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Broad Spectrum Bitter Taste Antagonists Discovery

Award Number: R42DC017693
ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2019
PERIOD OF PERFORMANCE END DATE: 03/31/2023

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Broad Spectrum Bitter Taste Antagonists Discovery - Principal Investigators for Small Business: DiscoveryBioMed, Inc. (DBM) and Monell Chemical Senses Center Project Summary Abstract Bitter taste in foods and medicines presents a barrier to overcoming global public health challenges: food insecurity, poor nutritional health, and poor compliance with medication use, particularly among children and the elderly. Sugar and salt, the mainstays to address these challenges, further erode nutritional health, and current alternatives have adverse taste attributes of their own. We propose to develop a reliable, human taste- cell screening platform to find bitter blockers of commercial interest to the food, flavor, and pharmaceutical industries, with the ultimate commercial aim to improve the taste and acceptance of nutritious and sustainable foods and medicines. This Phase 2 STTR proposal evolves from a successful Phase 1 STTR funded program to establish primary and immortal human taste-bud-derived epithelial cell cultures and lines (i.e., hTBEC platforms) from donors with bitter-sensitive genotypes and (b) to design, optimize, and implement hTBEC- based bioassays of bitter taste receptor function and other key end points to produce readout data for medium- throughput screening (MTS). Preliminary data is presented in support of the proposed MTS campaign. This Phase 2 STTR proposal seeks to deepen MTS with bitter-responsive hTBEC platforms as the key ingredient. Milestone 1 of the proposal will be underpinned by three specific experimental aims to complete MTS and perform cheminformatics to realize multiple chemical classes that are bitter taste antagonists. Genomic and qRT-PCR analysis of key TAS2R bitter receptors will be performed continually in parallel to insure stability and robustness of the bitter-responsive hTBEC platforms. Milestone 2 of the proposal will identify ‘broad spectrum’ bitter taste antagonists with future marketplace utility and will be underpinned by two specific experimental aims involving secondary validation of bitter taste antagonists in receptor-specific assays, ‘bitterome’ genomics, and human taste behavior. Industry collaborators will test our best candidate bitter taste antagonists independently for rigor and reproducibility against their bitter drugs (e.g., active product ingredients or APIs). Milestone 3 of the proposal will focus on characterizing deeply and selecting the best bitter-responsive hTBEC platforms and bioassays for clients and to optimize and partner bitter taste antagonists with industry to realize new formulations for bitter-tasting drugs and bitter-tasting foods and beverages. This collaboration between DiscoveryBioMed, Inc. and Monell Chemical Senses Center brings together expertise in (a) culture of human taste cells, (b) the creation of immortalized cell lines, (c) MTS, (d) genetics and (e) human sensory analysis. The guiding hypothesis is that hTBEC-platform-based bioassays will provide a more relevant robust way to discover novel ‘bitter blockers’, given the imperfect current methods of overexpressing known taste receptors in heterologous cells. The discovery of bitter taste receptor antagonists that alone or blended together block bitter taste can improve healthy eating by reducing reliance on salt and sugar and can improve compliance by patients taking medicines. Thus, we are confident that new bitter blockers will improve human health. PHS 398/2590 (Rev. 09/04, re-issued 4/2006) Page Continuation Format Page


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2021 ( Subtotal = $785,542 )
2021	2021	DISCOVERYBIOMED, INC.	400 RIVERHILLS BUSINESS PARK STE 435	BIRMINGHAM	AL	35242	SHELBY	USA	Research Related to Deafness and Communication Disorders	001	3	5/20/2021	SUPPLEMENT FOR EXPANSION	$20,940
2021	2021	DISCOVERYBIOMED, INC.	400 RIVERHILLS BUSINESS PARK STE 435	BIRMINGHAM	AL	35242	SHELBY	USA	Research Related to Deafness and Communication Disorders	000	3	3/30/2021	NON-COMPETING CONTINUATION	$764,602
														Subtotal = $785,542

Issue Date FY: 2020 ( Subtotal = $816,655 )
2020	2020	DISCOVERYBIOMED, INC.	400 RIVERHILLS BUSINESS PARK STE 435	BIRMINGHAM	AL	35242	SHELBY	USA	Research Related to Deafness and Communication Disorders	000	2	3/26/2020	COMPETING CONTINUATION	$816,655
														Subtotal = $816,655

Grand Total All Awards = $1,602,197

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Broad Spectrum Bitter Taste Antagonists Discovery

Award Number: R42DC017693

ORGANIZATION: NATIONAL INSTITUTE ON DEAFNESS AND OTHER COMMUNICATION DISORDERS

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 06/01/2019

PERIOD OF PERFORMANCE END DATE: 03/31/2023

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