THIS IS A NON-COMPETITIVE (NOTICE OF INTENT) COMBINED SYNOPSIS SOLICITATION TO AWARD A CONTRACT OR PURCHASE ORDER WITHOUT PROVIDING FOR FULL OR OPEN COMPETITION (INCLUDING BRAND-NAME).

The National Institute on Drug Abuse (NIDA), Office of Acquisition (OA), on behalf of the National Center for Advancing Translational Sciences (NCATS), intends to negotiate and award a purchase order without providing for full and open competition (including brand-name) to Pharmaron, Inc., 201 E Jefferson St., Louisville, KY 40202-1246. To ensure consistency among data, the current study must be conducted by the same vendor that conducted prior studies of this prodrug. Therefore, to ensure the continuity of science, this acquisition is restricted to Pharmaron, Inc.

DESCRIPTION

The COVID-19 pandemic poses the most significant health crisis of our lifetimes. While the race for several vital vaccines is underway, antiviral small molecule therapy will play an extremely important role in reducing the morbidity and mortality associated with COVID-19. Several studies have led to the discovery of existing compounds, such as remdesivir, which have been authorized for emergency use to combat the ongoing pandemic.

Niclosamide is an old anthelminthic drug. Its potential as an anti-cancer and anti-viral agent has been demonstrated in numerous recent publications and clinical trials aiming to utilize its potential beyond its historic use of treating tapeworm infections in the gut. These studies have continually faced challenges in terms of oral absorption due to niclosamide’s poor solubility and permeability.

We have discovered niclosamide analogs with better solubility, permeability and microsomal stability, indicative of better in vivo exposures, but with similar potency in their ability to rescue the cytopathic effect of SARS-CoV-2 infection in cell-based studies. We also invested efforts is discovering prodrugs that have better solubility and permeability and are effectively metabolized to the active drug. One of these promising prodrugs was subject to initial tolerability and pharmacokinetic (PK) studies in mice and hamsters.

The objective of this acquisition is to extend our initial 24-hour PK studies of this prodrug in a more comprehensive 6-day tolerability / PK study in the Golden Syrian Hamster model of SARS-CoV-2 infection.

See the attached Request for Quotations (RFQ), Statement of Work (SOW), and other attachments for complete requirement details.