Attachment 3 - SOW w-Appendix A_Preclinical Pain_6.7.23_pnH.docx.pdf

RFP 75N94023R00010

Attachment 3 - Statement of Work, Dated June 7, 2023

STATEMENT OF WORK

PRECLINICAL MEDICATIONS SCREENING IN DEPENDENCE, AFFECT AND PAIN

MODELS OF ALCOHOLISM

I. BACKGROUND AND INTRODUCTION

The National Institute on Alcohol Abuse and Alcoholism (NIAAA) supports a preclinical medication efficacy testing program to foster discovery of medication targets and lead compounds and biological agents that can be developed as treatments for Alcohol Use Disorder (AUD). The program is currently supported by three contracts: 1) Contract 75N94019C00008 with the University of South Carolina (a follow-on to contracts HHSN267200700038C and HHSN275201400004C), to assess the effects of proprietary compounds in standardized models of alcohol dependence-induced alcohol intake using mice for subjects; 2) Contract 75N94019C00009 with Indiana University (a follow-on to contracts HHSN267200700037C and HHSN275201400005C), which tests medications in alcohol preferring P and HAD1 rats selectively bred for alcohol preference; and 3) Contract HHSN275201800006C with the Louisiana State University Health Sciences Center (LSUHSC) for blind testing of reference compounds, compounds of interest, and proprietary compounds from industry suppliers on alcohol drinking in rats using models of various aspects of alcohol dependence including excessive drinking, negative affect and pain and allows for direct comparison of drug effects in mice and rats using the same model under the ongoing contracts with MUSC and Indiana University which expire in 2024. The current contract with the LSUHSC was awarded in September 27, 2018, with option periods through September 26, 2023.

There is a current need and anticipated future need for continued compound testing in standardized models of alcohol dependence-induced alcohol intake using rats. Therefore, to address the present and anticipated future needs of NIAAA’s Medication Development Program, the Division of Neuroscience and Behavior (DNB) seeks to award a follow-on contract for the blind testing on excessive alcohol drinking, hyperalgesia (pain) and negative affect in rats using models of Alcohol Use Disorder (AUD).

The contract will use mechanisms having intellectual property conditions favorable to compound providers from industry to eliminate a major barrier to testing optimized compounds having preclinical, as well as clinical toxicology data, and stimulate interest by the pharmaceutical industry in developing high quality, marketable compounds for Alcohol Use Disorder. (See Appendix A).

This project involves a continuing and recurring set of activities performed on a variety of proprietary compounds and involves testing of two (2) to three (3) compounds during the 12-month base contract and each potential option period identified in Paragraph III (F) below.

II. SCOPE

The scope of this project is to perform blind testing of compounds supplied to NIAAA from industry suppliers, reference compounds, and compounds of interest in rats using standardized models of excessive alcohol drinking, pain and negative affect driven by alcohol dependence and provide analysis of said testing.

III. TECHNICAL REQUIREMENTS

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary services qualified personnel, material, equipment, and facilities not otherwise provided by the Government, as needed to perform this Statement of Work. Specifically, the Contractor shall perform the activities and requirements below.

A. Compound Related Activities

1. Compound Testing

Based on study design information, such as drug dose, drug preparation instructions, and pretest administration interval provided by the Contracting Officer’s Representative (COR), the Contractor shall test effects of compounds in standardized models of voluntary limited-access drinking of unsweetened ethanol solutions, negative affect and pain sensitivity in male and female rats made dependent through repeated cycles of ethanol vapor exposure and withdrawal. Two-bottle choice or operant self-administration methods may be used. When compounds are provided by the COR, they will be supplied by a Material Transfer Agreement. In all other instances, the Contractor shall purchase the materials for testing. Minimally, testing protocols shall conform to the following standards: a) justification of sample size, including power calculation; b) blind testing; and c) random or stratified assignment of subjects to experimental conditions. The Contractor shall evaluate whether the test drug reached and engaged the intended target when possible. When requested, the Contractor shall assess effects of proprietary compounds on: (a) locomotor activity and interactions with alcohol; (b) alcohol induced hypnotic effects; and (c) alcohol pharmacokinetics, as measured by effects on blood alcohol elimination rates.

2. Compound Storage and Administration

The Contractor shall store compounds supplied to them by the COR, as well as proprietary materials acquired from industry suppliers, such that they cannot be readily accessed by personnel outside the Principle Investigator’s laboratory. The Contractor shall provide adequate storage conditions, including -70° C freezers, on site. The Contractor shall be responsible for providing all necessary reagents and supplies necessary for administering test medications according to instructions supplied by the COR.

3. Data Analysis and Reporting

The Contractor shall perform statistical analysis of the data and prepare a summary of the testing conditions and results including graphical displays. Reports shall also include interpretation of results written in language that can be understood by scientists not having specialized training in alcohol or addiction research. The report shall be submitted to the Contracting Officer (CO) and COR (along with copies of raw data, if requested) 30 calendar days after the completion of the medication test. Compound reports shall be submitted in accordance with Paragraph E.1. below.

4. Data Recording

Throughout the life of the contract, the Contractor shall maintain an electronic file of all experimental protocols. Protocols shall be written in accordance with lab management practices, with all details of the experiment recorded in such a way that another lab could replicate the study exactly. The electronic file shall contain all protocols proposed and/or tested during the duration of the contract and shall include notations regarding their status. A copy of any protocol shall be available to the CO and COR upon request.

5. Data Maintenance and Storage

The Contractor shall retain, for the duration of this contract, all laboratory notebooks in electronic format (which shall include electronic copies of raw data) and any electronic data files generated under this contract, as well as all coded proprietary test compounds received for evaluation under this contract. Electronic data files shall be labeled and recorded in a manner that allows their association with corresponding electronic laboratory notebook entries and electronic copies of raw data. On or before the expiration date of this contract, when instructed by the CO, the Contractor shall submit these items in electronic format to the COR and CO. The Contractor shall not enter data from studies unrelated to this contract in the electronic notebooks or on disks containing data generated under this contract.

B. Animal Welfare

This contract involves the use of rats as test subjects. Therefore, the Contractor shall have the appropriate knowledge and facilities capable of housing and caring for mice in a clean, safe, appropriate environment. Further, the Contractor shall follow those specific requirements regarding the use of rats in preclinical studies in accordance with PHS Policy on Humane Care and Use of Laboratory Animals located at https://olaw.nih.gov/policies-laws/phs-policy.htm, as stated in the various related clauses and Articles in this contract.

C. Special Contract Requirements

1. General Technical Requirements

This contract involves the use of rats as test subjects. Therefore, the Contractor shall have the appropriate knowledge and facilities capable of housing and caring for rats in a clean, safe, appropriate environment. Further the Contractor shall follow those specific requirements regarding the use of rats in preclinical studies as stated in the various related clauses and Articles in this contract.

2. Special Contract Requirements

In accordance with the Intellectual Property Option to the Provider clause of the contract, the Contractor will be free to publish data developed under this contract on compounds and materials (Materials) that are specified by the CO, in consultation with the COR, as publicly available. Most of the Material provided to the Contractor will be proprietary to third parties. Data generated from testing and evaluation of these Materials will also be considered to be proprietary by the provider.

Unless these data are protected, third parties are not likely to make their proprietary Materials available for testing and evaluation under the contract. Accordingly, the Contractor shall agree not to publish data regarding proprietary test Materials unless the COR obtains permission from the submitter. Additionally, in order to encourage third parties to submit their proprietary Materials for evaluation and testing, the Contractor shall agree to offer the provider an option to an exclusive license to any Contractor subject invention conceived or first actually reduced to practice using a provider’s proprietary Materials.

D. Project Management

The Contractor shall provide the overall management, integration and coordination of all contract activities. The Contractor shall also provide technical and administrative infrastructure to ensure the efficient planning, initiation, implementation, and timely completion of all tasks carried out under this contract and effective communications with the COR and the CO. The Contractor shall provide a Principal Investigator with responsibility for overall project management and communications, tracking, monitoring and reporting on project status and progress, and recommending modifications to project requirements and timelines.

1. Contract Initiation Meeting

Within 30 calendar days after the contract’s effective date, the Contractor shall participate in a Contract Initiation Meeting with the COR, CO, and other NIAAA personnel designated by the https://olaw.nih.gov/policies-laws/phs-policy.htm

COR, to be held via telephone conference. The purpose of this meeting is to discuss any issues related to the start-up of the new contract.

2. Final Transition

The Contractor shall ensure an orderly, secure, and efficient transition of contract-related materials and activities to a designated successor contractor or to the Government, as necessary.

A description of transition activities, timelines, and assigned staff shall be provided in a Draft and Final Transition Plan, both of which will be reviewed and approved by the CO, after recommendation by the COR.

The plan shall include the following:

• Status of any ongoing contract projects with anticipated completion dates, along with a timeline for completion of transition activities and the assigned staff.

• Plan for transferring all contract-related electronic data (i.e. experimental protocols electronic files, etc. as described in the Data Analysis and Reporting and Data Recording elements of this Statement of Work) to the CO and COR.

• Plan for final disposition of all contract Materials (i.e., Third Party Compounds and other

Materials kept in -70°C freezer(s) and in other storage locations) to the CO and COR.

• A Draft Transition Plan shall be submitted 120 calendar days prior to the completion date of the contract, and the Final Transition Plan shall be submitted 60 calendar days prior to the contract completion.

E. Reporting and Deliverable Requirements

1. Compound Evaluation Reports: For each compound evaluation that is completed, the Contractor shall submit an electronic Compound Evaluation Report as specified in Paragraph III.

A.3. above. Each Compound Evaluation Report shall be due thirty (30) calendar days after the test completion date. The format shall be as follows:

Front cover shall contain: Date, Title (to include test compound identification number or standard compound name), Agency: National Institutes of Health, Institute: National Institute of Alcohol Abuse and Alcoholism (NIAAA), Division: Division of Neuroscience and Behavior (DNB) and name/address/phone number of the COR, Contract Number, Contractor Name and Investigator Names.

Main body shall contain: (1) detailed methods, including drug preparation methods, vehicle, route of administration, pretreatment times; subject number, age, weight, housing conditions;

description of experimental design and study execution; (2) study results including appropriate statistical analysis. Specific values will be subject to approval by the COR. Depending on study results, tabular and graphical representations of data may be required.

2. Annual Progress Report: On or before the expiration date of the contract base period [or by the 5th working day following the end of the base contract period, if option periods are exercised], the Contractor shall submit an electronic version of a formal annual progress report, suitable for external distribution. The report shall contain a summary of work performed under the contract during the year. If appropriate, any difficulties and corrective measures shall be reported. The report shall also include any changes of personnel concerned with the project and state activity anticipated during the subsequent reporting period.

3. Final Report and Summary of Salient Results: Within ten (10) calendar days prior to the contract completion, the Contractor shall submit to the COR and CO an electronic version of the Final Report. This report shall summarize all work performed under the contract. The Final Report will incorporate the final Annual Report; separate reports will not be required.

4. Electronic Files. In accordance with Paragraph III.A.4. above, electronic files of all experimental protocols. A copy of any protocol shall be available to the COR and CO upon request.

5. Electronic Laboratory Records. In accordance with Paragraph III.A.5. above, all laboratory records (which shall include electronic copies of raw data) and any electronic data files generated under this contract, as well as all coded proprietary test compounds received for evaluation under this contract, shall be provided to the COR and CO upon request.

6. Draft and Final Transition Plan. A draft transition plan shall be submitted within 120 days of contract completion and the final transition plan shall be submitted within 60 days of contract completion, accordance with Paragraph III.D.2.

F. Options

Options for the continued recurring services for which the Government receives benefit may be exercised under the contract at the sole discretion of the Government. This Statement of Work prevails for the contract’s Base and for Options 1 through 4, should the Government decide to exercise said options.

The options are as follows:

Option 1 September 27,2024 – September 26, 2025 Option 2 September 27,2025 – September 26, 2026 Option 3 September 27,2026 – September 26, 2027 Option 4 September 27,2027 – September 26, 2028

INTELLECTUAL PROPERTY OPTION TO THE PROVIDER

Appendix A to Statement of Work

“Intellectual Property Option to the Provider” clause to be offered to the NIAAA’s Third Party Providers of Proprietary Material and Protection of Resultant Proprietary Data.

This Article Shall be Included In Any Prime Contract and Subcontract for Evaluation of Material. The Subcontractor Shall Then Have All the Obligations of the Contractor.

The goal of this contract is to promote the development of critical biological information by evaluating various materials for the treatment of alcohol dependence. For the purposes of this agreement, “material” includes compounds, compositions of matter, and associated information such as methods of making or using the compositions. It is expected that the great majority of materials will be proprietary to third parties. It is clear from the NIAAA’s experience that third party providers (“Provider”) will not provide their proprietary material (“Material”) without assurance that the intellectual property rights associated with their Materials will be protected.

Accordingly, to encourage Providers to provide their Materials for evaluation under this contract the Contractor agrees to this “Intellectual Property Option to the Provider”, which requires the Contractor and its subcontractors to provide a research use license and a commercialization license option to Subject Inventions made under the contract to the Providers as follows:

The Contractor agrees to promptly notify the NIAAA and the Provider in writing of any Subject Inventions of the Contractor, its principal investigator and/or any other employees or agents of the Contractor, whether patentable or not, which are conceived and/or first actually reduced to practice in the performance of work under this contract using a Provider’s Material (hereinafter “Contractor Invention”). The notice shall inform the Provider(s) of its right to the option set forth herein. This may be accomplished by attaching a copy of this “Intellectual Property Option to the Provider” to the notice.

With respect to Contractor Inventions resulting from the use of Material provided by a Provider, the Contractor agrees to grant to the Provider: (i) a paid-up nonexclusive, nontransferable, royalty-free, world-wide license to all Contractor Inventions for research purposes only; and (ii) a time-limited first option to negotiate an exclusive, world-wide royalty-bearing license for all commercial purposes, including the right to grant sub-licenses, to any Contractor Invention on terms to be negotiated in good faith by the Provider and the Contractor, subject to the following conditions:

The Contractor shall allow Provider three (3) months from the date the Contractor sends written notice to the Provider of the existence of a Contractor Invention (or such additional period as the Provider and the Contractor may agree) to notify the Contractor in writing, whether or not it wants to obtain an exclusive license to the Contractor Invention. If the Provider fails to notify the Contractor, in a timely fashion then the Contractor’s obligation to offer Provider a license option with respect to that Contractor Invention will expire, and the Contractor will be free to dispose of its interests in such Contractor Invention in accordance with the Contractor’s policies. If the Contractor and the Provider fail to reach agreement within ninety (90) days, (or such additional period as the Provider and the Contractor may agree) on the terms for an exclusive license for a particular Contractor Invention, then for a period of six (6) months thereafter the Contractor will not offer to license that Contractor Invention to any third party on materially better terms than those last offered to the Provider without first offering such terms to the Provider, in which case the Contractor will offer the Provider a period of thirty (30) days in which the Provider can accept or reject the offer. If the Provider does not notify the Contractor of its intent to accept the offer in a timely fashion the Contractor will be free to dispose of its interests in such Contractor Invention in accordance with the Contractor’s policies.

Provider Inventions The Contractor agrees that notwithstanding anything herein to the contrary, any invention or discovery, whether patentable or not, which is not a Subject Invention as defined in 35 USC 201(e)1 but arises out of an intentional and unauthorized use or modification of the Provider’s Material by the Contractor and/or any other employees or agents of the Contractor, will be the property of the Provider (hereinafter “Provider Invention”). The Contractor will promptly notify the Provider in writing of any such Provider Inventions and, at the Provider’s request and expense, the Contractor will cause to be assigned to the Provider all right, title and interest in and to any such Provider Inventions and give Provider any assistance reasonably necessary to obtain patents (including causing the execution of any invention assignment or other documents). The NIAAA recognizes that the Contractor may also be conducting other research using the Provider’s Material under the authority of a separate agreement with the Provider during the term of this contract; any invention arising under such separate agreement will not be subject to the terms of this provision entitled, “Provider Inventions”.

Protection of Proprietary Data All Materials, data and other information supplied by the Provider or the Project Officer shall be assumed to be confidential unless specifically identified as not confidential in writing by the Project Officer. The Contractor agrees that its principal investigator and/or any other employees or agents of the Contractor will provide the data generated under this contract exclusively to the NIAAA or if directed by the NIAAA, to the Provider and the FDA or other appropriate Federal agency. The Contractor understands that the NIAAA must negotiate individual agreements with the various Providers to obtain Materials and that the terms of the agreements may vary. The NIAAA intends that these agreements will provide for the Contractor’s right to publish results generated by the Contractor under this contract after a reasonable period of time to allow the Provider to file patent applications and to protect its proprietary information. The Contractor agrees to enter into confidentiality agreements with Providers when required by the Providers as a condition for the Contractor to receive Materials. Such agreements shall reference this contract by contract number and shall be consistent with any agreement the NIAAA has entered into with the Provider to obtain Materials. In the event the Contractor reasonably objects to the terms of the confidentiality agreement, the Contractor shall promptly bring such objection to the attention of the Contracting Officer for an appropriate resolution.

135 USC 201(e): The term ''subject invention'' means any invention of the contractor conceived or first actually reduced to practice in the performance of work under a funding agreement: Provided, That in the case of a variety of plant, the date of determination (as defined in section 41(d) of the Plant Variety Protection Act (7 U.S.C. 2401(d)) must also occur during the period of contract performance.

Page 2, Appendix A to Statement of Work