resTORbio (Historic)

What it was

resTORbio (founded 2017) was a Novartis spin-out developing RTB101 (dactolisib), a TORC1/2 inhibitor, and exploring low-dose everolimus for boosting elderly immune function. The thesis: brief intermittent mTOR inhibition improves vaccine response and reduces respiratory tract infections in older adults — based on Joan Mannick’s prior work at Novartis showing this in Phase 2.

What happened

• PROTECTOR-1 Phase 3 trial in elderly with respiratory tract infections failed to hit primary endpoint in 2019.
• Trial design and statistical analysis came under criticism.
• Company merged with Adagene in 2020, ending resTORbio as an independent entity.

What survived

The underlying scientific question — does brief mTOR inhibition benefit elderly immune function — remained open. Subsequent academic work and the PEARL trial of rapamycin in healthy older adults continued the line of inquiry with different protocols.

Joan Mannick continued mTOR-inhibitor longevity work via Tornado Therapeutics (a Cambrian Biopharma subsidiary).

Lessons

• Clinical-trial endpoint selection matters enormously in longevity contexts where intervention effects are often modest.
• Phase 2 → Phase 3 attrition is high even for promising mechanisms.
• The "rapamycin works in elderly humans" story has been told and re-told with mixed individual trial outcomes — the synthesis is still in progress.

Related entries

Rapamycin, mTOR, PEARL trial, Cambrian Biopharma.