Pieris was founded based on the groundbreaking discovery of Anticalin® proteins and their potential as therapeutics, which was made at the Technical University of Munich. The company's goal has always been to commercialize this technology through partnerships with pharmaceutical and biotech companies as well as through development of proprietary drugs.

On its own and together with its partners, Pieris is developing multiple Anticalin therapeutic programs and has tested multiple Anticalin proteins in humans to demonstrate good drug-like properties of the drug class members. In 2010, Pieris conducted the first clinical study of an Anticalin protein in oncology patients. Further clinical trials in healthy volunteers and patients with other Anticalin proteins have demonstrated the potential of this therapeutic drug class.

In 2017, Pieris signed transformative deals with Servier in immuno-oncology and with AstraZeneca in respiratory diseases, having retained co-development and co-commercialization rights on several programs within each alliance as part of the company's strategy to develop and ultimately market in transformative therapies in the United States to address challenging diseases.