75N95022R00005 SF-30 Amendment 2.pdf

OMB No. 0990-0115

AMENDMENT OF SOLICITATION/MODIFICATION OF CONTRACT

1. CONTRACT ID CODE PAGE

OF PAGES

2. AMENDMENT/MODIFICATION NO.

Two (2)

3. EFFECTIVE DATE

See Block 16C

4. REQUISITION/PURCHASE REQ. NO. 5. PROJECT NO. (if applicable)

6. ISSUED BY CODE 7. ADMINIS TERED BY (If other than Item 5) CODE

NINDS R&D Contracts Management Branch National Institute on Drug Abuse, NIH 6001 Executive Boulevard, Room 3287 Bethesda, MD 20892-9531

8. NAME AND ADDRESS OF CONTRACTOR (No., street, city, county, State and ZIP Code) (/) 9A. AMENDMENT OF SOLICITATION NO.

75N95022R00005

9B. DATED (SEE ITEM 11)

X

10A. MODIFICATION OF CONTRACT/ORDER NO.

CODE FACILITY CODE 10B. DATED (SEE ITEM 13)

12/13/2021

11. THIS ITEM ONLY APPLIES TO AMENDMENTS OF SOLICITATIONS

The above numbered solicitation is amended as set forth in item 14. The hour and date specified for receipt of Offers is extended, X is not extended. 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 Items 8 and 15, and returning copies of the amendment; (b) By acknowledging receipt of this amendment on each copy of the offer submitted; or By separate letter or telegram which includes a reference to the solicitation and amendment numbers. FAILURE OF YOUR ACKNOWLEDGMENT TO BE RECEIVED AT THE PLACE DESIGNATED FOR THE 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 hour 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 date, etc.) SET FORTH IN ITEM 14, PURSUANT TO THE AUTHORITY OF FAR 43.103(b).

C. THIS SUPPLEMENTAL AGREEMENT IS ENTERED INTO PURSUANT TO AUTHORITY OF: FAR 1-602-1 and FAR 43.103(a) D. OTHER (Specify type of modification and authority)

E. IMPORTANT: Contractor X is not, is required to sign this document and return__1 copies to the issuing Office.

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

The purpose of this amendment is the following:

• Answer questions submitted in response to the solicitation;

• Revise the Request for Proposals; and

• Revise Attachment 4: Statement of Work.

The proposal due date and time remains unchanged.

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.

NSN 7540-01-152-8070

PREVIOUS EDITION NOT USABLE

30-105

STANDARD FORM 30 (REV 10-83)

Prescribed by GSA

FAR (48 CFR) 53.214(a)

16A. NAME AND TITLE OF CONTRACTING OFFICER

Nancy Lamon-Kritikos, Contracting Officer, NINDS, CMB RED, NIDA, NIH

15B. CONTRACTOR/OFFEROR

BY

(Signature of person authorized to sign)

15C. DATE SIGNED 16B. UNITED STATES OF AMERICA

BY

(Signature of Contracting Officer)

16C. DATE SIGNED

SOLICITATION

RFP 75N95022R00005

Screening of Investigational Therapeutics to Treat, Modify or Prevent Epilepsy for the NINDS Epilepsy Therapy Screening Program (ETSP)

This amendment revises the following articles and paragraphs of the above numbered Request for Proposals ((RFP) as shown below.

ARTICLE B.2. PRICES/COSTS

Quantity Options

Quantity Options, if exercised, will be funded on a cost reimbursement, level-of-effort basis and will consist of options to increase the level of effort which can be exercised up to 10 times per year during Option Periods 1-4. Each quantity option will consist of a prenegotiated amount of labor hours and cost and will provide the Government with the option to increase the effort in performance of the requirements within the Statement of Work.

ARTICLE B.3. ESTIMATED COST – OPTION

e. If the Government exercises its option to increase the level-of-effort quantity pursuant to the OPTIONPROVISION Article in SECTION H of this contract, the Government's total estimated contract amount represented by the sum of the estimated cost plus the fixed fee will be increased as follows:

Period /Item Hours Number of times Option can be Exercised Total Hours

Base Period (9 mo.) 27,801 or TBD 1

Option Period 1 (12 mo.) 37,068 or TBD 1

Option Period 2 (12 mo.) 37,068 or TBD 1

Option Period 3 (12 mo.) 37,068 or TBD 1

Option Period 4 (12 mo.) 37,068 or TBD 1

Quantity Option 1 (Option Period 1)

TBD 10

Quantity Option 2 (Option Period 2)

TBD 10

Quantity Option 3 (Option Period 3)

TBD 10

Quantity Option 4 (Option Period 4)

TBD 10

Totals

ARTICLE F.3. LEVEL OF EFFORT (Applicable to level-of-effort CLINs)

a. During the period of performance of this contract, the Contractor shall provide TBD direct labor Hours. The labor Hours Include vacation, holiday, and sick leave. These labors Hours Include subcontractor labor Hours. It is estimated that the labor Hours are constituted as specified below and will be expended approximately as follows:

Option Period 1 (12 mo.) 37,068 or TBD 1

Option Period 2 (12 mo.) 37,068 or TBD 1

Option Period 3 (12 mo.) 37,068 or TBD 1

Option Period 4 (12 mo.) 37,068 or TBD 1

Quantity Option 1 (Option Period 1)

TBD 10

Quantity Option 2 (Option Period 2)

TBD 10

Quantity Option 3 (Option Period 3)

TBD 10

Quantity Option 4 (Option Period 4)

SECTION L - INSTRUCTIONS, CONDITIONS, AND NOTICES TO OFFERORS

d. LEVEL OF EFFORT

The Government's requirement for the work set forth in the Statement of Work of this solicitation is TBD direct labor hours. It is estimated that the labor hours are constituted as specified below and will be expended approximately as follows:

Option Period 1 (12 mo.) 37,068 or TBD 1

Option Period 2 (12 mo.) 37,068 or TBD 1

Option Period 3 (12 mo.) 37,068 or TBD 1

Option Period 4 (12 mo.) 37,068 or TBD 1

Quantity Option 1 (Option Period 1)

TBD 10

Quantity Option 2 (Option Period 2)

TBD 10

Quantity Option 3 (Option Period 3)

TBD 10

Quantity Option 4 (Option Period 4)

SECTION 3: TECHNICAL EVALUATION

TECHNICAL APPROACH

2. Performance Area 2

a. Demonstrate capacity and proficiency to perform annually the evaluation of investigational compounds (1 dose level) in a status epilepticus-induced chronic epileptic mouse (10 compounds) and rat (6 compounds) to identify investigational compounds with disease modifying and/or disease prevention effects.

5. Optional Tasks

a. Offeror must address the Optional Tasks described in SoW. Propose an additional rodent screening model of post-traumatic epilepsy that can be used to identify investigational compounds for disease prevention and/or modifying effects in epilepsy and that can increase likelihood of success in clinical trials.

Provide a rationale for the model proposed, how it differentiates from the other model(s) proposed for performance area 2 and screening protocol for identification of active investigational compounds in the model. Provide cost proposal for screening 10 investigational compounds per year at 1 dose level.

(End of revisions to RFP)

Statement of Work

Screening of Investigational Therapeutics to Treat, Modify or Prevent Epilepsy for the NINDS Epilepsy Therapy Screening Program (ETSP)

This amendment revises the following sections of the Statement of Work (SOW) as shown below.

I. PERFORMANCE AREAS

A. PERFORMANCE AREA 1 – Established Workflow for Drug Resistant Epilepsy

Technical Requirements:

Workflow for Performance Area 1 - Based on the recommendations of the NANDS Working Group (report available for review at (https://www.ninds.nih.gov/Current-Research/Focus-Research/Focus-Epilepsy/ETSP), further discussions with ETSP External Consulting Board (ECB) members and other scientific input, the screening paradigm below shall be implemented for the identification of investigational compounds for the treatment of drug resistant epilepsy. The models and approximate number of investigational compounds expected to be screened annually are also described below. The estimates of the numbers of tests required for each model are approximate numbers and provided for use when estimating the cost proposal only.

Workflow for Drug Resistant Epilepsy

Codes containing a number and letter combination (1a, 1b etc.) in the above workflow diagram correspond to models listed below.

1. Implement acute seizure models, identification phase of the screening workflow

a. 6 Hz electrical stimulation seizure model, mouse and rat (Approximately 100 investigational compounds time of peak effect determinations and approximately 80 ED-50 determinations in mice and 30 time of peak effect and ED-50 determinations in rats annually)

b. Maximal electroshock seizure model, mouse and rat (Approximately 100 investigational compounds time of peak effect determinations and approximately 80 ED-50 determinations in mice and 30 time of peak effect and ED-50 determinations in rats annually)

2. Implement behavioral tolerability screens

a. Rotarod assessment, mouse (Approximately 80 investigational compounds annually)

b. Minimal motor impairment assessment, rat (Approximately 30 investigational compounds annually)

c. Locomotor activity assessment, rat (Approximately 30 investigational compounds annually)

d. Modified Irwin test, rat (Approximately 20 investigational compounds annually)

3. Implement chronic seizure models, identification phase of the screening workflow

a. Corneal kindling seizure model, mouse (Approximately 35 investigational compounds annually)

b. Spontaneously bursting hippocampal slice from post-kainic acid status epilepticus rat, in vitro model (Approximately 10 investigational compounds annually)

4. Implement chronic seizure models, differentiation phase of the screening workflow - acute dosing

a. Intra-hippocampal kainate-induced spontaneous, recurrent, electrographic hippocampal paroxysmal discharges measured with EEG monitoring, mouse (Approximately 20 investigational compounds annually)

b. Lamotrigine-resistant amygdala kindling seizure model, rat. Behavioral seizure scores and the duration of EEG afterdischarge are primary endpoints (Approximately 15 investigational compounds annually)

5. Implement chronic seizure models, differentiation phase of the screening workflow - subacute dosing

a. Intra-amygdala kainate-induced spontaneous recurrent seizures measured with video-EEG monitoring, mouse (Approximately 12 investigational compounds annually)

b. Post-kainic acid status epilepticus-induced spontaneous recurrent seizures measured with video-EEG monitoring, rat: phase I pilot study with sub-chronic dosing by intraperitoneal (i.p.) or subcutaneous (s.c.) administration (Approximately 12 investigational compounds annually)

c. Post-kainic acid status epilepticus-induced spontaneous recurrent seizures measured with video-EEG monitoring, rat: phase II study with oral dosing administered via an automated feeding system (Approximately 6 investigational compounds annually)

6. Implement ancillary drug resistant epilepsy models

a. Benzodiazepine resistant lithium-pilocarpine status epilepticus model, rat (Approximately 6 investigational compounds annually)

b. Theiler’s Murine Encephalomyelitis Virus (TMEV) model, mouse (Approximately 15 investigational compounds annually)

c. Dravet syndrome model, mouse (Approximately 15 investigational compounds annually)

a. Subcutaneous and intravenous pentylenetetrazol seizure model, mouse and rat (Approximately 10 investigational compounds in mice and 2 in rats annually)

B. PERFORMANCE AREA 2 – Models of Disease Prevention and Modification

Objective:

Implement models to identify investigational compounds that prevent the development of epilepsy or are disease modifying. The models listed below at minimum are required for the disease prevention and modification workflow. The estimates of the numbers of tests required for each model are https://www.ninds.nih.gov/Current-Research/Focus-Research/Focus-Epilepsy/ETSP approximate numbers and provided for use when estimating the cost proposal only.

Technical Requirements:

1. Implement a test protocol in a post-kainic acid status epilepticus-induced chronically epileptic rat that can be used to identify investigational compounds with disease prevention and/or disease modifying effects in epilepsy. Development of spontaneous recurrent seizures measured by video EEG shall be the primary endpoint (Approximately 6 investigational compounds annually).

2. Implement a test protocol in a mouse model of mesial temporal lobe epilepsy (mTLE) induced by focal (amygdala and/or hippocampus) kainic acid injection to identify investigational compounds with disease prevention and/or disease modifying effects in epilepsy. Development of spontaneous recurrent seizures measured by video-EEG shall be the primary endpoint (Approximately 10 investigational compounds annually).

C. PERFORMANCE AREA 3 – PHARMACOKINETIC STUDIES

Objective:

Implement pharmacokinetic testing to support determination of plasma and brain levels of investigational compounds in rat and mouse. The estimates of the numbers of tests required for each model are approximate numbers and provided for use when estimating the cost proposal only.

Technical Requirements:

1. Implement methods to collect plasma and brain samples from naïve and epileptic rodents (approximately 30 compounds in mouse and 30 compounds in rat studies annually).

2. Develop and implement bioanalytical method and validation protocols to determine pharmacokinetics of reference and investigational compounds in naïve and epileptic rodents (approximately 10 compounds in mouse and 10 compounds in rat studies annually).

E. OPTIONAL TASKS

The Government may require, based on the evolving needs of the ETSP and in consultation with the ECB, additional capabilities for disease prevention and modification studies. During each Option Period (1-4), the contract includes 10 quantity options that, if exercised, will be funded on a cost reimbursement, level-of-effort basis. Each of these quantity options is based on anticipated level of effort required for testing one compound, based on current assumptions.

In advance of the NINDS’ exercise of a Quantity Option for Optional Tasks services, the Contractor shall provide a specific technical proposal and updated budget, if applicable, to implement or subcontract the specific expanded capabilities as directed by the COR. Additional capabilities including but not limited to rodent models of post-traumatic epilepsy may be implemented for investigation of new treatments for disease prevention and modification.

a. The Contractor shall develop technical proposals, budget and subcontracting plan and/or model development and implementation plan with timelines as directed by the COR. Additionally, the contractor shall provide a plan for communication with a potential subcontractor. If an updated budget is submitted for consideration by the Government, it shall illustrate any potential differences from assumptions in its final proposal revision to the specific needs, as defined by the NINDS COR at the time of the request to exercise an option. The Government may consider revision of the level-of-effort in each quantity option provided all options remain within the total contract ceiling.

b. The subcontractor, subcontracting plan and/or model development plan, budget and timelines must be approved by the Contracting Officer.

(End of revisions to SOW)