75N950-19R-00004_-_Ammendment_1_signed.pdf

OMB No. 0990-0115 AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT 1. CONTRACT ID CODE PAGE OF PAGES

1 8

2. AMENDMENT/MODIFICATION NO. 3. EFFECTIVE DATE 4. REQUISITION/PURCHASE REQ. NO. 5. PROJECT NO. (If applicable)

01 See Block 16C

6. ISSUED BY CODE tc 7. ADMINISTERED BY (If other than Item 6) CODE

National Institute on Drug Abuse, NIH NIDA Section, Contracts Management Branch Blue Office of Acquisition, NIDA 6001 Executive Blvd, Room 4211 - MSC 9559 Bethesda, MD 20892-9559

8. NAME AND ADDRESS OF CONTRACTOR (No., street, county, State and ZIP Code)

To All Potential Offerors

9A. AMENDMENT OF SOLICITATION NO.

75N950-19R-00004

9B. DATED (SEE ITEM 11)

March 21, 2019

10A. MODIFICATION OF CONTRACT/ORDER NO.

10B. DATED (SEE ITEM 13)

CODE FACILITY CODE

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

Offers must acknowledge receipt of this amendment prior to the hour and date specified in the solicitation or as amended, by one of the following methods:

(a) By completing Item 8 and 15, and returning 1 copies of the amendment; (b) acknowledging receipt of this amendment on each copy of the offer submitted; or (c) By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDG- MENT TO BE RECEIVED AT THE PLACE DESIGNATED FOR RECEIPT OF OFFERS PRIOR TO THE HOUR AND DATE SPECIFIED MAY RESULT IN REJECTION OF YOUR OFFER. If by virtue of this amendment you desire to change an offer already submitted, such change may be made by telegram or letter, provided each telegram or letter makes reference to the solicitation and this amendment, and is received prior to the opening hours and date specified.

12. ACCOUNTING AND APPROPRIATION DATA (If required)

13. THIS ITEM APPLIES ONLY TO MODIFICATIONS OF CONTRACTS/ORDERS,

IT MODIFIES THE CONTRACT/ORDER NO. AS DESCRIBED IN ITEM 14.

A. THIS CHANGE ORDER IS ISSUED PURSUANT TO: (Specify authority) THE CHANGES SET FORTH IN ITEM 14 ARE MADE IN THE CONTRACT/ORDER NO. IN ITEM 10A.

B. THE ABOVE NUMBERED CONTRACT/ORDER IS MODIFIED TO REFLECT THE ADMINISTRATIVE CHANGES (such as changes in paying office, appropriation data, etc.) SET FORTH IN ITEM 14, C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF:

D. OTHER (Specify type of modification and authority)

E. IMPORTANT: Contractor is not, is required to sign this document and return copies to the issuing office.

14. DESCRIPTION OF AMENDMENT/MODIFICATION (Organized by UCF section headings, including solicitation/contract subject matter where feasible.)

PURPOSE: To amend the Request for Proposal (RFP) to incorporate responses to Offerors’ questions and to update clauses in Section C. All other terms and conditions of the RFP remain unchanged.

Proposal Due Date: Monday, April 22, 2:00 PM EST (Unchanged)

Note: the Offeror should acknowledge on the cover page or first page of its business and technical proposals receipt of the RFP and this Amendment.

Except as provided herein, all terms and conditions of the document referenced in Item 9A or 10A, as heretofore changed, remains unchanged and in full force and effect.

15A. NAME AND TITLE OF SIGNER (Type or print) 16A. NAME AND TITLE OF CONTRACTING OFFICER (Type or print)

Lisa Bielen, Contracting Officer, NIDA Section, CMB Blue

15B. CONTRACTOR/OFFEROR 15C. DATE SIGNED 16B. UNITED STATES OF AMERICA 16C. DATE SIGNED

(Signature of person authorized to sign) (Signature of Contracting Officer)

NSN 7540 - 01 - 152 – 8070 STANDARD FORM 30 (REV. 10-83)

PREVIOUS EDITION UNUSABLE Prescribed by GSA

FAR (48CFR) 53.243

The above numbered solicitation is amended as set forth in Item 14. The hour and date specified for receipt of Offer is extended is not extended.

Title: Medication Discovery Using Rat Models of Relapse RFP No. 75N950-19R-00004

Request for Proposal (RFP) No. 75N950-19R-00004 is amended as follows:

PURPOSE: The purpose of this amendment is to: (1) include questions from offerors and responses in reference to the solicitation and (2) to update Article C.1. Statement of Work in accordance with Attachment 1 of this amendment.

QUESTIONS/ANSWERS

1. Question: What is the federal government’s current full time equivalent for person hours per year? Based on the language describing the options, it appears that the level is now 2000 hours per year. Is that correct?

Response: Offerors should propose personnel hours based on their determination of the requirements for performance of the Statement of Work, and their own internal policies regarding hours/level of effort.

2. Question: It is unclear to me whether this type of contract requires a flat budget from Year 1 through Option Years 2-4. Is cost escalation across years permitted under this contract?

Response: As the type of award contemplated is a cost-type contract, Offerors should propose costs based on their own business judgement and anticipated costs for performance of the requirements of the Statement of Work.

3. Question: The number of person hours specified is 12,784. Was this a misprint in that the 2014 RFP that could be considered the predecessor to this RFP specified nearly 1000 hours more (13,724) and the demands on throughput were less (10-30 compounds/yr vs 15-30 compounds/yr)?

Response: Task 1 of the Statement of Work should state that NIDA anticipates the contractor shall evaluate between 10-30 compounds per year. (See Task 1 of amended Statement of Work, attached below.)

However, NIDA does not anticipate, nor should the Offeror’s proposal assume, that the number of compounds to be evaluated under Task 1 will always be at the minimum of this range.

The Government provides an estimate as to the level of effort required to perform the work as specified (12,784 hours) for the base period and option periods (if exercised) to aid in proposal preparation based on its own judgement of direct labor requirements for performance of the Statement of Work. The exact number of hours proposed by the Offeror should be determined by their technical approach.

ARTICLE C.1. STATEMENT OF WORK, is superseded in whole as follows:

a. Independently and not as an agent of the Government, the Contractor shall be required to furnish all the necessary services, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government, as needed to perform the Statement of Work, below:

I. BACKGROUND INFORMATION

This contract supports the NIDA Addiction Treatment Discovery Program, providing for the in vivo evaluation, in rodents, of potential pharmacotherapies that would specifically prevent relapse to cocaine and other drugs of abuse. It also provides support for the development of methods and protocols to be used for compound evaluation including drug self-administration.

The Addiction Treatment Discovery Program was originally focused on the discovery and development of treatments that will produce two specific types of clinical effects. The first, agonist-type therapy, is based on the successful use of this type of treatment approach in the treatment of smokers (nicotine replacement) and heroin users (methadone and buprenorphine). The second, antagonist or blocking-type therapy, is based on successful use of this strategy for opiates (naltrexone). An existing set of other NIDA contracts support screening measures (locomotor activity, drug discrimination, and self-administration) that have been successful in identifying lead compounds for these two types of medications, some of which will be further evaluated for clinical efficacy.

However, there exists another identified clinical need in addition to agonist and antagonist therapy, and that is the need for medications to prevent relapse. Whereas it is possible that agonist/antagonist type medications may prevent craving and subsequent relapse to cocaine use, there now exist more advanced behavioral screens, using reinstatement of extinguished drug self-administration in models of relapse, which may prove useful in identifying additional medications. Such a screen incorporates several clinically relevant aspects of relapse, including exposure to stressors, exposure to cues associated with the drug, and exposure to low doses of the drug itself. Use of these relapse models may permit the discovery of medications that differ from agonist/ antagonist types of medications, and may include anxiolytics, antidepressants, and potential treatments with other non-dopaminergic mechanisms of action. As such, this project represents an important addition to the capabilities of the Addiction Treatment Discovery Program. In addition, NIDA wishes to continue its expansion of contract capabilities to enable use of models of relapse to other drugs of abuse (such as but not limited to methamphetamine, nicotine, opioids, and marijuana). This testing represents an essential component of the Division's medication development efforts; the resulting data guide decisions regarding advancement of compounds to preclinical safety evaluations and eventual clinical trials.

The NIDA Division of Therapeutics and Medical Consequences (DTMC) established a policy to encourage chemists and pharmaceutical companies to take part in NIDA's preclinical medication discovery programs, including the Addiction Treatment Discovery

Program. The policy provides that those who submit compounds to NIDA for evaluation in the programs have all rights to publish data generated on their compounds. NIDA sends the compounds, hereafter referred to as "test compounds," to NIDA testing sites in a blinded fashion. NIDA does not provide the identity of test compounds to the testing sites, but instead, provides only essential compound information, such as storage, solubility, and doses. Because the selected Contractor will serve as a testing site for the NIDA Addiction Treatment Discovery Program, it is unlikely that NIDA will allow the Contractor to publish any test compound data created under this contract. However, the Contractor may publish data created during the course of evaluating "standard compounds." Standard compounds are those compounds obtained directly by the Contractor for evaluation under the contract, with the resulting data available for immediate release to NIDA and the scientific community.

II. OBJECTIVES

In brief, the objectives of this contract are to determine the in vivo efficacy of novel compounds in animal models of relapse. This includes the following tests in animals trained to self-administer cocaine or other drugs of abuse;

(1) the ability of a test compound to block or reduce footshock- or other stressor-induced reinstatement of responding after a period of experimental extinction;

(2) the ability of a test compound to block or reduce drug-priming-induced reinstatement of responding after a period of extinction; and

(3) the ability of a test compound to block or reduce the effects of a conditioned cue (previously paired with drug) to reinstate responding for the training drug after a period of extinction.

An integral part of this work is to develop methods and to design and implement protocols for the evaluation of test compounds. A number of laboratories have used some of the methodologies described in the literature. While recognizing the need for methods development, NIDA anticipates that by Option Period 1, if Options are exercised, the majority of the Contractor's efforts will be devoted to test compound evaluations. The Contractor shall identify and acquire standard compounds that merit the aforementioned types of evaluation. In addition, if NIDA exercises specific contract options, this contract shall support follow-up rodent pharmacology studies of compounds identified as promising potential drug-dependence treatment agents including through the use of drug self-administration studies. The details of these latter studies cannot be specified before contract award; they will depend upon specific successes in NIDA's medication discovery efforts and scientific advances in the general field of drug abuse research. Written reports documenting the study findings are the anticipated end products of this contract.

III.Services to be Performed

A. GENERAL REQUIREMENTS

1. Independently, and not as an agent of the Government, the Contractor shall furnish all necessary labor, materials, supplies, equipment, and services (except as otherwise specified herein) and perform the work set forth below.

2. The Contracting Officers Representative (COR) will monitor all work under this contract.

B. SPECIFIC REQUIREMENTS

During the effective period of this contract Years 1 through 5 (if Options are exercised), the Contractor shall perform the work described in Tasks 1 through 5.

TASK 1. As directed by the NIDA COR, the Contractor shall devote up to 12,784-person hours per year to evaluating the efficacy of compounds in one or more models of relapse to drug self-administration. In these models, the Contractor shall train rats to self-administer cocaine (or another drug of abuse specified by the NIDA COR, for example, methamphetamine, nicotine, opioids, or THC) at stable levels.

Following training, the contractor will extinguish, and then reinstate the behavior using a stimulus that reliably reinstates the self-administration behavior. The Contractor shall develop standard protocols and characterize them with standard compounds. The Contractor will then utilize the standard protocols for evaluating the effects of test compounds on the ability of three types of stimuli to produce reinstatement. These stimuli are 1) a priming dose of the training drug,

2) exposure to a laboratory stressor, and 3) exposure to a drug-associated cue. The Contractor shall devote at least 24 chambers to this work if rats have additional "home" cages, or at least 36 chambers if rats will dwell in the test chambers. For those compounds specified by the NIDA COR, the Contractor shall also evaluate effects of test compounds on rats trained to respond for an alternative reinforcer (for example, food) under a procedure similar to that utilized for drug self-administration. NIDA anticipates that this latter testing will be required only for a limited number of compounds because this work is currently being conducted under another contract. The Contractor shall compare each dose of a compound to its vehicle with regard to its ability to prevent or reduce reinstatement of responding for drug or its ability to impair responding on the non-active lever. Unless otherwise directed by the NIDA COR, the Contractor shall use a minimum of 12 rats to evaluate the effects of each dose of compound under study. The specific details of each protocol, the specific compounds to be evaluated (standard compounds as well as test compounds), and the doses of each compound that the Contractor utilizes are subject to the approval of the NIDA COR. The NIDA COR shall specify the route of administration that the Contractor shall use for each test compound. Occasionally, the Contractor shall administer a test compound by oral gavage, if so directed by the NIDA COR. Although it is probable that the contract will require reinstatement studies involving cocaine, it is also possible that the Contract will require the development and utilization of similar reinstatement protocols for self-administration of another drug of abuse, such as but not limited to methamphetamine, nicotine, opioids, or THC.

The Contractor shall utilize protocols using drugs of abuse other than cocaine if directed by the NIDA COR. The Contractor shall blind the identity of all standard compounds under evaluation to those who are conducting the assays. NIDA recognizes the specific details of the reinstatement protocols adopted for this contract will influence the maximum number of compounds that the Contractor can evaluate using the operant chambers specified in this Task. Depending on the type(s) of reinstatement models in which the Contractor evaluates each compound and the final details of each protocol, NIDA anticipates that the contractor will evaluate 10 to 30 compounds per year. For each standard compound or test compound evaluated, the contractor shall prepare a Compound Evaluation Report.

TASK 2. Approximately every twelve months, the Contractor shall attend a meeting (up to two days) with NIDA staff and possibly as many as six consultants to review past, current, and future work under this contract. Prior to each meeting, the Contractor shall prepare and organize "pre-meeting packets" in 4 sections. Section 1 shall have a summary of all data presented and a description of relevant methods.

Section 2 shall provide a summary of all problems encountered when implementing the tasks required by the contract, as well as suggested solutions for those problems. Section 3 shall include proposals for improving or expanding protocols utilized for Task 1 evaluations.

Section 4 shall suggest compounds for potential evaluation under the contract and suggested doses to be evaluated for each compound. If so requested by the NIDA COR, methods included in Section 1 shall be in a research protocol format, with a description of each testing type. The Contractor shall provide this information (the pre-meeting packets) to the consultants and the NIDA COR at least two weeks in advance of the meeting. The Contractor shall present this information at the meeting and subsequently prepare a "meeting report" to summarize and synthesize the results of the meeting, including specific consultant recommendations. During the meeting, the Contractor shall obtain consultant suggestions regarding additional compounds that may merit evaluation under the contract and, by a method approved by the NIDA COR, use the consultants to prioritize the compounds suggested for each task. The Contractor shall include the resulting prioritized compound lists in the meeting report. In most cases, the meeting site is in the Washington, D.C. area. However, in some special circumstances the NIDA COR may designate another meeting site, such as at a professional meeting (e.g., a College on Problems of Drug Dependence meeting, a Society for Neuroscience meeting, etc.). NIDA will reimburse the Contractor's travel expenses (up to four people) to all consultant meetings in accordance with federal travel regulations.

Following each meeting, the NIDA COR shall approve a specific list of compounds for the Contractor to acquire. The Contractor shall attempt to obtain and evaluate those compounds. The Contractor shall not attempt to obtain any compounds for evaluation under this contract without approval of the NIDA COR. Throughout the life of the contract, the NIDA COR shall arrange for blinded test compounds to be sent to the Contractor for evaluation. Test compounds and standard compounds were differentiated above (see Background Information). Information generated on standard compounds must be immediately available for distribution to the scientific community (e.g., through presentation at a consultant meeting or through publication). Therefore, the Contractor, in the course of acquiring standard compounds, shall not enter into any agreement that would limit the availability of data generated on the compounds. In many cases, the Contractor will purchase standard compounds from a commercial source or obtain them free of charge from the NIDA Drug Supply Program. In all other cases, the Contractor shall request standard compounds through letters that include the following statement: "The contractor will evaluate the compound as a standard, and will make available to the scientific community the data that the contractor generates on the compound. Data on standard compounds will not be confidential."

In the event that the contract cannot obtain a standard compound, the NIDA COR may provide the compound to the contractor as a test compound. In some cases, NIDA may be able to arrange for (under a separate contract) the synthesis of an interesting compound for evaluation as either a standard compound or a test compound, depending upon the specific compound.

TASK 3. Throughout the life of the contract, the Contractor shall maintain a chronological log of compound receipt. When the Contractor receives compounds (standards compound or test compounds) sent by the COR for evaluation, then the Contractor shall make several log entries: (1) the test compound name or Addiction Treatment Discovery Program identification number and (2) tests authorized (3) the doses authorized (4) the vehicle (5) the pretreatment time, (6) the date of receipt.

TASK 4. Throughout the life of the contract, the Contractor shall maintain a log of compound evaluation. This log shall contain five columns. In Column 1, date of study initiation (date laboratory testing begins). In Column 2 identify the compound under study (compound name or Addiction Treatment Discovery Program code number). In Column 3 describe the study description. In Column 4 enter the study completion date (date that Contractor completes laboratory testing). In Column 5 enter the date that resulting Compound Evaluation Report is sent to the NIDA Project Officer. The Contractor shall maintain this table chronologically, by date of study initiation. The Contractor shall update this table at least once each month.

TASK 5. If appropriate contract options are exercised, the Contractor shall, as directed by the NIDA COR, utilize a specified number of person hours for several purposes. These person hours shall be used (1) for supplemental protocol development for Task 1; (2) for designated "follow-up studies for compounds identified as promising potential treatment agents which could include drug self-administration; (3) for additional testing of compounds in Task 1; and, (4) for the preparation of corresponding data reports. The details of these Task 5 studies cannot be specified in advance of contract award; rather, the NIDA COR shall specify the details as the decision is made to exercise contract options.

The Contractor and the NIDA COR will jointly determine study designs, which possibly could involve chronic test compound administration, cocaine reinstatement tests using female rats, or reinstatement protocols for methamphetamine self-administration or self-administration of other drugs of abuse. Data reports shall adhere to a format determined by the

NIDA COR.

During each period of the effective performance of this contract (Years 1 through 5), the Government may exercise any or all of the following options up to 4 times each.

Option 1: The Contractor shall devote up to 1,000-person hours to the work described under Task 5.

Option 2: The Contractor shall devote up to 2,000-person hours to the work described under Task 5.

Option 3: The Contractor shall devote up to 4,000-person hours to the work described under Task 5.

Option 4: The Contractor may incur up to $20,000 in direct cost for laboratory supplies, equipment, animals, and/or animal per diem charges as required for the work described under Task 5.

Option 5: The Contractor may incur up to $40,000 in direct cost for laboratory supplies, equipment, animals, and/or animal per diem charges as required for the work described under Task 5.

Option 6: The Contractor may incur up to $60,000 in direct cost for laboratory supplies, equipment, animals, and/or animal per diem charges as required for the work described under Task 5.

ALL OTHER TERMS AND CONDITIONS OF THE RFP REMAIN UNCHANGED AND IN

FULL FORCE AND EFFECT.