Biologic · JNJ-2056
JNJ-2056 (ACI-35.030)
- Fast Track
Investigational anti-phosphorylated-tau (pTau) active immunotherapy (therapeutic vaccine) for Alzheimer's disease. Built on AC Immune's SupraAntigen liposomal platform: a liposomal formulation displaying 16 copies of a synthetic tau fragment spanning residues 393-408, phosphorylated at the pathological residues S396 and S404, together with a non-tau T-helper peptide and adjuvant, designed to raise a strong, specific polyclonal antibody response against extracellular pathological pTau while sparing non-phosphorylated tau. The elicited antibodies are intended to inhibit the seeding and spreading of pathological tau, aiming to delay or prevent the onset of cognitive impairment. Originated at AC Immune SA (also designated VAC20121) and licensed to and developed by Janssen, a Johnson & Johnson company. Granted FDA Fast Track (Jul 2024); in the Phase 2b registration-enabling 'ReTain' study in preclinical Alzheimer's disease.
Also known as: JNJ-2056, ACI-35.030, ACI-35, JNJ-64042056, VAC20121
- Modality
- Biologic
- Chemical class
- Liposomal active immunotherapy (anti-pTau vaccine), Peptide vaccine
- Mechanism
- Tau (pT217) agonist
- Highest phase
- Phase 2
- Lead indication
- Alzheimer's disease
- Developer
- Johnson & Johnson (JNJ)
- Designations
- Fast Track
- Trials
- 2 tracked · 99 sites
- Next catalyst
- By end-2026 — Topline data (Alzheimer's disease)
Mechanism of action
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.
| Target | Action | Affinity |
|---|---|---|
| Tau (pT217)primaryMAPT | Agonist | —ⓘ |
Formulations
| Formulation | Route | Regimen | Pharmacokinetics |
|---|---|---|---|
| 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 | — | — |
Development timeline
- UpcomingPhase 2b ReTain (NCT06544616): primary completion estimated 22 Dec 2026 (ClinicalTrials.gov); timing may shift given the Feb-2026 recruitment pause.
- 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.↗
- 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.↗
- 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 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.
JNJ-2056 (ACI-35.030) for Alzheimer's disease
Phase 2ActiveAlzheimer's disease indication →
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).
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
NCT06544616ReTainPhase 2Activen=55
ReTain: A Study of JNJ-64042056 (JNJ-2056 / ACI-35.030) in Participants With Preclinical Alzheimer's Disease
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)
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.)
Identifiers
Sources
- A Study of JNJ-64042056 in Participants With Preclinical Alzheimer's Disease (ReTain) — NCT06544616 — ClinicalTrials.gov (Janssen Pharmaceutica N.V.)
- 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)
- 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)
- 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)
- JNJ-64042056 (ACI-35.030) therapeutic profile — Alzforum
- 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)
- 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)
- 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