Amendment_1.pdf

RFP No.: NIAID-DAIT-NIHAI201700100 Page 1 of 6

Amendment No. 1

Broad Agency Announcement (BAA) No.: NIAID-DAIT-NIHAI201700100 “Vaccine Adjuvant Discovery Program”

Amendment Number: One (1)

Amendment Issue Date: March 6, 2018

Response Date (Unchanged): July 31, 2018 by 3:00 PM, EST

Issued By: George Ralis

Contracting Officer

OA/DEA/NIAID/NIH/DHHS

5601 Fishers Lane, Room 3C19, MSC 9821 Rockville, Maryland 20852

Point of Contact: PRIMARY ralisg@niaid.nih.gov George Ralis, Contracting Officer Phone: 240-669-5146

Please note that we do NOT intend to extend the due date for submission of proposals as a result of this amendment. The date specified for receipt of proposals remains unchanged.

Offerors must acknowledge receipt of this amendment by identifying this amendment number and date of the amendment on each copy of the proposal submitted. Failure to receive your acknowledgement may result in the rejection of your proposal. Except as provided herein, all terms and conditions of the solicitation remain unchanged and in full force and effect.

The purpose of this amendment is to provide responses to questions which may be useful to all potential offerors.

QUESTION/ISSUE 1:

Does the solicitation require the adjuvant to be close to clinical trials?

RESPONSE:

The objective of the Adjuvant Discovery Program is to identify novel adjuvant candidates, and generate preclinical data which would support pursuing further preclinical development leading to a clinical trial. Such development activities are outside the scope of this solicitation and are supported by the NIAID through the Adjuvant Development program.

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QUESTION/ISSUE 2:

Does a vaccine adjuvant have to be a physical entity or can it be another type of intervention such as various forms of energy?

RESPONSE:

The BAA has four mandatory Study Areas, starting with the requirement to “screen compound libraries”. Non-physical types of adjuvants would not be responsive to this requirement.

Furthermore, the BAA only supports the search for new adjuvants and specifically excludes work on previously identified adjuvants. For such compounds (or interventions), the NIAID re-issued the Adjuvant Development BAA in 2017. Investigators are also encouraged to look for the FY19 HHS Omnibus SBIR Contract Solicitation and determine whether development activities on previously identified adjuvants will be supported by this mechanism.

QUESTION/ISSUE 3:

Can non-U.S. organizations submit proposals to this solicitation?

RESPONSE:

Non-U.S. organizations are able to submit proposals if they so desire. We’re looking for organizations that can satisfy the requirements as stated in the solicitation.

QUESTION/ISSUE 4:

Can you provide clarifications on the difference between a contract proposal and grant application?

RESPONSE:

Please review the information provided at the following two web addresses for greater detail on NIAID contracts and grants:

https://www.niaid.nih.gov/grants-contracts/contracts https://www.niaid.nih.gov/grants-contracts/apply-grant

QUESTION/ISSUE 5:

Would a proposal to develop, formulate and test an ID administered vaccine adjuvanted with a compound previously used in preclinical and clinical studies be responsive to the BAA?

RESPONSE:

The Adjuvant Discovery BAA is designed to continue to prime a pipeline of novel, immunostimulatory compounds. It requires, in Study Area 1, high-throughput screening of compound libraries to identify molecules with adjuvant activity, and their subsequent optimization. The use of “compounds already discovered to possess adjuvant activity” as well as work on “adjuvant candidates that are already at the stage of lead optimization, or adjuvants

RFP No.: NIAID-DAIT-NIHAI201700100 Page 3 of 6 presently or previously in preclinical or clinical testing….” will not be supported by this program (see Attachment 5, Research and Technical Objectives). NIAID supports such activities through the Adjuvant Development Program as well as the SBIR contract program.

QUESTION/ISSUE 6:

We are working with a new adjuvant that has already been licensed – would such a proposal be responsive to the solicitation?

RESPONSE:

The objective of solicitation NIAID-DAIT-NIHAI201700100 is to support the discovery of new candidate adjuvants through screening, preclinical testing, and early stage development.

Therefore, work on previously identified adjuvants, particularly those already in preclinical or clinical testing, is not supported (see Attachment 5, Research and Technical Objectives).

Previously identified adjuvants can, however, be co-delivered in vivo with newly identified adjuvant candidates to improve the efficacy of the new compounds. NIAID specifically encourages the discovery of novel adjuvant that can be delivered to mucosal sites (see Attachment 4, Background and Introduction).

QUESTION/ISSUE 7:

We are working on new oral vaccine adjuvants – would such a proposal be responsive to the solicitation?

RESPONSE:

NIAID specifically encourages the discovery of novel adjuvant that can be delivered to mucosal sites (see Attachment 4, Background and Introduction).

QUESTION/ISSUE 8:

Will there be an additional document beyond the solicitation?

RESPONSE:

Amendments to the current solicitation may be posted to Fedbizopps if applicable. I recommend that you periodically check Fedbizopps to see if that has occurred.

QUESTION/ISSUE 9:

Will there be an RFA? When should I expect that to be posted?

RESPONSE:

An RFA will not be prepared. The result of this requirement will be in the form of a contract, not a grant. The solicitation, and any possible amendments, will be posted to Fedbizopps.

QUESTION/ISSUE 10:

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Are you able to provide any additional insight into the nature of proposals that will be considered responsive? Is this aimed at later-stage development of existing adjuvants, or is the development of new experimental adjuvants being considered as well?

RESPONSE:

Solicitation NIAID-DAIT-NIHAI201700100 only supports the discovery of novel vaccine adjuvant candidates, but not work on previously identified adjuvants (see Attachment 5, Research and Technical Objectives). NIAID promotes the further development of previously discovered vaccine adjuvants through other programs, including the SBIR mechanism. Please see the following new council concept which was approved by the NIAID advisory council in January 2018:

Adjuvant Development for Vaccines and for Autoimmune and Allergic Diseases -https://www.niaid.nih.gov/grants-contracts/january-2018-dait-council-approved-concepts#06

QUESTION/ISSUE 11:

What is the anticipated split between industry and academic groups?

RESPONSE:

The affiliation of an offeror is not a criterion used in the selection process. NIAID has noticed a shift in the affiliation of awardees since the vaccine adjuvant program started in 2003. While the majority of offerors and awardees were from industry initially, most offerors and awardees in recent iterations of the programs are based at academic institutions, reflecting the increased technical capabilities of academic laboratories and/or their subcontractors.

QUESTION/ISSUE 12:

We are proposing to screen for MHC-I epitopes, conjugated to liposomes, for their ability to induce CD8 T cell responses in immunized mice. Would this approach be responsive to the

BAA?

RESPONSE:

Such a screen would not be responsive for two reasons: First, the objective of the program is to identify novel vaccine adjuvants, defined as “agents added to […] vaccine antigens to augment or potentiate specific immune responses to the antigen”. In the proposed project, the target of the screen is the antigen and not a novel adjuvant. Second, the BAA requires that these novel adjuvant candidates are identified through a “High-Throughput Screen”. While the NIAID does not establish a threshold for what constitutes HTS, since it depends on various parameters such as whether random or targeted compound libraries are screened, or whether a primary screen is conducted in vitro or in silico, a primary screen conducted in vivo would not qualify as “high throughput”.

QUESTION/ISSUE 13:

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We are proposing to screen libraries of hydrophobic compounds to promote the formation of antigen particles. Would this approach be responsive to the BAA?

RESPONSE:

If the expected function of lead molecules is to improve the formulation of a vaccine, but the molecule does not have any adjuvant function the proposal would not be responsive.

QUESTION/ISSUE 14:

We are proposing to develop combination adjuvants consisting of an innate immune agonist and a novel modulator of immune function (e.g., inhibitor of downregulatory pathways). Our proposed screen will identify inhibitors which can be paired with immune receptor agonists to tune the adjuvant effect. Would such an approach be responsive to the BAA?

RESPONSE:

Such a proposal would be responsive to BAA NIAID-DAIT-NIHAI201700100, since it meets the definition of adjuvants described in Attachment 4 (Background and Introduction, paragraph

3) of the BAA. Likewise, the BAA specifically supports the use of combination adjuvants which may contain a previously identified immunostimulatory agent as long as one of the compounds in the combination is being identified through the contract program.

QUESTION/ISSUE 15:

We have developed peptides which stimulate specific intracellular innate immune pathways, resulting in enhanced CD4 T cell responses. I would like to propose a project where we synthesize a large library of compounds, which are all derivatives of the core compound mentioned above, to determine their ability to activate the previously identified innate immune pathway and to identify SARs. We already know the MOA but will be looking to optimize the activity.

RESPONSE:

The described screening of compound libraries to identify new potential adjuvant candidates falls within the scope of Study Area 1 and would, therefore, be acceptable. The BAA allows the use of reporter cell lines whereby certain aspects of the MOA of hits would already be known.

Therefore, even though the overall molecular mechanism of the proposed compounds can be predicted, the proposed study would be responsive to the BAA.

QUESTION/ISSUE 16:

We are proposing to establish a signature profile in macrophages that predicts in vivo (long-lasting) immune responses. Would such an approach be responsive to the BAA?

RESPONSE:

In Study Area 1, the BAA requires high-throughput screening of compound libraries (in vitro or in silico) and a confirmatory in vitro assay. Reliable in vitro correlates of adjuvanticity remain elusive and it is the offeror’s responsibility to propose in vitro readouts that are expected to

RFP No.: NIAID-DAIT-NIHAI201700100 Page 6 of 6 translate into in vivo adjuvanticity. In previous iterations of this program, contractors have used for example NFkB-activation in reporter cell lines or the secretion of certain cytokines from cell lines or PBMCs to identify compounds for further analysis. Developing and employing more complex in vitro activation signatures may predict novel adjuvant candidates more reliably and would be an appropriate activity for Study Area 1.

QUESTION/ISSUE 17:

Should we focus on the vaccines specifically identified (pertussis, tetanus, HepB) or is influenza also an option?

RESPONSE:

The main objective of the NIAID Adjuvant Program, which is being renewed through BAA NIHAI201700100, is the identification of novel adjuvant candidates. Study Area 4 requires the in vivo testing of lead adjuvant candidates identified in Study Area 1, “using an experimental or FDA approved preventative or therapeutic vaccine against one or more pathogens relevant to human disease” (see Attachment 5, paragraph 3). Certain pathogens, such as pertussis, were cited to highlight the need for improving even licensed vaccines, but the use of any vaccines against pathogens that causes human disease, and which allow novel adjuvants to be evaluated in an animal model, is acceptable.

QUESTION/ISSUE 18:

Would there be interest in our adjuvant, which is not yet approved?

RESPONSE:

BAA NIHAI201700100 specifically supports work to identify novel adjuvant candidates but does not support work on previously identified adjuvants (see Attachment 5, section (B)). NIAID uses different mechanisms to support the further development of previously identified immunostimulatory compounds including the including the SBIR mechanism. Please see the following new council concept which was approved by the NIAID advisory council in January 2018: Adjuvant Development for Vaccines and for Autoimmune and Allergic Diseases (https://www.niaid.nih.gov/grants-contracts/january-2018-dait-council-approved-concepts#06)

QUESTION/ISSUE 19:

What is the view on collaboration with industry, e.g. to access vaccine antigens such as pertussis or tetanus antigens?

RESPONSE:

We're looking for offerors, with or without collaborators, that have the capabilities to satisfy the research objectives as written in the solicitation.

END OF AMENDMENT NO. 1, NIAID-DAIT-NIHAI201700100