75N95024Q00142

NOTICE OF INTENT to Sole Source

INTRODUCTION

THIS IS A PRE-SOLICITATION NON-COMPETITIVE (NOTICE OF INTENT) SYNOPSIS TO AWARD A CONTRACT WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME). 

 The NCATS Early Translation Branch (ETB) collaborates with investigators at NIH and in the academic, biopharmaceutical and nonprofit sectors to generate probes for studying a diverse cross-section of human biology, focusing specifically on new targets and untreatable diseases. This requisition is to procure ALT Liver Assay in Liver Spheroids to evaluate the liver toxicity associated with the systemic administration of antisense oligonucleotides (ASOs) in a mouse animal model. The project's primary goal is to develop a predictive model of candidate ASO therapies' safety and acute toxicity. It is routinely used in ETB for high number or limited amount of samples.

NORTH AMERICAN INDUSTRY CLASSIFICATION SYSTEM (NAICS) CODE and SET ASIDE STATUS

The intended procurement is classified under NAICS code 325414 Biological Product (except diagnostic) manufacturing with a Size Standard of 1,250 Employees.  

REGULATORY AUTHORITY 

This acquisition is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13—Simplified Acquisition Procedures. Contracts awarded using FAR Part 13—Simplified Acquisition Procedures are exempt from the requirements of FAR Part 6—Competition Requirements. FAR Subpart 13.106-1 (b) Soliciting from a single source provides that: For purchases not exceeding the simplified acquisition threshold, Contracting Officers may solicit from one source IF the contracting officer determines that the circumstances of the contract action deem only one source reasonably available (e.g., urgency, exclusive licensing agreements, brand-name OR industrial mobilization).

The resultant contract will include all applicable provisions and clauses in effect through the Federal Acquisition Circular (FAC) 2023-04 dated June 2, 2023.

DESCRIPTION OF REQUIREMENT

PURPOSE AND OBJECTIVES:

This requisition establishes a contract to evaluate the liver toxicity associated with the systemic administration of antisense oligonucleotides (ASOs) in a mouse animal model. The project's primary goal is to develop a predictive model of candidate ASO therapies' safety and acute toxicity.

The National Center for Advancing Translational Sciences (NCATS) focuses on treating rare diseases. A significant emphasis of NCATS is the rapid development of effective therapies for patients diagnosed with these conditions. Although each condition is individually rare, cumulative rare diseases lead to considerable morbidity and mortality among the American population. NCATS is directly addressing this problem by discovering new technologies and other approaches, such as ASO therapies, that could significantly accelerate developing and deploying solutions that all translational researchers can use.

The most significant bottleneck in terms of time and cost of ASO drug development is the animal toxicology experiments requested by the FDA. Having faster and cheaper screening methods for toxicology would address this critical issue. To facilitate the development of therapeutic ASOs, NCATS aims to develop streamlined and low-cost predictive toxicology assays for N=1 ASOs. These screening platforms rely on iPS cell cultures, organoids, and tissue bio-printing to predict the toxic side effects of ASOs and improve the safety pharmacology of this drug class. A parallel focus of our effort is to develop algorithms that predict toxicity, allowing toxic ASOs to be eliminated in the design phase. In this way, we aim to make developing disease-modifying therapies for rare diseases cheaper and faster by decreasing the burden of regulatory approval.

Our efforts use the 20-mer gapmer ASOs with phosphorothioate backbones and 2'-O-methoxyethyl-RNA (2'-MOE) modifications. We now want to validate these cell-based screening methods in animal models. This contract aims to provide sufficient and confirmatory in vivo data to the point that the FDA accepts cell-based in vitro data in place of conventional animal toxicology studies.

NCATS is seeking technical support to evaluate the safety and acute liver toxicity of candidate ASOs in mice. The results from these studies, in conjunction with existing cell-based assays, will help better predict the safety of future candidate ASOs intended for clinical use.

This contract aims to determine if the 3D Insight liver spheroids developed by InSphero can predict the hepatic cytotoxicity of ASOs. The studies are designed to characterize the assay. These studies will use a set of ASOs known to be hepatotoxic in humans or rodents (hepatotoxic ASOs) and a group of ASOs that show no hepatotoxicity in humans or rodents (safe ASOs). This project will generate proof-of-concept data.

The contractor will test each ASOs on multi-donor human, rat (Sprague Dawley) and mouse (C57/BL6) 3D Insight liver spheroids.

The contractor will analyze the data to determine if the 7-day assay is sufficient to predict the known toxicity of the ASO (hepatoxic or safe). The analysis will establish the cellular ALT and the highest non-toxic concentration of each ASO. An analysis will be conducted to identify transcriptomic signatures of hepatotoxic ASOs. The data from the human, rat, and mouse 3D Liver Microtissue assays will be compared.

CONTRACTING WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME) DETERMINATION

Non-Competitive (Single-sole Source (Including brand-name) Determination:

This notice of proposed acquisition is posted as an intent to award a purchase order on a non-competitive basis to InSphero INC. 74 Orion Street, Brunswick, ME 04011, USA

The Non-Competitive (Single-sole Source (Including brand-name) Determination is based upon the market research conducted. Specifically, only one source is capable of providing the supplies or services required pursuant to FAR 13.106-1(b)(1)(i), only one source is reasonably available.

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. 

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

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 Unique Entity ID (UEI), 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.

All responses must be received by the closing date and time of this announcement and must reference the solicitation number 75N95024Q00142. Responses must be submitted electronically to Giuliana Faller, Contract Specialist, at giuliana.faller@nih.gov. U.S. Mail and fax responses will not be accepted.