NodThera has reported positive Phase I study readouts of its NLRP3 inflammasome inhibitors, NT-0796 and NT-0249, to potentially treat central nervous system (CNS) and peripheral inflammatory diseases. 

An orally bioavailable chemotype, NT-0796 is a brain penetrant inhibitor of NLRP3. 

The Phase I trial of NT-0796 has concluded and established the compound’s brain penetration, with exceptional pharmacokinetic (PK) and pharmacodynamic (PD) profiles.

Exposures of the compound, as well as its bioactive metabolite NDT-19795, were observed to rise linearly with doses.

NT-0796 was also found to be safe and well tolerated, without any drug-associated liver function test (LFT) abnormalities reported.

NT-0249 is a peripherally restricted inhibitor of the NLRP3 inflammasome. 

Dosing with NT-0249 in the Phase I single ascending dose cohorts have also concluded, validating an excellent PK/PD profile, as well as the possibility for once-daily dosing. 

PK was validated as a reduced clinical dose of the compound for efficacy.

NT-0249 was reported to be safe and well tolerated, with proportional rises in drug exposure on increasing dosage. 

The combined data backs the further development and clinical assessment of these candidates for various CNS and peripheral inflammatory ailments.

NodThera CEO Adam Keeney said: “We are delighted that NT-0796 continues to demonstrate an exceptional and differentiated clinical profile. 

“Neurological and neurodegenerative diseases are a significant and growing burden to patients and society. 

“This is the first clinical demonstration of a brain penetrant inhibitor of the NLRP3 inflammasome, which represents a major milestone for addressing this urgent medical challenge.”

A clinical-stage biotechnology firm, NodThera focuses on the development of a new class of NLRP3 inflammasome inhibitors to treat chronic inflammation-driven ailments.