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 mechanism of action (MOA)-based drug discovery, to identify novel senescence-modifying/senolytic compounds. S/TAR’s foundational enabling technology is Mizar’s novel “Tilt-AutoFocus (Tilt-AF),” a proprietary super-resolution, high-content imaging system adapted to track single molecules in living cells with minimal phototoxicity that allows us to track the spatial and temporal movements of individual target molecules in living cells at a finer scale than ever before. The system allows single-molecule imaging and tracking in living cells without phototoxicity (which often mimics senescence), enabling sensitive detection of changes in target activity due to direct compound-target interactions within any cellular compartment and any cell type. By identifying specific changes in target activity at baseline and in response to treatment in real time, we can ensure that compounds act directly on the target and result in the immediate and downstream consequences that are desired. This provides validation of mechanistic efficacy that extends beyond the target and MOA validation that can be achieved with other methods. This in turn drives more accurate structure–activity relationship (SAR) modeling, improving the accuracy and efficiency of compound screens and helping to avoid costly and time-consuming mistakes due to inadequate efficacy or off-target activity. In Phase II, Mizar will leverage this platform and the cellular model developed in Phase I to screen a library of compounds and identify senescence-modifying countermeasures (CMs), which will be further validated in a selective senolysis assay in preparation for testing in a relevant space radiation environment. The S/TAR platform is a significant addition to the global drug discovery services market, with potential customers including pharmaceutical companies as well as government agencies like NASA.

Galactic cosmic radiation (GCR) is an obstacle to sending humans on long-duration missions beyond low-Earth orbit (BLEO), causing health risks such as cancer, central nervous system effects, premature aging, chronic inflammation, tumor development and cardiovascular risks. Though the long-term effects of GCR are currently unknown, even a short period of exposure can be detrimental to the health of astronauts and space travelers. Recent studies conducted in a mouse model revealed a progressive increase in p16-positive cells, suggesting cellular senescence as a driver of negative cellular effects following exposure to high-energy, heavy ion radiation. Senescent markers are currently evaluated at the population level using fluorescent or colorimetric assays, but the simplistic readout provides no mechanistic information, making it difficult to differentiate between compounds that act directly or indirectly. Additionally, although single-molecule (SM) imaging can reveal molecular mechanisms of cellular senescence, the use of high excitation power, and the resulting generation of reactive photochemical products, heat, and DNA damage cause phototoxicity, which actually mimics cellular senescence, impedes image capturing, and alters the biology of the observed cells. Mizar’s S/TAR platform provides a novel method to overcome the challenges of SM imaging of live cells by identifying radiation-specific senescent cell phenotypes and allowing for the visualization of molecular mechanisms without the risk of significant phototoxicity. This will promote enhanced screening of compounds that could modify the senescence phenotypes for the development of senescence CMs; this will then lead to the advent of senotherapeutics, a promising avenue for preventing and treating the negative impacts of space radiation. Overall, Mizar’s platform will improve the long-term health of astronauts following a BLEO mission and facilitate future civilian space travel. Mizar’s Tilt-AF and S/TAR platform offer unique advantages for enhancing the pace and sensitivity of compound screening and drug discovery. The platform overcomes the limitations of existing SM imaging techniques to dramatically improve in situ, nondestructive, volumetric, functional imaging and quantitative measurement of key processes in living organisms and systems. The Tilt-AF fully automated imaging platform leverages light sheet illumination technology, automated specimen processing via ML-based algorithms for SM tracking and data analysis, as well as liquid plate handling robotics for efficient sample preparation and loading. These features make it ideal for use as a drug discovery platform for many indications. As such, we plan to commercialize the Tilt-AF by collaborating with industry partners like pharmaceutical and biotech companies, as well as government agencies that can benefit from our drug discovery platform. Business development deals will likely include upfront technology access fees, and additional milestone payments for reaching R&D/commercial milestones, and potential licensing royalties. Mizar has already initiated a project outside of the current application to identify compounds capable of disrupting oncogenic EML4-ALK condensates that promote cancer genesis in ~15,000 cases of non-small-cell lung cancer in the U.S. annually, and has a pilot with a major pharma partner. Thus, further support from NASA to advance this technology will lead to benefits not only to astronauts but will also benefit the American public back on Earth by identifying new therapeutic molecules to improve the treatment of a wide range of diseases and conditions.

This is a mature technology (TRL 7+) — the realistic path in is usually NASA's Technology Transfer Program: licensing an existing NASA patent, or a Space Act Agreement to use NASA facilities/expertise directly. NASA also runs a startup licensing program with no upfront fee for companies formed to commercialize a specific NASA technology.

None of these are guaranteed paths for this specific project — TechPort itself doesn't have an "apply" button. Reaching out to the contact(s) above with a specific question is usually the fastest way to find out what's actually open.