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

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

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 • Transplantation • IL18 • IL1B • NLRP3

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

Research progress of NLRP3 inflammasome and its inhibitors with aging diseases. (PubMed, Eur J Pharmacol) - "At present, the only clinical approach to the treatment of NLRP3 inflammasome-related diseases is to use anti-IL-1β antibodies, but NLRP3-specific inhibitors may be better than the IL-1β antibodies. This article reviews the relationship between NLRP3 inflammasome and aging diseases: summarizes some of the relevant experimental results reported in recent years, and introduces the biological signals or pathways closely related to the NLRP3 inflammasome in a variety of aging diseases, and also introduces some promising small molecule inhibitors of NLRP3 inflammasome for clinical treatment, such as: ZYIL1, DFV890 and OLT1177, they have excellent pharmacological effects and good pharmacokinetics."

Journal • Review • Alzheimer's Disease • Cardiovascular • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • IL1B • NLRP3

DFV890-FCAS: Study of Safety, Tolerability and Efficacy of DFV890 in Participants With Familial Cold Auto-inflammatory Syndrome (FCAS) (clinicaltrials.gov) - P2 | N=4 | Completed | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Completed | Trial primary completion date: May 2023 ➔ Dec 2022

Trial completion • Trial primary completion date • Genetic Disorders • Inflammation

"Inflammasome inhibitors in development: - RRx-001 in cancer, ALS, parkinsons - OLT1177 in OA knee, gout, Schnitzlers - DFV890 in CAPs, knee OA - IZD174/334 in CAPS - ZYIL1 CAPS https://t.co/7E2jdx9TPA" (@RheumNow)

CNS Disorders • Gout • Inflammatory Arthritis • Movement Disorders • Oncology • Parkinson's Disease • Rheumatology

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 2024 ➔ Apr 2025 | Trial primary completion date: Mar 2024 ➔ Mar 2025

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

Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases (clinicaltrials.gov) - P1b | N=80 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Myelodysplastic Syndrome

"March 2023 WRAP of compounds I uncovered on Molecular Sherlock! ✨STARRING✨ DFV890: NLRP3i @Novartis in ph2 for osteoarthritis BI 1015550 ✅: PDE4i @Boehringer in ph3 for IPF MK-0616 ✅: PCSK9i @Merck in ph3 for hypercholesterolemia $MRK $NVS https://t.co/zeOO090cND" (@victoriacyanide)

Dyslipidemia • Immunology • Metabolic Disorders • Osteoarthritis • Pain • Rheumatology • NLRP3

"DFV890: an NLRP3 inhibitor by @Novartis currently in ph2 for the tx of osteoarthritis! $NVS How did I figure out the structure? A thread! 🧵1/13 PS - subscribe to my substack, Molecular Sherlock, for more small molecule detective work!👇 https://t.co/Pmu7MlMaz9" (@victoriacyanide)

Immunology • Osteoarthritis • Pain • Rheumatology • NLRP3

Dose Optimization and Expansion Study of DFV890 in Adult Patients With Myeloid Diseases (clinicaltrials.gov) - P1b | N=80 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P1 trial • Myelodysplastic Syndrome

DFV890: a new oral NLRP3 inhibitor-tested in an early phase 2a randomised clinical trial in patients with COVID-19 pneumonia and impaired respiratory function. (PubMed, Infection) - P2 | "DFV890 did not meet statistical significance for superiority vs. SoC in primary endpoint of combined APACHE II score at Day 14. However, early SARS-CoV-2 clearance, improved clinical status and in-hospital outcomes, and fewer fatal events occurred with DFV890 vs. SoC, and it may be considered as a protective therapy for CARDS."

Journal • P2a data • Acute Respiratory Distress Syndrome • Infectious Disease • Novel Coronavirus Disease • Pneumonia • Pulmonary Disease • Respiratory Diseases • CRP • NLRP3

DFV890-FCAS: Study of Safety, Tolerability and Efficacy of DFV890 in Participants With Familial Cold Auto-inflammatory Syndrome (FCAS) (clinicaltrials.gov) - P2 | N=6 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2022 ➔ Feb 2023 | Trial primary completion date: Aug 2022 ➔ Jan 2023

Trial completion date • Trial primary completion date • Genetic Disorders • Inflammation

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: Sep 2023 ➔ Apr 2024 | Trial primary completion date: Sep 2023 ➔ Apr 2024

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