Hangzhou,China,April2,2026—Highlightll Pharma today announced the successful completion of the Phase I clinical study of HL-400 in US. HL-400 is Highlightll’s proprietary brain-penetrant NLRP3 inhibitor with best-in-class potential.
Key findings include:
· Very well tolerated with only mild to moderate adverse events, mostly unrelated to study drug
· CSF drug exposure approaching plasma unbound levels (Kp, uu ~1), suggesting best-in-class brain penetration
· Achieved IC90 IL-1β inhibition for approximately 24 hours, supporting once-daily dosing
· Linear and predictable PK/PD, enabling clear dose–exposure-response relationships
The NOD-like receptor family pyrin domain containing 3 (NLRP3) is a key component of the innate immune system. Aberrant NLRP3 inflammasome activation has been implicated in a broad spectrum of diseases, including autoinflammatory disorders (e.g., cryopyrin-associated periodic syndromes), metabolic diseases (type 2 diabetes and obesity), neurodegenerative conditions (Alzheimer’s and Parkinson’s disease), cardiovascular diseases (atherosclerosis and myocardial infarction), and inflammatory conditions such as gout and non-alcoholic steatohepatitis. Consequently, NLRP3 has emerged as an attractive therapeutic target for the treatment of diverse inflammation-driven diseases.
HL-400 is Highlightll’s leading brain penetrant NLRP3 inhibitor being developed for CNS diseases. Highlightll is also developing a peripheral restricted NLRP3 inhibitor, HL-450, for systemic diseases.
Dr. Chris Liang, Founder and CEO of Highlightll Pharma, commented:
“We are pleased to see that HL-400 demonstrated excellent safety, achieved very high CNS exposure and robust target coverage in this clinical trial. We are rapidly expanding this clinical program to further demonstrate its therapeutical potentials. We are also accelerating the development of HL-450 with the goal of filing IND around the end of 2026.”
About Highlightll
Highlightll is a clinical stage biopharmaceutical company focusing on both peripheral and central autoimmune/inflammatory diseases. We strive to discover breakthrough medicines which would have a high impact on health care. We leverage resources and expertise worldwide and combine them with our unique perspectives to solve challenging medical problems. Our lead programs are the world's first highly potent and selective dual JAK1/TYK2 inhibitors. Girocitinib (TLL-018), a peripheral JAK1/TYK2 inhibitor, met the primary endpoints in its Phase III trial for chronic spontaneous urticaria (CSU) and is also in Phase III trial for rheumatoid arthritis (RA), while TLL-041, the world first brain-penetrant JAK1/TYK2 inhibitor was licensed to Biohaven in 2023. Biohaven advanced the BHV-8000/TLL-041 program to a global Phase II/III pivotal trial in Parkinson’s disease. NLRP3 is our second platform where we are developing HL-400 for CNS/neurodegenerative diseases and HL-450 for peripheral diseases.
