DFV890 / Novartis - LARVOL DELTA

Preliminary Safety and Biomarker Results of the NLRP3 Inflammasome Inhibitor DFV890 in Adult Patients with Myeloid Diseases: A Phase 1b Study (ASH 2024) - P1 | "Analysis of peripheral cytokines and hematologic parameters showed early indications of activity in a subset of patients, particularly those with mutations in TET2 and those transfusion independent at baseline. These findings will require confirmation with longer follow-up and in the dose expansion phase of the study."

Biomarker • Clinical • P1 data • Anemia • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • IL18 • IL1B • IL1R1 • IL6 • NLRP3 • TET2

Immunopharmacological reprogramming of innate immune memory in Alzheimer's disease: From microglial priming to therapeutic resilience. (PubMed, Biochem Pharmacol) - "We evaluate the emerging immunopharmacological toolbox designed to reverse maladaptive priming and restore neuroprotective resilience, focusing on small‑molecule NLRP3 inflammasome inhibitors (HT‑6184, DFV890, BGE‑102), TREM2 agonists (VG‑3927, MNA‑001), metabolic modulators (metformin, rapamycin), trained immunity‑based vaccination (BCG), specialized pro‑resolving mediators (maresin 1, resolvin D1, lipoxin A4), and senolytics...We argue that the next generation of AD therapeutics must move beyond target suppression toward the functional reprogramming of brain innate immunity, and we propose a biomarker-guided, patient-stratified framework that integrates multimodal immunopharmacology, combining NLRP3 inhibition, TREM2 agonism, metabolic reprogramming, and resolution pharmacology to restore immune homeostasis. Harnessing the plasticity of innate immune memory offers a transformative paradigm for disease‑modifying therapy in AD."

Journal • Review • Alzheimer's Disease • CNS Disorders • Inflammation • HIF1A • NLRP3

Characterization of DFV890 effect on synovitis activity measured by dynamic-contrast-enhenced (DCE)-MRI in patients with inflammatory knee osteoarthritis (EULAR 2026) - P2 | "Furthermore, the observed decrease in synovitis may be associated with a reduction in pain. Given the inherent challenges of objectively measuring pain in clinical settings, the study suggests that Ktrans, a quantitative measure of capillary permeability obtained through DCE-MRI, may serve as a reliable surrogate marker for local pain assessment in this patient population."

Clinical • Immunology • Orthopedics • Osteoarthritis • Pain • Rheumatology • IL1B • NLRP3 • TNFA

Phase II study of the NLRP3 inhibitor DFV890 as anti-inflammatory principle for the treatment of pain in osteoarthritis (EULAR 2026) - "Modulating key cytokine pathways, NLRP3 inhibition reduced synovitis. Further studies are needed to confirm these results and optimize patient selection."

First-in-human • P2 data • Addiction (Opioid and Alcohol) • Immunology • Metabolic Disorders • Musculoskeletal Pain • Osteoarthritis • Pain • Rheumatology • CRP • IL1B • NLRP3

Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases (clinicaltrials.gov) - P1 | N=59 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | N=105 ➔ 59

Enrollment change • Myelodysplastic Syndrome

Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases (clinicaltrials.gov) - P1 | N=105 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Myelodysplastic Syndrome

Safety and Preliminary Efficacy of DFV890 in Adult Patients with Myeloid Diseases: A Phase 1b Study (ASH 2023) - P1 | "Eligible pts must be 18 years of age, with an Eastern Cooperative Oncology Group performance status ≤2, candidates for serial bone marrow assessments who are willing to undergo a bone marrow aspirate/biopsy during the trial, and meet one of the following: (a) IPSS-R–defined LR-MDS who failed to respond to or did not tolerate erythropoiesis-stimulating agents (ESAs) or luspatercept or hypomethylating agents (HMAs) and pts with del 5q who failed to respond to or did not tolerate lenalidomide; (b) CPSS–defined LR-CMML who failed to respond to or did not tolerate hydroxyurea or HMAs. The study is currently enrolling in Singapore, Hong Kong, and the USA with plans to treat approximately 80 pts. The first patient first visit was achieved on May 8, 2023."

Clinical • P1 data • Chronic Myelomonocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • IL18 • IL1B • NLRP3

Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases (clinicaltrials.gov) - P1 | N=105 | Recruiting | Sponsor: Novartis Pharmaceuticals | N=80 ➔ 105

Enrollment change • Myelodysplastic Syndrome

Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2026 ➔ Feb 2027 | Trial primary completion date: Jun 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • Myelodysplastic Syndrome

Discovery of DFV890, a Potent Sulfonimidamide-Containing NLRP3 Inflammasome Inhibitor. (PubMed, J Med Chem) - "Replacement of the furan unit of CRID3 with a 5-substituted thiazole unit led to DFV890 ((R)-1), which potently inhibited IL-1β production in THP-1 cells and in primary human cells, blocked multiple downstream effectors of NLRP3 activation, and substantially improved PK properties and significantly lowered the predicted human dose compared to that for CRID3. DFV890 ((R)-1) was also effective in an air pouch model of gout."

Journal • Gout • Inflammatory Arthritis • Rheumatology • IL1B • NLRP3

Study of Efficacy, Safety and Tolerability of DFV890 in Patients With Knee Osteoarthritis (clinicaltrials.gov) - P2 | N=115 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Immunology • Osteoarthritis • Pain • Rheumatology • CRP

A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease and Elevated hsCRP (clinicaltrials.gov) - P2 | N=24 | Completed | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Completed

Trial completion • Cardiovascular • Coronary Artery Disease • Heart Failure • CRP • IL18 • IL6

A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 and MAS825 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease and Clonal Hematopoiesis of Indeterminate Potential (CHIP) (clinicaltrials.gov) - P2 | N=31 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Coronary Artery Disease • Heart Failure • Hematological Disorders • DNMT3A • IL18 • IL6 • TET2

Study of Efficacy, Safety and Tolerability of DFV890 in Patients With Knee Osteoarthritis (clinicaltrials.gov) - P2 | N=115 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Immunology • Osteoarthritis • Pain • Rheumatology • CRP

A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 and MAS825 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease and Clonal Hematopoiesis of Indeterminate Potential (CHIP) (clinicaltrials.gov) - P2 | N=31 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | Trial completion date: Feb 2026 ➔ Nov 2024 | Trial primary completion date: Feb 2026 ➔ Oct 2024

Enrollment closed • Trial completion date • Trial primary completion date • Cardiovascular • Coronary Artery Disease • Heart Failure • Hematological Disorders • DNMT3A • IL18 • IL6 • TET2

Study of Efficacy, Safety and Tolerability of DFV890 in Patients With Knee Osteoarthritis (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Apr 2025 ➔ Dec 2024 | Trial primary completion date: Mar 2025 ➔ Dec 2024

Trial completion date • Trial primary completion date • Immunology • Osteoarthritis • Pain • Rheumatology • CRP

First-in-human safety, tolerability, and pharmacokinetic results of DFV890, an oral low-molecular-weight NLRP3 inhibitor. (PubMed, Clin Transl Sci) - "Crystalline tablets of 100 mg once-daily or 25 mg twice-daily were sufficient to maintain ~90% of the IL-1β release inhibition over 24 h at steady state. Data support dose and formulation selection for further development in diseases, in which an overactivated NLRP3 represents the underlying pathophysiology."

Clinical • Journal • P1 data • P1 data • PK/PD data • Developmental Disorders • IL1B • NLRP3

A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 and MAS825 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease and Clonal Hematopoiesis of Indeterminate Potential (CHIP) (clinicaltrials.gov) - P2 | N=28 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Coronary Artery Disease • Heart Failure • Hematological Disorders • DNMT3A • IL18 • IL6 • TET2

Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2025 ➔ Jun 2026 | Trial primary completion date: Jun 2025 ➔ Jun 2026

Trial completion date • Trial primary completion date • Myelodysplastic Syndrome

A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 and MAS825 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease and Clonal Hematopoiesis of Indeterminate Potential (CHIP) (clinicaltrials.gov) - P2 | N=28 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals | Phase classification: P2a ➔ P2

Phase classification • Cardiovascular • Coronary Artery Disease • Heart Failure • Hematological Disorders • DNMT3A • IL18 • IL6 • TET2

A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease (clinicaltrials.gov) - P2 | N=24 | Recruiting | Sponsor: Novartis Pharmaceuticals | Phase classification: P2a ➔ P2

Phase classification • Cardiovascular • Coronary Artery Disease • Heart Failure • CRP • IL18 • IL6

Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases (clinicaltrials.gov) - P1 | N=80 | Recruiting | Sponsor: Novartis Pharmaceuticals | Phase classification: P1b ➔ P1

Phase classification • Myelodysplastic Syndrome

A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease (clinicaltrials.gov) - P2a | N=24 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Coronary Artery Disease • Heart Failure • CRP • IL18 • IL6

A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 and MAS825 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease and Clonal Hematopoiesis of Indeterminate Potential (CHIP) (clinicaltrials.gov) - P2a | N=28 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P2a trial • Cardiovascular • Coronary Artery Disease • Heart Failure • Hematological Disorders • DNMT3A • IL18 • IL6 • TET2

A Study to Investigate the Efficacy, Safety, and Tolerability of DFV890 for Inflammatory Marker Reduction in Adult Participants With Coronary Heart Disease (clinicaltrials.gov) - P2a | N=24 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P2a trial • Cardiovascular • Coronary Artery Disease • Heart Failure • CRP • IL18 • IL6