PADDOCK Clinical Trial

Broad Hematologic Improvements in Patients with PNH Shows APL-2 Has the Potential to Address Both Intravascular and Extravascular Hemolysis

Interim Results from 19 Patients Enrolled in the PADDOCK Phase 1b Trial (APL2-CP-PNH-204)

In the PADDOCK phase Ib trial, monotherapy with APL-2 (180 mg/day or 270 md/day) in complement inhibitor-naïve PNH patients resulted in rapid and durable normalization of hemoglobin (Hb), lactate dehydrogenase (LDH), absolute reticulocytes (ARC) and total bilirubin.

Decrease in Lactate Dehydrogenase (LDH) in Response to APL-2

Data chart illustrating the interim results from the PADDOCK phase 1b trial (APL2-CP-PNH-204). Data evaluate the activity of lactate dehydrogenase (LDH) in response to APL-2.
  • Reductions in LDH were rapid following initiation of APL-2 therapy, with 95% of subjects achieving an LDH in the normal range by day 29
  • Reductions in LDH have been sustained and durable, with mean LDH maintained within the normal range at all timepoints beyond day 29

Decrease in Absolute Reticulocyte Count (ARC) in Response to APL-2

Data chart showing the interim results from the PADDOCK phase 1b trial (APL2-CP-PNH-204). Data evaluate the absolute reticulocyte count (ARC) in response to APL-2.

Decrease in Serum Total Bilirubin in Response to APL-2

Data chart showing the interim results from the PADDOCK phase 1b trial (APL2-CP-PNH-204). Data evaluate the decrease in total bilirubin with APL-2.
  • Decreases in ARC and total bilirubin were rapid following initiation of treatment with APL-2
  • By day 29 mean ARC and total bilirubin were within the normal range:
    • With the exception of a non-compliant subject, ARC was reduced in all subjects and was within the normal range in 79% of subjects at day 29
    • With the exception of a non-compliant subject, total bilirubin was reduced in all subjects and was within the normal range in 95% of subjects at day 29

Treatment with APL-2 in eculizumab-naïve patients with paroxysmal nocturnal hemoglobinuria (PNH) demonstrated normalization of mean hemoglobin, indicating broad control of intravascular and extravascular hemolysis.


Increase in Hemoglobin (Hb) in Response to APL-2

Data chart showing the interim results from the PADDOCK phase 1b trial (APL2-CP-PNH-204). Data evaluate the effect of APL-2 on hematologic improvement in patients with PNH.
  • All 19 subjects responded rapidly after initiating APL-2 therapy, and by day 29 mean baseline Hb increased from 8.0 g/dL to 10.8 g/dL
  • Increases in Hb were sustained and durable as represented by a mean Hb of 12.2 g/dL at Day 85

Change From Baseline in FACIT Fatigue Score

Data chart showing the interim results from the PADDOCK phase 1b trial (APL2-CP-PNH-204). Data evaluate the change from baseline in FACIT fatigue score
  • The Functional Assessment of Chronic Illness Therapy (FACIT) is a quantitative measurement of health-related quality of life; an increase of >3 is considered clinically meaningful
  • Fatigue as measured by the FACIT-Fatigue instrument improved rapidly (within 2 weeks) after initiation of APL-2 therapy, and the mean (SE) change from baseline at day 29 was 6.4 (2.7)
  • The increase in FACIT score was durable and sustained as represented by a mean (SE) changed from baseline of 7.86 (2.2) at day 85

Treatment with APL-2 in complement inhibitor-naïve PNH patients resulted in rapid and durable normalization of Hb, LDH, ARC and total bilirubin.

Previously transfusion-dependent patients did not require any transfusions during maintenance treatment with APL-2.