Mizar S/TAR High-Throughput Platform for Identification of Senescence Altering Therapeutics

Mizar Therapeutics aims to leverage our Space/Time-Activity Relationship (S/TAR) platform, a new paradigm for target activity assays and drug discovery, for the identification of novel senotherapeutics. S/TAR’s foundational enabling technology is Mizar’s proprietary super-resolution, high-content imaging system adapted to track single molecules in living cells with minimal phototoxicity due to 6-10x greater photon efficiency. This allows us to track the spatial and temporal movements of individual target molecules in living cells at a finer scale than ever before, enabling target validation and the identification of specific changes in target activity at baseline and in response to various treatments in real-time and in a 96-well plate format. S/TAR provides a target activity assay, rather than a phenotypic one, enabling built-in target validation, enhancing mechanism of action studies, and driving more accurate structure–activity relationship modeling. This improves the accuracy and efficiency of compound screens and helps avoid costly and time-consuming mistakes due to misidentified targets. The unique advantages of the S/TAR platform make it an exceptional solution for more sensitive detection, quantification, and spatiotemporal delineation of cellular processes like senescence. In this Phase I SBIR project, Mizar will demonstrate the distinctive benefits of the S/TAR platform for the screening of countermeasures that target senescence as an approach to prevent radiation-induced health risks in astronauts.

Space radiation is a significant obstacle to sending humans on long-duration missions beyond low-Earth orbit (BLEO). Such radiation poses a number of health risks for astronauts, including cancer, central nervous system effects, and cardiovascular disease risks. While the long-term effects of BLEO radiation on astronauts are unknown, studies implicate cellular senescence as a potential mechanism driving some of the negative effects. Given the potentially large role of senescence in driving radiation-induced effects, the development of senotherapeutics aligns with NASA mission directives by offering a promising avenue for preventing or treating the negative impacts of space radiation. In order to develop senotherapeutics capable of preventing or treating space radiation-induced senescence, there is a critical need for a drug discovery platform capable of identifying radiation-specific senescent cell phenotypes and allowing for efficient screening of compounds that modify these phenotypes. In this Phase I SBIR project, Mizar aims to demonstrate the benefits of our S/TAR platform as an automated and high-content countermeasure screening platform for quantifying the effectiveness of various compounds in reducing the consequences of and/or number of senescent cells in ionized irradiated cells/tissues relevant to space exploration. This will provide a proof of principle demonstration that the S/TAR platform can be used in the future as a high-throughput screening platform for efficient discovery and development of novel senotherapeutics to reduce the effects of space radiation on astronauts. Mizar plans to commercialize the S/TAR platform for non-NASA applications by collaborating with industry partners, including pharmaceutical/biotech companies, on drug discovery and development projects. The current drug discovery and validation process is plagued by long timelines, high failure rates, and high costs. It takes on average 10-12 years and $1-2 billion to bring a new drug to market. Growth in R&D expenditures is one of the major factors propelling the drug discovery services market, which is valued at over $11.1 billion globally. Underlying these high costs and long timelines are the numerous inefficiencies of the current drug discovery process, which relies heavily on phenotypic screening to identify active and non-active compounds and to correlate chemical structure with biological activity. Unfortunately, phenotypic screens may identify compounds that act either directly or indirectly, and this process is time-consuming, inefficient, and may yield inconsistent and unreliable results. Moreover, this requires first identifying and validating an appropriate target, which can be a time-consuming and laborious process in and of itself. Mizar’s S/TAR modeling overcomes these challenges, as our platform for drug discovery is not only compatible with high-throughput screening but simultaneously provides mechanistic insight into target validation and target activity relationships, which informs SAR modeling to identify and develop new compounds more efficiently. Our platform will therefore provide considerable value to industry partners by reducing the long timelines and high costs of drug discovery and development.

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