Development and Characterization of an NGLY1 Deficiency Disorder Human-on-a-Chip Model

NON-COMPETITIVE
COMBINED SYNOPSIS / SOLICITATION

Title: Development and Characterization of an NGLY1 Deficiency Disorder Human-on-a- Chip Model

(i) This is a combined synopsis/solicitation for commercial items prepared in accordance with the format in Subpart 12.6 as supplemented with additional information included in this notice. This announcement constitutes the only solicitation; proposals are being requested and a written solicitation will not be issued.

(ii) The solicitation number is 75N95019Q00284 and the solicitation is issued as an request for quotation (RFQ).

This acquisition is for a commercial item or service and is conducted under the authority of the Federal Acquisition Regulation (FAR) Part 13-Simplified Acquisition Procedures and FAR Part 12-Acquisition of Commercial Items, and is not expected to exceed the simplified acquisition threshold.

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

The National Institute on Drug Abuse (NIDA), NIDA Office of Acquisitions - NCATS Section, on behalf of the National Center for Advancing Translational Sciences (NCATS), intends to negotiate and award a purchase order without providing for full and open competition (including brand-name) to Hesperos, Inc. 3259 Progress Drive #158, Orlando, FL 32826 for development and characterization of an NGLY1 deficiency disorder human-on-a-chip model.

This acquisition is conducted as non-competitive for a commercial item or service and is conducted under the authority of the FAR Subpart 13.5-Simplified Procedures for Certain Commercial Items and 13.501 Special documentation requirements and the authority of 41 U.S.C. 1901 and the FAR Subpart 13.106-1(b) Soliciting from a single source.

Pursuant to FAR Subpart 13.501 (a) (1) (iv) the rationale for the brand name justification is that Hesperos, Inc. possesses a fee-for-service technology able to differentiate patient-derived iPS cells to motor neurons, then test their unique neuromuscular junction (NMJ) two-organ model. This technology produces a functional muscular system, which can then be used to evaluate the effectiveness of drug treatment to the system. This patient-derived human disease model of the NMJ is critical to the TDB's NGLY1 project.

(iii) The solicitation document and incorporated provisions and clauses are those in effect through Federal Acquisition Circular 2019-02, dated May 6, 2019.

(iv) The associated NAICS code is 541714 and the small business size standard is 1000 employees. No set-aside restriction is applicable.

(v) The Therapeutic Development Branch (TDB) biology program's mission is to encourage and speed the development of new treatments for diseases with high-unmet medical needs. N-glycanase 1 (NGLY1) deficiency is an ultra-rare, multi-system disease characterized by neurological disorders. To study the pathophysiology of this disease and to facilitate therapeutic development, the TBD has generated induced pluripotent stem cells (iPSCs) from NGLY1 patient fibroblasts as a disease model.

The work completed as part of this solicitation will characterize the morphology and physiology of the diseased iPSC motor neurons compared to the wild type iPSC motor neurons, as well as test each line for neuromuscular junction formation and physiology. This work will be completed using the multi-organ, human-on-a-chip screening platform. This highly customizable model will enable the TBD to use its patient-derived iPSC and create a precise model for a rare disease.

(vi) Specific Requirements:

1. Summary:
Contractor will receive 4 lines of frozen iPSCs, provided by TDB biology, that were derived from patients with a NGLY1 deficiency disorder:
iPSC Lines (To be provided to contractor by NCATS TBD program):
1. Wild Type (WT) Control
2. Isogenic NGLY1 knockout
3. NGLY1 patient 1 sample
4. NGLY1 patient 2 sample

2. Shipping:
Cells will be shipped to contractor from NCATS via FedEx overnight shipping on dry ice. The program is responsible for sample/package preparation. TDB POC will inform vendor POC via email when cells have been shipped out. Upon receiving iPSCs lines, vendor will inspect vials and make certain cells arrive in proper conditions and will take necessary steps for proper storage of cells until project start date.

3. Project:
Project will be divided into two main phases followed by statistical analysis with specific steps outlined below:

Milestone 1: Characterize the morphology and physiology of the diseased iPSC-MNs compared to the WT iPSC-MNs:
1. Phase imaging
a) Contractor will look for axonal varicosities (protein agglomeration) using phase contrast microscopy
b) Specific differences in morphology, e.g. axon length and axon branching

2. Immunocytochemistry
a) Contractor will look for axonal varicosities (protein agglomeration) using confocal microscopy
i. Neurofilament or β-III tubulin
ii. Islet-1 (MN specific marker)
b) Specific differences in morphology, e.g. axon length and axon branching

3. Patch-clamp electrophysiology
a) Ion channel currents (Including Na+ and K+)
b) Single firing or repetitive firing action potential waveform

Milestone 2: Test each line for neuromuscular junction formation and physiology:
Determine the effects of NGLY1 deficiency on neuromuscular junction (NMJ) formation, stability and physiology (synchronous muscular contraction at increasing MN stimulation frequencies) in diseased iPSC-MN NMJ systems compared to WT control iPSC-MN NMJ systems.
NMJ system analysis:
1. Test ability to form NMJs by measuring the number of NMJs formed: total number of NMJs in each system.
2. Stability of NMJs: NMJ stability is defined as the ratio of total number of NMJs per system post-stimulation to the number of NMJs pre-stimulation.
3. Synchronous firing of a specific NMJ: One NMJ tested at five different frequencies (0.3, 0.5, 1, 2, and 4 Hz). The percentage of successful muscle contractions driven by electrically-induced MN action potential generation will be quantified.
4. Characteristic morphology of NMJs determined by immunocytochemistry
i. Acetylcholine receptor clustering (alpha-bungarotoxin) and colocalization with MN axons visualized by neurofilament (NF-H) staining

Statistical analysis:
The data generated will be analyzed using a multiple comparison test to determine statistical significance of changes in mutated lines compared to each other for degree of severity as well as to control. Subsequent analytical tests will be run to determine the significance of changes between groups.

4. Support:
Contractor scientists will be available to consult with TDB scientists throughout the project period. Support will be provided by email, phone, or web meeting per the sponsor preference.

LEVEL OF EFFORT:
• Milestone 1: 2-4 weeks
• Milestone 2: 8-12 weeks
• Statistical Analysis: 1-2 weeks

Government Responsibilities
Government will be responsible for providing the iPSCs lines that will used for this project.

Data Rights
All data used and analyzed is sole property of the government. Contractor has no right to any analyzed iPSCs lines provided by TDB.

Delivery or Deliverables
Statistical Analysis:
The data generated will be analyzed using a multiple comparison test to determine statistical significance of changes in mutated lines compared to each other for degree of severity as well as to control. Subsequent analytical tests will be run to determine the significance of changes between groups.

(vii) Delivery shall be to:

The National Center for Advancing Translational Sciences (NCATS)
9800 Medical Center Drive
Rockville, MD 20850

Delivery shall be 120 days ARO.

(viii) The provision at FAR clause 52.212-1, Instructions to Offerors - Commercial Items, applies to this acquisition.

(ix) Offers will be evaluated for technical criteria, price, and past performance. Technical criteria consist of matching the line items identified above. Technical and past performance, when combined, are significantly more important than price.

OR The provision at FAR clause 52.212-2, Evaluation - Commercial Items, applies to this acquisition.

(a) The Government will award a contract resulting from this solicitation to the responsible offeror whose offer conforming to the solicitation will be most advantageous to the Government, price and other factors considered. The following factors shall be used to evaluate offers:

(i) technical evaluation criteria and/or technical capability of the item offered to meet the Government requirement
(ii) price
(iii) past performance [see FAR 13.106-2(b)(3)]

Technical and past performance, when combined, are significantly more important than cost or price.

(b) Options. The Government will evaluate offers for award purposes by adding the total price for all options to the total price for the basic requirement. The Government may determine that an offer is unacceptable if the option prices are significantly unbalanced. Evaluation of options shall not obligate the Government to exercise the option(s).

(c) A written notice of award or acceptance of an offer, mailed or otherwise furnished to the successful offeror within the time for acceptance specified in the offer, shall result in a binding contract without further action by either party. Before the offer's specified expiration time, the Government may accept an offer (or part of an offer), whether or not there are negotiations after its receipt, unless a written notice of withdrawal is received before award.

(x) Offerors are to include a completed copy of the provision at FAR clause 52.212-3, Offeror Representations and Certifications-Commercial Items, with offers.

(xi) The FAR clause at 52.212-4, Contract Terms and Conditions - Commercial Items, applies to this acquisition. The following addendum applies:

SOLICITATION PROVISIONS INCORPORATED BY REFERENCE (FEB 1998)

This solicitation incorporates one or more solicitation provisions by reference, with the same force and effect as if they were given in full text. Upon request, the Contracting Officer will make their full text available. The offeror is cautioned that the listed provisions may include blocks that must be completed by the offeror and submitted with its quotation or offer. In lieu of submitting the full text of those provisions, the offeror may identify the provision by paragraph identifier and provide the appropriate information with its quotation or offer. Also, the full text of a clause may be accessed electronically at these addresses:

For FAR clauses: https://www.acquisition.gov/browsefar

For HHSAR clauses: https://www.hhs.gov/grants/contracts/contract-policies-regulations/hhsar/index.html

(end of clause)

The following FAR provisions or clauses are incorporated by reference:

52.204-7, System for Award Management (Oct 2018)
52.204-13, System for Award Management Maintenance (Oct 2018)
52.204-16, Commercial and Entity Code Reporting (Jul 2016)
52.204-18, Commercial and Entity Code Maintenance (Jul 2016)

52.212-4(g), Invoice, is supplemented by the NIH Invoice and Payment Instructions (2/2014).

(xii) FAR clause at 52.212-5, Contract Terms and Conditions Required to Implement Statutes or Executive Orders-Commercial Items, applies to this acquisition.

52.204-10 Reporting Executive Compensation and First-Tier Subcontract Awards (Oct 2018) (Pub. L. 109-282) (31 U.S.C. 6101 note).
52.219-28 Post Award Small Business Program Representation (Jul 2013) (15 U.S.C. 632(a)(2))
52.222-3 Convict Labor (June 2003)
52.222-19 Child Labor-Cooperation With Authorities and Remedies (Jan 2018)
52.222-21 Prohibition of Segregated Facilities (Apr 2015)
52.222-26 Equal Opportunity (Sep 2016)
52.222-36 Equal Opportunity for Workers With Disabilities (Jul 2014)
52.222-50 Combating Trafficking in Persons (Mar 2015)
52.223-18 Encouraging Contractor Policies to Ban Text Messaging While Driving (Aug 2011)
52.225-13 Restrictions on Certain Foreign Purchases (June 2008) (E.O.'s, proclamations, and statutes administered by the Office of Foreign Assets Control of the Department of the Treasury)
52.232-33 Payment by Electronic Funds Transfer-- System for Award Management (Jul. 2013)

(xiii) There are no additional contract requirement(s) or terms and conditions applicable to this acquisition.

(xiv) The Defense Priorities and Allocations System (DPAS) are not applicable to this requirement.

(xv) 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 solicitation must include sufficient information to establish the interested parties' bona-fide capabilities of providing the product or service.

The price quote shall include: unit price, list price, shipping and handling costs, delivery days after contract award, delivery terms, prompt payment discount terms, F.O.B. Point (Destination or Origin), product or catalog number(s); product description; and any other information or factors that may be considered in the award decision. Such factors may include: past performance; special features required for effective program performance; trade-in considerations; probable life of the item selected as compared with that of a comparable item; warranty considerations; maintenance availability; and environmental and energy efficiency considerations.

Respondents that believe that they are manufacturers or authorized resellers of the brand-name product specified in this announcement must provide, as part of their response: (a) product, catalog, model, and/or part number(s); (b) product description; (c) all relevant information and documentation that the item(s) offered meets the salient physical, functional, or performance characteristics as specified in the purchase description; quantity; estimated price or cost; shipping, handling, and/or installation charges; and delivery date after receipt of order.

In addition, the Dun & Bradstreet Number (DUNS), the Taxpayer Identification Number (TIN), and the certification of business size must be included in the response. All offerors must have an active registration in the System for Award Management (SAM) www.sam.gov.

A determination by the Government whether to compete this proposed contract based upon responses to this notice is solely within the discretion of the Government. Information received will be considered to determine whether to proceed on a non-competitive basis as indicated above, or to conduct a competitive procurement.

All responses must be received by August 15th, 2019 at 5:00pm, Eastern Standard Time and reference solicitation number 75N95019Q00284. Responses must be submitted electronically to Jessica Adams at jessica.adams@nih.gov.

Fax responses will not be accepted.

(xvi) The name and email address of the individual to contact for information regarding the solicitation: Jessica Adams at jessica.adams@nih.gov.

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