Notice of Ordering Period Extension-Clinical Evaluation of Phenserine Tartrate Extended Controlled Release Tablet

INTRODUCTION

PURSUANT TO RFO SUBPART 5.101- PRESOLICITATION NOTICE, THIS IS A NOTICE OF A PROPOSED CONTRACT ACTION.

THIS IS A NOTICE OF INTENT TO AWARD A MODIFICATION UNDER CONTRACT NO. 75N95024D00002 WITH THE UNIVERSITY OF EXETER, UNITED KINGDOM, TO EXTEND THE ORDERING PERIOD BY ONE (1) YEAR.

The National Institute on Aging (NIA) intends to modify the single-award Indefinite Quantity Indefinite Delivery (IDIQ) contract no. 75N95024D00002, Clinical evaluation of Phenserine tartrate Extended Controlled Release Tablet (ECRT) formulation in early mild Alzheimer’s disease and mild to moderate traumatic brain injury. This modification will extend the ordering period as denoted in IDIQ contract clause FAR 52.216-18, Ordering (AUG 2020), to be extended from August 1, 2026, to August 1, 2027.

The extension of the IDIQ ordering period will allow for work, especially initially planned task orders 2 and 3 of the IDIQ Statement of Work to be completed. There are no anticipated follow-on procurements at the writing of this Notice.

NORTH AMERICAN INDUSTRY CLASSIFICATION SYSTEM (NAICS) CODE

The requirement is classified under NAICS code is 541990: All Other Professional, Scientific, and Technical Services, with a size standard of $19.5M.

REGULATORY AUTHORITY

The resultant modification will include all the applicable provisions and clauses of the RFO initiative, in accordance with Executive Order 14275 and OMB Memorandum M-25-26.

STATUTORY AUTHORITY

This modification is conducted under the authority of 41 U.S.C. 3304(a)(1) and in accordance with RFO Subpart 6.103-1- Only one responsible source and no other supplies or services will satisfy agency requirements.

DESCRIPTION

Background

There is a significant unmet need for Alzheimer’s disease therapeutics as well as drugs that favorably impact the consequences of brain injury as it can initiate cascades of biological events that may lead to long-term neurodegenerative disorders such as Alzheimer’s disease (AD). One of the goals of the National Institute on Aging (NIA) is to conduct research to better understand the effects and effectiveness of pharmaceuticals on neurodegenerative disorders and, in particular, AD and traumatic brain injury (TBI). This Contract shall ensure that NIA is able to evaluate the potential of the candidate AD drug (-)-Phenserine tartrate ECRT formulation in relation to pharmacokinetic and pharmacodynamic measures with regard to achieving steady- state drug concentrations of the agent, and measures of drug/target engagement and efficacy when optimally dosed. Plasma samples obtained from the contract shall be evaluated both at NIA and by other organizations to quantify drug concentrations as well as markers of drug action (such assays will be outside this contract) – but shall be undertaken on samples obtained from this contract. Results from these assays will be related to tolerability and/or cognitive/imaging measures obtained within the present contract.

Specifically, this contract is to evaluate pharmacokinetic and pharmacodynamic measures of (-)-Phenserine tartrate ECRT formulation in subjects with early mild Alzheimer’s disease (AD) in a phase 1/2 clinical trial and in mild to moderate traumatic brain injury (TBI) subjects in a phase 1/2 clinical study. Specifically, the contract is to provide clinical services for the approved administration of the drug to two well-characterized patient populations, and to obtain blood and other sample/measures from them under rigorously safe conditions for later evaluation of pharmacokinetic and pharmacodynamic measures associated with drug plasma concentrations, blood markers of drug action, tolerability and brain/blood markers of efficacy.

Scope and Objectives

II. SCOPE AND OBJECTIVES The main objective of this contract is to provide a service to perform a phase 1/2 clinical trial evaluation of Phenserine tartrate ECRT in subjects with early mild Alzheimer’s disease (AD) and in mild to moderate traumatic brain injury (TBI). Specifically, the Contract shall perform clinical services to provide brain imaging, cognitive assessment as well as blood and other samples to support evaluation of pharmacokinetic and pharmacodynamic measures. This will involve a multiple ascending dose (MAD) study of Phenserine ECRT (Task Order 1), and then the selection of the optimal dose of drug to carry forward into a longer-term analysis of early efficacy in AD (Task Order 2) and TBI subjects (Task Order 3).

Independently and not as an agent of the Government, the Contractor shall furnish all the necessary resources, qualified personnel, material, equipment, and facilities, not otherwise provided by the Government under the terms of this Contract, as needed to perform the technical requirements outlined below through the individual Task Orders (TOs). (-)-Phenserine tartrate ECRT will be provided to the Contractor – as will Phenserine immediate dose formulation (if required within the TBI portion of the study – to achieve a more immediate steady-state blood level). Should the MAD (Task Order 1) phase of the project demonstrate that (-)-Phenserine tartrate ECRT does not adequately release (-)-phenserine/and metabolites to achieve a steady-state. (-)- Phenserine immediate release capsules can be provided to the Contractor by the Government (for administration up to 4 times daily to achieve an approx. steady-state) to allow Task Orders 2 and 3 to move ahead. All task orders will be issued off the below Task Area, Task Area 1.

Task Area 1. Clinical Trial Services: Following regulatory and other required approvals (such as IRB approval), subjects, qualifying and giving informed consent, shall be randomly assigned to treatment conditions: a minimum of 30 subjects and up to 40 clinical trial subjects. Additional subjects may then be assessed, as needed, to estimate power for future clinical studies.

(i) Alzheimer’s disease clinical study All AD patients shall discontinue their AChE inhibitor, donepezil or other, for one week. Subjects shall then receive their randomly assigned treatment of the previous dose of donepezil or donepezil 10 mg. q. d. or ECRT (-)-Phenserine tartrate (PhenT) according to treatment assignments. Since biomarkers are the outcome, double-blinding is not required. PhenT shall be dosed with a stepwise increase weekly* - until approx. steady-state 45 to 50% AChE inhibition is achieved (red blood cell assay); thereafter, this dose will be carried forward for a minimum of 26 weeks or as long as drug supplies last (except in the case of toxicity – where a dose reduction shall occur). The ideal total time of dosing is 52 weeks – but this time is dependent on the availability of (-)- Phenserine ECRT to provide 52 weeks of dosing at the optimal dose.

(ii) TBI clinical study Mild to moderate TBI subjects within 24 hr of injury, qualifying and giving informed consent (30 TBI subjects minimum), shall be randomly assigned to treatment conditions. Additional subjects may then be assessed, as needed, to estimate power for future clinical studies. Subjects shall receive their randomly assigned treatment of the best available non- pharmacological care (i.e., placebo) or ECRT Phenserine (PhenT) according to treatment assignments. Since biomarkers are a key outcome, double-blinding is not required. PhenT shall be dosed with a stepwise increase weekly* - until 45 to 50% AChE inhibition is achieved; thereafter, this dose shall be carried forward to 30 days. Thereafter pharmacological treatment will cease; however, both groups of subjects shall be followed for 1 year. In synopsis, as shown in the Table below, TBI subjects: 30 days treatment with placebo or ECRT PhenT in increasing doses (assessments shall be made: weekly to 30 days; with follow up: 90 days, 1 year).

Period of Performance

As a result of this modification, the ordering period of the IDIQ will be extended by one (1) year, from August 1, 2026, to August 1, 2027.

Closing Statement

This synopsis is not a request for competitive proposals and the government is not committed to award a contract pursuant to this announcement. However, interested parties may respond by identifying their interest, submitting capability statements, or submitting objections to the proposed contract modification. The government will consider responses, however, a determination by the government to proceed with the proposed contract modification is solely within the discretion of the government.

Any potential offeror must have an active registration in the System for Award Management (SAM), housed at www.sam.gov. In addition, the Unique Entity Identifier (UEI), Taxpayer Identification Number (TIN), and the certification of business size must be included in the response.

A determination by the government not to compete these requirements based upon responses to this notice is solely within the discretion of the government. The information received will normally be considered solely for the purposes for determining whether to proceed on a non-competitive basis or to conduct a competitive procurement.

Based upon market research, the government is not using RFO Part 12, Acquisition of Commercial Products and Commercial Services, to fulfill this requirement. However, interested persons may identify to the Contracting Officer their interest and capability to satisfy the Government’s requirement with a commercial item within 15 days of this notice.

All responses must be received by July 30, 2026, at 5:00 pm Eastern Prevailing Time. Responses must be solicited electronically to Kelly Dempsey, Contacting Officer, at kelly.dempsey@nih.gov. Please reference notice no, 75N95024D00002 in any responses or inquiries.