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

This is a Research and Development (R&D) Sources Sought notice. This is NOT a solicitation for proposals, proposal abstracts, or quotations. The purpose of this notice is to obtain information regarding the availability and capability of all qualified sources to perform a potential R&D requirement.

This notice is issued to help determine the availability of qualified companies technically capable of meeting the Government requirement and to determine the method of acquisition. It is not to be construed as a commitment by the Government to issue a solicitation or ultimately award a contract. Responses will not be considered as proposals or quotes. No award will be made as a result of this notice. The Government will NOT be responsible for any costs incurred by the respondents to this notice. This notice is strictly for research and information purposes only.

Background and Objectives:

National Institute of Neurological Disorders and Stroke (NINDS) has a need for ongoing screening of investigational therapeutics to treat, modify or prevent epilepsy in support of the NINDS Epilepsy Therapy Screening Program (ETSP).

The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease for all people.

To support this mission, NINDS:

• Supports and performs basic, translational, and clinical neuroscience research through grants-in-aid, contracts, scientific meetings, and through research in its own laboratories, and clinics.
• Funds and conducts research training and career development programs to increase basic, translational and clinical neuroscience expertise and ensure a vibrant, talented, and diverse work force.
• Promotes the timely dissemination of scientific discoveries and their implications for neurological health to the public, health professionals, researchers, and policy-makers.

Epilepsy is a chronic disease impacting 3 million Americans including a half-million children. The average domestic annual healthcare spending for epilepsy is approximately $25 billion. The NINDS Epilepsy Therapy Screening Program (ETSP), known as the Anticonvulsant Screening Program (ASP) until 2015, was established in 1975 to address a critical need for new anti-seizure medications and to promote industry interest in their clinical development. The screening process involves researchers from academia, small businesses, and research organizations (“ETSP participants”) submitting compounds to the ETSP for investigation in a series of test assays for seizures (acute and chronic) and epilepsy. These tests are performed blinded by the contract testing laboratory and through a written agreement between the NINDS and the ETSP participant. The NINDS ETSP program office performs due diligence on project enrollment, plans testing, reports test results to participants and provides advice on future steps for promising compounds, while protecting confidentiality and intellectual property. ETSP has contributed to bringing 11 new medications for clinical use to treat epileptic seizures in children and adults. However, an unmet need remains with a third of people with epilepsy not able to attain sufficient seizure control with currently available therapies. Further, there are currently no approved therapies that modify disease severity of epilepsy or prevent development of epilepsy.

The ETSP program is routinely reviewed, most recently in 2020, by Working Groups commissioned by the National Advisory Neurological Disorders and Stroke (NANDS) Council. The 2012 and 2015 Working Groups’ review reports recommended prioritizing treatments for drug resistant epilepsy and disease prevention and modification (anti-epileptogenesis) over the identification of new undifferentiated anti-seizure drugs. The new name of the program given in 2015 emphasizes that a major focus is going beyond the symptomatic treatment of seizures to identifying agents that have the potential to prevent epilepsy development or disease progression. Additional details on the reports containing the Working Group’s recommendations are available for review at https://www.ninds.nih.gov/Current-Research/Focus-Research/Focus-Epilepsy/ETSP.

Project requirements: The Contractor during the performance period of the contract shall perform various preclinical pharmacological evaluations of potential new therapeutic agents for the treatment of epilepsy and related disorders using human-focused assays, in vivo tests and in vitro assays. In addition, the Contractor shall conduct supporting pharmacokinetic studies. On an “as needed” basis, Contractor shall also adapt, develop, validate, and implement new testing approaches, including human-based research approaches such as organoids, iPSCs, or human brain slices to support the ETSP mission.

TECHNICAL REQUIREMENTS

This contract will support the conduct of preclinical pharmacological evaluations of potential therapeutic agents (small molecules, natural products, synthetic peptides, biologics that will be referred to hereafter as ETSP “investigational compounds”) for the prevention and treatment of epilepsy and related disorders. The contract may also require evaluation of biomedical devices for the treatment of epilepsy and related disorders. This contract shall require the Contractor to conduct studies evaluating investigational compounds in the following performance areas: 1) established workflow testing for drug resistant epilepsy, 2) disease prevention and modification (antiepileptogenesis) assays, and 3) pharmacokinetic studies. In addition, the Contractor shall be required to perform human-based and ancillary studies to support the evolving requirements of the ETSP.

The Government expects the preponderance of work to be performed by the prime Contractor. Given factors including the complexity of the tasks, need for uniformity and consistency of results, protection of intellectual property rights, and management of controlled substances, the operational pieces must be well coordinated and controlled which is more likely to be successfully accomplished when the work is performed within the same organization. It is recognized that some subcontracting may be required with domestic entities where the Contractor does not have the capability to perform certain tasks in-house. In any event, the Contractor, despite the use of subcontracting shall be responsible for full and complete performance of all aspects of the Statement of Work (SOW).

Performance Areas shall include:

PERFORMANCE AREA 1 – Established Workflow for Drug Resistant Epilepsy

Objective: Implement both acute and chronic seizure assays in a workflow for evaluation of investigational compounds for the treatment of drug resistant epilepsy. The assays listed below at minimum are required for the drug resistant epilepsy workflow.

1. Implement acute seizure assays, identification phase of the screening workflow
   1. 6 Hz electrical stimulation in vivo seizure assay (Approximately 190 tests annually)
   2. Maximal electroshock in vivo seizure assay, (Approximately 190 tests annually)
2. Implement behavioral tolerability screens
   1. Rotarod assessment (Approximately 150 tests annually)
   2. Minimal motor impairment assessment (Approximately 40 tests annually)
   3. Locomotor activity assessment (Approximately 40 tests annually)
   4. Modified Irwin test (Approximately 40 tests annually)
3. Implement chronic seizure assays, identification phase of the screening workflow
   1. Corneal kindling seizure model (Approximately 75 tests annually)
   2. In vitro assay, spontaneously bursting hippocampal slice obtained from in vivo post-kainic acid status epilepticus, (Approximately 20 tests annually)
4. Implement chronic seizure assays, differentiation phase of the screening workflow - acute dosing
   1. Intra-hippocampal kainate-induced spontaneous, recurrent, electrographic hippocampal paroxysmal discharges seizure model measured with EEG monitoring (Approximately 20 tests annually)
   2. Lamotrigine-resistant amygdala kindling seizure model. Behavioral seizure scores and the duration of EEG afterdischarge are primary endpoints (Approximately 20 tests annually)
5. Implement chronic seizure assays, differentiation phase of the screening workflow - subchronic dosing
   1. Intra-amygdala kainate-induced spontaneous recurrent seizure models measured with video-EEG monitoring (Approximately 6 tests annually)
   2. Post-kainic acid status epilepticus-induced spontaneous recurrent seizures measured with video-EEG monitoring: phase I pilot study with subchronic dosing by intraperitoneal (i.p.) or subcutaneous (s.c.) administration (Approximately 15 tests annually)
   3. Post-kainic acid status epilepticus-induced spontaneous recurrent seizures measured with video-EEG monitoring: phase II study with oral dosing administered via an automated feeding system (Approximately 7 tests annually)
6. Implement New Approaches Methods (NAMs) or human-focused preclinical approaches
7. Implement ancillary drug-resistant epilepsy assays
   1. Dravet syndrome genetic seizure model, (Approximately 14 tests annually)
   2. Benzodiazepine resistant lithium-pilocarpine status epilepticus model (Approximately 15 tests annually)
   3. Theiler’s Murine Encephalomyelitis Virus (TMEV) seizure model (Approximately 14 tests annually)
   4. Subcutaneous and intravenous pentylenetetrazol seizure model, (Approximately 15 tests each annually)

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.

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 10 tests 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 tests annually).

PERFORMANCE AREA 3 – PHARMACOKINETIC STUDIES

Objective: Implement pharmacokinetic testing to support determination of plasma and brain levels of investigational compounds in rat and mouse.

ANCILLARY STUDIES that the Government may require, depending on the evolving needs of the ETSP, studies and models including but not limited to the following:

1. Models and assays associated with recognized co-morbidities of epilepsy
2. Supporting ADME studies including formulation screening

Anticipated period of performance: The anticipated period of performance shall include one 12-month base period effective from 1/01/2027 to 12/31/2027. It is anticipated that 12-month option periods to extend the term of the contract shall also be included. A future solicitation will specify the specific number of option periods at a minimum of four 12-month option periods, but up to a maximum of nine 12-month option periods to extend the term of the contract may be required.

Other important considerations:

Animal Facility shall be accredited by or registered as follows:

• The Contractor and any subcontractor shall be fully accredited by the Association for Assessment and Accreditation of Laboratory Animal Care (AAALAC) International or equivalent and maintain that accreditation for the life of the contract.
• The Contractor shall have an approved Animal Welfare Assurance for the Office of Extramural Research (OER), Office of Laboratory Animal Welfare (OLAW).
• (http://grants.nih.gov/grants/olaw/olaw.htm), Office of the Director, NIH, as required by Section I-43-30 of the Public Health Service Policy on Humane Care and Use of Laboratory Animals. The Contractor shall maintain such assurance for the duration of this contract, and any subcontractors performing work under this contract involving the use of animals shall also obtain and maintain an approved Animal Welfare Assurance.
• The Contractor and any subcontractor shall comply with the Public Health Service (PHS) Policy on Humane Care and Use of Laboratory Animals (http://grants.nih.gov/grants/olaw/references/phspol.htm) and conduct work in compliance with recommendations established in the Guide for the Care and Use of Laboratory Animals (http://www.nap.edu/openbook.php?record_id=5140).
• The Contractor’s Institutional Animal Care and Use Committee (IACUC) shall approve all animal procedures under this contract.

Animal Requirements include:

The Contractor shall comply with the HHSAR clause 352.270(5)(b), Care of Live Vertebrate Animals (DEC 2015). All available animal assurances and related laboratory inspections will be provided to the COR on an annual basis throughout the period of the contract and such assurances must also be assessable when required. Any violations of protocol resulting in issues, warnings or the need for corrective measures will be reported immediately in writing to both the COR and

Contracting Officer. All relevant explanations related to the nature of the violation as well as planned remedy or actions need to accompany the report.

Other important requirements include rigor, proper storage of investigational compounds,  and data security, storage, access and transfer to NINDS.

Capability statement /information sought.

Small business concerns that believe they possess the capabilities to provide the required products or services should submit documentation of their ability to meet each of the project requirements to the Contracting Officer. The capability statement must specifically address each of the project requirements separately. Additionally, the capability statement should include 1) the total number of employees, 2) the professional qualifications of personnel as it relates to the requirements outlined, 3) any contractor GSA Schedule contracts and/or other government-wide acquisition contracts (GWACs) by which all of the requirements may be met, if applicable, and 4) any other information considered relevant to this program. Small businesses must also provide their Company Name, UEI number, Physical Address, and Point of Contact Information.

Interested small businesses are required to identify their type of business, applicable North American Industry Classification System (NAICS) Code, and size standards in accordance with the Small Business Administration. The government requests that no proprietary or confidential business data be submitted in a response to this notice. However, responses that indicate the information therein is proprietary will be properly safeguarded for Government use only. Capability statements must include the name and telephone number of a point of contact having authority and knowledge to discuss responses with Government representatives. Capability statements in response to this market survey that do not provide sufficient information for evaluation will be considered non-responsive. When submitting this information, please reference the solicitation notice number.

The respondent must also provide their UEI number, organization name, address, point of contact, and size and type of business (e.g., 8(a), HubZone, etc., pursuant to the applicable NAICS code and any other information that may be helpful in developing or finalizing the acquisition requirements.

One (1) copy of the response is required and must be in Microsoft Word or Adobe PDF format using 11-point or 12-point font, 8-1/2” x 11” paper size, with 1” top, bottom, left and right margins, and with single or double spacing.

The information submitted must be in and outline format that addresses each of the elements of the project requirement and in the capability statement /information sought paragraphs stated herein. A cover page and an executive summary may be included but is not required.

The response is limited to ten (10) page limit. The 10-page limit does not include the cover page, executive summary, or references, if requested.

The response must include the respondents’ technical and administrative points of contact, including names, titles, addresses, telephone and fax numbers, and e-mail addresses.

All responses to this notice must be submitted electronically to the Contract Specialist and Contracting Officer. Facsimile responses are NOT accepted.

The response must be submitted via e-mail to the Contracting Officer, Rieka Plugge, at rieka.plugge@nih.gov.

The response must be received on or before 4/07/2026, 9:00 A.M., Eastern Standard Time.

“Disclaimer and Important Notes:  This notice does not obligate the Government to award a contract or otherwise pay for the information provided in response. The Government reserves the right to use information provided by respondents for any purpose deemed necessary and legally appropriate. Any organization responding to this notice should ensure that its response is complete and sufficiently detailed to allow the Government to determine the organization’s qualifications to perform the work.

Respondents are advised that the Government is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted. After a review of the responses received, a presolicitation synopsis and solicitation may be published in Federal Business Opportunities. However, responses to this notice will not be considered adequate responses to a solicitation.

Confidentiality: No proprietary, classified, confidential, or sensitive information should be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).”