JNJ-2056 / AC Immune, J&J - LARVOL DELTA

Reτain: A Study of JNJ-64042056 in Participants With Preclinical Alzheimer's Disease (clinicaltrials.gov) - P2 | N=55 | Active, not recruiting | Sponsor: Janssen Pharmaceutica N.V., Belgium | N=498 ➔ 55 | Trial completion date: Jul 2032 ➔ Dec 2026 | Trial primary completion date: Jul 2031 ➔ Dec 2026

Enrollment change • Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders

ENHANCING RECRUITMENT IN ALZHEIMER'S TRIALS USING SPEECH-BASED COGNITIVE BIOMARKERS: PRELIMINARY FINDINGS FROM THE RETAIN STUDY (ADPD 2026) - P2 | "Aims: RETAIN (NCT06544616) is a phase 2b trial evaluating a phosphorylated tau-targeted active immunotherapy (JNJ-64042056) for the treatment of Alzheimer's disease (AD) in participants with preclinical AD... These findings support the scalability and predictive value of the composite SB-C score as a pre-screening tool. Using conservatively low thresholds can prioritize sensitivity and NPV to avoid excluding potentially eligible participants. This approach may streamline recruitment and improve cost-efficiency in preclinical AD trials."

Biomarker • IO biomarker • Alzheimer's Disease • CNS Disorders

J&J halts enrollment in phase 2 trial of AC Immune-partnered Alzheimer's therapy (FierceBiotech) - "The four-year-long Retain study kicked off in 2024 with an aim of recruiting 500 participants with presymptomatic Alzheimer’s who would receive either the anti-tau immunotherapy—dubbed ACI-35.030 or JNJ-2056—or placebo...The Swiss biotech was keen to stress in the filing that the study itself is continuing and that the recruitment pause is 'voluntary and not related to new safety findings.'"

Enrollment closed • Alzheimer's Disease

Reτain: A Study of JNJ-64042056 in Participants With Preclinical Alzheimer's Disease (clinicaltrials.gov) - P2 | N=498 | Active, not recruiting | Sponsor: Janssen Pharmaceutica N.V., Belgium | Recruiting ➔ Active, not recruiting

Enrollment closed • IO biomarker • Alzheimer's Disease • CNS Disorders

Reτain: A Study of JNJ-64042056 in Participants With Preclinical Alzheimer's Disease (clinicaltrials.gov) - P2 | N=498 | Recruiting | Sponsor: Janssen Pharmaceutica N.V., Belgium | Trial completion date: Jun 2034 ➔ Jul 2032

IO biomarker • Trial completion date • Alzheimer's Disease • CNS Disorders

AC Immune’s Tau-targeting therapy shows promise in early Alzheimer’s trial (PharmaTimes) - "ACI-35.030 demonstrated a rapid, potent and sustained polyclonal antibody response against pathological forms of Tau, including phosphorylated Tau (pTau) and brain-derived Tau (ePHF), after a single dose...All participants were classified as anti-pTau IgG responders within two weeks, with response rates between 94% and 100% maintained through week 74 in high-dose cohorts. The therapy also showed specificity, as antibody levels against normal Tau declined with subsequent doses...In contrast, JACI-35.054 produced a more variable response and required multiple administrations to reach consistent antibody levels. It also induced antibodies against normal Tau after the second dose, which increased with further treatment."

P1/2 data • Alzheimer's Disease

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. (PubMed, EBioMedicine) - P1/2 | "ACI-35.030 and JACI-35.054 were well tolerated. ACI-35.030 induced a more rapid and sustained antibody response selective to p-Tau species with evidence of altering AD-related plasma biomarkers and was selected for testing in the ongoing Phase 2b trial."

IO biomarker • Journal • P1/2 data • Alzheimer's Disease • CNS Disorders • Pain

Reτain: A Study of JNJ-64042056 in Participants With Preclinical Alzheimer's Disease (clinicaltrials.gov) - P2 | N=498 | Recruiting | Sponsor: Janssen Pharmaceutica N.V., Belgium | Trial completion date: May 2033 ➔ Jul 2034

Trial completion date • Alzheimer's Disease • CNS Disorders

IMMUNIZATION WITH JNJ -64042056 GENERATES ANTIBODIES IN NON -HUMAN PRIMATES THAT INHIBIT TAU AGGREGATION IN A NEURONAL TAU SEEDING MODEL (ADPD 2025) - "JNJ-64042056, an active immunotherapy currently in clinical trials for the treatment of AD, induces the generation of polyclonal antibodies in NHP which displayed the functional capacity of inhibiting Tau aggregation in a rodent neuronal model."

Alzheimer's Disease • CNS Disorders

ANTIBODIES GENERATED BY JNJ-64042056, AN ACTIVE ANTI-PTAU IMMUNOTHERAPY, IN CLINICAL TRIAL ACI-35-1802 CAN BLOCK TAU SEEDING IN NEURONS. (ADPD 2025) - P2 | "Conclusions This work demonstrates that JNJ-64042056 induces an immune response in patients with AD that is capable of binding to AD-tau seeds and, therefore, has the potential to prevent tau aggregation induction and spreading in the human brain, which is the intended mode of action set for this anti-tau active immunotherapy. JNJ-64042056 is currently being tested in participants who have preclinical AD with confirmed tau pathology (ReTain Phase 2b trial, NCT06544616)."

Clinical • Alzheimer's Disease • CNS Disorders

3440: INDUSTRY SYMPOSIUM 02 (NO CME/CPD CREDIT): Unlocking active immunotherapy for tailored prevention strategies in neurodegenerative diseases (ADPD 2025) - "Günther Staffler will present ACI-7104.056, an anti-a-syn active immunotherapy currently evaluated in the Phase 2 VacSYn trial in early PD...Lennert Steukers will then present the ReTain Phase 2b trial, the first prevention trial for an active immunotherapy in preclinical Alzheimer's, evaluating ACI-35.030/JNJ-2056, an anti-pTau active immunotherapy...Anke Post will provide an update on ACI-24.060, an anti-Abeta active immunotherapy being evaluated in the ABATE Phase 1b/2 trial in both early Alzheimer's disease (AD) and Down syndrome-associated Alzheimer's (DSAD). We will conclude with a Q&A to discuss how active immunotherapies, early detection and biomarker-driven strategies might reshape the future of prevention and treatment in Alzheimer's and Parkinson's diseases."

IO biomarker • Alzheimer's Disease • CNS Disorders • Developmental Disorders • Genetic Disorders • Movement Disorders • Parkinson's Disease

THE FIRST ACTIVE IMMUNOTHERAPY BEING INVESTIGATED FOR AD PREVENTION: ACI-35.030/JNJ2056 IN THE PHASE 2B REΤAIN STUDY (ADPD 2025) - "Supported by AC Immune"

P2b data • CNS Disorders

AC Immune Announces Upcoming Presentations and Industry Symposium on Active Immunotherapies at AD/PD™ 2025 (GlobeNewswire) - "AC Immune SA...announced upcoming presentations highlighting its precision medicine pipeline at the International Conference on Alzheimer’s and Parkinson’s Diseases (AD/PD 2025) taking place in Vienna, Austria, on April 1 – 5, 2025. AC Immune will host an industry symposium highlighting advances in the clinical development of active immunotherapies featuring key opinion leaders, industry experts and AC Immune leadership."

Clinical data • Alzheimer's Disease • Parkinson's Disease

AC Immune Receives Second Milestone Payment Following Progress in Phase 2b ReTain Trial of ACI-35.030 in Preclinical Alzheimer’s Disease (Yahoo Finance) - "AC Immune SA...today announced that it will receive the second ReTain-related milestone payment (CHF 24.6 million) under its agreement with Janssen Pharmaceuticals, Inc. (Janssen), a Johnson & Johnson company. The milestone payment has been triggered by the rapid rate of prescreening in the potentially registrational Phase 2b ReTain trial investigating active-immunotherapy candidate ACI-35.030...to treat preclinical (pre-symptomatic) Alzheimer’s disease (AD). With last December’s milestone payment, this brings the total milestone payments received for ACI-35.030 related to this trial to CHF 40 million."

Financing • Alzheimer's Disease • CNS Disorders

Reτain: A Study of JNJ-64042056 in Participants With Preclinical Alzheimer's Disease (clinicaltrials.gov) - P2 | N=498 | Recruiting | Sponsor: Janssen Pharmaceutica N.V., Belgium

New P2 trial • Alzheimer's Disease • CNS Disorders

AC Immune’s ACI-35.030 (now 'JNJ-2056') Granted FDA Fast Track Designation for Alzheimer’s Disease (GlobeNewswire) - "AC Immune SA...today announced that its active-immunotherapy candidate, ACI-35.030...has received Fast Track designation from the U.S. Food and Drug Administration (FDA). The recently initiated Phase 2b clinical trial ReTain is currently recruiting participants with preclinical Alzheimer’s disease, where individuals have yet to show clinical symptoms."

Fast track • Trial status • Alzheimer's Disease • CNS Disorders

AC Immune Reports First Quarter 2024 Financial Results and Provides a Corporate Update (Yahoo Finance UK) - "ACI-7104.056 VacSYn Phase 2 trial of anti-a-syn active immunotherapy in Parkinson’s disease (PD) on track for safety and immunogenicity interim data in H2 2024...ACI-35.030 anti-pTau active immunotherapy First patient treated in ReTain Phase 2b clinical trial expected in the coming months..."

P2 data • Trial status • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Parkinson's Disease

ACI-35.030 ANTI-PHOSPHO-TAU ACTIVE IMMUNOTHERAPY PRODUCES ANTIBODIES THAT PREVENT PATHOLOGICAL TAU SEEDING IN VITRO (ADPD 2024) - "Clinical stage active anti-pTau immunotherapy, ACI-35.030, induced antibodies in NHP which reduced PHF-induced Tau seeding in vitro. This antibody functionality models the capacity for prevention of cell-to-cell Tau spreading in vivo, further supporting the biological rationale and plausibility of ACI-35.030 for a potential clinical benefit and Alzheimer's disease-modifying effect."

Preclinical • Alzheimer's Disease • CNS Disorders

AC Immune Reports Second Quarter 2023 Financial Results And Provides A Corporate Update (AC Immune Press Release) - "ACI-24.060 anti-Abeta active immunotherapy: Additional interim safety and immunogenicity data from AD cohorts of ABATE study expected in H2 2023; Interim safety and immunogenicity data from DS cohort of ABATE study expected in H2 2023; Initial Abeta-PET data on amyloid plaque reduction in AD expected in H1 2024; ACI-7104.056 anti-a-syn active immunotherapy: Completion of recruitment of first cohort in the Phase 2 VacSYn study in Parkinson's disease expected in H2 2023; ACI-35.030 anti-pTau active immunotherapy: Initiation of next trial in AD expected in H2 2023 (to be followed by a milestone payment); Semorinemab anti-Tau antibody: Results from the open-label extension of the Phase 2 Lauriet trial in mild-to-moderate AD expected in H2 2023..."

Enrollment status • New trial • P1/2 data • P2 data • Alzheimer's Disease • CNS Disorders • Parkinson's Disease • Tauopathies And Synucleinopathies

AC Immune Progress Update on Phase 2 Active Immunotherapy Clinical Pipeline for Alzheimer's and Parkinson diseases (GlobeNewswire) - "AC Immune’s wholly-owned anti-alpha-synuclein (a-syn) active immunotherapy, to treat Parkinson’s disease (PD). Enrollment of cohort 1 in the Phase 2 VacSYn clinical trial evaluating ACI-7104.056, is completed, with 16 patients randomized, and cohort 2 enrollment and randomization has begun. No safety concerns have been reported to date with no reports of moderate or severe adverse events. Safety and immunogenicity updates from the trial will be reported in H2 2024. ACI-35.030: AC Immune’s partnered investigational targeted active immunotherapy, selective for pathological phosphorylated Tau (pTau)....Under the terms of the licensing agreement, AC Immune has received a milestone payment of CHF15 million and expects to receive another milestone payment of CHF 25 million related to achieving an undisclosed enrollment target in 2025."

Enrollment closed • Licensing / partnership • P2 data • CNS Disorders • Parkinson's Disease

AC Immune’s Targeted Anti-pTau Active Immunotherapy for Alzheimer’s Disease Advances into Phase 2b Trial (GlobeNewswire) - "AC Immune SA...today announced that its development partner has programmed the launch of a Phase 2b clinical study to evaluate ACI-35.030 (JNJ-64042056) in patients with preclinical Alzheimer’s disease (AD), those individuals not yet showing symptoms....Under the terms of the licensing agreement with Janssen Pharmaceuticals, Inc. (Janssen), a Johnson & Johnson company, AC Immune will now receive a milestone payment of CHF 15 million and will receive another milestone payment of CHF 25 million related to achieving a non-disclosed enrollment target....The Phase 2b ReTain trial is a potentially registration-enabling trial and is a randomized, multicenter, double-blind, placebo-controlled clinical study in participants with preclinical AD to assess the clinical effect of active immunization with ACI-35.030."

Commercial • New P2b trial • Alzheimer's Disease • CNS Disorders

AC Immune Reports Third Quarter 2023 Financial Results and Provides a Corporate Update (GlobeNewswire) - "ACI-24.060 anti-Abeta active immunotherapy: Additional interim safety and immunogenicity data from AD cohorts of ABATE study expected in Q4 2023; First Abeta-PET data on amyloid plaque reduction in AD following 6 months of treatment expected in H1 2024; ACI-7104.056 anti-a-syn active immunotherapy: Completion of cohort 1 enrollment and initial safety findings in the Phase 2 VacSYn study in PD expected by year-end; ACI-35.030 anti-pTau active immunotherapy: Initiation of next trial in AD expected in Q4 2023 (to be followed by a milestone payment); Anti-TDP-43 antibody: Advancement of candidate into preclinical development (tox) expected in Q4 2023..."

New trial • P1/2 data • P2 data • Preclinical • Alzheimer's Disease • Amyotrophic Lateral Sclerosis • CNS Disorders • Parkinson's Disease

ACI-35.030 anti-phospho-Tau active immunotherapy for the treatment of early Alzheimer's Disease (AD): Update from the Phase 1b/2a study data and perspectives. (CTAD 2023) - P1/2 | "Background: Two active immunotherapies, ACI-35.030 (liposomal formulation) and JACI-35.054 (conjugated formulation), targeting phosphorylated-Tau (pTau) are currently being tested in a Phase 1b/2a clinical trial (NCT04445831) to evaluate the safety, tolerability and immunogenicity of different doses of these clinical candidates. In general, the liposome-based active immunotherapy ACI-35.030 showed a better antibody profile in terms of rapid response, higher responder rate, homogeneity of the antibody response across study participants, epitope coverage and evidence of antibody maturation towards pathologic forms of Tau. ACI-35.030 has been selected to move into the next stage of clinical development in preclinical AD."

P1/2 data • Alzheimer's Disease • CNS Disorders • Dementia

AC Immune Announces Upcoming Presentations at the 16th CTAD Conference (GlobeNewswire) - "AC Immune SA...today announced upcoming presentations highlighting its precision medicine pipeline at the 16th Clinical Trials on Alzheimer’s Disease (CTAD) Conference, taking place in Boston, USA, on October 24-27, 2023."

Biomarker • P1/2 data • Preclinical • Alzheimer's Disease • CNS Disorders

A Study to Evaluate the Safety, Tolerability and Immunogenicity of Tau Targeted Vaccines in Participants With Early Alzheimer's Disease (clinicaltrials.gov) - P1/2 | N=57 | Completed | Sponsor: AC Immune SA | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia • Aβ42