remternetug (LY3372993) / Eli Lilly - LARVOL DELTA

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

A Study of Remternetug (LY3372993) in Early Alzheimer's Disease (TRAILRUNNER-ALZ 3) (clinicaltrials.gov) - P3 | N=1200 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders

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 | Not yet recruiting ➔ Recruiting

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

A Study of Remternetug in Early Alzheimer's Disease (clinicaltrials.gov) - P3 | N=1200 | Not yet recruiting | Sponsor: Eli Lilly and Company

New P3 trial • Alzheimer's Disease • CNS 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 | Not yet recruiting | Sponsor: Washington University School of Medicine

New P2/3 trial • Alzheimer's Disease • CNS Disorders • Cognitive Disorders • Dementia

Study design for TRAILRUNNER-ALZ 3: A double-blind, placebo-controlled, Phase 3 clinical trial investigating subcutaneous remternetug in early Alzheimer's disease (CTAD 2024) - No abstract available

Clinical • Late-breaking abstract • P3 data • Alzheimer's Disease • CNS Disorders

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 | Not yet recruiting | Sponsor: Washington University School of Medicine | Trial completion date: Mar 2035 ➔ Jun 2034 | Trial primary completion date: Nov 2029 ➔ Mar 2034

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

A Study of Remternetug (LY3372993) in Participants With Alzheimer's Disease (TRAILRUNNER-ALZ 1) (clinicaltrials.gov) - P3 | N=1667 | Active, not recruiting | Sponsor: Eli Lilly and Company | N=600 ➔ 1667

Enrollment change • Alzheimer's Disease • CNS Disorders

Anti-amyloid Antibody Drugs as Disease-Modifying Therapies for Alzheimer's Disease (PubMed, Brain Nerve) - "Notable drugs such as aducanumab, lecanemab, and donanemab have shown potential in clinical trials, leading to the approval of aducanumab and lecanemab, and approval is also expected for donanemab. Other anti-amyloid drugs such as remternetug and trontinemab are also under development...This paper outlines the current status of DMT for AD, including the clinical trial results and current applications of these drugs. It also discusses the existing challenges to improve the safety and accessibility of DMTs."

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

A Study of Remternetug (LY3372993) in Participants With Alzheimer's Disease (TRAILRUNNER-ALZ 1) (clinicaltrials.gov) - P3 | N=600 | Active, not recruiting | Sponsor: Eli Lilly and Company | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2026 ➔ Mar 2026 | Trial primary completion date: Oct 2025 ➔ Jun 2024

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

Navigating the Dementia Landscape: Biomarkers and Emerging Therapies. (PubMed, Ageing Res Rev) - "Notably, Leqembi recently received full FDA approval, marking a significant breakthrough in AD treatment. Additionally, ongoing phase 3 clinical trials are investigating novel therapies, including Masitinib and NE3107, focusing on cognitive and functional improvements in AD patients...Lastly, ongoing clinical trials in anti-amyloid therapy for AD, such as Simufilam, Solanezumab, Gantenerumab, and Remternetug, offer hope for individuals affected by this devastating disease, with the potential to alter the course of cognitive decline. These advancements collectively illuminate the evolving landscape of dementia research and the pursuit of effective treatments for these challenging conditions."

Biomarker • Journal • Review • Alzheimer's Disease • CNS Disorders • Dementia • Frontotemporal Lobar Degeneration • TARDBP

A Study of LY3372993 in Participants With Alzheimer's Disease (AD) and Healthy Participants (clinicaltrials.gov) - P1 | N=224 | 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 Participants With Alzheimer's Disease (TRAILRUNNER-ALZ 1) (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Feb 2026 ➔ Oct 2026 | Trial primary completion date: Feb 2025 ➔ Oct 2025

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

A Study of Remternetug (LY3372993) in Participants With Alzheimer's Disease (TRAILRUNNER-ALZ 1) (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Mar 2025 ➔ Feb 2026 | Trial primary completion date: Mar 2024 ➔ Feb 2025

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

"Exciting early results for @LillyTrials #Remternetug for amyloid plaque clearance #ADPD2023" (@BetterResearch)

SAFETY AND AMYLOID PLAQUE REDUCTION EFFECTS OF REMTERNETUG IN PATIENTS WITH ALZHEIMER'S DISEASE: INTERIM ANALYSIS FROM A PHASE 1 STUDY (ADPD 2023) - No abstract available

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

A Study of Remternetug (LY3372993) in Participants With Alzheimer's Disease (TRAILRUNNER-ALZ 1) (clinicaltrials.gov) - P3 | N=600 | Recruiting | Sponsor: Eli Lilly and Company | N=400 ➔ 600

Enrollment change • Alzheimer's Disease • CNS Disorders

A Study of LY3372993 in Participants With Alzheimer's Disease (AD) and Healthy Participants (clinicaltrials.gov) - P1 | N=224 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Jan 2024 ➔ Jun 2024 | Trial primary completion date: Jan 2024 ➔ Jun 2024

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

A Study of Remternetug (LY3372993) in Participants With Alzheimer's Disease (TRAILRUNNER-ALZ 1) (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Eli Lilly and Company | Trial completion date: Nov 2025 ➔ Mar 2025 | Trial primary completion date: Aug 2024 ➔ Mar 2024

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

A Study of Remternetug (LY3372993) in Participants With Alzheimer's Disease (TRAILRUNNER-ALZ 1) (clinicaltrials.gov) - P3 | N=400 | Recruiting | Sponsor: Eli Lilly and Company | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders