DT-101 · program
DT-101 for Major depressive disorder
DT-101, a next-generation AMPA receptor positive allosteric modulator, for major depressive disorder. This is Draig Therapeutics' lead and only clinical programme, and MDD is its only disclosed indication. Two Phase 2 studies are running in parallel, both randomised, double-blind and placebo-controlled with a primary endpoint of change from baseline in MADRS total score. Tarian-1 (NCT07300969, DT-101/201) is the global monotherapy study: approximately 300 adults aged 18-75 with recurrent MDD by DSM-5-TR, randomised to one of two blinded DT-101 dose levels or placebo, primary endpoint at Day 42, across 40 registered sites in the United States (23), the United Kingdom (6), Bulgaria (5), Czechia (3) and Poland (3). It started 2025-12-16 following FDA clearance of the IND on 2025-10-02, and company guidance at that time put topline in the second half of 2027. AERON-1 (NCT07610473, DT-101/202) is the smaller US adjunctive study: approximately 118 adults with MDD already receiving pharmacological therapy for depression, DT-101 or placebo added on, primary endpoint at Day 56, estimated start June 2026. The programme rests on a completed first-in-human package in 66 healthy volunteers — SAD, MAD and a standalone double-blind MEG crossover (n=19) — which reported no serious adverse events and no discontinuations, adverse event rates comparable to placebo with headache most common, dose-proportional pulsatile PK supporting once-daily dosing, CSF concentrations equivalent to unbound plasma, and MEG-demonstrated functional target engagement that correlated with plasma exposure and was used to select the Phase 2 doses. That Phase 1 programme has no public registry entry. DT-101 holds no regulatory designation of any kind, and no discontinuation, dose-arm drop, protocol amendment or safety signal has been publicly disclosed; both Phase 2 studies were still listed as Recruiting on ClinicalTrials.gov at their most recent updates (2026-07-06 and 2026-07-17 respectively).
Development timeline
- UpcomingTopline results from Tarian-1, the global Phase 2 monotherapy study of DT-101 in major depressive disorder (primary endpoint: change from baseline in MADRS total score at Day 42), anticipated in the second half of 2027.↗
- UpcomingClinicalTrials.gov estimated primary completion of AERON-1, the US Phase 2 adjunctive study of DT-101 in MDD (primary endpoint: change from baseline in MADRS total score at Day 56): May 2027.
- Estimated start of AERON-1 (NCT07610473, DT-101/202), the second Phase 2 study, evaluating DT-101 as an adjunct in adults with MDD already receiving pharmacological therapy for depression (118 participants, primary endpoint change from baseline in MADRS at Day 56). ClinicalTrials.gov gives the start as '2026-06' with type ESTIMATED and no day, so this date is the month anchor, not a confirmed first-patient-in. Status Recruiting as of the record's 2026-07-17 update; the 2026-07-14 Series B release also described both Phase 2 studies as ongoing.
- Actual start date of Tarian-1 (NCT07300969, DT-101/201), the global Phase 2 monotherapy study of DT-101 in MDD, per ClinicalTrials.gov — the true Phase 2 transition. Registered on ClinicalTrials.gov 2025-12-24. Status Recruiting; estimated enrolment 300; primary endpoint change from baseline in MADRS at Day 42; two blinded DT-101 dose arms plus placebo.
- FDA cleared the Investigational New Drug application for the Phase 2 study of DT-101 in major depressive disorder, enabling Draig to initiate Tarian-1 in Q4 2025. The release described the study as multi-centre, randomised, double-blind and placebo-controlled in more than 300 participants, launching first in the US and expanding to the UK and selected EU countries subject to regulatory approval, with a MADRS primary endpoint and topline anticipated in the second half of 2027. Recorded here rather than as an events[] row because the closed event vocabulary has no code for IND clearance (see _comment, gap 5). Phase is still logged as phase_1 on this date because clearance authorises but does not constitute the phase advance — no participant had been dosed in Phase 2.↗
- First public disclosure of the programme, on emergence from stealth. Draig announced a $140 million total investment and stated that DT-101's Phase 1 programme in over 60 subjects was complete and had demonstrated target engagement using magnetoencephalography, with Phase 2 in major depressive disorder planned for 2025. The Phase 1 study is not registered on ClinicalTrials.gov, ISRCTN or the EU register — it was a UK healthy-volunteer CTIMP, for which publication requirements are deferred — so this date is the first citable public confirmation of completion and is an UPPER BOUND on the true completion date, not the completion date itself.↗
Readouts
- 2H 2027AnticipatedTopline dataNCT07300969
Topline results from Tarian-1, the global Phase 2 monotherapy study of DT-101 in major depressive disorder (primary endpoint: change from baseline in MADRS total score at Day 42), anticipated in the second half of 2027. ↗
- May 2027AnticipatedRegistry resultsNCT07610473
ClinicalTrials.gov estimated primary completion of AERON-1, the US Phase 2 adjunctive study of DT-101 in MDD (primary endpoint: change from baseline in MADRS total score at Day 56): May 2027.
Clinical trials in Major depressive disorder
NCT07610473DT-101/202Phase 2Recruitingn=118
A Phase 2 Double-blind, Randomised, Placebo-controlled Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of DT-101 in Adults With Major Depressive Disorder Receiving Pharmacological Therapy for Depression (AERON-1)
NCT07300969DT-101/201Phase 2Recruitingn=300
A Phase 2 Double-blind, Randomised, Placebo-controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of DT-101 in Adults With Major Depressive Disorder (MDD) (Tarian-1)
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| DT-101 oral, once daily (pulsatile PK) Doses are not publicly disclosed at any stage. Tarian-1 (NCT07300969) randomises two blinded active dose levels, labelled only 'DT-101 A' and 'DT-101 B', against placebo; AERON-1 (NCT07610473) has a single blinded DT-101 arm against placebo. The Phase 1 single- and multiple-ascending-dose levels were never published — the ASCP 2026 MEG poster refers only to 'three dose cohorts (18:6 DT-101:placebo)' in the MAD and to 'low-dose' and 'high-dose' periods in the crossover. Dosage form (tablet vs capsule) has not been stated; 'oral' is from the compound being described as orally bioavailable and from once-daily oral dosing in both Phase 2 protocols. | Oral | Once daily | — |
Mechanism of action
Positive allosteric modulator of the AMPA subtype of ionotropic glutamate receptor. AMPA receptors mediate fast excitatory glutamatergic neurotransmission and are the downstream effector through which rapid-acting antidepressant mechanisms are thought to drive synaptic plasticity; potentiating them enhances glutamatergic signalling and plasticity without direct receptor agonism. Earlier AMPAR PAMs were constrained by suboptimal pharmacokinetics and a narrow therapeutic index, and DT-101 is described as a structurally novel next-generation compound engineered for a substantially broader index through optimised receptor modulation. The design thesis is pharmacokinetic as much as pharmacodynamic: a pulsatile once-daily exposure profile giving transient rather than sustained receptor engagement, on the hypothesis that intermittent potentiation is what engages synaptic plasticity mechanisms and yields fast, durable antidepressant effect while avoiding the tolerability ceiling of continuous AMPAR potentiation. Human functional target engagement was shown with magnetoencephalography rather than PET: single and repeated doses produced dose-related reductions in low-frequency resting-state oscillatory power (the inverse of the pattern reported for the AMPAR antagonist perampanel), dose-dependent increases in stimulus-induced occipital activity up to the gamma band on high-contrast visual gratings, and increased 40 Hz auditory steady-state response power without a change in inter-trial coherence; auditory mismatch negativity was unaffected. MEG effects correlated with plasma exposure and were used to select Phase 2 doses. Cerebrospinal fluid concentrations were equivalent to unbound plasma concentrations, confirming CNS exposure. No receptor subunit selectivity, binding affinity or functional potency has been published for DT-101, and no off-target or selectivity panel is in the public domain.
| Target | Action | Affinity |
|---|---|---|
| AMPA receptorprimary | PAM | —ⓘ |
← Full DT-101 compound page (identity, identifiers, all indications)
Sources
- Draig Therapeutics Announces US FDA Clearance of IND Application for Phase 2 Study of DT-101 for the Treatment of Major Depressive Disorder (2025-10-02, Cardiff dateline; Tarian-1 design, >300 participants, MADRS primary, topline anticipated 2H 2027) — Draig Therapeutics Ltd (via GlobeNewswire)
- Draig Therapeutics Launches with $140 Million (£107 Million) Total Investment to Advance its Portfolio of Next-Generation Therapies for Major Neuropsychiatric Disorders (2025-06-18) — Draig Therapeutics Ltd (via GlobeNewswire)
- Draig Therapeutics Presents New Phase 1 Data Demonstrating Safety, Tolerability, Pulsatile PK and Target Engagement by DT-101, a Novel AMPA Receptor Potentiator, at ASCP Annual Meeting (2026-05-28; 66 healthy volunteers, no SAEs, CSF exposure, MEG target engagement) — Draig Therapeutics Ltd (via BioSpace)
- NCT07300969 (DT-101/201, Tarian-1) — A Phase 2 Double-blind, Randomised, Placebo-controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of DT-101 in Adults With Major Depressive Disorder (MDD) — ClinicalTrials.gov (U.S. National Library of Medicine)
- NCT07610473 (DT-101/202, AERON-1) — A Phase 2 Double-blind, Randomised, Placebo-controlled Trial to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of DT-101 in Adults With Major Depressive Disorder Receiving Pharmacological Therapy for Depression — ClinicalTrials.gov (U.S. National Library of Medicine)
- Pipeline — DT-101 (AMPA receptor positive allosteric modulator, Phase 2, MDD), DT-201 (alpha5-GABA-A NAM, preclinical), DT-301 (alpha2/alpha3-GABA-A PAM, preclinical) — Draig Therapeutics Ltd