remternetug (LY3372993) / Eli Lilly - LARVOL DELTA

A Study of Remternetug (LY3372993) in Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=24 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion

Evaluating emerging amyloid-β centric drugs for the treatment of Alzheimer's disease. (PubMed, Expert Opin Emerg Drugs) - "The recent approvals of lecanemab and donanemab offered the first convincing evidence that reducing Aβ burden can modestly slow cognitive decline in early AD. Beyond these first-generation monoclonal antibodies, the pipeline includes next-generation antibodies with enhanced brain penetration (trontinemab), therapies designed also for presymptomatic intervention (remternetug tested for secondary prevention), and novel approaches targeting galectin-3 to disrupt Aβ aggregation and neuroinflammation. Active immunotherapies like UB-311 and small molecules such as ALZ-801, avoiding amyloid-related imaging abnormalities (ARIA), broaden the therapeutic horizon with potentially safer and more accessible options, but with no proven efficacy...Regulators have begun to restrict approval to genetically defined subgroups according to apolipoprotein E genotype, underscoring the need for precision medicine. Therefore, while Aβ-centric therapies are incremental, they represent essential..."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • APOE

A Study of Remternetug (LY3372993) in Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Jan 2027 ➔ Aug 2026

Trial completion date

A Study of Remternetug (LY3372993) in Participants With Alzheimer's Disease (TRAILRUNNER-ALZ 1) (clinicaltrials.gov) - P3 | N=1667 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion • Alzheimer's Disease • CNS Disorders

A Study of Remternetug (LY3372993) in Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=24 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed

Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease. (PubMed, Cochrane Database Syst Rev) - "The effect of amyloid-beta-targeting monoclonal antibodies on cognitive function and dementia severity at 18 months in people with mild cognitive impairment or mild dementia due to Alzheimer's disease is trivial, while on functional ability, it is small at best. Amyloid-beta-targeting monoclonal antibodies increase the risk of amyloid-related imaging abnormalities. Both desirable outcomes and adverse events were inconsistently reported in the studies included in the review. Successful removal of amyloid from the brain does not seem to be associated with clinically meaningful effects in people with mild cognitive impairment or mild dementia due to Alzheimer's disease. Future research on disease-modifying treatments for Alzheimer's disease should focus on other mechanisms of action."

Clinical • Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

DIFFERENTIAL INDUCTION OF ARIA-LIKE PATHOLOGIES BY ANTI-AΒ IMMUNOTHERAPIES IN 5XFAD MICE: A COMPREHENSIVE ANALYSIS OF 12-WEEKS DOSING WITH CLINICAL-STAGE ANTIBODIES (ADPD 2026) - "Aims: The pathophysiological mechanisms and the differential risk profiles among antibodies, particularly next-generation agents like Remternetug, remain incompletely understood in aspect of Amyloid-Related Imaging Abnormalities (ARIA), adverse events associated with anti-amyloid-beta (Aβ) immunotherapies for Alzheimer's disease. We treated 40-weeks-old 5XFAD mice (n=5-10 group) for 12 weeks with weekly (QW) intraperitoneal injections of: 1) Isotype-mIgG2 control, 2) 3D6-mIgG2 (murine precursor of bapineuzumab), 3) Aducanumab-mIgG2 (humanized), or 4) Remternetug-mIgG2 (humanized). This head-to-head study in a robust amyloidosis model demonstrates that the risk of inducing ARIA-like pathology is highly dependent on the specific antibody's properties. These preclinical findings provide critical mechanistic insights into ARIA pathogenesis and underscore the importance of antibody selection for mitigating treatment-emergent adverse events."

Preclinical • Alzheimer's Disease • Amyloidosis • CNS Disorders • Hematological Disorders • GFAP

SCREENING AND BASELINE CHARACTERISTICS IN TRAILRUNNER-ALZ 3: A PHASE 3 CLINICAL TRIAL INVESTIGATING SUBCUTANEOUS REMTERNETUG IN ALZHEIMER'S DISEASE STAGES 1-3 (ADPD 2026) - P3 | "Baseline characteristics indicate that TRAILRUNNER-ALZ 3 enrolled participants with AD stages 1-3, allowing the opportunity to evaluate whether remternetug slows clinically meaningful progression in this population."

Clinical • P3 data • Alzheimer's Disease • Cerebral Hemorrhage • CNS Disorders • Dementia • Hematological Disorders

A Study of Remternetug (LY3372993) in Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=24 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open

A Study of Remternetug (LY3372993) in Healthy Participants (clinicaltrials.gov) - P1 | N=72 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed

Trial completion

A Study of Remternetug (LY3372993) in Healthy Chinese Participants (clinicaltrials.gov) - P1 | N=24 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P1 trial

Feasibility of Participants with Symptomatic Alzheimer's Disease to Self-Administer Remternetug Subcutaneously: Results from the TRAILRUNNER-ALZ 1 Phase 3 Trial (CTAD 2025) - No abstract available

P3 data • Alzheimer's Disease • CNS Disorders

Early Phase 3 Data Highlight Convenience and Feasibility of Self-Administered Alzheimer Agent Remternetug (NeurologyLive) - "A newly presented analysis of the phase 3 TRAILRUNNER-ALZ-1 trial (NCT05463731) showed that remternetug (Eli Lilly), a self-administered investigational monoclonal antibody targeting amyloid-ß (Aß), was feasible to use in patients with Alzheimer disease (AD) in stages 3 and 4...Presented at the 2025 Clinical Trials on Alzheimer’s Disease (CTAD) Conference...The trial, which is expected to be completed by 2026, uses percentage of patients who reach amyloid plaque clearance, measured through amyloid PET scans, as the primary outcome measure....As mentioned, 56.9% (n = 112) of participants had at least 1 non-healthcare professional (HCP) SC injection. Among these patients, most injections (88.5%; 1019 of 1151) were self-administered (43.1%) or administered by a study partner (45.4%), and only 10.5% were administered by a healthcare professional."

P3 data • Trial completion date • Alzheimer's Disease

DIAN-TU: A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset AD Caused by a Genetic Mutation (clinicaltrials.gov) - P2/3 | N=280 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Jun 2030 ➔ Aug 2034 | Trial primary completion date: Jun 2030 ➔ Mar 2034

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

A Study of Remternetug (LY3372993) in Early Alzheimer's Disease (TRAILRUNNER-ALZ 3) (clinicaltrials.gov) - P3 | N=1400 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed • Alzheimer's Disease • CNS Disorders

A Study of Remternetug (LY3372993) in Healthy Participants (clinicaltrials.gov) - P1 | N=72 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting

Enrollment closed

DIAN-TU: A Study of Potential Disease Modifying Treatments in Individuals at Risk for or With a Type of Early Onset AD Caused by a Genetic Mutation (clinicaltrials.gov) - P2/3 | N=280 | Recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Aug 2034 ➔ Jun 2030 | Trial primary completion date: Mar 2034 ➔ Jun 2030

Trial completion date • Trial primary completion date • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

A Study of Remternetug (LY3372993) in Healthy Participants (clinicaltrials.gov) - P1 | N=72 | Recruiting | Sponsor: Eli Lilly and Company

New P1 trial

Chimeric antigen receptors discriminate between tau and distinct amyloid-beta species. (PubMed, J Transl Med) - "Our findings demonstrate that CARs can detect and discriminate between tau PFFs, Aβ1-42, and Aβp3-42 aggregates. This highlights the potential of repurposing AD antibodies for CAR-based therapies to selectively target tau NFTs and distinct forms of Aβ senile plaques."

IO biomarker • Journal • Alzheimer's Disease • CNS Disorders • Oncology • CD4 • CD69 • IL2RA

TRAILRUNNER-ALZ 3: A DOUBLE-BLIND, PLACEBO-CONTROLLED, PHASE 3 CLINICAL TRIAL OF SUBCUTANEOUS REMTERNETUG DESIGNED TO ENROLL A STAGE 1-3 AD POPULATION (ADPD 2025) - P3 | "Enrollment opened in Q4, 2024. Conclusions The TR3 study entry criteria are anticipated to facilitate enrollment of the appropriate population to test the hypothesis that remternetug meaningfully slows clinical progression in individuals with AD Stages 1-3."

Clinical • P3 data • Alzheimer's Disease • CNS Disorders • Dementia

IMMUNOGENICITY AND SUBCUTANEOUS BIOAVAILABILITY OF REMTERNETUG IN PARTICIPANTS WITH ALZHEIMER'S DISEASE AND HEALTHY PARTICIPANTS IN A PHASE 1 STUDY (ADPD 2025) - P1 | "In healthy volunteers, the absolute bioavailability of remternetug was estimated at 61% after a single SC dose. Conclusions The immunogenicity profile and bioavailability of remternetug support development of SC remternetug for people with AD."

Clinical • P1 data • Alzheimer's Disease • CNS Disorders • Immunology

A Study of LY3372993 in Participants With Alzheimer's Disease (AD) and Healthy Participants (clinicaltrials.gov) - P1 | N=139 | Completed | Sponsor: Eli Lilly and Company | Active, not recruiting ➔ Completed | N=224 ➔ 139

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

Chimeric Antigen Receptors Discriminate Between Tau and Distinct Amyloid-Beta Species. (PubMed, bioRxiv) - "To investigate this, we engineered CARs based on AD antibodies targeting tau (E2814), Aβ (Lecanemab and Aducanumab), and truncated pyroglutamate form of Aβ (Aβp3-42; Donanemab and Remternetug). Our findings demonstrate that CARs can detect and discriminate between tau preformed fibrils (PFFs), Aβ 1-42 , and Aβp3-42 aggregates. This highlights the potential of repurposing AD antibodies for CAR-based therapies to selectively target tau NFTs and distinct forms of Aβ senile plaques."

Journal • Alzheimer's Disease • CNS Disorders • Oncology

Successes and failures: the latest advances in the clinical development of amyloid-β-targeting monoclonal antibodies for treating Alzheimer's disease. (PubMed, Expert Opin Biol Ther) - "The preliminary success of the recent Phase III randomized clinical trials (RCTs) of lecanemab, donanemab, and remternetug, and lessons learned from the failure of previous anti-Aβ monoclonal antibodies RCTs, provided critical evidence to support the role of Aβ in AD pathogenesis. The loss of free Aβ instead of an Aβ toxicity may promote AD neuropathology. Cerebrospinal fluid analyses (i.e. increases in Aβ1-42) may indicate a potential benefit of anti-Aβ monoclonal antibodies in AD and downstream biomarkers should be considered for providing comprehension in cognitive and clinical efficacy of future AD RCTs."

Clinical • Journal • Review • Alzheimer's Disease • CNS Disorders • Cognitive Disorders

DIAN-TU-002: A Study of a Potential Disease Modifying Treatment in Individuals at Risk for or With a Type of Early Onset AD Caused by a Genetic Mutation (clinicaltrials.gov) - P2/3 | N=280 | Recruiting | Sponsor: Washington University School of Medicine | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia