Drugs that act on mTOR and are in clinical or late preclinical development, with what the Atlas's own evidence says about the reason each one exists. The common thread is one problem: rapamycin and its relatives block mTORC1, but with long exposure they also block mTORC2, and in mice the insulin resistance rapamycin causes is traced to that second hit (LAM2012).
Status checked 9 Oct 2026 · company and trial facts from the sources under each drug · evidence from studies in the Atlas
8programmes followed
6have reached human trials
7registered trials linked
2stopped, kept on purpose
13Atlas studies cited
The one problem behind most of these drugs
mTOR works inside two different protein complexes. Blocking the first, mTORC1, is what extends lifespan in animals and shrinks some tumours. The trouble starts when the second, mTORC2, gets blocked too.
Rapamycin, taken for a long time
RapamycinmTORC1blocked: the effect we wantmTORC2blocked too: insulin resistance in mice (LAM2012)
Selective mTORC1 inhibitor
New drugmTORC1blocked: the effect we wantmTORC2left working: the hope, not yet shown in people
The other route is to keep the old drug and change the dose: smaller or once-weekly doses that hit mTORC1 harder than mTORC2. That is what the ageing trials below test.
Phase 1 in healthy adults completed (89 participants). A placebo-controlled phase 2 in tuberous sclerosis complex with drug-resistant epilepsy is registered, not yet recruiting, 42 planned participants. The company raised a $55 million Series B in December 2025 to fund that phase 2.
What the Atlas says
No study on AV078 is in the Atlas yet. The reason a brain-penetrant mTORC1 inhibitor is tried in tuberous sclerosis is covered: everolimus shrinks TSC brain and kidney tumours in randomised trials (FRA2013, BIS2013), while a 2026 trial found no clear benefit on cognition (SAX2026).
Bi-steric mTORC1-selective inhibitor (binds both the rapamycin site and the kinase site)
Preclinical
Phase 1
Phase 2
Phase 3
First-in-human dose-escalation trial in advanced solid tumours completed. A phase 1 trial in recurrent glioblastoma was terminated in April 2026 because the drug was no longer provided by the sponsor. AdisInsight lists no development reported as of May 2026.
What the Atlas says
In the phase 1 trial (57 patients, no comparison arm) high blood sugar caused by treatment was uncommon (4%) and not dose-limiting (SCH2025). That fits the idea that sparing mTORC2 avoids metabolic side effects, but an uncontrolled trial cannot show it. The preclinical basis, its sister compound RMC-6272 in breast cancer models, is MEN2023.
Selective mTORC1 inhibitor from a rapalog portfolio licensed from Novartis
Preclinical
Phase 1
Phase 2
Phase 3
Cambrian Bio lists TOR-101 as "Phase 1 Prepared" for healthspan and intrinsic capacity, and says its platform received up to $30.8 million from ARPA-H's PROSPR programme. No TOR-101 trial was found on ClinicalTrials.gov.
What the Atlas says
No study on TOR-101 is in the Atlas. The case for an mTORC1-only drug in ageing rests on mouse work: chronic rapamycin also disrupts mTORC2 and causes insulin resistance, while lowering mTORC1 alone extended lifespan in female mice without it (LAM2012).
Academic (University of Wisconsin-Madison, Buck Institute)
Preclinical
Rapamycin analogue about 40 times more selective for mTORC1 than rapamycin
Preclinical
Phase 1
Phase 2
Phase 3
Published in mice in 2019: inhibited mTORC1 without impairing glucose homeostasis and with reduced or no effects on lipid metabolism and the immune system. No clinical trial found.
Sirolimus (rapamycin) and everolimus are approved drugs. These trials ask whether a dose or schedule exists that helps older people without the side effects.
UW
Everolimus, EVERLAST
University of Wisconsin-Madison, funded by the National Institute on Aging
Phase 2, completed
Rapalog (inhibits mTORC1; with long exposure also mTORC2)
Preclinical
Phase 1
Phase 2
Phase 3
106 participants aged 55 to 80 with insulin resistance, 24 weeks of daily 0.5 mg or weekly 5 mg everolimus against placebo. Primary outcome: insulin sensitivity. Completed July 2026; no results posted yet.
What the Atlas says
The Atlas has no result yet. The daily-versus-weekly comparison follows mouse work in which intermittent rapamycin largely spared glucose control and the immune system while still inhibiting mTORC1 (ARR2015) and, started late in life, extended female lifespan (ARR2016).
University of Wisconsin-Madison, funded by the NIH and the National Institute on Aging
Phase 1, recruiting
Rapalogs, once-weekly dosing
Preclinical
Phase 1
Phase 2
Phase 3
Dose-finding: 5, 10 or 15 mg once a week for 6 weeks in adults aged 55 to 89, measuring drug levels, mTOR signalling in blood and muscle, and side effects. Primary completion expected March 2027.
What the Atlas says
This is the trial behind the open question of which weekly dose inhibits mTORC1 in older people while sparing mTORC2. See the Atlas page on rapamycin for the human studies so far.
Described by the sponsor as a TORC1 inhibitor; chemically BEZ235, a catalytic PI3K/mTOR inhibitor
Preclinical
Phase 1
Phase 2
Phase 3
PROTECTOR 1 randomised 1,024 adults aged 65 and over to RTB101 10 mg or placebo daily for 16 weeks. It did not reduce clinically symptomatic respiratory illness, and development for that use stopped in November 2019.
What the Atlas says
The phase 2a with low-dose BEZ235 plus everolimus was associated with fewer infections (MAN2018). The phase 3 moved the antiviral-gene biomarker but not the clinical outcome (MAN2021). The Atlas uses it as the clearest case of a biomarker that did not become a benefit.
The opposite direction: an mTORC1 activator, binding Sestrin2, developed for depression
Preclinical
Phase 1
Phase 2
Phase 3
In about 250 adults with treatment-resistant depression, 4 weeks of SPN-820 did not beat placebo on the MADRS depression scale (change -12.3 versus -11.9). Announced February 2025.
What the Atlas says
No clinical study of NV-5138 is in the Atlas. It appears only as a laboratory tool for switching mTORC1 on (RAUCH2026).
Already approved and not listed above: sirolimus (transplant rejection, lymphangioleiomyomatosis), everolimus (several cancers, tuberous sclerosis tumours and seizures, transplant), temsirolimus (kidney cancer) and nab-sirolimus (PEComa). See the drug pages in the Atlas.
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