Hematide™, a Synthetic Peptide-Based Erythropoiesis Stimulating Agent (ESA), Demonstrates Erythropoietic Activity in a Phase 2 Single Dose, Dose Escalating Study in Patients with Chronic Kidney Disease (CKD).
Authors: Duliege Anne-Marie , Macdougall Iain , Duncan Neill , Wessels Dawie , Iwashita Julie , Schatz Pete , Naso Robert , Stead Richard , Lambert John 
Published: April 2020

Abstract
Hematide is a PEGylated synthetic peptidic ESA that binds to and activates the erythropoietin (EPO) receptor. It has demonstrated potent and sustained dose dependent erythropoietic activity in healthy volunteers (HV).
Methods: A randomized double-blind placebo controlled dose escalation study is being conducted to assess safety, pharmacokinetics (PK) and pharmacodynamics (PD) of Hematide administered as a single intravenous (IV) injection in EPO-naïve patients with Chronic Kidney Disease (CKD) pre-dialysis. Cohorts of 9 patients each (7 on Hematide and 2 on placebo) are planned with escalating doses. The results of this study are compared with those of a recently completed Phase 1 dose escalating study of Hematide in 4 cohorts of HV in which the pharmacologically active dose (PAD; i.e., the dose resulting in a statistically and clinically significant increase in hemoglobin) of Hematide was defined.
Results: 28 day follow up of the 9 patients in Cohort 1 is complete. As of this date, the study remains blinded and we assume that increases in reticulocytes and hemoglobin (Hgb) are due to Hematide. Injections were well tolerated with no adverse events reported as related to study drug injection. In 7 patients whose reticulocytes increased, counts peaked at 7–10 days with a mean change from baseline of 151.4 ± 18.4 x 109/L before returning within baseline at 21 days post-injection. A Hgb increase was also observed in these 7 patients with a mean difference in change from baseline Hgb between these 7 responding and the 2 non-responding subjects of 0.80 g/dL at Day 10 (p = 0.028) and 1.16 g/dL (p = 0.08) at Day 28 post-injection. The PD profile of these 7 responding patients is comparable to that of the 10 HV receiving a PAD of Hematide. For example, the average maximum Hgb increase from baseline was 1.22 g/dL (SD: 0.37) in patients versus 1.36 g/dL (SD: 0.39) in HV. However, the PAD for CKD patients was half the Hematide dose that was required to obtain a similar Hgb effect in HV. Unblinded results from the complete study, including dose responses, follow-up after 28 days, PK data, additional PD data, EPO levels and iron status assessment will be presented and compared to the results in HV.
Conclusion: A single IV injection of Hematide administered to patients with CKD was well tolerated and demonstrated potent and sustained erythropoietic activity of the same magnitude as that observed in HV. The PAD in patients with CKD was half of that observed in HV. These preliminary data suggest that patients with CKD may be more sensitive to Hematide and/or might have a different PK profile compared to HV. The sustained increases in Hgb levels for at least one month following a single dose of Hematide are compatible with anticipated monthly dosing of Hematide to maintain Hgb in target range. This is a reduced frequency of administration compared to that of currently available ESAs. These results serve as a basis to plan studies of repeat doses of Hematide in patients with anemia related to cancer or CKD and this plan will be outlined.