Small Molecule · NTX-1472

NTX-1472

Phase 2F. Hoffmann-La Roche Ltd (ROG)

Oral, potent, highly selective and brain-penetrant arginine-vasopressin V1a receptor (AVPR1A) antagonist in Phase 2 development by Newleos Therapeutics for generalized social anxiety disorder. Originated at F. Hoffmann-La Roche as RO6953958, the follow-on to Roche's earlier V1a antagonist balovaptan (whose Phase 3 V1aduct trial in autism was stopped for futility in 2020); Roche took RO6953958 through a complete Phase 1 package (first-in-human study BP41695, NCT04475848, London, 2020-2022) inside its autism franchise and then out-licensed it, with global rights, to Newleos in the four-asset ex-Roche portfolio deal announced 2025-02-13. The therapeutic rationale is circuit-specific rather than monoaminergic: vasopressin acting at V1a receptors in the lateral septum and extended amygdala amplifies the response to social threat, and V1a antagonism reduces anxiety-potentiated startle in humans and anxious behaviour in preclinical models, so blocking V1a is hypothesized to act directly on social-threat processing rather than on serotonergic tone. Newleos reports a V1a Ki of 0.5 nM and at least 6,000-fold binding selectivity for V1a, with cerebrospinal-fluid concentrations equal to the unbound fraction in plasma (i.e. brain-penetrant), and PK supporting once-daily dosing. No public chemical structure, CAS number, InChIKey, UNII, ChEMBL or PubChem entry exists for this molecule as of 2026-07-24, and no INN has been published.

Also known as: NTX-1472, RO6953958, NTX1472, RO-6953958

Data current as of

Key facts

Modality
Small molecule
Mechanism
V1a receptor antagonist
Highest phase
Phase 2
Lead indication
Social anxiety disorder
Developer
F. Hoffmann-La Roche Ltd (ROG)
Trials
2 tracked · 1 recruiting · 12 sites
Next catalyst
January 2027 — Registry results (Social anxiety disorder)

Mechanism of action#

NTX-1472 is a potent, highly selective, brain-penetrant antagonist of the arginine-vasopressin V1a receptor (AVPR1A), a Gq-coupled class-A GPCR. Arginine vasopressin (AVP) is an affiliative neuropeptide, closely related to oxytocin, that enhances the response to social threat and negative emotional stimuli; V1a receptors are densely expressed in the lateral septum, central amygdala and bed nucleus of the stria terminalis — regions central to social and threat processing — and V1a expression tracks social recognition and anxiety behaviour in preclinical models. The sponsor reports a V1a binding affinity of Ki = 0.5 +/- 0.04 nM with at least 6,000-fold binding selectivity for V1a, and toxicology in rats and cynomolgus monkeys supporting up to 12-week dosing. Central exposure is supported clinically: cerebrospinal-fluid concentrations equalled the unbound fraction in plasma in the first-in-human study. The clinical hypothesis, carried over from Roche's predecessor V1a antagonist balovaptan and from human work showing that V1a antagonists reduce amygdala activation to threatening social cues and attenuate anxiety-potentiated startle, is that V1a blockade acts directly on social-threat processing rather than through monoaminergic mechanisms — potentially avoiding the 4-6 week onset, high discontinuation rates and sedation/dependence liabilities of SSRIs and benzodiazepines.

TargetActionAffinity
V1a receptorprimaryAVPR1AAntagonistKi 0.5 nMⓘ

Formulations#

FormulationRouteRegimenPharmacokinetics
NTX-1472 oral capsule (210 mg once daily)
Phase 2 SOAR (NCT07323784): NTX-1472 210 mg orally once daily for 8 weeks against a matched look-alike placebo capsule; a single dose level, selected from the Phase 1 data. Phase 1 (Roche, study BP41695 / NCT04475848): single ascending doses 5-360 mg orally including a fed arm (n=48, starting dose 5 mg); multiple ascending doses 45-210 mg once daily for 10 days (n=24, starting dose 45 mg); midazolam drug-drug-interaction part at 210 mg once daily for 12 days (n=16). Second Phase 1 study (itraconazole DDI, n=16): NTX-1472 45 mg fed in period 1, then itraconazole 200 mg twice daily on day 1 and 200 mg once daily on days 2-10 with NTX-1472 45 mg on day 4.
OralOnce daily—

Development timeline#

20232024202520262027TodayPhase 113 Feb 2025 — Licensing deal — Newleos in-licenses NTX-1472 (RO6953958) and three other clinical-stage neuropsychiatry assets from Roche13 Feb 2025 — Financing — Newleos Therapeutics launches with an oversubscribed $93.5 million Series A6 Feb 2022 — phase change — Phase 1 package completed under Roche. Study BP41695 (NCT04475848), a randomized, investigator/subject-blind, placebo-controlled single- and multiple-ascending-dose, food-effect and midazolam-DDI study in 88 healthy male participants at Hammersmith Medicines Research, London, ran 2020-07-15 to 2022-02-06 (actual primary completion and actual completion the same date; results posted on ClinicalTrials.gov 2024-07-10). REGISTRY-FIDELITY CAVEAT: Roche registered this study under autism-spectrum conditions, not social anxiety disorder — it sat inside Roche's autism franchise as the follow-on to balovaptan. It is recorded here because it is the Phase 1 package that Newleos's SAD Phase 2 dose selection rests on, but it is deliberately NOT loaded into trials[] (the loader would re-attribute its sponsor to Newleos and its indication to SAD). A second, open-label 2-period itraconazole drug-drug-interaction study in 16 participants was also completed under Roche; it is not registered on ClinicalTrials.gov under either of the two study codes the sponsor has published for it.Phase 230 Jun 2027 — upcoming — Topline data from the Phase 2 SOAR proof-of-concept study of NTX-1472 210 mg once daily versus placebo in generalized social anxiety disorder — safety/tolerability primary, LSAS the key efficacy secondary — expected 1H 2027.31 Jan 2027 — upcoming — ClinicalTrials.gov estimated primary completion of the SOAR Phase 2 study (NCT07323784): January 2027 (estimated study completion also January 2027).26 May 2026 — Conference presentation — Newleos presents the NTX-1472 clinical programme at the 2026 ASCP Annual Meeting7 Jan 2026 — Trial registered — SOAR Phase 2 study (NCT07323784) first posted on ClinicalTrials.gov9 Dec 2025 — phase change — SOAR (NCT07323784) actual study start per ClinicalTrials.gov. The record was first posted 2026-01-07 and last updated 2026-07-09, with overall status RECRUITING; 10 of the 11 US sites are recruiting and the Las Vegas site is active-not-recruiting. Newleos announced the first participant dosed on 2026-01-06.9 Dec 2025 — Trial started — SOAR Phase 2 study of NTX-1472 in generalized social anxiety disorder starts1 Oct 2025 — phase change — Entry into Phase 2 for social anxiety disorder. Newleos announced on 2025-10-01 that the FDA had cleared its Investigational New Drug application to begin the Phase 2 SOAR study of NTX-1472 in SAD in the United States. The study had not yet initiated at that date. This is the compound's first regulatory step in an anxiety indication under Newleos and the basis for last_phase_change. NOTE: there is no closed-vocabulary event code for an IND clearance, so this milestone is carried in the status history rather than as an events[] row.
Phase change Readout Event UpcomingHover a marker for details.
Phase 2Oct 2025 – Jun 2027
  1. UpcomingTopline data from the Phase 2 SOAR proof-of-concept study of NTX-1472 210 mg once daily versus placebo in generalized social anxiety disorder — safety/tolerability primary, LSAS the key efficacy secondary — expected 1H 2027.↗
  2. UpcomingClinicalTrials.gov estimated primary completion of the SOAR Phase 2 study (NCT07323784): January 2027 (estimated study completion also January 2027).
  3. Conference presentationNewleos presents the NTX-1472 clinical programme at the 2026 ASCP Annual Meeting↗
  4. Trial registeredSOAR Phase 2 study (NCT07323784) first posted on ClinicalTrials.gov
  5. SOAR (NCT07323784) actual study start per ClinicalTrials.gov. The record was first posted 2026-01-07 and last updated 2026-07-09, with overall status RECRUITING; 10 of the 11 US sites are recruiting and the Las Vegas site is active-not-recruiting. Newleos announced the first participant dosed on 2026-01-06.
  6. Trial startedSOAR Phase 2 study of NTX-1472 in generalized social anxiety disorder starts
  7. Entry into Phase 2 for social anxiety disorder. Newleos announced on 2025-10-01 that the FDA had cleared its Investigational New Drug application to begin the Phase 2 SOAR study of NTX-1472 in SAD in the United States. The study had not yet initiated at that date. This is the compound's first regulatory step in an anxiety indication under Newleos and the basis for last_phase_change. NOTE: there is no closed-vocabulary event code for an IND clearance, so this milestone is carried in the status history rather than as an events[] row.↗
Phase 1Feb 2022 – Feb 2025
  1. Licensing dealNewleos in-licenses NTX-1472 (RO6953958) and three other clinical-stage neuropsychiatry assets from Roche↗
  2. FinancingNewleos Therapeutics launches with an oversubscribed $93.5 million Series A↗
  3. Phase 1 package completed under Roche. Study BP41695 (NCT04475848), a randomized, investigator/subject-blind, placebo-controlled single- and multiple-ascending-dose, food-effect and midazolam-DDI study in 88 healthy male participants at Hammersmith Medicines Research, London, ran 2020-07-15 to 2022-02-06 (actual primary completion and actual completion the same date; results posted on ClinicalTrials.gov 2024-07-10). REGISTRY-FIDELITY CAVEAT: Roche registered this study under autism-spectrum conditions, not social anxiety disorder — it sat inside Roche's autism franchise as the follow-on to balovaptan. It is recorded here because it is the Phase 1 package that Newleos's SAD Phase 2 dose selection rests on, but it is deliberately NOT loaded into trials[] (the loader would re-attribute its sponsor to Newleos and its indication to SAD). A second, open-label 2-period itraconazole drug-drug-interaction study in 16 participants was also completed under Roche; it is not registered on ClinicalTrials.gov under either of the two study codes the sponsor has published for it.

NTX-1472 for Social anxiety disorder#

Phase 2RecruitingSocial anxiety disorder indication →

NTX-1472 (Roche's RO6953958), a potent, highly selective, brain-penetrant vasopressin V1a receptor antagonist, for generalized social anxiety disorder (SAD-g) — Newleos Therapeutics' most advanced programme and its only Phase 2 asset. Development is a single study: SOAR (SOcial Anxiety Reduction, NCT07323784 / NTX-1472-201), a Phase 2, multicentre, randomized, double-blind, placebo-controlled, parallel-arm proof-of-concept trial of NTX-1472 210 mg once daily versus placebo for 8 weeks in 100 adults aged 18-65 (50 per arm, randomization stratified by sex), across 11 US sites. Enrolment requires a DSM-5 diagnosis of generalized SAD confirmed by the SCID-5-CT and a clinician-administered Liebowitz Social Anxiety Scale (LSAS) total score of at least 70 at screening; performance-only SAD, current MDD/PTSD/ADHD/ASD and HDRS-17 of 16 or more are exclusions, while comorbid generalized anxiety disorder is permitted. Total participant duration is 99 days (up to 30 days screening, up to 59 days treatment, up to 10 days follow-up). The PRIMARY endpoint is the incidence and severity of treatment-emergent adverse events — this is a safety-primary proof-of-concept study, and every efficacy measure (LSAS total and its fear/avoidance subscales, LSAS response and remission rates, HAM-A, CGI-S, PGI-S, DASS-21 stress, UCLA Loneliness Scale, PSQI, STAI-state) is SECONDARY. The Phase 1 package supporting it was generated by Roche: study BP41695 (NCT04475848, London, 2020-07-15 to 2022-02-06) covering single ascending doses to 360 mg, 10-day multiple ascending doses to 210 mg and a midazolam DDI, plus a second open-label itraconazole DDI study, together dosing 86 healthy participants with no drug-related SAEs. FDA cleared the Phase 2 IND on 2025-10-01; the study started 2025-12-09 and the first participant was dosed on 2026-01-06. Newleos guides topline data for 1H 2027. No regulatory designations have been granted, and no efficacy data of any kind exist yet for this compound in any indication.

Readouts

  • 1H 2027AnticipatedTopline dataNCT07323784

    Topline data from the Phase 2 SOAR proof-of-concept study of NTX-1472 210 mg once daily versus placebo in generalized social anxiety disorder — safety/tolerability primary, LSAS the key efficacy secondary — expected 1H 2027. ↗

  • January 2027AnticipatedRegistry resultsNCT07323784

    ClinicalTrials.gov estimated primary completion of the SOAR Phase 2 study (NCT07323784): January 2027 (estimated study completion also January 2027).

Clinical trials#

NCT07323784NTX-1472-201Phase 2Recruitingn=100

A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Efficacy of NTX-1472, a V1a Receptor Antagonist, in Adults With Social Anxiety Disorder (SOAR)

Started Dec 2025· Primary completion Jan 2027· 11 sites across 1 country

United States

NCT04475848BP41695Phase 1Completedn=88

A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants

Started Jul 2020· Primary completion Feb 2022· 1 site across 1 country

United Kingdom

Conference coverage#

NTX-1472 appears in 2 CNS Pulse conference abstracts:

Sources#

  1. Lago T, Gutierrez M, Pichereau S, Simmons A, Smyrnios S, Duncanson S, Bolognani F. A New Dawn for Social Anxiety Treatment: Clinical Advancement of the Novel V1aR Antagonist, NTX-1472 — poster W10, 2026 ASCP Annual Meeting (Phase 1 study schematics, MAD adverse-event table, SOAR 210 mg once-daily schema) — Newleos Therapeutics, Inc. and F. Hoffmann-La Roche Ltd
  2. Lago T. A New Dawn for Social Anxiety Treatment: Clinical Advancement of the Novel V1a Receptor Antagonist, NTX-1472 — presentation slides, 2026 ASCP Annual Meeting (V1a Ki 0.5 nM, >=6000-fold selectivity, Phase 1 doses, SOAR design, 1H 2027 topline guidance) — Newleos Therapeutics, Inc.
  3. NCT04475848 (BP41695) — A Randomized, Investigator-/Subject-blind, Single- and Multiple-ascending Dose, Placebo-controlled Study to Investigate Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 (Including RO6953958 Effect on Midazolam) Following Oral Administration in Healthy Male Participants; sponsor Hoffmann-La Roche; n=88; completed 2022-02-06; results posted 2024-07-10 — ClinicalTrials.gov (U.S. National Library of Medicine)
  4. NCT07323784 (NTX-1472-201, SOAR) — A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Assess the Safety, Tolerability, and Efficacy of NTX-1472, a V1a Receptor Antagonist, in Adults With Social Anxiety Disorder — ClinicalTrials.gov (U.S. National Library of Medicine)
  5. Newleos Therapeutics Announces Clinical Progress Across Neuropsychiatric Pipeline (2025-10-01) — FDA clearance of the IND for the Phase 2 study of NTX-1472 in social anxiety disorder — Newleos Therapeutics, Inc. (via BioSpace)
  6. Newleos Therapeutics Debuts with $93.5 Million Oversubscribed Series A Financing to Transform the Treatment of Neuropsychiatric Disorders through the Advancement of Novel Medicines (2025-02-13) — Newleos Therapeutics, Inc. (via Business Wire)
  7. VC Longwood Fund unveils neuro biotech with $93M, assets licensed from Roche (2025-02-13) — Newleos Therapeutics licenses ralmitaront as NTX-2001 for alcohol use disorder — Fierce Biotech