiencies, detailing the methods, data, and analysis used.

· The Contractor shall utilize applicable technical methods to assess transmigration efficiencies for BBB-targeted nanobody therapies. Contractor shall deliver a comprehensive report assessing transmigration efficiencies, detailing the methods, data, and analysis used.

· The Contractor shall utilize applicable technical methods to establish a BBB model of NHP origin, providing a species-relevant model for human BBB-targeted nanobody therapy assessment. Contractor shall deliver a validated BBB model and a detailed characterization report. Validation criteria must be pre-approved by the Technical Representative.

· The Contractor shall work with USAMRIID to provide subject-matter expertise on in vitro BBB models and advise on optimal targets for BBB targeting nanobody therapeutics. Contractor shall provide documented subject-matter expertise and guidance, demonstrated through meeting minutes, reports, and other documentation.

4. PLACE AND PERIOD OF PERFORMANCE (POP)

The contract shall be an IDIQ contract with a five-year ordering period for novel large surface area microparticle drug products suitable for treatment in animal models of infectious disease. A six month FAR 52.217-8 Option Period, if required, will be exercised.

5. ADMINISTRATIVE TASKS

The Contractor shall provide study protocol and budget; integrated master schedule; market sustainment plan; monthly IPT meetings; quarterly task status reports that describe the progress made within the period and costs incurred; spend plan; and documents inclusive of a final study report. Each of these items must be addressed in the Offeror’s SOW.

The Government will utilize a Quality Assurance Surveillance Plan (QASP) that serves to monitor performance and to assure that the Government is receiving the services specified in the contract and that the services meet the performance standards specified in the contract. By employing a fully developed QASP, the Government and the Contractor achieve an understanding of performance expectations and how performance will be measured against those expectations. The QASP may be negotiated between the Government and the contractor prior to final contract award.

USE OF TECHNICAL REFERENCE FACILITY

To the extent practical the Contractor shall utilize the technical reference facilities of the Defense Technical Information Center (DTIC) for the purpose of surveying existing knowledge and avoiding needless duplication of scientific and engineering effort and the expenditure thereby represented. The DTIC headquarters office is located at 8725 John J. Kingman Road, Fort Belvoir, VA 22060-6218. Information can also be obtained via the Internet at http://www.dtic.mil or via the toll-free number for the DTIC help desk, 1-800-225-3842. To the extent practical, all other sources, whether Government controlled, should be consulted for the same purpose.