Chemistry Center for Combating Antibiotic-Resistant Bacteria (CC4CARB)   3

Multidrug-resistant (MDR) Gram-negative bacteria are key pathogens responsible for the alarming rates of drug resistance in healthcare and community settings. The Centers for Disease Control and Prevention (CDC) has developed a list of organisms considered Antimicrobial Resistance (AR) threats. Many of these organisms are MDR Gram-negative bacteria, including carbapenem-resistant Enterobacteriaceae designated as an urgent threat. Serious AR threats include MDR Acinetobacter and MDR Pseudomonas aeruginosa. These Gram-negative bacteria have acquired new resistance traits over the past decade to the point that in some cases there are no effective treatment options, and the pipeline for new drugs targeting these bacteria is extremely short. The problem of MDR bacterial infections is exacerbated by the scarcity of novel compounds effective against Gram-negative bacteria. For several years, in publications as well as in many public forums (including NIAID workshops), the scientific community has identified the lack of suitable chemical libraries accessible for screening as a major scientific bottleneck for the discovery and development of novel antimicrobial drugs. There is a scarcity of novel chemical classes and natural compounds with properties appropriate for Gram-negative cell penetration (and efflux avoidance). In a report produced with the help of key opinion leaders by the PEW Charitable Trust titled Scientific Roadmap for Antibiotic Discovery, the problem of appropriate chemical libraries is recognized as one of the key problems in antibiotic discovery. This report states that the need to generate and tailor chemical matter for antibacterial discovery and to build prototype libraries tailored for antibacterial discovery is a fundamental part of the critical path to new antibacterials. Although detailed structure-activity relationships (SAR) or rules that define the chemical space for optimal antibacterial activity, currently are not fully established, recent advances in assays and computational approaches are making these efforts more feasible.
The aim of this solicitation is to create an innovative chemistry center to design, synthesize and deliver rationally designed compound libraries to the scientific community for use in antibacterial drug discovery programs. This center will fit within the broader aims put forth in the National Action Plan for Combating Antibiotic-Resistant Bacteria (CARB) by synthesizing and delivering new compounds that enable an understanding of a SAR for optimal activity against Gram-negative bacterial pathogens and that provide the basis for a robust antibacterial development pipeline. Critical to the success of this center are three core requirements: 1) Chemical Library Design - a well-organized and transparent process for solicitation, review and approval of design proposals from external scientists, 2) Compound Synthesis - a robust capability for high-quality and timely synthesis of diverse chemotypes, and 3) Compound Management- a seamless mechanism for managing the storage and distribution of the resulting compound libraries to the scientific community. In addition, a single Principal Investigator (PI), who ideally is skilled in synthetic chemistry, shall be accountable for coordinating all contract activities, along with comprehensive project management support, and for communicating progress and recommending approval decisions to the NIAID Contracting Officer's Representative (COR).
It is anticipated that one (1) cost-reimbursement plus fixed-fee, level-of-effort type contract will be awarded with a 12-month base period of performance beginning on or around February 01, 2021. Awards are expected to include four (4) one-year term option periods which replicate the base period activities. In addition, there will be three (3) term options for compound management that may only be exercised after the initial 5-year (base plus 4 options) period is completed. There will also be 20 quantity options for increased level-of effort that may be exercised any time prior to contract completion.
The Government's level-of-effort requirement is estimated at 28,000 direct labor hours for the base and each term option (A1-A4). The government's level-of-effort requirement is estimated at 4,000 direct labor hours for each term option A5-A7. The total contract performance period, including the base and all exercised options will be for a period of eight (8) years.

The basis for establishing the performance schedule will allow the Contractor to produce up to 20,000 rationally designed and structurally diverse compounds over the contract's life cycle and will allow storage and distribution of the compound libraries to the scientific community as needed.
The NIAID recognizes that a single organization or institution may not have the full spectrum of expertise or facilities required to perform all activities set forth in the Statement of Work. Contractors may need to be supported to a certain extent by the expertise and resources of other organizations or persons through consortia agreements, partnerships, subcontracts, and/or consultants. However, contractors shall be responsible for ALL work performed and shall be responsible for project planning, initiation, implementation, management and communication; evaluation, selection, and management of subcontractors; and for all deliverables specified in this contract.