Our oral, first in class, wholly owned BTK inhibitor, rilzabrutinib (formerly known as PRN1008), is currently being evaluated in three different disease indications
We believe there are many disease indications that may benefit from BTK inhibition. Similarly, there is potentially broad utility for rilzabrutinib in immune mediated diseases. Using our proprietary Tailored Covalency® technology, rilzabrutinib was designed to optimize its safety and efficacy profile, resulting in prolonged and reversible action at the target site while being rapidly eliminated from the body. We designed rilzabrutinib to limit its systemic exposure, thereby enabling rapid clinical reversibility of unwanted effects on the immune system, with the potential to be a chronic therapy.
Why are we primarily focused on immune-mediated diseases when so much progress in BTK inhibition has been made in the field of oncology?
Our mission is to make best-in-class medicines to address unmet medical needs. The first-generation BTK inhibitors that addressed the oncology opportunity were also the inspiration for the development of our next- generation BTK inhibitors. With Tailored Covalency, our goal is to optimize how our drug candidates bind to their target to minimize off-target effects while achieving high clinical benefit. We believe that avoiding the off-target effects of many first-generation BTK inhibitors will prove to be more suitable for the chronic immune-mediated diseases that are our primary focus.
Rilzabrutinib is being evaluated in patients with pemphigus, a group of rare, debilitating, autoimmune diseases that cause blistering of the skin and mucous membranes. We believe rilzabrutinib has the potential to demonstrate benefit in people with pemphigus, including rapid anti-inflammatory effects, neutralization of the effects of pathogenic autoantibodies and blockade of the production of new autoantibodies without depleting B cells.
We have an ongoing Phase 3 clinical trial in patients with moderate to severe pemphigus. We have completed a Phase 2 Part A trial in patients with pemphigus and, in conjunction with this trial, we have an ongoing Phase 2 Part B trial to increase the active treatment period from three to six months. Between the Phase 2 Parts A and B of the pemphigus trial, we have been able to observe consistent safety and efficacy data in approximately 40 pemphigus patients.
We have received orphan drug designation from the United States Food and Drug Administration for rilzabrutinib for the treatment of pemphigus vulgaris and from the European Commission for the treatment of pemphigus (pemphigus vulgaris and pemphigus foliaceus).
Immune Thrombocytopenia (ITP)
Rilzabrutinib is also being evaluated in patients with ITP, a rare autoimmune disease that causes high risk for bleeding, excessive bruising, fatigue and potential for life threatening intracranial bleeding due to destruction of platelets. We believe that rilzabrutinib is highly suited to address the most common underlying cause of ITP—the pathogenic autoantibodies that destroy the platelets—and lead to better long-term outcomes in ITP. Importantly, in an ex vivo study utilizing blood from ITP patients and healthy volunteers, rilzabrutinib did not impair platelet aggregation, thereby promising to avoid the bleeding and bruising risk typically associated with BTK inhibitors.
We have an ongoing open-label Phase 2 clinical trial in patients with ITP that includes a long-term extension cohort, both for responders and, if needed, to enroll additional patients to inform the design of a Phase 3 program. Preliminary results demonstrated rilzabrutinib was active in over one-third of heavily pre-treated patients with relapsed/refractory primary or secondary ITP who have no available treatment options.
Learn more about our ongoing clinical trials.