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Functional high-throughput contractility assay suite to develop therapeutics for asthma andhypertension

Award Number: R44TR002350
ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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SUMMARY / ABSTRACT Asthmatic bronchoconstriction and hypertensive vasoconstriction are extremely common disease states in which excessive contractile cellular forces directly contribute to the pathophysiology. Existing treatments for these diseases, which affect 25 million and 75 million Americans, respectively, have severe side-effects, become desensitized over prolonged use, or lack efficacy altogether. In particular, LABAs used in asthma management carry a “black-box” warning, and 15-20% of hypertensive patients require >3 drugs to control blood pressure. Despite understanding the role of cellular force in these scenarios, drug developers have lacked the drug discovery tools that directly target this critically important phenotype. Instead, many new drug development efforts continue to focus on known pathways. Clearly, there is a significant clinical unmet need in treating resistant asthma and hypertension, and there are large associated (>$20B) markets worldwide. Specifically, there is need to develop new classes of drugs with molecular mechanisms of action that are orthogonal to existing therapies that promote smooth muscle cell relaxation causing bronchodilation or vasodilation. Forcyte Biotechnologies is an early-stage bio-pharmaceutical company based in Los Angeles that is leveraging a UCLA-borne microtechnology known as FLECS – a high-throughput screening (HTS) platform that measures contractility of single-cells in a 384-wellplate format – to identify and bring to market new compound classes that act on force-generating pathways within cells. This is the first and only reported assay that obtains functional force generation data for single cells, at HTS scales. Our initial programs will focus on treatment resistant asthma and hypertension, but can extend to other diseases associated with abnormal cellular force. In this proposal, we will focus on the natural progression of our platform, seeking to first design and implement workflows to automate the end-to-end execution the assay to enable throughputs of 10K cmpds/day and we will automate the multiplexing strategies we established feasibility for during phase 1. We will also build on our phase 1 research to develop the first truly high-throughput quantitative tissue-level (“tissuoid”) contractility assay (in a 384-wellplate format) to supplement our single-cell assays and enable for the first time, the engineering of treatment-resistant contractile disease models on-chip, completing our commercial assay suite. Finally, we will perform a large-scale validation screen of a small molecule library to obtain key performance metrics of our assay workflow, and to validate the strength of our technique. The products and services enabled by this research are novel and will address urgent needs for both pharmaceutical companies seeking to bolster their pipelines, and researchers working on early drug discovery.


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: 2023 ( Subtotal = $0 )
2023	2020	FORCYTE BIOTECHNOLOGIES, INC.	1100 GLENDON AVE	LOS ANGELES	CA	90024	LOS ANGELES	USA	National Center for Advancing Translational Sciences	000	3	5/15/2023	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2022 ( Subtotal = $0 )
2022	2020	FORCYTE BIOTECHNOLOGIES, INC.	1100 GLENDON AVE FL 17	LOS ANGELES	CA	90024	LOS ANGELES	USA	National Center for Advancing Translational Sciences	000	3	12/24/2021	NON-COMPETING CONTINUATION	$0
														Subtotal = $0

Issue Date FY: 2020 ( Subtotal = $876,721 )
2020	2020	FORCYTE BIOTECHNOLOGIES, INC.	1100 GLENDON AVE FL 17	LOS ANGELES	CA	90024	LOS ANGELES	USA	National Center for Advancing Translational Sciences	000	2	5/14/2020	SUPPLEMENT FOR EXPANSION	$66,248
2020	2020	FORCYTE BIOTECHNOLOGIES, INC.	1100 GLENDON AVE FL 17	LOS ANGELES	CA	90024	LOS ANGELES	USA	National Center for Advancing Translational Sciences	001	3	6/18/2020	NON-COMPETING CONTINUATION	$810,473
														Subtotal = $876,721

Issue Date FY: 2019 ( Subtotal = $826,810 )
2019	2019	FORCYTE BIOTECHNOLOGIES, INC.	1100 GLENDON AVE FL 17	LOS ANGELES	CA	90024	LOS ANGELES	USA	National Center for Advancing Translational Sciences	001	2	9/4/2019	COMPETING CONTINUATION	$0
2019	2019	FORCYTE BIOTECHNOLOGIES, INC.	1100 GLENDON AVE FL 17	LOS ANGELES	CA	90024	LOS ANGELES	USA	National Center for Advancing Translational Sciences	000	2	8/6/2019	COMPETING CONTINUATION	$826,810
														Subtotal = $826,810

Grand Total All Awards = $1,703,531

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Functional high-throughput contractility assay suite to develop therapeutics for asthma andhypertension

Award Number: R44TR002350

ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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