Developing safer and more effective mTOR inhibitors to treat disease and extend healthy lifespan

Rapamycin was the first therapeutic definitely shown to extend lifespan in mammals

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Rapamycin extended lifespan in mice even when started late in life and when given intermittently. These findings suggest that rapalogs may be of benefit for treating or preventing aging-related conditions in humans.

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A rapalog that inhibits mTOR specifically within the TORC1 complex is predicted to be safer than currently approved rapalogs

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mTOR signals within 2 multiprotein complexes called TORC1 and TORC2. Inhibition of TORC1 upregulates protective pathways, prevents overactive mTOR cell signaling and extends lifespan in multiple species. Inhibition of TORC2 may be important for inhibiting cell proliferation but decreases lifespan and causes adverse events such as hyperglycemia and hyperlipidemia.

mTOR is a protein kinase that has been conserved across billions of years of evolution and links the supply of nutrients to growth and reproduction

When nutrients are abundant, mTOR is activated and stimulates the building blocks that organisms need to grow and reproduce.

When nutrients are scarce, mTOR is inhibited and upregulates stress resistance protective pathways. The stress resistance pathways that are upregulated by mTOR inhibition may also be important for protecting organisms from aging-related deterioration.

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Subhead: founding research (or milestone) that led to company

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Activity of the protein kinase mTOR regulates aging

mTOR inhibition extends lifespan in every species studied to date. The lifespan extending effects of mTOR inhibition have been conserved across a billion years of evolution

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Tornado is developing a portfolio of next generation rapalogs that are predicted to have superior safety and/or efficacy to currently approved first generation rapalogs

Currently approved rapalogs inhibit mTOR both within the TORC1 and TORC2 complex. Tornado has in-licensed a portfolio of next generation rapalogs developed by expert chemists at Novartis that includes multiple compounds that are potent TORC1-specific inhibitors. These compounds are predicted to have better safety and efficacy than first generation rapalogs for treating aging-related diseases and extending healthy lifespan.

In addition Tornado’s portfolio of rapalogs includes multiple compounds that are more potent inhibitors of TORC1 and TORC2 as compared to first generation rapalogs and may have superior efficacy as compared to currently approved rapalogs in conditions such autoimmune diseases and cancer.

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Subhead: the breakthrough research

This description is roughly 150 characters and roughly 30+ words. Describe the technology in brief but clear detail. Do not over elaborate.

Subhead: founding research (or milestone) that led to company

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MannickJB, Del Giudice G, Lattanzi M et al., mTOR inhibition improves immune functionin the elderly. Sci Tranl Med 6, 268ra179, doi:10.1126/scitranslmed.3009892 (2014).
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Mannick, JB, MorrisM, Hockey HP et al. TORC1inhibition enhances immune function and reduces infections in the elderly. Sci Transl Med 10,doi:10.1126/scitranslmed.aaq1564 (2018).

Targeting the biology of ageing with mTOR inhibitors to improveimmune function in older adults: phase 2b and phase 3 randomised trials. Mannick JB,Teo G, Bernardo P, Quinn D, Russell K, Klickstein L, Marshall W, Shergill S.Lancet Healthy Longev. 2021 May;2(5):e250-e262. doi:10.1016/S2666-7568(21)00062-3. Epub 2021 May 6.

Chen C, Liu Y, Liu Y et al mTOR regulationand therapeutic rejuvenation of aging hematopoietic stem cells. Sci. Signal. 2(98): ra75 (2009).
Johnson, S. C., Rabinovitch, P. S. &Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature 493, 338-345,doi:10.1038/nature11861 (2013).
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Rapamycin fed late in lifeextends lifespan in genetically heterogeneous mice.- Harrison DE,Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE,Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA.Nature. 2009 Jul 16;460(7253):392-5. doi: 10.1038/nature08221.Epub 2009 Jul 8.

Developing safer and more effective mTOR inhibitors to treat disease and extend healthy lifespan

Rapamycin was the first therapeutic definitely shown to extend lifespan in mammals

Subhead: the breakthrough research

Subhead: founding research (or milestone) that led to company

A rapalog that inhibits mTOR specifically within the TORC1 complex is predicted to be safer than currently approved rapalogs

mTOR is a protein kinase that has been conserved across billions of years of evolution and links the supply of nutrients to growth and reproduction

Subhead: the breakthrough research

Subhead: founding research (or milestone) that led to company

Activity of the protein kinase mTOR regulates aging

Tornado is developing a portfolio of next generation rapalogs that are predicted to have superior safety and/or efficacy to currently approved first generation rapalogs

Subhead: the breakthrough research

Subhead: founding research (or milestone) that led to company

Our CEO Dr. Joan Mannick gives insight into mTOR's Role in Aging

Our leadership team has extensive pharmaceutical and biotech expertise

Read about mTOR