VHB-937 / Novartis - LARVOL DELTA

IGSF-TREM2 ACTIVATION BY VHB937 AMELIORATES PATHOLOGY IN ANIMAL MODELS OF AMYLOIDOSIS AND TAUOPATHY (ADPD 2026) - "Activating TREM2 with an IgSF-binding antibody like VHB937 has significant effects in two different animal models on pathological hallmarks of AD such as dystrophic neurites and tau pathology as well as reducing cytokines/chemokines, microgliosis and astrogliosis."

Preclinical • Alzheimer's Disease • Amyloidosis • CNS Disorders • CCL3 • GFAP • IL6 • TNFA

TREM2 BINDING SITE MATTERS. VHB937, AN IGSF-BINDING ANTIBODY, TRIGGERS A MICROGLIAL ACTIVATION PROFILE DIFFERENT TO THAT OF A STALK-BINDING ANTIBODY. (ADPD 2026) - "Interestingly, in FIH studies the stalk binding Ab AL002 (DOI:10.1186/s13195-024-01599-1) showed elevation of SPP1 in CSF but decreased for VHB937. Activating TREM2 with an IgSF-binding antibody like VHB937 produces substantially different downstream signaling patterns compared to those produced by binding at the stalk region."

CNS Disorders • SPP1 • TREM2

VHB937, a TREM2 stabilizing and activating fully human monoclonal antibody: A Phase 2 study design in Alzheimer's disease and rationale (CTAD 2025) - No abstract available

P2 data • Alzheimer's Disease • CNS Disorders

New Phase 2 Trial to Test TREM2-Stabilizing Agent VHB937 in Alzheimer Disease (NeurologyLive) - "In the poster presentation, Graf et al shared preclinical and first-in-human data that further supported VHB937’s potential as a treatment for AD. In a hTREM2-APP23-PS45 amyloidosis mouse model, treatment with the agent led to reduced dystrophic neuritis. An additional TREM2KIxtau58.4 tauopathy model revealed lowered AT8 phosphorylated tau levels in the spinal cord of treated mice....In a first-in-human single-ascending-dose study of 64 healthy participants, VHB937 was detectable in CSF and produced dose-dependent reductions in proinflammatory biomarkers such as SPP1, sCSF1R, and CCL3, aligning with preclinical findings."

First-in-human • P2 data • Preclinical • Alzheimer's Disease

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