Table 2.
Functional characteristics of HexaBody-CD38 in comparison with daratumumab.
| Functional Characteristics | HexaBody-CD38 | daratumumab | Significance |
|---|---|---|---|
| Binding | |||
| Binding to soluble CD38 (Affinity, KD; average ± SD) | 1.1 ± 0.17 nM | 3.9 ± 0.48 nM | P = 0.0058a CI 1.9–3.8 |
| Binding to membrane-expressed CD38 (Apparent affinity, EC50; average ± SD) | 0.087 ± 0.042 μg/mL | 0.148 ± 0.038 μg/mL | P = 0.10161a CI −0.0298 to 0.152 |
| CDC | |||
| EC50 (geometric mean; geometric standard deviation [GSD]) | 0.044 μg/mL; GSD 1.52 | 0.31 μg/mL; GSD 1.40 | P < 0.0001b |
| Max lysis (average ± SD) | 72 ± 29% | 44 ± 38% | P < 0.0001b |
| ADCC Loss of Daudi cells | |||
| EC50 (average ± SD) | 0.290 ± 0.231 ng/mL | 2.192 ± 2.376 ng/mL | P = 0.1204a CI −0.0002837 to 0.001797 |
| Max loss (average ± SD) | 42 ± 9% | 40 ± 11% | P = 0.1602c |
| ADCP Macrophages with phagocytic activity | |||
| EC50 (average ± SD) | 2.719 ± 2.080 ng/mL | 7.517 ± 6.828 ng/mL | P = 0.0305d CI −0.009108 to −0.0004880 |
| Max activity (average ± SD) | 25 ± 12% | 25 ± 11% | ND |
| ADCP Loss of Daudi cells | |||
| EC50 (average ± SD) | 5.779 ± 7.554 ng/mL | 16.248 ± 24.21 ng/mL | P = 0.2593d CI −0.03325 to 0.008984 |
| Max loss (average ± SD) | 68 ± 22% | 67 ± 25% | ND |
| Trogocytosis | |||
| EC50 (average ± SD) | 8.79 ± 2.49 ng/mL | 17.99 ± 1.82 ng/mL | P = 0.0218e CI 0.002451–0.01596 |
| Apoptosis | |||
| Mean max % of early apoptotic cells after crosslinking | 39% | 39% | ND |
| Mean max % of late apoptotic cells after crosslinking | 12% | 11% | ND |
| CD38 cyclase activity | |||
| EC50 (average ± SD) | 0.419 ± 0.097 μg/mL | 0.179 ± 0.038 μg/mL | P = 0.0085e CI 0.07884–0.4028 |
| Max inhibition (%) | 59 ± 2% | 37 ± 4% | P = 0.4386f |
| CD38 hydrolase activity | |||
| EC50 (average ± SD) | 0.335 ± 0.115 μg/mL | 0.028 ± 0.008 μg/mL | P = 0.0114e CI 0.08747–0.5268 |
| Max stimulation (%) | 20 ± 4% | 16 ± 3% | P = 0.3017f |
ADCC, Antibody-dependent cellular cytotoxicity; ADCP, Antibody-dependent cell-mediated phagocytosis; BLI, BioLayer Interferometry; CDC, Complement-dependent cytotoxicity; EC50, Half maximal effective concentration; GSD, Geometric standard deviation; max, maximum; SD, Standard deviation. ND, Not determined, statistical testing was not performed if results were clearly not different.
a
Paired T test.
b
F-test.
c
Wilcoxon matched-pairs signed rank test.
d
Mixed effects analysis with Tukeys test, due to missing values.
e
One-way ANOVA, Tukey multiple comparison test.
f
Friedman test with uncorrected Dunn's posthoc test.