Selective mTORC1 Inhibitors

(RTB101 and RTB101/RAD001)

Immune System

TRIAL PHASE
MECHANISMINDICATION(S)PRODUCT NAMEPreclinicalPhase 1Phase 2Phase 3
Selective mTORC1 Inhibitors
Immunosenescence and Aging-Related Disorders, Respiratory Tract Infections
resTORbio
(RTB101 and RTB101/RAD001)

Immune System

Selective mTORC1 Inhibitors
INDICATION(S):Immunosenescence and Aging-Related Disorders, Respiratory Tract Infections
NAME:resTORbio (RTB101 and RTB101/RAD001)
STAGE:Phase 2
Immunosenescence / Immuno autophagy

 

Our resTORbio affiliate is developing therapeutics to address aging-related diseases. mTOR (mechanistic target of rapamycin) inhibition has been shown in model organisms to extend lifespan and ameliorate aging-related pathologies, including immunosenescence, heart failure, and neurodegenerative diseases. Many of the beneficial effects of mTOR inhibition on aging may be mediated by inhibition of the target of rapamycin complex 1 (TORC1), a downstream signaling complex of mTOR. Our lead program is focused on selective TORC1 inhibitors, with a first-in-class immunotherapy designed to enhance the immune system of the elderly in order to reduce the incidence of respiratory tract infections (RTIs). RTIs, the majority of which are caused by unknown viruses, are a leading cause of death in the elderly, and few therapies exist to treat them. We intend to leverage learnings from our clinical study in RTIs to expand our program into additional aging-related indications. 


  • 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.
    • RTIs are the fifth leading cause of death in people aged 85 and over (US), and seventh 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 US
    • We intend 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 to have many beneficial effects on aging, including increased lifespan in preclinical models, while TORC2 inhibition has been associated with adverse events, including decreased lifespan, hyperglycaemia, and hypercholesterolemia.
    • Our product candidates selectively inhibit TORC1 and may therefore have therapeutic potential to ameliorate multiple aging-related conditions with a favorable safety profile. 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
    • We have 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.
    • Our patent portfolio also includes a recently-filed patent application owned by resTORbio which is directed to compositions of matter for novel mTOR inhibitors.
  • Team
    • The Board of Directors consists of Mr Chen Schor (resTORbio), Mr Jonathan Silverstein, JD (Managing Director, OrbiMed Advisors), Mr Paul Fonteyne (Chief Executive Officer Boehringer Ingelheim USA Corporation), Ms Daphne Zohar (PureTech Health), Mr David Steinberg (PureTech Health), and Ms Lynne Sullivan (Senior Vice President, Biogen).
    • Mr Chen Schor and Dr Joan Mannick serve as CEO and Chief Medical Officer, respectively. The team includes Ms Sarb Shergill, Mr Abdellah Sentissi, Ms Karen Jauregui, Mr John McCabe and Dr Grace Teo.
  • Milestones Achieved
    • On January 30 2018, resTORbio announced the closing of its initial public offering (IPO) on NASDAQ, raising gross proceeds of $97.8 million.
    • In November 2017, resTORbio completed an oversubscribed $40 million Series B financing led by OrbiMed, with participation from Fidelity Management and Research Company, Rock Springs Capital, Quan Capital and Nest Bio.
    • In October 2017, resTORbio completed its Series A financing, with PureTech Health, Novartis, and OrbiMed, with gross proceeds of $25 million.
    • resTORbio advanced its 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.
    • RTB101 and everolimus, along with more than 75 issued patents, were in-licensed from Novartis in March 2017 for ageing-related indications.
    • Data from a Phase 2a clinical trial conducted by Novartis became available in 2016 and showed the following:
      • In the RTB101 monotherapy and RTB101+everolimus combination treatment arms in the intent-to-treat population, statistically significant and clinically meaningful reductions in the annual rate of infections of 33 percent (p=0.008) and 38 percent (p=0.001), respectively, compared to placebo, were observed, despite only six weeks of treatment.
      • Both RTB101 monotherapy and the RTB101+everolimus combination therapy were observed to reduce the incidence of RTIs at one year by 42 percent (p=0.006) and 36 percent (p=0.01), respectively, in the intent-to-treat population.
      • Both RTB101 monotherapy and the RTB101+everolimus combination therapy were observed to reduce the incidence of RTIs at 16 weeks following initiation of therapy by 45 percent (p=0.039) and 50 percent (p=0.013), respectively, in the intent-to-treat population. The typical winter cold and flu season is approximately 16 weeks.
  • Expected Milestones and Timing
    • The Phase 2b clinical study is expected to read out in the second half of 2018 and 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.

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.