notice_of_intent.pdf

PRE-SOLICITATION NON-COMPETITIVE (NOTICE OF INTENT) SYNOPSIS

INTRODUCTION

THIS IS A PRE-SOLICITATION NON-COMPETITIVE (NOTICE OF INTENT)

SYNOPSIS TO AWARD A PURCHASE ORDER WITHOUT PROVIDING FOR FULL

OR OPEN COMPETITION.

The National Heart, Lung, and Blood Institute (NHLBI), Office of Acquisitions (OA) on behalf of the National Institute of Dental and Craniofacial Research (NIDCR) intends to negotiate and award a purchase order without providing for full and open competition (Including brand-name) to Dr. Perez Riveros, for Professional Services.

NORTH AMERICAN INDUSTRY CLASSIFICATION SYSTEM (NAICS) CODE

The intended procurement is classified under NAICS code 812990, All Other Professional Services, Small Business Size, $8 Million.

REGULATORY AUTHORITY

The resultant contract will include all applicable provisions and clauses in effect through the Federal Acquisition Circular (FAC) 2021-06, effective 07/12/2021.

This acquisition is conducted under the authority of the Federal Acquisition Regulations (FAR) Subpart 13.106-1. (b) Soliciting from a single source. (2) For purchases exceeding the simplified acquisition threshold. The requirements at 13.501(a) apply to sole-source (including brand-name) acquisitions of commercial items conducted pursuant to subpart 13.5.

STATUTORY AUTHORITY

This acquisition is for a commercial item or service and is conducted under the authority of the FAR Subpart 13.5—Simplified Procedures for Certain Commercial Items, section 4202 of the Clinger-Cohen Act of 1966) and the statutory authority of FAR 6.302-1— Only one responsible source and no other supplies or services will satisfy agency requirements 41 U.S.C. 253(c)(1).

DESCRIPTION OF REQUIREMENT

Background Potential mechanisms of immune dysregulation in Sjogren’s Syndrome, pathogenic inflammation and resultant tissue dysfunction and destruction (e.g., salivary glands) are a core research aim of the Salivary Disorders Unit. Pathogenic Type I interferon signaling is implicated in SS and lies downstream to activation of JAK-STAT and cGAS- STING pathways. Uncontrolled Type I interferon signaling results in the recruitment of inflammatory cells, activation of B cells and production of antibodies, and dysfunction and destruction of secretory cells (e.g., the salivary and lacrimal glands). For this requirement, the contractor will develop assays for assessing cGAS-STING pathway activation in subject samples, patient derived primary cells, sera, and peripheral blood mononuclear cells from healthy donors and patients with Sjogren’s Syndrome. Assays will include, but are not limited to, tissue culture and Western immunoblots for phospho- STING, phospho-TBK1, STING and TBK1, as well as, phosho-flow assays and flow cytometry analysis for immunophenotyping healthy volunteers and Sjogren’s Syndrome PBMCs. In vitro, and if viable, in vivo assays testing STING antagonist compounds on patient-derived samples (primary cells, PBMCs) and in mouse models of SS are a logical and clinically relevant continuation of this research. These assays will elucidate the impact of STING antagonism of pathogenic cytokine signaling and the impact on inflammation in systemic and target organs of Sjogren’s Syndrome. Additional assays will include bulk and single cell RNA sequencing and qRT-PCR/droplet digital PCR validation to evaluate expression of inflammatory cytokine signatures in target tissues (e.g., salivary glands) by cell type, and PBMCs, as well as measurement of serum cytokines using multiplex assays. These studies are covered under protocols NCT01425892 and NCT02327884.

Purpose and Objectives The Sjogren’s Syndrome and Salivary Gland Dysfunction Unit of the, Division of intramural Research (DIR), National Institutes of Dental and Craniofacial Research (NIDCR) has a need for the services of an expert scientist who can perform short term primary tissue culture, histology, and assess validation experiments focused on the antagonizing the cGAS-STING pathway. This expertise is necessary in order to expand upon NIDCR current studies in patients suffering from Sjogren’s Syndrome. Primary Sjogren’s Syndrome (pSS) is a systemic autoimmune disorder characterized by exocrine gland dysfunction primarily involving the salivary and lacrimal glands. The histologic hallmark of Sjogren’s Syndrome is a periductal inflammatory infiltrate. The conventional explanation of salivary gland dysfunction assumes a causal relationship between this chronic inflammatory process and the decreased saliva production is limited. Moreover, anti-inflammatory and immunosuppressive treatments have thus far had little effect on saliva production. These may be in part due to upstream or downstream pathway alterations (e.g., activation of cGAS via cytosolic viral nucleic acids). Although various physiologic abnormalities related to inflammatory mediators have been described, none of these satisfactorily explains the SG dysfunction. On the other hand, no study has addressed whether patients with Sjogren’s Syndrome have any intrinsic abnormalities in the salivary gland that may predispose them to SG dysfunction.

Period of Performance Base Year: August 5, 2021 – August 4, 2022 Option Year 1: August 5, 2022 – August 4, 2023 Option Year 2: August 5, 2023 – August 4, 2024 Option Year 3: August 5, 2024 – August 4, 2025

Project Description Scope of Work Contractor Requirements:

The Salivary Disorders Unit investigators propose that STING-mediated inflammation driven by cytoplasmic DNA is hypothesized to play a critical role in the pathogenesis of diseases such as Sjogren’s syndrome. The inhibition of STING and its downstream mediators could ameliorate the symptoms, protect targeted tissues (e.g., salivary and lacrimal glands), and potentially slow disease progression in a subset of Sjogren’s syndrome patients demonstrating a significant type I interferon response.

In this requirement, the primary objective of this project is to validate gene expression, autoantibodies, and somascan analyte detection assay results on patient samples. This will initially require extensive review of the collected data followed by assay design, validation, and testing.

Minor salivary glands represent an accessible primary tissue for analysis of the effect of AQP1 expression on recovery of gland function. This analysis will identify biomarkers that can be used in the identification of mechanism of response as well as those patients who might benefit from this therapeutic approach.

Specific Tasks:

i. Measure STING pathway activation in cells/tissues of patients diagnosed with Sjogren’s syndrome compared to healthy controls, to do this we plan to assess activation of the STING pathway by immunoblotting and immunofluorescent confocal microscopy for phospho-STING, STING, phospho-TBK1 and TBK1, phospho-IRF3 and IRF3, DDX41 in Sjogren’s syndrome patient-derived primary cells and tissues.

ii.To correlate with target activation, we will measure the presence of mitochondrial DNA in the plasma using ddPCR/qRT-PCR or detection of 2’,3’-cGAMP by LC-MS/MS.

An general cytokine profile in plasma/serum evaluation of the cytokine levels will be performed using ELISAs/Somalogic/ and/or other multiplexed proteomics platforms. The expression of signature cytokine genes in peripheral blood cells and/or glandular tissue using qRT-PCR or RNA-sequencing

Deliverables

• The contractor’s work will be reviewed weekly for appropriate progress and accuracy of the data.

• Research data, including results obtained through the process, as well as other relevant patient data, will be collected and maintained on a daily basis in the lab on-site in Building 10. The completed final summary must be submitted within thirty days after one-year period ends

• The contractor may be required to present findings at scientific meetings on behalf of the Salivary Disorders Unit. This deadline may be extended at the discretion of Dr. Blake M. Warner, Salivary Disorder Unit, DIR, NIDCR by arrangement prior to the due date.

Required Skills and Qualifications

1. The contractor is preferred to have a PhD in Biomedical Science and understanding of molecular biology, histology, PBMCs culture and analysis, NGS, SomaScan data processing, and Sjogren’s Syndrome and signaling pathway analysis.

2. The contractor should have extensive experience in the area of gene expression analysis, and histological analysis of salivary glands as well as establishing short term primary cultures of salivary glands, PBMCs and an experience in signal transduction in the salivary gland.

3. The contractor should have a background in industry for management of clinical data and immunology/ autoimmunity viral biology in SG. Experience in industry is beneficial.

4. The Contractor should have a demonstrated record of publications in peer reviewed scientific journals.

Location of Services Salivary Disorder Unit lab space

NIH/NIDCR

10 Center Dr.

Bethesda, MD 20892

CONTRACTING WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION

(INCLUDING BRAND-NAME) DETERMINATION

The determination by the Government to award a contract without providing for full and open competition is based upon the market research conducted as prescribed in FAR Part 10—Market Research.

The determination by the Government to make a single-sole source is based upon the market research conducted as prescribed in FAR Part 10-Market Research. The results of the market research concluded that Dr. Perez Riveros has the background, knowledge and experience needed for this research project. Dr. Perez Riveros obtained her PhD in Biomedical sciences in 2007 from the University of Chile and post-doctoral work at the National Institutes of Health in 2015. During her post-doctoral training Dr.

Perez Riveros gained extensive experience in gene expression, and histological analysis of salivary glands as well as establishing short term primary cultures. Since completing post-doctoral training Dr. Perez Riveros has gained an extensive background in industry for the production of recombinant gene transfer vectors. Dr.

Perez Riveros' background and experience fits well with the needs of our current research project as a contractor. Dr. Perez Riveros previously provided this service to NIDCR in 2019 and 2020 which was under 75N92019P00306.

CLOSING STATEMENT

This synopsis is not a request for competitive proposals. However, interested parties may identify their interest and capability to respond to this notice. Responses to this notice shall contain sufficient information to establish the interested parties’ bona-fide capabilities for fulfilling the requirement and include: unit price, list price, shipping and handling costs, the delivery period after contract award, the prompt payment discount terms, the F.O.B. Point (Destination or Origin), the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.”

A determination by the Government not to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government. The information received will normally be considered solely for the purposes of determining whether to proceed on a non-competitive basis or to conduct a competitive procurement.

All responses must be received by 07/27/2021 at 12:00pm EST. Responses must be submitted via the FedConnect webportal (www.fedconnect.net). Potential Offerors do not need to register to view a notice; however, in order to submit questions and/or response to this Notice, an account will need to be established. Should you require a waiver not to use FedConnect, please contact the Contracting Officer listed in this notice.

http://www.sam.gov/ http://www.fedconnect.net/

“All responsible sources may submit a capability statement, proposal, or quotation, which shall be considered by the agency.”