Hematide™ is a PEGylated synthetic dimeric peptide. Initial peptide sequences were identified by screening a human erythropoietin receptor (HuEPOr) with Recombinant Peptide Diversity libraries possessing > 1010 different chemical structures. Following extensive chemical analoging and introduction of novel architectural features, a compound containing a dimeric peptide having no detectable sequence identity to natural human EPO was created and this compound is substantially equipotent to natural EPO. The portion of the molecule containing the peptide was linked to polyethylene glycol to yield Hematide, a potent stimulator of erythropoiesis with sustained plasma persistence. Antibodies generated experimentally to Hematide peptide do not cross-react with recombinant human EPO and therefore this peptide-based HuEPOr agonist is unlikely to cause aplastic anemia and loss of potency for either recombinant erythropoietin receptor agonists or for the recipient patient’s endogenous EPO. Pharmacokinetic studies in rats, dogs and monkeys have demonstrated the extended plasma half-life of Hematide. In the rat, elimination half-life is between 21.5 to 30.7 hours, steady state volume of distribution (Vss) is between 42.7 to 65.6 mL/kg and clearance is slow at 1.3–2.3 mL/h/kg. In the dog, elimination half-life was 73.7 hours while clearance and Vss were 0.69 mL/h/kg and 69.6 mL/kg, respectively. Prolonged half-lives and slow clearance times are also evident in the monkey. At a dose of 1.35 mg/kg, a half-life of 58.4 hours was obtained with a clearance rate of 0.96 mL/h/kg. Erythropoietic activity of Hematide has been demonstrated in the normocythemic mouse, rat, dog, and monkey, and in the nephrectomized rat. Pharmacology studies following single dose administration in mice, rats (normocythemic and nephrectomized) and monkeys indicate that the rise in hemoglobin is dose-dependent. Erythropoietic activity was demonstrated in Sprague-Dawley rats when Hematide was given every week for 6 weeks at doses up to 1.35 mg/kg. There was a pronounced erythropoietic response and no anti-Hematide antibodies were detected in any of the dose groups. In conclusion, Hematide is a potent erythropoietin receptor agonist with prolonged half-life and slow clearance times. It is anticipated that similar prolonged clearance will be observed in the clinic, potentially enabling dosing intervals of 3 to 4 weeks that may translate into improved patient convenience and compliance.