JNJ-2056 · program

JNJ-2056 (ACI-35.030) for Alzheimer's disease

Phase 2ActiveJohnson & Johnson (JNJ)
  • Fast Track

JNJ-2056 (ACI-35.030) is in the Phase 2b 'ReTain' study (NCT06544616), a multicenter, randomized, double-blind, placebo-controlled, potentially registration-enabling trial in participants with PRECLINICAL Alzheimer's disease (cognitively normal, tau-positive) — the first time an active immunotherapy targeting tau is tested in a preclinical AD population. FDA Fast Track designation was granted in July 2024. On 17 Feb 2026 AC Immune disclosed (SEC Form 6-K) that Janssen had TEMPORARILY PAUSED RECRUITMENT in ReTain; the pause is voluntary, NOT related to new safety findings, and the pre-specified interim immunogenicity threshold was met, with dosing and follow-up of already-enrolled participants continuing. ClinicalTrials.gov status is 'Active, not recruiting' (verified 2026-06-25). Phase set to phase_2 (a temporary recruitment hold, not a program discontinuation).

Data current as of

Development timeline

Phase 2Jul 2024 – Dec 2026
  1. UpcomingPhase 2b ReTain (NCT06544616): primary completion estimated 22 Dec 2026 (ClinicalTrials.gov); timing may shift given the Feb-2026 recruitment pause.
  2. pendingPhase 2b ReTain (NCT06544616): Janssen temporarily paused recruitment (17 Feb 2026); voluntary, not safety-related, pre-specified interim immunogenicity threshold met; dosing/follow-up of enrolled participants continues.↗
  3. metPhase 1b/2a (NCT04445831) full results published in eBioMedicine: ACI-35.030 induced anti-pTau IgG in 100% of early-AD participants, no safety concerns; ACI-35.030 selected to advance.↗
  4. Phase 2b 'ReTain' study (NCT06544616) in preclinical AD started 22 Jul 2024 (ClinicalTrials.gov study start date). FDA Fast Track designation announced 25 Jul 2024.↗
Phase 1/2Sept 2023
  1. Phase 1b/2a study NCT04445831 (ACI-35.030 + JACI-35.054 vs placebo in early AD, n=57) completed (last participant last visit 5 Sep 2023). ACI-35.030 induced anti-pTau IgG in 100% of participants and was selected to advance.

Readouts

  • By end-2026AnticipatedTopline dataNCT06544616

    Phase 2b ReTain (NCT06544616): primary completion estimated 22 Dec 2026 (ClinicalTrials.gov); timing may shift given the Feb-2026 recruitment pause.

  • 2026-02-17ReportedInterim analysispendingNCT06544616

    Phase 2b ReTain (NCT06544616): Janssen temporarily paused recruitment (17 Feb 2026); voluntary, not safety-related, pre-specified interim immunogenicity threshold met; dosing/follow-up of enrolled participants continues. ↗

  • 2025-09-25ReportedFull resultsmetNCT04445831

    Phase 1b/2a (NCT04445831) full results published in eBioMedicine: ACI-35.030 induced anti-pTau IgG in 100% of early-AD participants, no safety concerns; ACI-35.030 selected to advance. ↗

Clinical trials in Alzheimer's disease

NCT06544616ReTainPhase 2Activen=55

ReTain: A Study of JNJ-64042056 (JNJ-2056 / ACI-35.030) in Participants With Preclinical Alzheimer's Disease

Started Jul 2024· Primary completion Dec 2026· 📍 90 sites across 9 countries (United States, Japan, United Kingdom, Spain)

NCT04445831Phase 1/2Completedn=57

Phase 1b/2a Study of Tau-Targeted Vaccines (ACI-35.030 and JACI-35.054) in Early Alzheimer's Disease (sponsor: AC Immune SA; collaborator: Janssen R&D)

Started Jul 2019· Primary completion Sept 2023· 📍 9 sites across 4 countries (Finland, Netherlands, Sweden, United Kingdom)

metsafetySafety and tolerability

No clinically relevant safety or tolerability concerns observed for ACI-35.030 (or JACI-35.054); the most frequent adverse events were injection-site reactions and headache. (eBioMedicine, Sep 2025.)

metimmunogenicityImmunogenicity — anti-pTau IgG antibody response (ACI-35.030 arm)

ACI-35.030 induced anti-phospho-tau IgG antibodies in 100% of participants after a single injection, with titres consistently increasing on boosting; the response bound pathological PHF-tau from AD brain while sparing non-phosphorylated tau. ACI-35.030 was selected to advance into the Phase 2b ReTain trial. (eBioMedicine, Sep 2025; NCT04445831, n=57.)

Formulations

FormulationRouteRegimenPharmacokinetics
JNJ-2056 / ACI-35.030 intramuscular liposomal vaccineLiposomal SupraAntigen platform: conformationally-constrained, membrane-bound phosphorylated-Tau (pTau) peptide antigen (16 copies of a synthetic tau fragment anchored in the lipid bilayer) with MPLA adjuvant and non-Tau T-helper peptides
Phase 1b/2a: 300, 900, or 1800 ug given as four intramuscular (deltoid) injections at weeks 0, 8, 24, and 48. Phase 2b ReTain: three immunizations in the first six months, then boosters every six months for up to four years.
Intramuscular——

Mechanism of action (compound-wide)

JNJ-2056 (ACI-35.030) is an active immunotherapy: a liposomal vaccine that presents a conformationally constrained synthetic phospho-tau peptide antigen (tau residues 393-408 phosphorylated at S396 and S404) along with a T-helper peptide and adjuvant. Vaccination stimulates the patient's immune system to generate a robust polyclonal IgG antibody response selectively recognizing pathological pTau while sparing non-phosphorylated tau. These host-generated antibodies are intended to bind and neutralize extracellular pathological pTau, inhibiting tau seeding and cell-to-cell spreading in the brain. Mechanistically this is immune stimulation (active immunization) rather than direct receptor/enzyme pharmacology, so no small-molecule binding affinity applies.

TargetActionAffinity
Tau (pT217)primaryMAPTAgonist—ⓘ

← Full JNJ-2056 compound page (identity, identifiers, all indications)

Sources

  1. A Study of JNJ-64042056 in Participants With Preclinical Alzheimer's Disease (ReTain) — NCT06544616 — ClinicalTrials.gov (Janssen Pharmaceutica N.V.)
  2. A Study to Evaluate Safety, Tolerability and Immunogenicity of Tau Targeted Vaccines in Early Alzheimer's Disease — NCT04445831 — ClinicalTrials.gov (AC Immune SA; collaborator Janssen R&D)
  3. AC Immune SA Form 6-K — update on Alzheimer's (ReTain) trial recruitment pause and cash runway — U.S. SEC EDGAR (AC Immune SA, 17 Feb 2026)
  4. AC Immune's ACI-35.030 (now 'JNJ-2056') Granted FDA Fast Track Designation for Alzheimer's Disease — AC Immune SA via GlobeNewswire (25 Jul 2024)
  5. JNJ-64042056 (ACI-35.030) therapeutic profile — Alzforum
  6. Peer-reviewed results from Phase 1b/2a Trial of Anti-pTau Active Immunotherapy from AC Immune Published in eBioMedicine — AC Immune SA Investor Relations (25 Sep 2025)
  7. Safety and immunogenicity of two Tau-targeting active immunotherapies, ACI-35.030 and JACI-35.054, in participants with early Alzheimer's disease: a phase 1b/2a study — eBioMedicine (via PubMed Central)
  8. Safety and immunogenicity of two Tau-targeting active immunotherapies, ACI-35.030 and JACI-35.054, in participants with early Alzheimer's disease: a phase 1b/2a, multicentre, double-blind, randomised, placebo-controlled study — eBioMedicine (The Lancet Discovery Science), 2025