dapansutrile (OLT1177) / Olatec Therap - LARVOL DELTA

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

NLRP3 inflammasome activation triggers severe inflammatory liver injury in N, N-dimethylformamide-exposed mice. (PubMed, Sci Total Environ) - "Interestingly, DMF-induced liver injury was effectively suppressed by two inflammasome inhibitors, MCC950 and Dapansutrile. Finally, the depletion of hepatic macrophages by clodronate liposomes significantly reduced the liver damage caused by DMF. These results suggest that NLRP3 inflammasome activation is the upstream molecular event in the development of acute liver injury induced by DMF."

Journal • Preclinical • Hepatology • Liver Failure • NLRP3

The NLRP3 inhibitor, OLT1177 attenuates brain injury in experimental intracerebral hemorrhage. (PubMed, Int Immunopharmacol) - "OLT1177 (dapansutrile) could significantly attenuate the brain edema after ICH and effectively alleviate the neurological deficit. This result suggests that the novel NLRP3 inhibitor, OLT1177, might serve as a promising candidate for the treatment of ICH."

Journal • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Inflammation • Vascular Neurology • CASP1 • IL1B • NLRP3

Systemic inflammatory cytokine profiles in patients with gout during flare, intercritical and treat-to-target phases: TNFSF14 as new biomarker. (PubMed, Ann Rheum Dis) - "Gout flare involves multiple inflammatory mediators that may be used as potential therapeutic targets."

Biomarker • Journal • Gout • Inflammation • Inflammatory Arthritis • Oncology • Rheumatology • CSF1 • IL6 • TNFSF14

Pilot Study of Dapansutrile Capsules in Schnitzler's Syndrome (clinicaltrials.gov) - P2 | N=2 | Terminated | Sponsor: Olatec Therapeutics LLC | N=10 ➔ 2 | Recruiting ➔ Terminated; The study was terminated due to study design issues that did not allow for determination of efficacy and safety in subjects with Schnitzler Syndrome who are currently well controlled on anakinra therapy.

Enrollment change • Trial termination

Olatec Therapeutics to Conduct a Phase 2 Clinical Trial in Patients with Early Parkinson’s Disease with its NLRP3 Inhibitor, Dapansutrile (Businesswire) - "Olatec Therapeutics, Inc...announced that Cure Parkinson’s granted an award to initiate a Phase 2 clinical trial investigating the potential of oral dapansutrile to slow or stop the progression of Parkinson’s disease....This investigator-initiated study entitled 'Anti-inflammatory Intervention with Dapansutrile (OLT1177) for Parkinson’s Disease Modification (DAPA-PD): A Randomised Double-Blind Placebo-Controlled Phase II Trial' is targeting to commence in mid-2024, subject to completion of all contractual agreements and regulatory authorizations. The trial will seek to enroll 36 participants with early Parkinson’s disease."

New P2 trial • CNS Disorders • Parkinson's Disease

The Use of Schisandrin B to Combat Triple-Negative Breast Cancers by Inhibiting NLRP3-Induced Interleukin-1β Production. (PubMed, Biomolecules) - "This was confirmed using an NLRP3 inhibitor, OLT1177, which revealed a similar beneficial effect in combating TNBC progression. Sch B treatment also inhibits IL-1β-induced EMT expression of TNBC cells, which may contribute to the anti-tumor response."

IO biomarker • Journal • Biliary Cancer • Brain Cancer • Breast Cancer • Cholangiocarcinoma • CNS Tumor • Gastrointestinal Cancer • Glioma • Hepatocellular Cancer • Hepatology • Liver Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • IL1B • NLRP3