Amendment 1 CC4CARB.pdf

RFP-NIAID-75N93019R00024 Page 1 of 4

AMENDMENT #1

RFP-NIAID-75N93019R00024

“CHEMISTRY CENTER FOR COMBATING ANTIBIOTIC-RESISTANT BACTERIA (CC4CARB)”

AMENDMENT No. 1

Amendment Number: One (1)

Amendment Issue Date: January 24, 2020

Proposal Due Date: March 16, 2020 3:00PM EST (UNCHANGED)

Issued By:

Jonathan Bryan Contracting Officer Office of Acquisitions, DEA National Institute of Allergy and Infectious Diseases National Institutes of Health 5601 Fishers Lane, Room 3D30

MSC 9821

Rockville, Maryland 20852-9821

Point of Contact:

Jonathan Bryan, Contracting Officer Email: jonathan.bryan@nih.gov.

Offerors must acknowledge receipt of the final posting of Amendment #1, on each copy of the proposal submitted. Failure to receive your acknowledgment of this Amendment may result in the rejection of your proposal.

The hour and date specified for receipt of proposals HAS NOT been extended.

PURPOSE OF SOLICITATION AMENDMENT:

The purpose of this amendment is to address questions regarding RFP 75N93019R00024.

Question 1: Does the Government have any objection to using team members in other countries as vendors/subcontractors? Is there any limitation on the amount of work within the scope that can be conducted by these groups?

Answer 1: This contract is considered full and open competition. The prime, subcontractors/vendors may come from any country. Please see FAR Clause 52.215-23, Limitations on Pass-Through Charges and 52.215-22, Limitations on Pass-Through Charges--Identification of Subcontract Effort, regarding the amount of work that can be conducted by these groups.

Question 2: What exactly is meant by Library? Are these libraries to be (i) created around conceptual themes that will be provided to end users (such as from the Pew Trust), (ii) are they mailto:jonathan.bryan@nih.gov.

RFP-NIAID-75N93019R00024 Page 2 of 4 expected to be combinatorial, (iii) are they sets of compounds to expand upon existing hits or leads that an end user might have, (iv) some combination of these, or (v) something else?

Answer 2: Definition of Library: Compound Library refers to a collection of discrete small-molecules (not mixtures of compounds) designed based on new conceptual themes or as an expansion of existing, non-proprietary compounds. The Government anticipates producing 20,000 rationally designed and structurally diverse small-molecules originating from >150 compound libraries over the period of the contract. Based on these estimates, each design project will comprise sets of compounds or libraries that range in size from 50 – 150 compounds per project. The potential sources of the library designs are described below. As outlined, the design ideas are expected to be diverse in nature and can include requests to resynthesize known compounds or to develop synthesis for completely novel designs. The resulting compounds will be made publicly available and freely distributed to the scientific community; therefore, this contract is not likely appropriate for synthesis of proprietary compounds that are direct lead candidates for drug discovery. However, compounds that may provide early screening hits or research tools for supporting therapeutics discovery programs are encouraged and expected from the design project solicitation efforts that will be part of this contract.

Source of compound- or library-design ideas: The specific lists of compounds or compound libraries that will be synthesized under this contract ultimately will be directed by the NIAID COR. However, as defined by the Chemical Library Design requirement (Appendix 1 SOW, Section 1 and 3A), the contractor is expected to devise “a well-organized and transparent process for solicitation, review and approval of design proposals from external scientists” that will be recommended to the COR for approval for entering into the synthesis queue. The contractor is expected to develop and implement a plan for soliciting design ideas on a regular basis from the broad scientific community for the design of small-molecules with diverse physicochemical properties, specifically designed for targeting Gram-negative bacterial pathogens. These ideas will be reviewed through a proposal submission and review process defined by the contractor, and selected design projects will be prioritized and recommended to the COR for approval and submission for chemical synthesis. This effort will include formation of a Scientific Advisory Board (SAB) to assist with the process of reviewing and prioritizing synthesis plans for recommendation to the COR. In addition, the contractor is expected to establish a process for regular outreach to the scientific community to identify gaps that may be addressed through the synthesis of compounds to enhance the understanding of optimal physicochemical properties required for targeting Gram-negative bacterial pathogens. These efforts may include internal designs for new compound libraries, acquisition of existing compounds and/or re-synthesis of known compounds that would benefit the scientific community at large. Please note that the names of potential SAB members must NOT be included in the proposal, although a description of expected qualifications for SAB members and a description of the plans for engaging them in the library design process are required.

Question 3: We understand that library requests would be made from the Scientific community and would be vetted by a Scientific Advisory Board. It is described that libraries would be rationally designed. Would libraries be at the idea stage or would it be necessary to have proof of concept synthetic routes in place in order to recommend for library synthesis.

Answer 3: Ideally the chemical synthesis is precedented; however, a proposed chemical

RFP-NIAID-75N93019R00024 Page 3 of 4 synthesis with supporting references for specific steps will be acceptable. The library design submitter will support the chemical synthesis with contingency plans for less precedented chemical synthetic steps and remain engaged with the project as a consultant during execution of synthesis to help troubleshoot issues and/or provide input into redesign efforts if needed.

Question 4: Since we are expected to develop a plan to solicit proposals for library development, would we be able to then set the requirements for preliminary chemistry justification to support the synthetic route?

Answer 4: Yes, with approval of the COR, a description of required chemistry justification is acceptable, keeping in mind the intent of the contract is to contribute novel small-molecules to the scientific community as well as resynthesis of some known compounds. Although some degree of chemistry precedent is useful, it is expected that some of the design projects will require scouting of novel synthetic routes which comes along with an increased difficulty and risk of failure. It is expected that the contractor, working with the SAB and COR, will balance these risks in the selection/prioritization of design projects that advance into and progress through the synthesis queue.

Question 5: Where would the screening of the libraries be done? Is it assumed we would put together a plan or will this be coordinated by NIAID?

Answer 5: This contract does not include biological screening or testing assays. Screening will be the responsibility of the compound requestor.

Question 6: How much input would the CC4CARB Center have on projects selected?

Answer 6: The COR will ultimately be responsible for project selection using the library evaluations/feedback of the contractor/SAB.

Question 7: Is there a possibility for internal projects to be developed?

Answer 7: The design project ideas submitted internally by the contractor would have to follow the same evaluation/selection process as external submissions.

Question 8: Would compounds be curated at both the CC4CARB Center and NIAID?

Answer 8: No, they will be curated at CC4CARB center and the contractor will be responsible for maintenance of the combined library and distribution to external requestors.

Question 9: Are there any recommendations for IP, given that library design ideas will be suggested by one Institution and then synthesis executed at the CC4CARB center followed biological testing at another?

Answer 9: Compounds prepared under this contract and synthetic routes will be made publicly available and freely distributed to the scientific community; therefore, this contract is not appropriate for synthesis of proprietary compounds with IP protection.

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Question 10: "Compound Synthesis - a robust capability for high-quality and timely synthesis of diverse chemotypes" Can this be all outsourced to external chemistry CROs or does it has to be from the Prime C contractor's internal chemistry capability?

Answer 10: Yes, this may be outsourced.

Question 11: Compound Management- a seamless mechanism for managing the storage and distribution of the resulting compound libraries to the scientific community.

Can this be also outsourced but will be managed and overseen by the Prime?

Answer 11: Yes, this may be outsourced and managed by Prime.