Small Molecule · ABX-002

Elunetirom (ABX-002)

Phase 2Autobahn Therapeutics, Inc.
  • Fast Track

Oral, once-daily, brain-penetrant small-molecule amide prodrug (INN elunetirom; code names ABX-002, MA-JD21) that crosses the blood-brain barrier and is cleaved by fatty acid amide hydrolase (FAAH) to an active metabolite (LL-340001 / GtoPdb 'ABX-002A') acting as a potent, selective, CNS-directed agonist of thyroid hormone receptor beta (TRbeta / THRB). Designed to deliver the brain-activating benefits of thyroid hormone signaling (mitochondrial/energetic and neuroplastic effects) while minimizing the peripheral liabilities of synthetic thyroid hormone (e.g., T3). Developed by Autobahn Therapeutics as an adjunctive treatment for bipolar depression and major depressive disorder. FDA Fast Track for adjunctive bipolar depression (May 2026); positive open-label Phase 2 topline (AMPLIFY-BD) reported June 2026.

Also known as: ABX-002, MA-JD21, LL-340001, elunetirom, 2156649-32-8, 2-[3,5-dichloro-4-[(4-hydroxy-3-propan-2-ylphenyl)methyl]phenoxy]-N-methylacetamide

Data current as of

Modality
Small molecule
Chemical class
Thyromimetic, Diphenylmethane, Phenoxyacetamide
DEA schedule
Unscheduled
Chemistry
Achiral · Prodrug
Mechanism
TRbeta agonist
Highest phase
Phase 2
Lead indication
Bipolar depression
Developer
Autobahn Therapeutics, Inc.
Designations
Fast Track
Trials
2 tracked · 1 recruiting · 64 sites
Next catalyst
Q3 2026 — Topline data (Major depressive disorder)

Mechanism of action

Elunetirom (ABX-002) is a blood-brain-barrier-penetrant amide prodrug that is cleaved by fatty acid amide hydrolase (FAAH) to the active metabolite ABX-002A (LL-340001), a potent, selective, centrally acting agonist of thyroid hormone receptor beta (TRbeta / THRB). Selective CNS TRbeta agonism is hypothesized to relieve depression by enhancing neuronal mitochondrial/energy metabolism (reflected in 31P-MRS brain phosphate measures) and neuroplasticity, while the prodrug design and TRbeta selectivity limit the peripheral cardiac/metabolic effects of systemic thyroid hormone. No clean published TRbeta binding constant (Ki/EC50) is catalogued for elunetirom or ABX-002A in IUPHAR/GtoPdb, so affinity is left null.

TargetActionAffinity
TRbetaprimaryTHRBAgonist—ⓘ

Formulations

FormulationRouteRegimenPharmacokinetics
Elunetirom oral solutionOral solution in 1-mL cyclic olefin polymer prefilled syringes, taken on an empty stomach in the morning followed by 240 mL (8 oz) of water
Oral, once-daily brain-penetrant small-molecule prodrug (prodrug of LL-340001); dosed once daily for six weeks in the Phase 2 adjunctive bipolar-depression trial
OralOnce daily—

Development timeline

Phase 2Sept 2024 – Sept 2026
  1. UpcomingAMPLIFY Phase 2 topline (adjunctive MDD): HAMD-17 change at Week 6 vs. placebo, expected Q3 2026.Major depressive disorder↗
  2. metAMPLIFY-BD met its primary endpoint: HAMD-17 -16.8 at Week 6 (p<0.001), 75% response, 50% remission in adjunctive bipolar depression.Bipolar depression↗
  3. Autobahn announced initiation of the open-label Phase 2 bipolar depression trial (AMPLIFY-BD); ClinicalTrials.gov records an actual start date of 28 Mar 2025.Bipolar depression↗
  4. FDA cleared the IND for ABX-002 as an adjunctive treatment for bipolar depression; company planned to begin the Phase 2 trial by year-end 2024.Bipolar depression↗
  5. Autobahn announced initiation of the AMPLIFY Phase 2 trial of ABX-002 as an adjunctive treatment for major depressive disorder (randomized, double-blind, placebo-controlled, ~230 patients, 6-week HAMD-17 primary endpoint). ClinicalTrials.gov records an actual start date of 20 Sep 2024.Major depressive disorder↗

Elunetirom (ABX-002) for Bipolar depression

Phase 2ActiveBipolar depression indication →

Adjunctive bipolar I/II depression. Open-label Phase 2 AMPLIFY-BD (NCT06869187, ABX-002-2002) evaluating 6 weeks of once-daily oral ABX-002 added to existing therapy, with brain energy-metabolism neuroimaging (31P-MRS) and depression rating scales. Initiation announced 8 Jan 2025 (CT.gov actual start 28 Mar 2025). Positive topline reported 4 Jun 2026: mean HAMD-17 reduction of 16.8 points at Week 6 (p<0.001), 75% response and 50% remission. FDA granted Fast Track designation for adjunctive bipolar depression on 26 May 2026. Program remains active (active, not recruiting) with full data anticipated 2H 2026.

Readouts

  • 2026-06-04ReportedTopline datametNCT06869187

    AMPLIFY-BD met its primary endpoint: HAMD-17 -16.8 at Week 6 (p<0.001), 75% response, 50% remission in adjunctive bipolar depression. ↗

Elunetirom (ABX-002) for Major depressive disorder

Phase 2RecruitingMajor depressive disorder indication →

Adjunctive major depressive disorder. Phase 2 AMPLIFY (NCT06633016): a randomized, double-blind, placebo-controlled (1:1) trial of once-daily oral ABX-002 added to a stable-dose SSRI/SNRI in adults (18-65) with moderate-to-severe MDD and inadequate response to current antidepressant therapy (MADRS >24). Primary endpoint is change from baseline in HAMD-17 at Week 6. Trial initiation announced 16 Sep 2024 (ClinicalTrials.gov actual start 20 Sep 2024); enrollment target 230; primary completion June 2026 (estimated). Per the 4 Jun 2026 company update, topline data are expected in the third quarter of 2026; no results have been reported and the trial remains recruiting. FDA Fast Track designation was granted for adjunctive bipolar depression only and does NOT extend to this MDD indication.

Readouts

  • Q3 2026AnticipatedTopline dataNCT06633016

    AMPLIFY Phase 2 topline (adjunctive MDD): HAMD-17 change at Week 6 vs. placebo, expected Q3 2026. ↗

Clinical trials

NCT06869187ABX-002-2002Phase 2Activen=35

A Phase 2 Open-label Study of the Effect of Adjunctively Administered ABX-002 in Adults With Bipolar Disorder Experiencing an Episode of Depression (AMPLIFY-BD)

Started Mar 2025· Primary completion Apr 2026· 📍 14 sites across 1 country (United States)

metsecondaryHAMD-17 change from baseline at Week 2 — mean reduction 9.7 points (<0.001)

Early, rapid antidepressant effect at Week 2 (-9.7 points, p<0.001) per company topline.

metsecondaryHAMD-17 change from baseline at Week 4 — mean reduction 13.7 points (<0.001)

Continued separation at Week 4 (-13.7 points, p<0.001) per company topline.

metsecondaryCorrelation of change in anterior cingulate cortex NTP/Pi and PCr/Pi (31P-MRS) with percent change in HAMD-17 at Week 6

Pre-specified key secondary 31P-MRS brain energy-metabolism endpoints plus significant changes in functional brain connectivity were reported as supportive of target engagement; quantitative correlation values not disclosed in topline.

metprimaryHAMD-17 total score change from baseline to Week 6 — mean reduction 16.8 points (<0.001)

Open-label adjunctive ABX-002 produced a mean 16.8-point HAMD-17 reduction at Week 6 (p<0.001) in 21 adults with bipolar I/II depression in the topline analysis; 75% response (>=50% HAMD-17 reduction) and 50% remission (HAMD-17 <=7).

NCT06633016Phase 2Recruitingn=230

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of ABX-002 for the Adjunctive Treatment of Major Depressive Disorder (AMPLIFY)

Started Sept 2024· Primary completion Jun 2026· 📍 50 sites across 1 country (United States)

Conference coverage

ABX-002 appears in 2 CNS Pulse conference abstracts:

Identifiers

Sources

  1. AMPLIFY-BD: Phase 2 open-label study of adjunctive ABX-002 in bipolar depression (NCT06869187) — ClinicalTrials.gov
  2. AMPLIFY: Phase 2 randomized, double-blind, placebo-controlled study of adjunctive ABX-002 in major depressive disorder (NCT06633016) — ClinicalTrials.gov
  3. Autobahn announces FDA clearance of IND for ABX-002 as adjunctive treatment for bipolar depression (22 Oct 2024) — Autobahn Therapeutics
  4. Autobahn announces initiation of its AMPLIFY Phase 2 trial of ABX-002 as an adjunctive treatment for major depressive disorder (16 Sep 2024) — Autobahn Therapeutics
  5. Autobahn reports positive Phase 2 topline data for elunetirom in bipolar depression (4 Jun 2026) — Autobahn Therapeutics
  6. Autobahn Therapeutics Announces Initiation of Phase 2 Trial of ABX-002 as an Adjunctive Treatment for Bipolar Depression — Autobahn Therapeutics
  7. Elunetirom (ABX-002, ligand 12973) - brain-penetrant TRbeta agonist amide prodrug (FAAH-cleaved to ABX-002A) — IUPHAR/BPS Guide to Pharmacology
  8. Study of ABX-002 for the Adjunctive Treatment of Bipolar Depression (AMPLIFY-BD), NCT06869187 — ClinicalTrials.gov