Clinical Evaluation of Phenserine Tartrate Extended Release Tablet

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 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