Category: Parkinson’s Disease: Clinical Trials
Objective: The objective of the study is to evaluate the safety, tolerability, and pharmacokinetics of BT-409.
Background: Chronic activation of innate immune pathways has emerged as a central driver of neurodegeneration. The NOD-like receptor protein (NLRP3) inflammasome is a pivotal sensor of cellular stress and damage. Upon activation, NLRP3 promotes release of proinflammatory cytokines interleukin (IL)- 1β and IL-18 and is a critical driver of neuroinflammation in Parkinson’s disease (PD) and other neuroinflammatory disorders including Multiple sclerosis and Alzheimer’s disease.
Method: BT-409-101 is a randomized, double-blind, placebo-controlled Phase 1 study evaluating the safety, tolerability, and pharmacokinetics of BT-409. The objective of the study is to evaluate the safety, tolerability, and pharmacokinetics of BT-409. The study is conducted in 3 parts: a single ascending dose, a multiple ascending dose, and a single cohort with adults diagnosed with PD. Standard safety monitoring and pharmacokinetic measures in plasma and urine are collected. Pharmacodynamic biomarker panel, including ASC speck, IL-1β, IL-18, IL-6, and IL-8 in plasma and cerebrospinal fluid, measures both proximal NLRP3 inflammasome activity and downstream neuroinflammatory signaling.
Results: Preclinical studies demonstrated that BT-409 is a potent inhibitor of NLRP3 and has high target selectivity towards IL-1β pathways while not affecting TNFα pathways. BT-409 dose-dependently decreased LPS-induced IL-1β and IL-6 levels in plasma and brain of mice. In the experimental autoimmune encephalomyelitis (EAE) model in mice, BT-409 inhibited development of EAE symptoms at 30 mg/kg and completely prevented development of EAE at 100 mg/kg. The brain/plasma unbound ratio in dogs was 2.3. The 28-day GLP toxicology studies indicate a broad safety and tolerability profile. As of March 12, 2026, BT-409 has been dosed in healthy adults.
Conclusion: Pharmacological blockade of NLRP3 shows promise in preclinical models and early clinical studies. BT-409 has preferential distribution in the central nervous system, with potential to maximize central exposures while minimizing peripheral exposures. Thus, BT-409 may provide a differentiated safety and efficacy profile for treating neuroinflammation-associated disorders.
To cite this abstract in AMA style:
T. Dam, A. Mathias, E. Remeeva, D. Hilt, M. Mcgill, A. Pushechnikov, R. Karapetyan, N. Savchuk, I. Dukes, V. Kazey, K. Dokukina. Phase 1 Study of BT-409, a potent, selective, brain-penetrant, and oral small molecule inhibitor of NLRP3 in Healthy Volunteers and Adults with Parkinson’s disease [abstract]. Mov Disord. 2026; 41 (suppl 1). https://www.mdsabstracts.org/abstract/phase-1-study-of-bt-409-a-potent-selective-brain-penetrant-and-oral-small-molecule-inhibitor-of-nlrp3-in-healthy-volunteers-and-adults-with-parkinsons-disease/. Accessed October 1, 2026.« Back to 2026 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/phase-1-study-of-bt-409-a-potent-selective-brain-penetrant-and-oral-small-molecule-inhibitor-of-nlrp3-in-healthy-volunteers-and-adults-with-parkinsons-disease/