Biotech company NodThera has announced positive phase 1 clinical readouts for its first and second clinical candidates, NT-0796 and NT-0249.
A phase 1 study has been completed for NT-0796, confirming brain penetration with excellent pharmacokinetic (PK) and pharmacodynamic (PD) profiles and for NT-0249, dosing of the phase 1 single ascending dose cohorts has been completed, confirming a potentially best-in-class PK/PD profile and the potential for once-a-day dosing.
The results collectively support further development and clinical evaluation in a range of central nervous system (CNS) and peripheral inflammatory diseases.
“We are delighted that NT-0796 continues to demonstrate an exceptional and differentiated clinical profile,” said Adam Keeney, chief executive officer at NodThera.
“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.”
NodThera’s trial details
NT-0796 is a novel chemotype, designed as an orally bioavailable, brain penetrant NLRP3 inhibitor. The phase 1 study showed exposures of NT-0796 and its bioactive metabolite NDT-19795 increased linearly with dose. A dose-dependent pharmacodynamic effect was also observed through inhibition of stimulated IL-1β and IL-18 in ex vivo blood samples, which translated into an anti-inflammatory effect via reduction of key inflammatory biomarkers, including C-reactive protein (CRP).
Blood-brain barrier penetration of NT-0796 was verified with cerebrospinal fluid (CSF) drug concentrations in excess of anti-inflammatory free blood concentrations. Overall, NT-0796 was safe and well tolerated and no drug-related liver function test (LFT) abnormalities were observed.
NodThera’s second clinical compound, NT-0249, is a peripherally restricted NLRP3 inflammasome inhibitor that has successfully completed its phase 1 single ascending dose study. NT-0249 was safe and well tolerated with proportional increases in drug exposure with increasing dose. This profile has the potential to be best-in-class as a peripheral NLRP3 inflammasome inhibitor, demonstrating pharmacokinetics consistent with a once-a-day therapy and pharmacodynamics confirming a low clinical dose for efficacy.
“From design to development, the success of our phase 1 data represents a breakthrough in targeting the NLRP3 inflammasome both peripherally and in the CNS,” said Alan Watt, NodThera’s CSO and president of R&D.
“Delivery of NT-0796 into the CNS and the positive interim data for NT-0249 continues to reinforce NodThera’s leadership in the NLRP3 inflammasome field.”