Adicet Bio, Inc. (formerly ResTORbio, Inc.) is developing RTB101, an oral medication that inhibits target of rapamycin complex 1 (TORC1). Using a combination of RTB101 and everolimus, another TORC1 inhibitor, the company is testing a comprehensive immunotherapy program to fight respiratory tract infections in the elderly, improving the immune system rather than attempting to target individual infectious agents.
The mammalian target of rapamycin (mTOR) pathway uses the multiprotein complexes TORC1 and TORC2 to conduct signaling. While inhibiting TORC2 has been observed to decrease lifespan, TORC1 inhibition has been shown to have multiple positive effects, including enhanced brain functions, reduction of adipose tissue, and delaying the onset of age-related pathology. Inhibiting TORC1 with both RTB101 and everolimus decreases S6K while increasing 4EBP1 and Atg; affecting each of these downstream products in this way is reported to enhance lifespan.
In 2018, the company reported that a phase 2b trial of RTB101 has returned positive results for boosting the immune system to respond better to respiratory infections. The trial saw 652 aged people with increased risk of RTIs enroll and compared to the control group; there were significantly fewer patients treated with RTB101 who suffered from one or more RTIs during a 16-week trial period. The next step for resTORbio is to conduct a study of its effects on other infections, heart failure, or autophagy-related diseases later in 2018.
Concluding the successful Phase 2 and 2b studies, the company had agreed with the FDA to proceed to a large-scale Phase 3 clinical trial scheduled to begin later in 2019.
On Friday 15th November 2019, resTORbio announced that the phase 3 trial had failed to meet its primary goal for the reduction of respiratory tract infections in people aged 65 and older. This is an unfortunate setback for the approach and highlights the unpredictable nature of medicine. However, the company is continuing to test the drug for other age-related diseases, including Parkinson’s, and the company expected to release data from its mid-stage Parkinson’s trial in mid-2020.
In 2020, the company merged with Adicet Bio, Inc. and is now continuing research under the Adicet name.
As of July 2021, it appears that Adicet has discontinued development of RBT101 to concentrate on its CAR gamma-delta T cell therapy oncology program.
