The clinical trial pipeline for NLRP3 protein inhibitors is expanding, with over 20 pharmaceutical companies actively developing therapeutics for a range of diseases. Research indicates that these inhibitors may be effective in treating neurodegenerative diseases such as Alzheimer’s, Parkinson’s, and multiple sclerosis, as well as metabolic conditions like gout and non-alcoholic steatohepatitis (NASH).
Key Players and Pipeline Therapies
Several companies are advancing NLRP3 protein inhibitors, including Halia Therapeutics, Ventus Therapeutics, EpicentRx, Zydus Lifesciences Limited, Monte Rosa Therapeutics, Inflammasome Therapeutics, Ventyx Biosciences, Biolexis Therapeutics, Olatec Therapeutics, Secarna Pharmaceuticals, Novo Nordisk, and NodThera. Promising pipeline therapies include HT6184, VENT 02, Nibrozetone, ZYIL1, MRT-8102, Kamuvudine-9, VTX 3232, Dapansutrile, NNC6022-0001, NLRP3 Research Program, and NT 0796.
Recent Developments
- Halia Therapeutics and Biolexis Therapeutics: In August 2024, the companies announced a collaboration that identified a novel brain-penetrant small molecule candidate targeting NLRP3-driven neuroinflammation, using Biolexis' MolecuLern™ AI-enabled approach. This advancement is aimed at treating neuroinflammatory disorders, including Parkinson's disease.
- NodThera: In June 2024, NodThera announced positive data from its Phase Ib/IIa cardiovascular risk study in inflamed obese subjects, evaluating the effects of its oral, brain-penetrant NLRP3 inflammasome inhibitor NT-0796, on inflammatory, cardiovascular and metabolic risk parameters.
- Novo Nordisk: In May 2024, Novo Nordisk dosed the first participant in a Phase I clinical study for NNC6022-0001 (formerly known as VENT-01), an oral NLRP3 inhibitor licensed by Novo Nordisk in September 2022.
- Ventus Therapeutics: In April 2024, Ventus Therapeutics announced results from its Phase I clinical trial of VENT-02, a novel, oral, brain-penetrant NLRP3 inhibitor. The trial evaluated the pharmacodynamics, pharmacokinetics, safety, and tolerability of VENT-02 across a broad range of single and multiple ascending doses in adult healthy volunteers.
- Parkinson’s UK and Neumora Therapeutics: In March 2024, Parkinson’s UK announced an investment of GBP 2.1 million to support Neumora Therapeutics in preclinical testing of NMRA-NLRP3, a NLRP3 inhibitor with the potential to reduce inflammation and protect brain cells in Parkinson’s.
NLRP3 Inhibitors: Mechanism and Therapeutic Potential
NLRP3 protein is a key component of the innate immune system, activating the inflammasome and releasing pro-inflammatory cytokines like IL-1β and IL-18. Overactivation of the NLRP3 inflammasome is implicated in various diseases, including autoimmune disorders, metabolic syndromes, neurodegenerative diseases, and cancers. NLRP3 inhibitors block the NLRP3 protein or interfere with its activation pathway, preventing inflammasome assembly and cytokine release.
Pipeline Overview
| Drug | Company | Phase | Indication | RoA |
| -------------- | ---------------------------- | ----- | ----------------------------------------------------------------------- | ---------- |
| Nibrozetone | EpicentRx | II/III| Small cell lung cancer | Intravenous|
| ZYIL 1 | Zydus Cadila | II | Amyotrophic lateral sclerosis; Cryopyrin-associated periodic syndromes | Oral |
| HT6184 | Halia Therapeutics | II | Inflammatory pain; Myelodysplastic syndromes | Oral |
| VTX 3232 | Ventyx Biosciences | II | Parkinson's disease | Oral |
| VENT 02 | Ventus Therapeutics | I | Neurodegenerative disorders | Oral |
| NNC6022-0001 | Novo Nordisk | I | Cardiometabolic Diseases | Oral |
| Kamuvudine-9 | Inflammasome Therapeutics | I | Thyroid Eye Disease | Oral |
| MRT-8102 | Monte Rosa Therapeutics | Preclinical | Inflammation | Oral |
The development of NLRP3 inhibitors represents a significant advancement in treating chronic inflammatory diseases by targeting the root cause of inflammation.
