The reduced ability of the aging immune system to effectively detect and fight infections results in increased susceptibility of people over 65 years of age to respiratory tract infections, which in turn negatively impacts such patients’ overall health and quality of life. People age 65 and older are the fastest growing population in the world. According to global census data, there are nearly 150 million people age 65 and older, and approximately 20 million people age 85 years and older in the United States, the major European countries and Japan. Despite age being the major risk factor for multiple chronic diseases, no approved therapies exist to target the aging immune system.
Recent scientific findings, including those published in the scientific journals Cell, Nature, and Science, suggest that aging and aging-related conditions, such as immunosenescence, are attributable not only to random cellular wear and tear, but also to specific intra-cellular signaling pathways, including the mTOR pathway. mTOR is a protein kinase that signals via two multiprotein complexes, known as TORC1 and TORC2. TORC1 inhibition has been observed to prolong lifespan, enhance immune function, ameliorate heart failure, enhance memory and mobility, decrease adiposity and delay the onset of aging-related diseases in multiple preclinical animal studies. On the other hand, TORC2 inhibition has been observed to decrease lifespan and cause hyperlipidemia and hyperglycemia in certain animals and humans. Therefore, the optimal approach for the treatment of aging-related conditions through mTOR inhibition may be a regimen that inhibits TORC1 without inhibiting TORC2, such as that being developed by resTORbio.
resTORbio licensed the worldwide rights to its TORC1 program, including RTB101 alone or in combination with everolimus, from Novartis International Pharmaceutical Ltd. Everolimus is an orally administered small molecule that partially inhibits TORC1 by changing the shape of TORC1, a mechanism known as allosteric inhibition. The combination of RTB101 and an allosteric TORC1 inhibitor such as everolimus or sirolimus may yield complete and selective TORC1 inhibition.