RESTORBIO (Selective mTORC1 Inhibitors)

(RTB101 and RTB101/RAD001)

Selectively inhibiting TORC1 for conditions of aging, including immunosenescence and neurodegeneration

Founded by PureTech Health, resTORbio is developing innovative medicines that target the biology of aging to prevent or treat aging-related disorders. resTORbio’s lead program selectively inhibits the target of rapamycin complex 1 (TORC1), an evolutionary conserved pathway that contributes to the decline in function of multiple organ systems, including the immune, cardiovascular, and central nervous systems.


In 2017, we advanced our RTB101 and RTB101+everolimus product candidates for the selective inhibition of the TORC1 pathway into a Phase 2b clinical study in RTIs in the elderly. The study, which is expected to read out in the second half of 2018, will evaluate the effectiveness of RTB101 alone or in combination with everolimus in reducing the incidence of RTIs in elderly patients at increased risk of morbidity and mortality related to RTIs.

  • Patient Need & Market Potential
    • Immunosenescence, the age-dependent decline in immune function, is associated with a decreased ability to fight infections, an increase in cancer incidence, and a decline in organ function in the elderly. With a rapidly aging population, there is an urgent need to address these and other aging-related diseases.
    • Respiratory Tract Infections (RTIs) are the second leading cause of hospitalization in people aged 85 and over, and fourth for those 65 and older.
    • The majority of RTIs are caused by unknown viruses, with few therapies to treat them.
    • The very elderly (age 80 and over) is the fastest growing population in the U.S.
    • resTORbio intends to leverage learnings from its clinical study in RTIs to expand its program into additional aging-related indications.
  • Our Approach to Solving the Problem
    • mTOR is a protein serine/threonine kinase that regulates multiple cell functions, including cell growth and metabolism, via two complexes: TORC1 and TORC2.
    • TORC1 inhibition has been shown in preclinical models to have many beneficial effects on aging, including increased lifespan, while TORC2 inhibition in preclinical models has been associated with adverse events, including decreased lifespan, hyperglycemia, and hypercholesterolemia.
    • resTORbio’s product candidate, RTB101, selectively inhibits TORC1s and may therefore have therapeutic potential to ameliorate multiple aging-related conditions. Preclinical data suggests that TORC1 inhibitors may enhance immune response to vaccines and improve tendon stiffening, cardiac dysfunction, cognitive dysfunction, aging-related mobility issues, and laminopathies.
  • Intellectual Property
    • resTORbio has broad intellectual property coverage worldwide, having exclusive rights to a patent portfolio licensed from Novartis International Pharmaceutical Ltd. directed to composition of matter of RTB101 and its salts, formulations of everolimus, and methods of using RTB101 in combination with everolimus to enhance the immune response, among treatment of other diseases and conditions.
  • Team
    • Mr. Chen Schor (previously Teva Pharmaceuticals) serves as Chief Executive Officer, Dr. Joan Mannick (previously Novartis Institute of Biomedical Research) serves as Chief Medical Officer, and Ms. Meredith Manning (previously Shire) serves as Chief Commercial Officer.
    • The Board of Directors consists of Mr. Chen Schor, Mr. Jonathan Silverstein (OrbiMed), JD, Mr. Paul Fonteyne (previously Boehringer Ingelheim), Ms. Lynne Sullivan (Biogen), Mr. David Steinberg (Longwood Fund), Dr. Jeffrey Chodakewitz (previously Vertex Pharmaceuticals), and Mr. Michael Grissinger (previously Johnson & Johnson).
  • Milestones Achieved
    • In April 2019, resTORbio announced the initiation of a Phase 1b/2a trial of RTB101 alone or in combination with sirolimus, in Parkinson’s disease.
    • In March 2019, resTORbio announced a positive End-of-Phase 2 meeting with the FDA and planned initiation of a global Phase 3 program for RTB101.
    • In October 2018, resTORbio announced additional positive results from its Phase 2b study of RTB101, as well as results from pre-specified analyses for any infection and urinary tract infections (UTIs). The data demonstrated decreased incidence of laboratory-confirmed RTIs with severe symptoms, total infections, and UTIs.
    • In July 2018, resTORbio announced positive topline results from its Phase 2b study of RTB101. The Phase 2b study successfully identified dose and patient populations with high unmet need for planned Phase 3 clinical trials.
  • Expected Milestones and Timing
    • resTORbio expects to initiate a Phase 3 study of RTB101 in clinically symptomatic respiratory illness in the second quarter of 2019, with data expected in 2020, pending trial enrollment. 

resTORbio’s lead product candidate, RTB101, is an oral, selective, and potent inhibitor of TORC1. RTB101 inhibits the phosphorylation of multiple targets downstream of TORC1. Inhibition of TORC1 has been observed to extend lifespan and healthspan in aging preclinical species and to improve immune, cardiac and neurologic functions, suggesting potential benefits in several aging-related diseases.

mTOR is an evolutionarily conserved pathway that regulates aging

RTB101/everolimus in combination provide more selective and complete TORC1 inhibition than either agent alone (Nyfeler et al 2012)

Why the very elderly need a drug that reduces respiratory tract infections