Pharming Group N.V. announced the first commercial shipments of Joenja® (leniolisib) to patients in the United States. Joenja®, an oral, selective PI3Kd inhibitor, is the first and only treatment approved in the U.S. for activated phosphoinositide 3-kinase delta (PI3Kd) syndrome (APDS), a rare and progressive primary immunodeficiency, in adult and pediatric patients 12 years of age and older. Under the terms of Pharming's 2019 exclusive license agreement with Novartis for leniolisib, the corresponding first commercial sale of Joenja® triggers a $10 million milestone payment by Pharming to Novartis.

About Activated Phosphoinositide 3-Kinase d Syndrome (APDS): APDS is a rare primary immunodeficiency that was first characterized in 2013. APDS is caused by variants in either one of two identified genes known as PIK3CD or PIK3R1, which are vital to the development and function of immune cells in the body. Variants of these genes lead to hyperactivity of the PI3Kd (phosphoinositide 3-kinase delta) pathway, which causes immune cells to fail to mature and function properly, leading to immunodeficiency and dysregulation.

APDS is characterized by a variety of symptoms, including severe, recurrent sinopulmonary infections, lymphoproliferation, autoimmunity, and enteropathy. Because these symptoms can be associated with a variety of conditions, including other primary immunodeficiencies, it has been reported that people with APDS are frequently misdiagnosed and suffer a median 7-year diagnostic delay. As APDS is a progressive disease, this delay may lead to an accumulation of damage over time, including permanent lung damage and lymphoma.

A definitive diagnosis can be made through genetic testing. APDS affects approximately 1 to 2 people per million worldwide. About Joenja® (leniolisib): Joenja® (leniolisib) is an oral small molecule phosphoinositide 3-kinase delta (PI3K?) inhibitor approved in the US as the first and only targeted treatment of activated phosphoinositide 3-kinase delta (PI3Kd) syndrome (APDS) in adult and pediatric patients 12 years of age and older.

Joenja® inhibits the production of phosphatidylinositol-3-4-5-trisphosphate, which serves as an important cellular messenger and regulates a multitude of cell functions such as proliferation, differentiation, cytokine production, cell survival, angiogenesis, and metabolism. Results from a randomized, placebo-controlled Phase II/III clinical trial demonstrated clinical efficacy of Joenja® in the co-primary endpoints; demonstrating statistically significant impact on immune dysregulation and normalization of immunophenotype within these patients, and interim open label extension data has supported the safety and tolerability of long-term Joenja® administration.8 Leniolisib is currently under regulatory review by the European Medicines Agency, with plans to pursue further regulatory approvals in the UK, Canada, Australia and Japan. Leniolisib is also being evaluated in a Phase III clinical trial in children aged 4 to 11 with APDS, with a further trial planned in children aged 1 to 6 years with APDS.