Principia Biopharma initiates clinical trial for PRN1008 in patients with Immune Thrombocytopenia Purpura

Preclinical Data Presented at American Society of Hematology Annual Meeting Support ITP Indication 
SOUTH SAN FRANCISCO, CALIF., December 13, 2017 
Principia Biopharma, a private, clinical-stage biopharmaceutical company, today announced that it has initiated a clinical trial for PRN1008, a reversible covalent Bruton’s Tyrosine Kinase (BTK) inhibitor, in patients with Immune Thrombocytopenia Purpura (ITP) in the US. ITP, an autoimmune disorder characterized by thrombocytopenia – a decreased number of circulating platelets – is the second indication for which Principia is evaluating PRN1008. Principia also has an on-going clinical program for PRN1008 in patients with pemphigus, another autoimmune disease, where it has seen a promising efficacy and safety profile to date.
Supporting advancement into clinical trials, the company recently presented preclinical data at the 59th American Society of Hematology (ASH) Annual Meeting & Exposition in Atlanta (abstract #1052). The results from the studies showed that PRN1008 did not adversely affect platelet aggregation in blood from both healthy volunteers and ITP patients. Additionally, results in an animal model of ITP showed that animals treated with PRN1008 had significantly higher platelet counts than control animals (p<0.05).
“These preclinical results are encouraging and provide strong evidence that PRN1008, an oral, BTK inhibitor, inhibits antibody-mediated thrombocytopenia, supporting its study in ITP patients,” said Steve Gourlay, MBBS, Ph.D., chief medical officer of Principia Biopharma. “New treatments and modalities are needed for patients with relapsed ITP that are effective in the majority of patients, with fewer toxicities and easier administration than current treatments. Based on these promising early findings, we have initiated the first human clinical trial of PRN1008 in patients with ITP.”
Preclinical study design and results
The effect of PRN1008 on platelet function was evaluated in-vitro in the blood from both normal healthy volunteers and patients with ITP. Results showed that treatment with PRN1008 at therapeutically relevant concentrations had no effect on platelet aggregation in either healthy volunteers or ITP patients, and did not interfere with responses to all other platelet agonists tested. In contrast, ibrutinib, a United States Food and Drug Administration-approved BTK inhibitor, had a significant effect on platelet aggregation in healthy volunteers, consistent with published literature.
Additionally, the pharmacologic effect of PRN1008 was evaluated in an animal model of ITP. Animals given three different doses of PRN1008 were challenged with platelet-targeting antibodies, and blood platelet counts were measured. PRN1008 demonstrated significant dose-dependent prevention of platelet loss at six hours compared with the control animals (p<0.05).
About PRN1008
PRN1008 is an oral, reversible covalent BTK inhibitor (Bruton’s Tyrosine Kinase – a component of B-cell signaling and inflammatory pathways in most white blood cell types other than T-cells and plasma cells). It was designed using Principia’s proprietary Tailored Covalency™ technology to optimize its safety and efficacy profile, resulting in a prolonged and reversible action at the target site while being rapidly eliminated from the body. This approach limits systemic exposure of PRN1008 and enables rapid clinical reversibility of effects on the immune system.
About Immune Thrombocytopenia Purpura
ITP is a chronic autoimmune disease characterized by a decreased number of circulating platelets, which play a key role in clot formation. The disorder affects approximately 70,000 adults in the United States and over 200,000 in the European Union. The typical age of onset of chronic ITP is 40 to 60 years. Individuals with ITP have a tendency to bleed and easily bruise due to blood leaking from capillaries into the skin and mucous membranes. They also suffer from fatigue, diminished quality of life and the risk of mortality (including intracranial hemorrhage).
Approved therapies in the United States for ITP include corticosteroids, intravenous immunoglobulin (IVIg) and splenectomy (surgical removal of the spleen) to stop platelet depletion, and TPO receptor agonists to increase platelet production. There is no cure for ITP and most patients relapse.
About BTK inhibition in autoimmune disease
Bruton’s Tyrosine Kinase (BTK) is a protein important to the proper function of the immune system. BTK is a key part of the signaling pathway downstream of the B-cell and Fcγ receptors on most types of white blood cells except T-cells and plasma cells. Inhibition of BTK results in the down-regulation of various cellular activities that are activated in autoimmune and inflammatory diseases.
About Principia Biopharma
Principia Biopharma Inc., a private, clinical-stage biopharmaceutical company, has created a revolutionary new way to design and develop oral small molecule therapies that are more potent, selective, durable and safer than currently available drugs. The Company has utilized its proprietary Tailored Covalency™ technology to develop a portfolio of drug candidates that exhibit antibody-like specificity to benefit patients with autoimmune and inflammatory diseases and cancer. PRN1008, a reversible covalent BTK inhibitor, is currently being evaluated in a Phase 2 clinical trial in patients with pemphigus, an orphan autoimmune disease. PRN1371, a covalent FGFR1-4 inhibitor, is currently being evaluated in a Phase 1 clinical trial in cancer patients with various solid tumors. PRN2246, a low dose covalent BTK inhibitor which crosses the blood brain barrier, is currently being evaluated in a Phase 1 clinical trial, and has been licensed to Sanofi. The company has entered into a collaboration with AbbVie for the development of oral immunoproteasome inhibitors in the field of immunology. For more information, please visit the Company’s website at
Media Contact:
Kelly Boothe, Pure Communications
Investor Contact:
Christopher Chai, Principia Biopharma