Principia Announces Positive Data from its Phase 2 Part B Trial in Pemphigus

Clear dose-response combined with decreased daily corticosteroid usage

Response rate increased with extended duration of treatment to six months while maintaining a favorable safety profile

SOUTH SAN FRANCISCO, Calif., June 12, 2020 (GLOBE NEWSWIRE) -- Principia Biopharma Inc. (Nasdaq: PRNB), a late-stage biopharmaceutical company focused on developing treatments for immune-mediated diseases, today announced positive data from its Phase 2 Part B open-label trial in pemphigus, BELIEVE-PV. The full data set was presented as part of the virtual Late-Breaker session of the American Academy of Dermatology.

“The significance of this Phase 2 Part B trial is that rilzabrutinib, a reversible covalent oral BTK inhibitor, demonstrated a 40 percent complete remission (CR) rate after 24 weeks of treatment while the median corticosteroid (CS) dose was reduced to 6 mg. It is also very encouraging to see that 60 and 87 percent of patients achieved control of disease activity (CDA) -- the primary endpoint -- by the 4th and 12th week, respectively, which is unusually fast,” said Dr. Dedee Murrell, Professor and Head of the Department of Dermatology at The St. George Hospital Clinic School, University of New South Wales in Sydney, Australia, who is the Principal Investigator of the ongoing PEGASUS Phase 3 trial.

Among the 15 patients with newly diagnosed/relapsed, mild-to-severe pemphigus in this trial, a clinically meaningful decrease in the daily CS use was observed -- the median CS dose was 18 mg/day (0.201 mg/kg/day) at baseline and in the 14 patients that completed 12 and 24 weeks of treatment the median CS dose decreased to 11 mg/day (0.125 mg/kg/day) at 12 weeks and decreased again to 6 mg/day (0.076 mg/kg/day) at 24 weeks. “Importantly, we observed that whilst patients on 400 mg once-a-day dosing were able to reach CDA, 400 mg twice-a-day dosing is needed to achieve rapid CR rates. We believe this data supports a dose response as well as lower CS usage,” said Dolca Thomas, MD, chief medical officer at Principia Biopharma.

All treatment related adverse events with rilzabrutinib were mild-to-moderate (including grade 1 and 2 nausea, abdominal distension, and dizziness), consistent with the Phase 2 Part A trial.

An oral therapy such as rilzabrutinib has the potential to benefit patients with pemphigus in multiple ways, including rapid anti-inflammatory effects, neutralization of effects of autoantibodies, and blockage of the production of new autoantibodies, while not depleting B cells.

About PEGASUS -- the Phase 3 Trial of Rilzabrutinib

Principia is currently enrolling patients in a global, randomized, double-blind, placebo-controlled, pivotal, Phase 3 clinical trial, the PEGASUS study, in approximately 120 participants to evaluate rilzabrutinib versus placebo, using a background treatment of tapering doses of corticosteroids (CS). The trial entry criteria include participants with moderate to severe pemphigus who are either newly diagnosed or relapsing with chronic disease. This demographic will potentially represent three quarters of the pemphigus patient population. The primary efficacy endpoint is the ability of rilzabrutinib to achieve durable complete remission (CR) after 36 weeks of treatment. Durable CR is defined as a state in which all lesions have healed on very low dose CS (5mg/day), and no new lesions have appeared for a period of at least eight weeks. Key secondary endpoints include cumulative CS use and time to CR. After 36 weeks, all patients will have the option be treated with active rilzabrutinib therapy in an open-label extension period of 24 weeks. Rilzabrutinib has been granted orphan drug designation by the U.S. Food and Drug Administration for the treatment of patients with pemphigus vulgaris (PV) and by the European Commission for treatment of patients with PV and pemphigus foliaceus.

For more information on the rilzabrutinib pemphigus trials, please visit the section of Principia’s website.

About Rilzabrutinib

Rilzabrutinib, Principia’s most advanced drug candidate, is an oral, small molecule, reversible covalent inhibitor of Bruton’s tyrosine kinase (BTK), which is present in the signaling pathways of most types of white blood cells except for T cells and plasma cells. Rilzabrutinib was designed utilizing Principia’s proprietary Tailored Covalency^® platform to optimize rilzabrutinib’s safety and efficacy profile, resulting in prolonged and reversible action at the target site while being rapidly eliminated from the body. Principia believes this approach limits systemic exposure of rilzabrutinib and enables rapid clinical reversibility of effects on the immune system and is thus designed for use as a chronic therapy in immune-mediated diseases.

About Principia Biopharma

Principia is a late-stage biopharmaceutical company dedicated to bringing transformative therapies to patients with significant unmet medical needs in immune-mediated diseases. Through Principia’s proprietary Tailored Covalency^® platform, our strategy is to build and advance a pipeline of best-in-class drug candidates with significant therapeutic benefits, limit unintended side effects, improve quality of life and over time modify the course of disease. This highly reproducible approach enables the company to pursue multiple programs efficiently, having discovered three drug candidates. Rilzabrutinib, a reversible covalent BTK inhibitor, is being evaluated in a global Phase 3 clinical trial in participants with pemphigus, a Phase 1/2 clinical trial in participants with immune thrombocytopenia (ITP), and the company plans to initiate a Phase 2 clinical trial in participants with IgG4-Related Diseases and a Phase 3 trial in ITP. PRN2246/SAR442168 is a covalent BTK inhibitor which crosses the blood-brain barrier and is partnered with Sanofi. Sanofi has announced that PRN2246/SAR442168 will be evaluated in four Phase 3 clinical trials in participants with relapsing and progressive forms of multiple sclerosis. PRN473 Topical, a topical reversible covalent BTK inhibitor designed for immune mediated diseases that could benefit from localized application to the skin, is being evaluated in a Phase 1 trial. For more information, please visit .

Forward-Looking Statements

This press release contains forward-looking statements. These forward-looking statements reflect 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, the potential patient benefits of Principia’s pipeline, including of rilzabrutinib to rapidly and effectively treat pemphigus while significantly reducing the exposure to moderate to high CS doses, the safety and efficacy of rilzabrutinib, the planned patient enrollment for the Phase 3 PEGASUS trial, and the initiation, timing, scope and success of additional clinical trials and results. Such forward-looking statements involve known and unknown risks, uncertainties, and other important factors that may cause Principia’s actual results, performance, or achievements to be materially different from those expressed or implied by the forward-looking statements. For a description of the risks and uncertainties that could cause actual results to differ from those expressed in these forward-looking statements, as well as risks relating to the Principia’s business in general, see the risk factors set forth in Principia’s reports filed with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Principia specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise.