On November 8, 2021 Pieris Pharmaceuticals, Inc. (NASDAQ:PIRS), a clinical-stage biotechnology company advancing novel biotherapeutics through its proprietary Anticalin technology platform for respiratory diseases, cancer, and other indications, and Servier, a global pharmaceutical group, reported that the first patient has been dosed in the phase 1/2 study of PRS-344/S095012, a next generation 4-1BB/PD-L1 Anticalin-based bispecific for the treatment of solid tumors, triggering an undisclosed milestone payment to Pieris (Press release, Pieris Pharmaceuticals, NOV 8, 2021, View Source [SID1234594680]). The global, open-label phase 1/2 dose escalation study will evaluate the safety, tolerability, potential optimal dosage, and potential anti-tumor activity of PRS-344/S095012 in patients with advanced solid tumors whose cancer progressed on standard-of-care treatment.
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PRS-344/S095012 is a tetravalent bispecific fusion protein comprising 4-1BB-targeting Anticalin proteins and a PD-L1-targeting antibody. Preclinical studies showed that PRS-344/S095012 is superior to the combined administration of separate PD-L1- and 4-1BB- targeting molecules. Further, in anti-PD-L1-resistant mouse models, the bispecific induces a dose-dependent anti-tumor response and significantly extends survival. In vitro, PRS-344/S095012 enhances effective CD8+ T cell response and proinflammatory cytokine release. Furthermore, preclinical models reflect that PRS-344/S095012-mediated 4-1BB activation is PD-L1 dependent, reducing the risk of peripheral toxicity, and 4-1BB co-stimulation only occurs in combination with simultaneous TCR signaling, restricting its activity to antigen-specific T cells.
"This marks an important step in our development of PRS-344/S095012, our broader 4-1BB bispecifics franchise, and our strategic alliance with Servier. Our 4-1BB/PD-L1 bispecific has been designed to address localized 4-1BB agonism while driving PD-L1 antagonism benefit, thereby facilitating a meaningful therapeutic window," said Tim Demuth, M.D., Ph.D., Chief Medical Officer of Pieris.
"PRS-344/S095012 has shown clear synergistic benefit in preclinical studies thanks to its bispecific format. We are excited to have begun clinical development of PRS-344/S095012, which may provide patients with a new treatment option and significant clinical impact. The dosing of the first patient in this study marks a meaningful step to developing a potential future treatment for cancer patients with limited options," said Patricia Belissa-Mathiot, Director of Clinical Development and R&D Chief Medical Officer at Servier.