Pieris Pharmaceuticals Presents Clinical Data for its Hepcidin Antagonist Program, Prs-080, at the 2015 American Society of Hematology (Ash) Annual Meeting

Pieris Pharmaceuticals, Inc. (NASDAQ: PIRS), a biotechnology company advancing its proprietary Anticalin® bio therapeutic technologies, announced today that it will present detailed data today summarizing the results from a Phase I clinical study in healthy male volunteers with its PRS-080 Anticalin hepcidin antagonist at the 57th Annual Meeting of the American Society of Hematology (ASH) taking place in Orlando, FL.

The oral presentation entitled, "A Phase I Study Investigating Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Activity of the Hepcidin Antagonist PRS-080#022. Results from a Randomized, Placebo Controlled, Double-Blind Study Following Single Administration to Healthy Subjects," outlined the favorable safety profile of the drug, as well as demonstrable proof of mechanism shown by increased serum iron levels as well as transferrin saturation in treated subjects.
PRS-080 was well tolerated, with no serious adverse events (SAEs) observed in the single ascending dose (SAD) study at six dose levels administered by intravenous infusion in 48 healthy male subjects ranging from 0.08 to 16.0 mg/kg (clinicaltrials.gov identifier NCT02340572). Reported AEs were of mild to moderate severity with no apparent dose dependency or difference between active and placebo treatment groups. The plasma half-life of PRS-080 ranged between 71 and 81 hours among dose cohorts.

Within one hour of PRS-080 administration, a marked decrease in plasma hepcidin was observed, followed by dose-dependent elevations of both serum iron concentration and transferrin saturation. Moreover, the durations of serum iron elevation and transferrin saturation also increased in a dose-dependent manner. Among all subjects receiving PRS-080 doses of 1.2 mg/ml and higher, statistically significant increases in total serum iron mobilization were observed relative to placebo (p = .005).

Louis Matis, M.D., Pieris SVP and Chief Development Officer commented, "We are extremely pleased by the safety profile as well as the pharmacodynamic activity of our hepcidin antagonist in these healthy subjects. Hepcidin is the root cause of and therefore, an attractive target for treating the hypoferremia and iron-restricted reduction of erythropoiesis seen in anemias of chronic disease (ACD), which are often associated with poor prognosis and lower quality of life. Management of ACD using intravenous iron and erythropoiesis stimulating agents is ineffective for subsets of patients and may have adverse effects, driving the need for new alternative therapies. We expect to soon initiate the dosing of anemic patients with chronic kidney disease (CKD) undergoing hemodialysis, for whom elevated hepcidin is strongly associated with the severity of anemia."

PRS-080 is a fully proprietary Anticalin protein that sequesters hepcidin, typically regarded as the master negative regulator of iron metabolism. With a pharmacokinetic profile tuned to remove hepcidin in line with target turnover dynamics, PRS-080 is intended to optimally mobilize iron trapped in iron storage cells, particularly in anemic patients with iron-restricted erythropoiesis due to functional iron deficiency. Funded in part by an EC FP7 health program grant, Pieris' hepcidin antagonist program was supported by the EUROCALIN consortium.

See the full presentation here.

About Anemias of Chronic Disease
Anemia of Chronic Disease (ACD), also known as Anemia of Inflammation (AI), is the most prevalent anemia in hospitalized patients worldwide. It occurs in patients with acute or chronic inflammatory conditions including infections, cancer, rheumatoid arthritis, and chronic kidney disease. ACD is generally characterized by a normocytic anemia, impaired erythropoiesis, low serum iron and low transferrin saturation, but often normal to high body iron stores with iron sequestered in intracellular compartments. The molecular mechanisms and pathogenesis of the iron distribution abnormalities in ACD have been elucidated, and it has now been shown that inflammatory cytokines released during acute infection or chronic disease alter systemic iron metabolism by inducing excess synthesis of the iron regulatory hormone hepcidin. In turn, hepcidin inhibition of iron export from cells by blocking ferroportin activity has been established as the major underlying cause of the hypoferremia and iron-restricted erythropoiesis seen in ACD. Current treatment of the anemia generally includes administration of intravenous iron and erythropoiesis stimulating agents. However, the fact that these approaches do not directly address the high levels of hepcidin responsible for functional iron deficiency, together with concerns over adverse effects from these therapies, have driven the need for alternative treatments.