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 both 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 Anticalins in humans to demonstrate good drug-like properties of the drug class members. In 2010, Pieris conducted the first clinical study of an Anticalin in oncology patients. A further clinical trial in healthy volunteers with another Anticalin to treat anemia was initiated in December 2014 and completed in 2015, while a first-in-patient trial in dialysis-dependent patients was conducted in 2016 and completed in 2017. In 2017, the company plans to initiate Furthermore, several Anticalin programs are advancing towards and in the clinic, including Daiichi Sankyo's partnered Anticalin protein targeting PCSK9, where a Phase I clinical study was initiated in November 2015.

In 2017, Pieris signed transformative deals with Servier in immuno-oncology and AstraZeneca in respiratory disease, 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 the US transformative therapies to address challenging diseases.