dapansutrile (OLT1177) / Olatec Therap - LARVOL DELTA

Beyond Lipids and Platelets: A Review of Anti-Inflammatory Strategies in Secondary Prevention of Acute Coronary Syndromes. (PubMed, J Clin Med) - "Colchicine, now FDA-approved for cardiovascular risk reduction, lowered major adverse cardiovascular events in COLCOT and LoDoCo2. Canakinumab (IL-1β inhibition) reduced recurrent events in proportion to IL-6 and hsCRP suppression, while ziltivekimab (IL-6 inhibition) achieved profound biomarker reductions but remains investigational. Early-phase studies of anakinra (IL-1 receptor antagonist) and dapansutrile (oral NLRP3 inhibitor) showed anti-inflammatory effects in early trials, whereas varespladib and darapladib illustrated the challenges of targeting lipid-associated pathways...Additional emerging avenues include triptolidiol, dasatinib, and BTK or JAK/STAT inhibitors, while novel approaches, such as nanozyme delivery systems and CRISPR-based editing, extend the therapeutic horizon. This review highlights the potential of inflammation-targeted therapies to advance secondary prevention in ACS by integrating current evidence and perspectives on future therapeutic..."

Journal • Review • Acute Coronary Syndrome • Atherosclerosis • Cardiovascular • Coronary Artery Disease • Immunology • Inflammation • Myocardial Infarction • CRP • IL1B • NLRP3

Inflammasomes as Potential Therapeutic Targets to Prevent Chronic Active Viral Myocarditis-Translating Basic Science into Clinical Practice. (PubMed, Int J Mol Sci) - "Additionally, we discuss both novel and established therapeutic strategies targeting inflammatory and anti-fibrotic mechanisms, including IL-1 receptor blockers (anakinra, canakinumab), NOD-like receptor protein 3 (NLRP3) inhibitors (colchicine, MCC950, dapansutrile, INF200), NF-κB inhibitors, and angiotensin receptor-neprilysin inhibitors (ARNI), as well as microRNAs. Our aim is to emphasize the clinical importance of early identification of patients at risk of transitioning from acute to chronic inflammation, elucidate the role of inflammasomes, and present emerging therapies that may improve outcomes by balancing effective pathogen clearance with limitation of chronic cardiac damage."

Journal • Review • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Infectious Disease • Inflammation • Respiratory Diseases • IL18 • IL1B • NLRP3

Metabolic Alterations Associated with Loss of TET2 Potentiates Inflammation in Myeloid Cells Driving Breast Cancer Progression (ASH 2023) - "The increased tumor burden in Tet2+/- mice was shown to be NLRP3-dependent as Tet2+/-mice receiving the NLRP3 inhibitor, OLT1177, exhibited significantly decreased tumor growth compared to Tet2+/- mice with no treatment (Figure 1)...Importantly, LPS induced TNFα and IL-18 only decreased after 2-DG and 6-AN treatment in Tet2+/- myeloid cells suggesting metabolic changes associated with loss of TET2 affect not only NLRP3 priming but TNFα secretion as well. Overall, these studies demonstrate how TET2-driven CHIP alters the tumor microenvironment in breast cancers through aberrant NLRP3 activation and characterizes the underlying metabolic alterations subsequent to loss of TET2, offering further mechanistic insight into the hyperinflammatory phenotype in myeloid cells associated with TET2-driven CHIP."

Breast Cancer • Hematological Malignancies • Oncology • Solid Tumor • IL18 • IL1B • IL6 • NLRP3 • TET2 • TNFA

DAPA-PD: A Trial to Test the Use of Dapansutrile, an Anti-inflammatory Medication, in People With Parkinson's Disease (clinicaltrials.gov) - P2 | N=36 | Not yet recruiting | Sponsor: Cambridge University Hospitals NHS Foundation Trust

New P2 trial • CNS Disorders • Movement Disorders • Parkinson's Disease

Multimodality Cardiovascular Imaging for the Translation of Therapies for Vascular Activation After MI (clinicaltrials.gov) - P1 | N=60 | Not yet recruiting | Sponsor: University of Virginia | Trial completion date: Oct 2028 ➔ Jan 2029 | Trial primary completion date: Dec 2027 ➔ Dec 2028

Trial completion date • Trial primary completion date • Cardiovascular • Myocardial Infarction

A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma (clinicaltrials.gov) - P1/2 | N=26 | Recruiting | Sponsor: April Salama, M.D. | Trial completion date: Apr 2025 ➔ Apr 2026 | Trial primary completion date: Apr 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare (clinicaltrials.gov) - P2/3 | N=300 | Recruiting | Sponsor: Olatec Therapeutics LLC | Trial completion date: Oct 2025 ➔ Dec 2025

Trial completion date • Gout • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Rheumatology

NLRP3 Mediates NOXs-Induced Iron Overload and Inflammation but Not Oxidative Damage in Colons of DSS-Treated Mice. (PubMed, J Inflamm Res) - "The mice were randomly divided into five groups: normal control group, DSS-induced ulcerative colitis model group (DSS), DSS + Dapansutrile group, DSS + Diphenyleneiodonium chloride group, and DSS + Dapansutrile + Diphenyleneiodonium chloride group...Notably, the inhibition of NOXs significantly inhibited the expression of NLRP3 and oxidative damage, but the inhibition of NLRP3 had no significant effect on the expression of NOXs and oxidative damage, suggesting NOXs may exert their effects other than oxidative damage through NLRP3. To our knowledge, this work is the first to reveal that NLRP3 mediates NOXs-induced colonic iron overload and inflammation rather than oxidative damage in ulcerative colitis murine model, suggesting that the NOXs might promote ulcerative colitis by inducing colonic iron overload and macrophage infiltration dependent or partially dependent on NLRP3, as well as oxidative damage independent of NLRP3, which imply that both NOXs and NLRP3 are..."

Journal • Preclinical • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Immunology • Inflammation • Inflammatory Bowel Disease • Ulcerative Colitis • NLRP3

NLRP3 Inflammasome-mediated pyroptosis in acute lung injury: Roles of main lung cell types and therapeutic perspectives. (PubMed, Int Immunopharmacol) - "Various NLRP3 inhibitors (e.g., MCC950, CY-09, OLT1177) and pyroptosis inhibitors have demonstrated significant anti-inflammatory and tissue-protective effects in preclinical models. However, the clinical translation of NLRP3-targeted therapies remains challenging due to off-target effects, potential immunosuppression, lack of patient stratification strategies, and compensatory activation of alternative inflammasomes (e.g., AIM2, NLRC4). Future studies should focus on optimizing the selectivity of NLRP3 inhibitors, developing personalized therapeutic approaches, and exploring combination strategies to enhance their clinical applicability in ALI."

Journal • Review • Acute Lung Injury • Inflammation • Respiratory Diseases • CASP4 • NLRP3

Dapansutrile mitigates concanavalin A- induced autoimmune hepatitis: Involvement of NLRP3/IL-1β and JNK/ p38 MAPK pathways. (PubMed, Biomed Pharmacother) - "Our results showed that intraperitoneal administration of Dapan could be a therapeutic opportunity to inhibit the development of AIH via inhibition of inflammatory pathways."

Journal • Autoimmune Hepatitis • Hepatology • Immunology • Inflammation • CD4 • CD8 • IL1B • IL6 • NLRP3 • TNFA

IL1 (3 -upregulated SFXN1 promotes HSC activation and liver fibrosis through inducing mitochondrial dysfunction and NLRP3 inflammasome activation (APASL 2025) - "Our study revealed that SFXN1 is upregulated in HSC activation and liver fibrosis. IL1β upregulated SFXN1 expression through c-MYC, and SFXN1 promoted mitochondrial Fe2+ transport, mitochondrial dysfunction and NLRP3 activation, and thus promoting HSCs activation and liver fibrosis. HSC-specific knockdown of SFXN1 and treatment with OLT1177 ameliorated CCl4-induced liver fibrosis in mice."

Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • IL1B • MYC • NLRP3 • SFXN

Dapansutrile Regulates Mitochondrial Oxidative Stress and Reduces Hepatic Lipid Accumulation in Diabetic Mice. (PubMed, Curr Issues Mol Biol) - "DAPA treatment also ameliorated lipid accumulation and mitochondrial-related functions and inflammation in HepG2 cells through the NLRP3-Caspase-1 signaling axis. (4) Targeting NLRP3 with DAPA may represent a novel therapeutic approach for diabetes-related fatty liver diseases."

Journal • Preclinical • Diabetes • Hepatology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus • NLRP3

Suppression of NF-κB/NLRP3 by Nanoligomer Therapy Mitigates Ethanol and Advanced Age-Related Neuroinflammation. (PubMed, J Leukoc Biol) - "Using a NLRP3-specific inhibitor (OLT1177) and a novel brain-penetrant Nanoligomer that inhibits NF-κB and NLRP3 translation (SB_NI_112), we find ethanol-induced microglial reactivity can be attenuated by OLT1177 and SB_NI_112 in microglia from aged mice. These data suggest early indicators of neurodegeneration occurring with advanced age and binge ethanol exposure are driven by NF-κB and NLRP3. Further investigation is warranted to explore the use of targeted immunosuppression via Nanoligomers to attenuate neuroinflammation after alcohol consumption in the aging populations."

Journal • CNS Disorders • Inflammation • IL1B • NLRP3

Screening NLRP3 Drug Candidates in Clinical Development:Lessons from Existing and Emerging Technologies (ACR Convergence 2024) - P2, P2/3 | "The most clinically relevant promise of NLRP3 inhibitors as an emerging new therapeutic class is to safely control inflammation when administered chronically. Although new screening technologies such as NanoBRET® have been proposed, they come with relevant caveats and assay-specific limitation that must be understood for interpretation, clinical relevance and generalizability to all NLRP3 inhibitor compounds in development."

Clinical • CNS Disorders • Diabetes • Gout • Inflammation • Inflammatory Arthritis • Metabolic Disorders • Movement Disorders • Parkinson's Disease • Rheumatology • Type 2 Diabetes Mellitus • IL1B • NLRP3

NLRP3 Inflammasome Inhibition With Dapansutrile in Type 2 Diabetes and Elevated Systemic Inflammation: Rationale and Design of the DAPAN-DIA study (AHA 2024) - P2 | "DAPAN-DIA is the first placebo-controlled, adequately powered, large, multi-center study with an oral NLRP3-specific Inhibitor, dapansutrile. The trial will generate important data on a new clinically relevant dimension in T2D care where consideration at diagnosis of inflammatory parameters are of importance for the transition to T2D-related complications."

Cardiovascular • Congestive Heart Failure • Diabetes • Heart Failure • Infectious Disease • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • Type 2 Diabetes Mellitus • CRP • IL1B • IL6 • NLRP3

Translational Inhibition of NF-kB/NLRP3 by Nanoligomer Mitigates Advanced Age- and Ethanol-Related Microglia Activation and Associated Markers of Neurodegeneration (Neuroscience 2024) - "Making use of a NLRP3-specific inhibitor (OLT1177) and a novel brain-penetrant Nanoligomer that inhibits NF-κB and NLRP3 translation (SB_NI_112), we find that ethanol-induced microglial reactivity can be attenuated by OLT1177 or SB_NI_112 in primary microglia from aged mice...These data suggest early indicators of neurodegeneration occurring with advanced age and binge ethanol exposure are NF-κB- and NLRP3-dependent. Further investigation is warranted to explore the use of targeted immunosuppression via Nanoligomers to attenuate neuroinflammation after alcohol consumption in the aged."

Metastases • Addiction (Opioid and Alcohol) • CNS Disorders • IL1B • NLRP3

The NLRP3 inhibitor Dapansutrile improves the therapeutic action of lonafarnib on progeroid mice. (PubMed, Aging Cell) - "The combination of both drugs reduced the inflammation and senescence, extended survival and ameliorated various progeroid defects both in vitro and in vivo, compared with treatment using lonafarnib alone. These findings and the safety of dapansutrile demonstrated in several clinical trials proposes it as a possible co-adjuvant treatment with lonafarnid in HGPS."

Journal • Preclinical • Hepatology • Inflammation • NLRP3

Can We Exploit Inflammasomes for Host-Directed Therapy in the Fight against Mycobacterium tuberculosis Infection? (PubMed, Int J Mol Sci) - "Studies show that medicinal plant derivatives like silybin, andrographolide, and micheliolide and small molecules such as OLT1177, INF39, CY-09, JJ002, Ac-YVAD-cmk, TAK-242, and MCC950 can modulate inflammasome activation. Molecular tools like gene silencing and knockouts may also be used for severe TB cases. This review explores these strategies as potential adjunctive HDTs in fighting TB."

Journal • Review • Infectious Disease • Inflammation • Pulmonary Disease • Respiratory Diseases • Tuberculosis • IL18 • IL1B

Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare (clinicaltrials.gov) - P2/3 | N=300 | Recruiting | Sponsor: Olatec Therapeutics LLC | Trial completion date: Dec 2025 ➔ Oct 2025 | Trial primary completion date: Nov 2025 ➔ Sep 2025

Trial completion date • Trial primary completion date • Gout • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Rheumatology

Study of Dapansutrile Tablets in Subjects With an Acute Gout Flare (clinicaltrials.gov) - P2/3 | N=300 | Recruiting | Sponsor: Olatec Therapeutics LLC | Trial completion date: Oct 2024 ➔ Dec 2025 | Trial primary completion date: Oct 2024 ➔ Nov 2025

Trial completion date • Trial primary completion date • Gout • Immunology • Inflammatory Arthritis • Musculoskeletal Diseases • Musculoskeletal Pain • Orthopedics • Pain • Rheumatology

First Patient Enrolled in a Phase 2 Study in Patients with Type 2 Diabetes with Olatec's NLRP3 Inhibitor, Dapansutrile (PRNewswire) - "Olatec Therapeutics...announced patients with type 2 diabetes mellitus (T2D) and diabetes-related complications (the DAPAN-DIA Study) are being enrolled in a Phase 2 clinical trial in Basel, Switzerland....The DAPAN-DIA Study is a randomized, double-blind, placebo-controlled multi-center trial of the efficacy and safety of dapansutrile in subjects with T2D and diabetes-related complications. Target enrollment is approximately 300 patients..."

Trial status • Type 2 Diabetes Mellitus

Dapansutrile OLT1177 suppresses foreign body response inflammation while preserving vascularisation of implanted materials. (PubMed, J Mater Chem B) - "Mechanistic studies revealed that this occurred through activation of early pro-angiogenic markers while suppressing late-stage anti-angiogenic markers. These findings establish OLT1177 as a promising therapeutic approach for mitigating implant fibrosis while supporting vascularisation, suggesting a highly promising selective immunosuppressive strategy for the FBR warranting further research to explore its optimal integration into medical materials and devices."

Journal • Fibrosis • Immunology • Inflammation • NLRP3

Dapansutrile in Diabetes and Diabetes-Related Complications - Dapan-Dia (clinicaltrials.gov) - P2 | N=300 | Recruiting | Sponsor: University Hospital, Basel, Switzerland | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • CRP

A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma (clinicaltrials.gov) - P1/2 | N=26 | Recruiting | Sponsor: April Salama, M.D. | Trial completion date: Apr 2024 ➔ Apr 2025 | Trial primary completion date: Apr 2024 ➔ Apr 2025

Metastases • Trial completion date • Trial primary completion date • Melanoma • Oncology • Solid Tumor

Dapansutrile in Diabetes and Diabetes-Related Complications - Dapan-Dia (clinicaltrials.gov) - P2 | N=300 | Not yet recruiting | Sponsor: University Hospital, Basel, Switzerland | Initiation date: Nov 2023 ➔ Apr 2024

Trial initiation date • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus • CRP