VHB-937 / Novartis - LARVOL DELTA

A study to evaluate the efficacy and safety of VHB937 in people with ALS: Interim baseline data from the ASTRALS double-blind, randomized, placebo-controlled study (ALS-MND 2025) - P2 | "Eligible participants must have an ALS diagnosis with symptom onset within 24 months prior to screening, be untreated or treated with stable ALS standard of care treatment (riluzole and/or edaravone) and meet specific criteria such as slow vital capacity (SVC) ~60% and an ALSFRS-R score ≥30. This study will focus on the clinical outcomes change in ALS using a TREM2 monoclonal antibody."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • CCL3 • CSF1R • NEFL • SPP1

ASTRALS: A Clinical Trial to Learn About the Effects of VHB937 in People With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P2 | N=251 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial primary completion date: Jan 2027 ➔ Sep 2026

Trial primary completion date • Amyotrophic Lateral Sclerosis • CNS Disorders

ASTRALS: A Clinical Trial to Learn About the Effects of VHB937 in People With Amyotrophic Lateral Sclerosis (ALS) (clinicaltrials.gov) - P2 | N=251 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Amyotrophic Lateral Sclerosis • CNS Disorders

A Clinical Trial to Learn About the Effects of VHB937 in People With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=407 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Alzheimer's Disease • CNS Disorders

VHB937, a TREM2 stabilizing and activating antibody changes microglial state, reduces pro-inflammatory biomarkers in vivo, displays efficacy in animal models of neuroinflammation and reduces pro-inflammatory markers in a First-in-human study (ECTRIMS 2025) - "The current pre-clinical profile of VHB937 supports further development for the treatment of MS and other neurologic diseases where microglia are thought to be involved."

First-in-human • P1 data • Preclinical • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • TREM2

A Clinical Trial to Learn About the Effects of VHB937 in People With Early Alzheimer's Disease (clinicaltrials.gov) - P2 | N=407 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P2 trial • Alzheimer's Disease • CNS Disorders

SAFETY, PHARMACOKINETICS AND PHARMACODYNAMICS OF VHB937, A TREM2 STABILIZING AND ACTIVATING ANTIBODY IN HEALTHY VOLUNTEERS: PRELIMINARY FIRST-IN-HUMAN RESULTS (ADPD 2025) - "Conclusions In this Phase 1 study, VHB937 showed favorable safety and PK characteristics. Additionally, biomarker Results were consistent with preclinical biomarker findings associated with a shifting of pro-inflammatory microglia phenotype to pro-resolution/neuroprotective phenotype."

Clinical • P1 data • PK/PD data • CCL3 • CSF1R • SPP1 • TREM2

VHB937, A TREM2 STABILIZING AND ACTIVATING ANTIBODY CHANGES MICROGLIAL STATE, REDUCES PRO-INFLAMMATORY BIOMARKERS AND IS EFFICACIOUS IN ANIMAL MODELS FOR NEUROINFLAMMATION AFTER PERIPHERAL ADMINISTRATION (ADPD 2025) - "The current pre-clinical profile of VHB937 supports clinical development in neurodegenerative conditions."

Preclinical • Amyloidosis • CNS Disorders • Inflammation • CCL3 • CSF1R • SPP1 • TREM2

VHB937, a TREM2 stabilizing and activating antibody, strongly reduces pathology after peripheral administration in a broad range of animal models for neuroinflammation and neurodegeneration (ALS-MND 2024) - "VHB937 is a fully human mAb that activates selectively TREM2 in human M2A macrophages and human induced pluripotent stem cell (iPS) microglia cells with subnanomolar affinities and increases TREM2 cell surface expression by reduction of shedding. Intracellularly, the antibody increases Syk-phosphorylation and drives calcium signaling. VHB937 facilitates key functions of microglia cells such as chemotaxis and phagocytosis in vitro."

Preclinical • CNS Disorders • Inflammation • SYK • TREM2

A study to evaluate the efficacy and safety of VHB937 in participants with ALS: The ASTRALS double-blind, randomized, placebo-controlled study (ALS-MND 2024) - " The planned study will evaluate the effect of targeting the TREM2 pathway to favorably alter microglial phenotype to slow ALS disease progression. The study design incorporates guidance from ALS experts, health authorities, and people living with ALS, to balance the perspectives of these stakeholder groups."

Clinical • Amyotrophic Lateral Sclerosis • CNS Disorders • Inflammation • NEFL