Press Release Details
Principia Biopharma Presents Phase 1 Clinical Data from CNS Penetrating BTK Inhibitor Candidate PRN2246/SAR442168 at ACTRIMS 2019
-- Orally administered PRN2246 achieved full BTK occupancy in peripheral blood --
-- PRN2246 exhibited blood-brain barrier permeability and CNS exposure --
“We are pleased with the tolerability profile of PRN2246/
The Phase 1 Trial: Phase 1 Clinical Trial of PRN2246
The Phase 1 trial was a first-in-human randomized, double-blind, placebo-controlled study that included five single ascending dose (SAD) cohorts (5 to 120 mg), and five multiple ascending dose (MAD) cohorts (7.5 to 90 mg once daily). The MAD cohorts consisted of ten days of treatment. In an additional cohort, cerebral spinal fluid (CSF) exposure was measured through lumbar puncture after a single 120 mg dose. The primary objective of the study was to evaluate the safety and tolerability of single ascending doses and multiple ascending doses of PRN2246/
SAR442168was well tolerated in the study, with all treatment related events being mild in nature (Grade 1);
SAR442168exposure increased with dose and with the expected rapid absorption and clearance profile;
- BTK occupancy increased in a dose dependent manner—high levels of peripheral BTK occupancy were achieved after single doses of 30 mg and higher. In the MAD portion of the study, after 10 days, BTK occupancy approached maximal levels in the lowest dose group (7.5 mg) studied; and
- CSF exposure was achieved in all subjects who underwent lumbar puncture, confirming blood-brain barrier permeability. The potential to impact B cell driven inflammation in the CNS will be evaluated in the next phase of development.
Principia is a late-stage biopharmaceutical company dedicated to bringing transformative oral therapies to patients with significant unmet medical needs in immunology and oncology. Principia’s proprietary Tailored Covalency® platform enables Principia to design and develop reversible and irreversible covalent, small molecule inhibitors with potencies and selectivities that have the potential to rival those of injectable biologics yet maintain the convenience of a pill. PRN1008, a reversible covalent BTK inhibitor, is being evaluated in a Phase 3 clinical trial in patients with pemphigus, an orphan autoimmune disease, and in a Phase 2 clinical trial in patients with immune thrombocytopenic purpura, a rare hematological disease. PRN2246/
This press release contains forward-looking statements. All statements other than statements of historical fact contained herein are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to, Principia’s expectations regarding the Principia pipeline of product candidates, Sanofi’s advancement of PRN2246/
Source: Principia Biopharma Inc.