ARCA biopharma, Inc. announced results for ASPEN-COVID-19, a 160 patient Phase 2b clinical trial evaluating rNAPc2, a highly potent and specific inhibitor of tissue factor, as a potential treatment for patients hospitalized with COVID-19. In the clinical trial, both doses of rNAPc2 demonstrated a treatment benefit for patients, however, neither dose achieved statistical significance for the primary efficacy endpoint of change in D-dimer level from Baseline to Day 8 compared to standard of care heparin. This clinical trial used a 1:1:2 randomization between lower dose rNAPc2, higher dose rNAPc2 and standard of care heparin that was delivered in prophylactic doses in 93% of the patients.

rNAPc2 patients received three sub-cutaneous (SC) doses on days 1, 3 and 5 and then received heparin beginning on day 8. This Phase 2b study was designed to understand the safety of the doses selected relative to standard of care, and to provide efficacy data that might support further study in a pivotal Phase 3 program. For the entire cohort for pooled rNAPc2 versus heparin, in the intention to treat (ITT) population, rNAPc2 was associated with a change in D-dimer of -16.8 (-45.7, 36.8) %, P=0.41 compared to -11.2 (-36, 34.4) %, P=0.91 in the Heparin group (between groups P=0.47). For the per protocol analysis (N=81) of the 38 rNAPc2 patients who received all three doses and remained hospitalized long enough to have the day 8 end-of-efficacy period D-dimer levels measured, there was a reduction from baseline of -28.7 (-49.1,14.0) %, P=0.23, while the Heparin group change from baseline was an increase of 1.1 (-45.2,108) %, P=0.33; between groups P=0.33.

The clinical trial statistical analysis plan called for analysis of data stratified by a modified WHO COVID-19 Severity Scale that assigned randomized patients to either Mild or Severe groups. There was an imbalance by rNAPc2 dose group between these strata with more higher dose group patients in the Severe stratum (15 vs 10 lower dose) and more higher dose in the Mild stratum. Because treatment effects were different in these strata, dose response had to be analyzed within each stratum.

In the ITT analysis, WHO Mild patients (N= 84) had baseline median (IQR) D-dimer levels of 314 (206,473) D-Dimer Units (DDUs, ng/ml). D-dimer levels as percent change decreased at day 8 or hospital discharge in both the pooled high and low dose rNAPc2 arms (-32.7 (-44.7,4.3), P=0.009) and in the heparin arm (-16.8 (-36.0.0.5), P= 0.010); this decrease was statistically significant in the higher dose rNAPc2 group (-32.3 (-43.7,-2.4), P=0.016) but not in the lower dose group (-33.0 (-45.8,8.0), P=0.17). In contrast, in WHO Severe patients (N= 51, baseline DDU median 546 (318,872), P<0.0001 vs.

Mild) D-dimer levels increased in the heparin group (% change 29.0 (-14.9,145), P=0.022) but did not change in the pooled rNAPc2 group (25.9 (-49.1,136), P=0.16) or in either rNAPc2 dose group (lower, -12.1(-50.2,498), P=0.84; higher, 36.8 (-41.7,136) P=0.13). ASPEN-COVID-19 was a Phase 2b randomized, multi-center, international clinical trial that evaluated two dose regimens of rNAPc2 versus standard of care heparin in 160 hospitalized SARS-CoV-2 positive patients that also had an elevated D-dimer level. The primary endpoint of the clinical trial was the change in D-dimer level from baseline to Day 8 relative to standard of care heparin.

D-dimer is a biomarker commonly used for assessing coagulation activation, which is commonly elevated in hospitalized COVID-19 patients and is associated with adverse clinical outcomes. Heparin is an anticoagulant commonly given to any patient hospitalized in the United States for COVID-19. Summary efficacy results: Change in D-dimer levels from baseline at Day 8: in ITT analysis, rNAPc2 combined dose arms median reduction of 16.8%, Heparin group reduction of 11.2% (P =0.47 between groups).

Per protocol analysis (all 3 doses of rNAPc2 administered) reduction in D-dimer of 28.7% in rNAPc2 dose pooled group, heparin increased by 1.1% (P=0.33 between groups). WHO Severe patients Heparin group increase in D-dimer by 29.0%, P=0.022 within group; rNAPc2 change by 25.9%, P=0.16 within group.