MHV370 / Novartis - LARVOL DELTA

FUNCTIONAL MAPPING OF AUTOIMMUNE PATIENTS BASED ON SERUM IMMUNE COMPLEXES REVEALS A COMMON TLR7/8 ENDOTYPE (EULAR 2024) - "MHV370 differentiated from other compounds used for SLE therapy, e.g. hydroxychloroquine or inhibitors of IFN signaling, suggesting that TLR7/8 responses are a likely contributor to pathology. Functional characterization of patient sera uncovered a TLR7/8 driven endotype across certain systemic autoimmune diseases. These translational studies highlight the potential of targeting TLR7/8 and support clinical basket trials."

Clinical • IO biomarker • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Rheumatology • Systemic Lupus Erythematosus • TLR7

Discovery of the TLR7/8 Antagonist MHV370 for Treatment of Systemic Autoimmune Diseases. (PubMed, ACS Med Chem Lett) - "Here, we describe how structure-based optimization of compound 2 resulted in the discovery of 34 (MHV370, (S)-N-(4-((5-(1,6-dimethyl-1H-pyrazolo[3,4-b]pyridin-4-yl)-3-methyl-4,5,6,7-tetrahydro-1H-pyrazolo[4,3-c]pyridin-1-yl)methyl)bicyclo[2.2.2]octan-1-yl)morpholine-3-carboxamide). Its in vivo activity allows for further profiling toward clinical trials in patients with autoimmune disorders, and a Phase 2 proof of concept study of MHV370 has been initiated, testing its safety and efficacy in patients with Sjögren's syndrome and mixed connective tissue disease."

Journal • Immunology • Inflammation • Inflammatory Arthritis • Lupus • Rheumatology • Sjogren's Syndrome • Systemic Lupus Erythematosus • TLR7 • TLR8

First-in-Human Study of the Safety, Pharmacokinetics, and Pharmacodynamics of MHV370, a Dual Inhibitor of Toll-Like Receptors 7 and 8, in Healthy Adults. (PubMed, Eur J Drug Metab Pharmacokinet) - "The safety, pharmacokinetic and pharmacodynamic data support the further development of MHV370 in systemic autoimmune diseases driven by the overactivation of TLR7 and TLR8."

IO biomarker • Journal • P1 data • PK/PD data • Immunology • Inflammatory Arthritis • Lupus • CD69 • TLR7 • TLR8

A novel TLR7/8 antagonist blocks pro-inflammatory function of immune complexes from lupus patients and abrogates lupus-like disease in mice (EULAR 2023) - "Unlike hydroxychloroquine, MHV370 interfered with cytokine production triggered by immune complexes between systemic lupus erythematosus patient sera and necrotic cell extract, suggesting differentiation from clinical standard of care. Conclusion The pharmacological data presented here support further development of MHV370 towards clinical proof of concept trials in man."

IO biomarker • Preclinical • Glomerulonephritis • Immunology • Inflammatory Arthritis • Lupus • Lupus Nephritis • Nephrology • Systemic Lupus Erythematosus

Preclinical characterization of the Toll-like receptor 7/8 antagonist MHV370 for lupus therapy. (PubMed, Cell Rep Med) - "Unlike hydroxychloroquine, MHV370 potently blocks interferon responses triggered by specific immune complexes from systemic lupus erythematosus patient sera, suggesting differentiation from clinical standard of care. These data support advancement of MHV370 to an ongoing phase 2 clinical trial."

IO biomarker • Journal • Preclinical • Immunology • Inflammatory Arthritis • Lupus • Systemic Lupus Erythematosus • TLR7

A Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjogren's Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD) (clinicaltrials.gov) - P2 | N=30 | Terminated | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Terminated; Sponsor decision

Pan tumor • Trial termination • Immunology • Rheumatology • Sjogren's Syndrome

A Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjogren's Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD) (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jan 2024 ➔ Mar 2023 | Trial primary completion date: Dec 2023 ➔ Mar 2023

Pan tumor • Trial completion date • Trial primary completion date • Immunology • Rheumatology • Sjogren's Syndrome

A Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjogren's Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD) (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=60 ➔ 30

Enrollment change • Enrollment closed • Immunology • Rheumatology • Sjogren's Syndrome

A Study to Evaluate the Safety, Tolerability and Efficacy of MHV370 in Participants With Sjogren's Syndrome (SjS) or Mixed Connective Tissue Disease (MCTD) (clinicaltrials.gov) - P2; N=60; Recruiting; Sponsor: Novartis Pharmaceuticals; Not yet recruiting ➔ Recruiting

Clinical • Enrollment open • Pan tumor • Immunology • Rheumatology • Sjogren's Syndrome