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In Silico Biophysical Developability Predictor Benchmark

This report details the cross-validated performance of AbLead's in silico developability prediction engine, trained on the 137 clinical-stage antibodies from Jain et al. (2017) comparing With Structure (Seq + 3D Struct) and Sequence Only (DeepSP) models.

Side-by-Side Benchmark Performance (LOOCV)

Biophysical Assay LOOCV ρ (With Struct) LOOCV ρ (Seq Only) ROC-AUC (With Struct) ROC-AUC (Seq Only) Top Drivers (With Struct) Top Drivers (Seq Only)
Hydrophobicity (HIC RT min) +0.602 +0.567 0.710 0.718 SAP_pos_CDR, SCM_pos_CDRH2 SAP_pos_CDR, SCM_pos_CDRH2
Colloidal Stability (SMAC RT min) +0.577 +0.538 0.702 0.715 SAP_pos_CDRH2, H3 SAP_pos_CDR, H3
Self-Association (AC-SINS Δλmax nm) +0.412 +0.412 0.589 0.589 SCM_neg_CDRH2, pI (Bjellqvist) SCM_neg_CDRH2, pI (Bjellqvist)
Self-Association (SGAC-SINS mM) +0.547 +0.477 0.661 0.671 SAP_pos_CDR, SAP_pos_Hv SAP_pos_CDR, SAP_pos_Hv
Polyreactivity (PSR SMP Score) +0.415 +0.415 0.750 0.750 pI (Bjellqvist), SCM_neg_CDRH1 pI (Bjellqvist), SCM_neg_CDRH1
Polyreactivity (BVP ELISA Score) +0.509 +0.467 0.851 0.850 AbLang2 FR, SCM_pos_CDR SCM_pos_CDR, AbLang2 FR
Cross-Interaction (CIC RT min) +0.527 +0.543 0.760 0.756 SCM_neg_CDRL1, SCM_neg_Lv L3, SCM_neg_CDRH1
Thermostability (DSF Fab Tm °C) +0.401 +0.401 0.637 0.637 AbLang2 Full, H2 AbLang2 Full, H2
Expression Titer (HEK mg/L) +0.417 +0.417 0.687 0.687 AbLang FR, IgBert FR AbLang FR, IgBert FR
Viscosity (150 mg/mL, cP) +0.492 +0.461 0.784 0.737 SAP_pos_Fv, SCM_pos_CDR SAP_pos_Fv, IgBert Full

Four-Quadrant Clinical Triage Methodology & Color Legend

Rather than evaluating developability strictly as a continuous linear regression, benchmark evaluations are structured as Four-Quadrant Clinical Triage Plots bisected along both axes by the Clinical Liability Threshold (\(p_{90}\) for liability traits like HIC, SMAC, AC-SINS, Viscosity; \(p_{10}\) for favorable traits like \(T_m\) and Titer), accompanied by a \(\pm 0.75\,\sigma_{\text{assay}}\) Concordance Corridor around the identity line:

  • ● True Clean (Green Circle): Predicted clean and experimentally confirmed clean. Safe to advance in lead optimization.
  • ■ True Liability Caught (Crimson Square): Predicted liability and experimentally confirmed severe liability. Successfully flagged and eliminated in silico.
  • ▲ False Alarm (Gold Triangle): Predicted liability but experimentally clean. Over-conservative flag (acceptable trade-off in early library enrichment).
  • ✖ Slipped Liability (Purple Cross): Predicted clean but experimentally a severe liability. This is why characterization assays will still be needed after initial lead panel reduction.

Feature Insights by Biophysical Property

Hydrophobicity (HIC RT min)

Hydrophobicity Actual vs Predicted

  • With Structure: Spearman ρ = +0.602, Pearson r = +0.358, Liability ROC-AUC = 0.710
  • Sequence Only: Spearman ρ = +0.567, Pearson r = +0.343, Liability ROC-AUC = 0.718
  • Structural Model Weights:
    • DeepSP: SAP_pos_CDR: +0.5020
    • DeepSP: SCM_pos_CDRH2: -0.4099
    • Surface Properties: SPN: -0.3335
    • pI: pI (Bjellqvist): -0.2744
    • DeepSP: SCM_neg_CDRH2: -0.1751
    • DeepSP: SAP_pos_CDRH1: -0.0958
  • Sequence-Only Model Weights:
    • DeepSP: SAP_pos_CDR: +0.8404
    • DeepSP: SCM_pos_CDRH2: -0.5191
    • DeepSP: SAP_pos_Fv: -0.3205
    • DeepSP: SCM_neg_CDRH2: -0.2687
    • DeepSP: SCM_pos_CDRL2: -0.1878

Colloidal Stability (SMAC RT min)

Colloidal Stability Actual vs Predicted

  • With Structure: Spearman ρ = +0.577, Pearson r = +0.284, Liability ROC-AUC = 0.702
  • Sequence Only: Spearman ρ = +0.538, Pearson r = +0.261, Liability ROC-AUC = 0.715
  • Structural Model Weights:
    • DeepSP: SAP_pos_CDRH2: +0.4524
    • CDR Length (North): H3: +0.3160
    • Surface Properties: SPN: -0.2814
    • DeepSP: SAP_pos_CDR: +0.2305
    • DeepSP: SCM_pos_CDR: -0.1898
    • DeepSP: SCM_neg_Lv: +0.0811
  • Sequence-Only Model Weights:
    • DeepSP: SAP_pos_CDR: +0.4418
    • CDR Length (North): H3: +0.3856
    • DeepSP: SCM_neg_CDRH1: -0.2285
    • DeepSP: SCM_pos_CDRL2: -0.2210
    • DeepSP: SCM_pos_CDRH2: -0.1310

Self-Association (AC-SINS Δλmax nm)

Self-Association AC-SINS Actual vs Predicted

  • With Structure: Spearman ρ = +0.412, Pearson r = +0.195, Liability ROC-AUC = 0.589
  • Sequence Only: Spearman ρ = +0.412, Pearson r = +0.195, Liability ROC-AUC = 0.589
  • Structural Model Weights:
    • DeepSP: SCM_neg_CDRH2: -1.1554
    • pI: pI (Bjellqvist): +0.8592
  • Sequence-Only Model Weights:
    • DeepSP: SCM_neg_CDRH2: -1.1554
    • pI: pI (Bjellqvist): +0.8592

Self-Association (SGAC-SINS mM)

Self-Association SGAC-SINS Actual vs Predicted

  • With Structure: Spearman ρ = +0.547, Pearson r = +0.360, Liability ROC-AUC = 0.661
  • Sequence Only: Spearman ρ = +0.477, Pearson r = +0.329, Liability ROC-AUC = 0.671
  • Structural Model Weights:
    • DeepSP: SAP_pos_CDR: -169.8280
    • DeepSP: SAP_pos_Hv: +128.6042
    • Surface Properties: SPN: +98.9797
    • CDR Length (North): L3: -95.7968
    • DeepSP: SAP_pos_CDRL3: +63.5710
    • pI: pI (Bjellqvist): +28.8756
  • Sequence-Only Model Weights:
    • DeepSP: SAP_pos_CDR: -195.8135
    • DeepSP: SAP_pos_Hv: +140.7063
    • CDR Length (North): L3: -90.0946
    • DeepSP: SAP_pos_CDRL3: +62.7099
    • DeepSP: SCM_neg_CDRH1: +61.5034

Polyreactivity (PSR SMP Score)

Polyreactivity PSR Actual vs Predicted

  • With Structure: Spearman ρ = +0.415, Pearson r = +0.314, Liability ROC-AUC = 0.750
  • Sequence Only: Spearman ρ = +0.415, Pearson r = +0.314, Liability ROC-AUC = 0.750
  • Structural Model Weights:
    • pI: pI (Bjellqvist): +0.0515
    • DeepSP: SCM_neg_CDRH1: -0.0301
  • Sequence-Only Model Weights:
    • pI: pI (Bjellqvist): +0.0515
    • DeepSP: SCM_neg_CDRH1: -0.0301

Polyreactivity (BVP ELISA Score)

Polyreactivity BVP ELISA Actual vs Predicted

  • With Structure: Spearman ρ = +0.509, Pearson r = +0.416, Liability ROC-AUC = 0.851
  • Sequence Only: Spearman ρ = +0.467, Pearson r = +0.383, Liability ROC-AUC = 0.850
  • Structural Model Weights:
    • AbLang/AbLang2 Score: AbLang2 FR: -1.4216
    • DeepSP: SCM_pos_CDR: +1.3691
    • AbLang/AbLang2 Score: IgBert Full: +1.0548
    • CDR Length (North): CDR Sum: +0.9641
    • Surface Properties: SPP: +0.3402
    • DeepSP: SCM_pos_CDRH1: +0.3352
    • DeepSP: SCM_neg_Lv: -0.2965
  • Sequence-Only Model Weights:
    • DeepSP: SCM_pos_CDR: +1.9562
    • AbLang/AbLang2 Score: AbLang2 FR: -1.2333
    • AbLang/AbLang2 Score: IgBert Full: +0.7677
    • DeepSP: SCM_neg_CDRH3: +0.4871

Cross-Interaction (CIC RT min)

Cross-Interaction CIC Actual vs Predicted

  • With Structure: Spearman ρ = +0.527, Pearson r = +0.376, Liability ROC-AUC = 0.760
  • Sequence Only: Spearman ρ = +0.543, Pearson r = +0.471, Liability ROC-AUC = 0.756
  • Structural Model Weights:
    • DeepSP: SCM_neg_CDRL1: -0.3153
    • DeepSP: SCM_neg_Lv: +0.2655
    • DeepSP: SCM_neg_CDRH1: -0.2273
    • AbLang/AbLang2 Score: AbLang FR: -0.1879
    • Surface Properties: SPN: -0.1187
    • DeepSP: SAP_pos_CDRL2: +0.1165
  • Sequence-Only Model Weights:
    • CDR Length (North): L3: +0.2254
    • DeepSP: SCM_neg_CDRH1: -0.2250
    • DeepSP: SAP_pos_CDRL2: +0.1828
    • AbLang/AbLang2 Score: IgBert Full: +0.1824
    • AbLang/AbLang2 Score: AbLang2 FR: -0.1763
    • AbLang/AbLang2 Score: AbLang Full: -0.1753
    • pI: pI (Bjellqvist): +0.1627

Thermostability (DSF Fab Tm °C)

Thermostability DSF Tm Actual vs Predicted

  • With Structure: Spearman ρ = +0.401, Pearson r = +0.432, Liability ROC-AUC = 0.637
  • Sequence Only: Spearman ρ = +0.401, Pearson r = +0.432, Liability ROC-AUC = 0.637
  • Structural Model Weights:
    • AbLang/AbLang2 Score: AbLang2 Full: +1.2380
    • CDR Length (North): H2: -1.0319
    • AbLang/AbLang2 Score: IgBert Full: -0.9021
    • DeepSP: SAP_pos_CDRL2: +0.8000
    • DeepSP: SAP_pos_CDRL3: +0.7033
    • DeepSP: SCM_neg_CDRL2: -0.4507
  • Sequence-Only Model Weights:
    • AbLang/AbLang2 Score: AbLang2 Full: +1.2380
    • CDR Length (North): H2: -1.0319
    • AbLang/AbLang2 Score: IgBert Full: -0.9021
    • DeepSP: SAP_pos_CDRL2: +0.8000
    • DeepSP: SAP_pos_CDRL3: +0.7033
    • DeepSP: SCM_neg_CDRL2: -0.4507

Expression Titer (HEK mg/L)

Expression Titer Actual vs Predicted

  • With Structure: Spearman ρ = +0.417, Pearson r = +0.349, Liability ROC-AUC = 0.687
  • Sequence Only: Spearman ρ = +0.417, Pearson r = +0.349, Liability ROC-AUC = 0.687
  • Structural Model Weights:
    • AbLang/AbLang2 Score: AbLang FR: -20.5649
    • AbLang/AbLang2 Score: IgBert FR: +17.3603
    • DeepSP: SCM_pos_CDRL1: -10.8147
    • DeepSP: SCM_neg_CDRL1: +9.8121
    • AbLang/AbLang2 Score: CVV FR: -7.4888
  • Sequence-Only Model Weights:
    • AbLang/AbLang2 Score: AbLang FR: -20.5649
    • AbLang/AbLang2 Score: IgBert FR: +17.3603
    • DeepSP: SCM_pos_CDRL1: -10.8147
    • DeepSP: SCM_neg_CDRL1: +9.8121
    • AbLang/AbLang2 Score: CVV FR: -7.4888

Viscosity (150 mg/mL, cP)

Viscosity 150 mg/mL Actual vs Predicted

  • With Structure: Spearman ρ = +0.492, Pearson r = +0.302, Liability ROC-AUC = 0.784
  • Sequence Only: Spearman ρ = +0.461, Pearson r = +0.273, Liability ROC-AUC = 0.737
  • Structural Model Weights:
    • DeepSP: SAP_pos_Fv: +7.4795
    • DeepSP: SCM_pos_CDR: +6.8753
    • AbLang/AbLang2 Score: IgBert Full: +5.4399
    • Surface Properties: SPN: +3.9465
    • DeepSP: SCM_pos_CDRH3: -3.4260
    • AbLang/AbLang2 Score: CVV FR: -2.3374
  • Sequence-Only Model Weights:
    • DeepSP: SAP_pos_Fv: +7.3482
    • AbLang/AbLang2 Score: IgBert Full: +5.6551
    • DeepSP: SCM_pos_CDR: +3.1955
    • AbLang/AbLang2 Score: CVV FR: -3.0866

Actual vs. Predicted Biophysical Readouts (Jain et al. 2017, N=137)

The table below details experimental clinical measurements (Act) alongside leave-one-out cross-validated (LOOCV) model predictions (Pred) across all 137 clinical-stage therapeutic antibodies from Jain et al. (2017).

Closeness Color-Coding Methodology

Because each biophysical assay operates across different physical scales, measurement units, and dynamic ranges, prediction accuracy is evaluated using the Standardized Absolute Error normalized by the assay population standard deviation (\(\sigma_{\text{assay}}\)):

\[\text{Normalized Error} = \frac{|\text{Predicted} - \text{Actual}|}{\sigma_{\text{assay}}}\]

Predictions are color-coded in accordance with AbLead's standard severity color system:

  • Close Agreement: \(\text{Normalized Error} \le 0.5\,\sigma\) (within \(\approx 10\text{–}15\%\) of dataset range). Highly accurate; well within typical experimental assay repeatability variance.
  • Moderate Deviation: \(0.5\,\sigma < \text{Normalized Error} \le 1.0\,\sigma\). Moderate discrepancy; captures general ranking and correct clinical liability quartile.
  • Outlier / High Deviation: \(\text{Normalized Error} > 1.0\,\sigma\). Significant divergence between predicted in silico score and physical in vitro measurement.

Assay Standard Deviations (Normalization Baseline)

  • HIC RT: \(\sigma = 2.09\text{ min}\)SMAC RT: \(\sigma = 3.03\text{ min}\)AC-SINS: \(\sigma = 10.36\text{ nm}\)SGAC-SINS: \(\sigma = 318.06\text{ mM}\)BVP ELISA: \(\sigma = 4.31\)
  • PSR SMP: \(\sigma = 0.20\)CIC RT: \(\sigma = 0.84\text{ min}\)DSF Fab \(T_m\): \(\sigma = 5.84^\circ\text{C}\)HEK Titer: \(\sigma = 62.41\text{ mg/L}\)
Antibody HIC Act HIC Pred SMAC Act SMAC Pred AC-SINS Act AC-SINS Pred SGAC Act SGAC Pred BVP Act BVP Pred PSR Act PSR Pred CIC Act CIC Pred DSF Tm Act DSF Tm Pred HEK Titer Act HEK Titer Pred
abituzumab 9.23 10.44 8.72 9.96 1.46 7.21 900.00 623.98 2.72 2.03 0.17 0.15 8.62 9.30 75.5 72.0 89.6 135.6
abrilumab 9.41 10.09 8.70 9.53 -0.93 1.38 900.00 658.91 1.82 1.22 0.00 -0.06 8.38 8.68 71.0 70.2 100.2 153.0
adalimumab 8.82 9.08 8.67 9.28 1.06 5.85 900.00 830.06 1.49 2.28 0.00 0.05 8.87 8.37 71.0 71.7 134.9 135.9
alemtuzumab 8.77 7.46 8.67 9.15 -0.79 8.22 1000.00 767.95 1.46 6.31 0.00 0.19 8.51 8.91 74.5 66.1 144.7 133.2
alirocumab 9.04 10.13 8.68 9.65 1.23 7.47 900.00 703.63 2.18 5.32 0.00 0.15 8.76 9.25 71.5 71.4 69.2 104.3
anifrolumab 8.80 10.69 8.63 9.87 -0.56 6.03 700.00 619.97 1.62 0.32 0.00 0.13 8.49 9.08 62.5 69.5 82.0 159.4
atezolizumab 13.35 10.45 19.28 9.14 14.97 7.17 300.00 539.25 6.20 9.23 0.07 0.14 10.76 9.50 73.5 74.8 164.1 156.3
bapineuzumab 8.86 9.81 8.65 9.63 -0.73 7.96 1000.00 661.59 3.55 4.69 0.00 0.18 8.62 9.24 73.0 70.8 151.1 153.3
basiliximab 9.58 9.81 8.58 9.33 28.76 7.95 0.00 1036.80 2.14 6.11 0.40 0.22 9.45 9.31 60.5 69.1 107.5 153.5
bavituximab 11.50 10.37 12.69 9.96 29.85 5.21 0.00 641.45 1.69 4.51 0.56 0.10 11.39 9.21 59.5 68.2 45.1 132.6
belimumab 10.46 12.34 9.27 11.79 0.77 6.74 800.00 170.87 12.23 5.80 0.00 0.15 8.59 9.11 60.0 68.7 10.5 124.1
benralizumab 9.47 9.63 9.09 10.05 5.98 7.52 800.00 809.60 1.42 2.16 0.35 0.19 9.63 8.40 76.0 71.4 146.7 156.7
bevacizumab 11.77 10.84 11.07 10.42 0.79 6.68 700.00 601.66 2.78 4.86 0.00 0.14 9.82 9.50 63.5 72.5 50.0 166.3
bimagrumab 10.12 10.47 8.83 9.52 29.65 8.71 0.00 463.57 5.33 7.09 0.70 0.23 12.33 9.67 72.0 71.2 150.2 152.7
blosozumab 9.24 9.45 8.63 9.36 11.47 -1.07 600.00 752.86 12.85 4.30 0.21 -0.11 8.87 8.35 70.5 71.8 120.0 156.0
bococizumab 10.18 9.78 9.11 10.13 29.65 8.56 0.00 653.44 18.88 5.62 0.76 0.23 10.60 9.39 67.0 71.6 95.8 140.2
brentuximab 10.54 10.70 8.68 9.42 -0.54 4.83 800.00 818.07 2.24 1.96 0.25 -0.02 8.55 8.63 72.0 69.5 268.1 160.3
briakinumab 9.36 10.25 8.74 9.49 29.65 8.59 0.00 355.73 10.22 5.85 0.56 0.23 10.39 9.89 71.5 72.3 122.0 147.3
brodalumab 9.08 9.79 8.74 9.53 11.21 8.45 900.00 700.09 2.93 2.04 0.27 0.21 8.97 9.32 74.5 69.8 150.9 167.2
canakinumab 9.32 10.73 8.73 10.33 0.67 4.60 800.00 639.19 2.55 3.26 0.00 0.14 8.63 9.12 72.0 72.5 45.7 105.3
carlumab 11.17 11.82 9.31 13.37 -0.44 5.23 700.00 507.86 8.88 3.40 0.21 0.06 8.62 9.02 69.5 70.2 243.3 173.2
certolizumab 11.48 10.81 10.81 10.95 0.16 6.43 500.00 586.61 1.65 2.12 0.00 0.12 9.31 9.63 81.5 76.0 186.7 136.7
cetuximab 10.11 11.12 8.91 10.13 1.30 7.24 400.00 629.90 1.09 0.99 0.00 0.16 8.91 9.54 68.5 71.2 109.2 113.6
cixutumumab 11.76 12.08 10.72 14.54 29.65 7.65 0.00 345.95 11.90 6.75 0.66 0.18 9.66 9.58 73.5 69.1 154.3 170.4
clazakizumab 9.57 9.46 8.87 9.42 0.93 4.57 800.00 511.09 4.12 2.74 0.00 0.08 8.73 8.69 69.5 72.6 113.5 142.7
codrituzumab 8.84 10.05 8.59 9.01 -0.29 5.97 1000.00 673.95 14.87 5.44 0.15 0.12 8.45 8.85 73.0 71.1 66.3 108.4
crenezumab 10.03 10.63 8.70 9.10 6.37 7.06 700.00 560.15 2.78 1.25 0.10 0.13 8.90 9.15 72.0 70.1 149.3 153.6
dacetuzumab 8.47 10.36 8.61 9.42 -0.01 8.43 1000.00 666.40 1.34 3.29 0.00 0.22 8.47 9.41 68.0 71.1 128.5 118.2
daclizumab 9.29 10.19 8.75 9.43 -0.11 6.75 900.00 626.46 1.41 5.30 0.00 0.16 8.48 9.19 74.0 72.3 245.1 153.5
dalotuzumab 9.89 10.31 8.70 9.58 13.68 7.73 800.00 624.82 8.25 6.60 0.40 0.19 9.12 9.55 77.0 75.0 82.4 116.1
daratumumab 9.51 12.04 8.93 10.93 1.81 7.52 800.00 589.10 3.15 3.16 0.00 0.15 8.85 9.41 71.0 69.9 233.3 167.7
denosumab 8.50 10.15 8.60 10.02 5.91 8.31 1000.00 652.66 17.75 4.16 0.00 0.21 8.81 9.57 69.5 70.4 134.2 151.2
dinutuximab 9.83 9.85 8.96 8.51 3.64 7.64 800.00 476.36 1.69 12.52 0.30 0.19 9.40 8.84 69.0 71.0 76.4 9.3
drozitumab 9.29 9.56 8.72 9.39 29.65 6.12 0.00 614.78 1.48 6.34 0.00 0.03 8.79 8.28 63.0 68.4 22.1 143.0
duligotuzumab 10.21 11.04 8.94 10.30 29.65 2.61 0.00 641.83 9.63 1.64 0.33 -0.06 9.53 9.69 67.5 74.6 192.6 156.1
dupilumab 10.16 11.05 9.01 10.26 10.80 7.27 700.00 358.74 19.27 8.66 0.15 0.14 9.75 9.38 76.5 71.9 163.5 130.5
eculizumab 10.41 11.28 9.28 10.77 0.04 5.96 700.00 450.50 3.00 4.38 0.00 0.08 8.50 9.47 66.0 71.3 226.5 139.3
efalizumab 8.67 11.01 8.64 10.02 0.68 7.77 900.00 682.36 1.24 3.03 0.00 0.20 8.54 9.50 72.5 70.6 167.0 150.8
eldelumab 12.42 11.33 25.00 11.42 1.21 6.08 500.00 411.75 1.75 4.87 0.00 0.14 10.16 9.38 59.5 72.3 89.3 149.2
elotuzumab 10.31 11.09 9.29 10.01 -0.22 5.15 700.00 625.47 1.26 4.02 0.00 0.07 8.47 9.27 83.5 69.9 213.2 172.1
emibetuzumab 9.64 7.83 8.68 9.54 29.65 7.87 0.00 534.20 8.33 3.80 0.64 0.17 9.53 9.18 71.5 71.2 98.7 143.0
enokizumab 12.93 10.70 10.88 10.34 1.53 5.51 600.00 610.05 3.24 5.03 0.13 0.08 9.03 9.19 68.0 71.4 239.8 138.3
epratuzumab 9.19 10.99 8.63 9.61 3.01 5.83 900.00 747.67 2.34 4.84 0.13 0.16 8.69 9.15 65.0 72.0 78.2 138.9
etrolizumab 9.32 9.72 8.77 9.76 2.02 7.80 900.00 865.92 4.23 1.77 0.42 0.18 8.77 8.89 76.0 73.9 173.8 167.0
evolocumab 10.36 9.87 9.13 9.58 2.24 7.94 700.00 649.94 1.75 4.52 0.20 0.19 9.25 9.28 65.0 67.0 260.7 176.5
farletuzumab 9.49 9.93 9.06 9.59 -0.50 7.26 800.00 641.39 1.32 2.21 0.00 0.15 8.69 8.82 75.5 73.0 220.8 123.7
fasinumab 10.03 9.65 8.71 9.42 -0.67 -0.10 900.00 841.08 2.53 1.59 0.00 -0.04 8.36 8.09 71.0 71.6 110.4 144.4
fezakinumab 11.80 10.74 13.71 10.11 2.50 7.51 600.00 455.66 2.15 3.51 0.26 0.17 11.26 9.42 69.0 69.7 141.5 152.2
ficlatuzumab 9.42 10.09 8.88 9.37 -0.89 6.68 900.00 630.20 1.23 0.90 0.00 0.11 8.49 9.09 75.0 70.0 249.0 163.0
figitumumab 10.74 11.38 9.86 10.61 29.65 7.99 0.00 624.62 5.65 8.64 0.38 0.19 10.53 9.40 66.5 70.6 119.9 145.8
fletikumab 11.04 10.26 9.14 10.67 -0.13 6.40 700.00 644.76 1.41 4.08 0.00 0.10 8.47 9.15 71.5 69.9 220.4 147.7
foralumab 9.84 9.86 8.57 10.33 28.09 8.05 0.00 553.45 4.71 4.70 0.37 0.22 9.32 9.51 66.0 70.3 174.4 166.0
fresolimumab 10.88 11.80 9.14 12.52 -0.52 4.87 700.00 514.61 3.51 2.47 0.00 0.09 8.47 9.19 74.0 69.6 166.0 151.0
fulranumab 9.33 9.79 9.34 9.95 11.56 7.54 900.00 859.72 6.92 4.93 0.19 0.16 9.35 9.36 68.5 70.7 142.0 158.9
galiximab 12.20 11.83 14.77 10.93 1.09 7.39 600.00 453.25 3.81 6.44 0.00 0.16 8.87 9.26 67.5 69.8 174.1 126.8
ganitumab 9.33 10.24 8.77 9.77 4.77 7.75 800.00 584.85 4.91 4.22 0.55 0.18 9.48 9.82 78.5 73.0 229.4 155.6
gantenerumab 9.00 9.15 8.49 9.68 6.96 8.59 1000.00 672.01 22.75 8.24 0.55 0.22 8.71 9.32 77.5 70.2 162.7 151.9
gemtuzumab 12.26 10.71 13.93 10.40 1.02 7.06 500.00 620.96 1.70 -0.06 0.00 0.14 9.11 8.82 72.5 73.0 171.3 146.8
gevokizumab 8.83 9.91 8.61 9.20 -0.51 5.00 1000.00 823.00 1.93 5.81 0.00 0.17 8.58 8.83 71.5 73.2 136.4 174.8
girentuximab 9.08 10.21 8.68 10.09 -0.75 7.63 1000.00 776.36 1.39 4.66 0.00 0.20 8.52 9.26 63.0 71.1 30.7 116.1
glembatumumab 13.68 9.68 25.00 10.00 28.88 7.93 0.00 553.55 2.22 3.23 0.17 0.19 13.50 9.23 70.5 72.8 152.7 160.8
golimumab 11.36 11.09 12.75 11.10 22.97 7.79 0.00 356.24 2.71 7.41 0.23 0.20 11.23 9.48 70.0 70.0 163.2 164.9
guselkumab 11.40 10.81 9.20 9.86 3.37 8.10 700.00 430.60 5.87 6.48 0.47 0.21 10.11 9.75 69.5 74.0 167.3 159.2
ibalizumab 10.24 10.73 9.77 10.33 -0.34 4.71 800.00 703.87 1.13 1.95 0.00 0.12 8.66 9.00 72.0 72.8 133.3 129.4
imgatuzumab 10.09 9.70 8.90 9.63 0.89 8.53 800.00 722.13 11.77 5.51 0.00 0.22 8.99 9.53 71.5 71.5 187.7 144.6
infliximab 10.36 11.74 8.89 10.23 29.65 5.21 0.00 564.70 1.37 4.99 0.00 0.05 9.01 9.20 64.5 66.7 6.6 104.8
inotuzumab 9.72 10.67 9.05 10.16 4.03 8.18 800.00 599.43 5.40 5.42 0.25 0.21 9.29 9.23 83.0 72.8 169.8 116.1
ipilimumab 11.57 10.44 12.98 9.94 10.41 7.61 400.00 555.64 1.69 2.67 0.23 0.20 10.94 9.62 73.0 70.7 169.6 156.1
ixekizumab 10.94 12.09 9.08 10.33 19.95 6.61 500.00 516.65 10.40 7.67 0.81 0.13 9.64 9.25 83.0 73.1 97.3 100.7
lampalizumab 9.25 9.22 8.77 8.51 0.49 3.45 800.00 1212.51 1.34 -3.35 0.00 -0.03 8.46 8.20 67.0 71.1 187.1 296.1
lebrikizumab 12.38 9.73 15.71 8.86 0.26 5.93 500.00 812.87 1.46 3.74 0.00 0.07 9.07 9.31 66.0 74.0 61.6 153.2
lenzilumab 8.72 8.62 8.61 8.88 29.65 8.78 0.00 652.27 19.60 7.97 0.66 0.24 10.12 9.35 74.0 71.0 184.7 146.4
lintuzumab 10.87 10.34 9.43 10.15 0.89 6.10 700.00 628.30 1.25 3.80 0.00 0.12 8.93 8.69 75.5 71.8 230.0 185.9
lirilumab 25.00 11.58 25.00 11.89 21.00 6.09 300.00 535.09 3.55 2.97 0.18 0.11 10.56 9.24 70.0 68.8 270.5 172.4
lumiliximab 9.54 10.02 8.78 9.41 1.44 7.42 800.00 643.67 2.22 2.63 0.14 0.17 8.81 9.18 64.5 71.6 86.3 129.7
matuzumab 9.84 9.82 8.83 9.73 -0.93 6.98 900.00 670.48 1.03 1.69 0.00 0.11 8.63 9.11 72.0 71.4 224.3 179.4
mavrilimumab 10.30 10.39 8.67 9.40 -0.78 -0.47 700.00 549.92 2.16 7.00 0.00 -0.07 8.50 8.36 68.5 71.0 150.5 148.3
mepolizumab 9.24 10.49 8.82 9.98 -0.96 7.88 900.00 662.31 1.05 4.22 0.00 0.18 8.41 9.12 78.5 76.5 221.5 81.3
mogamulizumab 9.64 11.19 8.82 10.69 -0.51 7.36 800.00 544.31 2.17 3.89 0.00 0.15 8.63 9.34 68.5 72.4 89.8 135.0
motavizumab 9.69 9.52 8.82 9.72 2.52 6.26 800.00 753.91 5.36 3.68 0.00 0.15 8.66 8.90 86.0 73.5 133.6 140.0
muromonab 8.90 9.19 8.58 9.20 2.31 8.06 1000.00 809.52 3.94 5.18 0.18 0.19 9.05 8.85 74.5 67.0 113.5 140.4
natalizumab 9.70 10.22 8.84 10.51 0.82 7.37 900.00 727.09 1.52 3.89 0.00 0.17 8.76 9.14 79.5 71.8 251.7 166.9
necitumumab 10.81 11.07 9.90 10.63 1.30 7.09 600.00 583.00 1.31 2.83 0.00 0.14 8.77 9.15 76.5 69.9 198.6 155.6
nimotuzumab 25.00 10.70 8.88 10.08 -0.59 7.06 900.00 666.15 3.42 6.66 0.00 0.16 8.46 8.68 65.5 69.2 15.1 111.3
nivolumab 9.02 8.95 8.65 9.29 2.42 7.41 900.00 900.28 1.32 1.69 0.14 0.17 8.85 9.03 66.0 68.0 178.8 160.0
obinutuzumab 10.64 11.29 8.96 10.35 1.83 4.90 600.00 575.26 1.63 4.53 0.11 0.15 8.80 9.37 73.0 72.0 176.4 162.4
ocrelizumab 9.91 10.39 8.83 10.06 17.88 7.98 300.00 638.94 1.67 3.11 0.00 0.20 9.53 9.26 70.5 70.4 137.8 132.0
ofatumumab 9.73 10.66 9.52 10.11 1.21 7.25 800.00 610.70 1.18 3.95 0.00 0.13 9.25 9.18 68.0 69.0 249.8 165.6
olaratumab 10.61 10.82 8.96 11.02 0.31 7.70 700.00 659.91 2.58 4.58 0.48 0.17 9.42 9.20 62.5 72.6 141.9 143.9
olokizumab 9.91 9.76 8.97 9.74 -0.50 5.54 700.00 664.67 1.23 4.16 0.00 0.03 8.75 9.17 69.0 69.3 115.3 158.2
omalizumab 9.52 10.30 8.74 9.50 -0.44 4.90 800.00 831.05 1.17 4.22 0.00 0.03 8.54 8.65 77.5 74.2 150.4 176.2
onartuzumab 9.92 10.11 8.87 9.64 -0.05 6.81 800.00 668.61 1.19 0.60 0.00 0.17 8.91 9.38 80.0 74.2 147.9 134.8
otelixizumab 9.08 9.28 8.72 9.35 4.44 7.72 1000.00 945.35 1.40 -0.50 0.00 0.16 8.72 7.93 75.5 69.5 152.1 61.2
otlertuzumab 10.96 10.21 10.27 9.70 2.26 6.95 600.00 540.48 1.78 5.68 0.00 0.17 9.52 9.73 68.5 69.2 149.6 152.8
ozanezumab 10.03 10.04 8.63 9.18 27.69 8.14 0.00 615.85 4.45 3.03 0.77 0.18 9.05 9.36 67.0 71.4 97.1 196.1
palivizumab 9.33 9.22 8.71 9.33 -0.85 6.18 900.00 840.85 2.88 5.41 0.00 0.17 8.49 8.94 79.5 73.2 243.1 143.7
panitumumab 9.48 11.02 8.80 10.33 -1.08 5.77 900.00 659.77 1.18 1.50 0.00 0.06 8.42 9.06 78.5 72.9 179.6 165.2
panobacumab 9.83 9.59 8.85 8.66 -0.42 7.73 900.00 925.66 1.90 4.47 0.00 0.18 8.99 8.83 69.0 72.8 107.6 139.2
parsatuzumab 9.11 10.47 8.78 10.38 7.40 5.35 900.00 587.06 17.40 5.62 0.13 0.09 8.65 8.90 64.5 68.9 40.0 147.0
patritumab 10.15 10.06 9.32 9.52 13.09 7.71 600.00 776.56 4.35 4.40 0.52 0.18 9.44 9.41 71.5 72.3 68.8 131.5
pembrolizumab 11.07 11.05 13.48 9.84 5.62 7.73 500.00 552.68 2.23 3.54 0.30 0.17 10.92 9.28 66.0 73.1 64.9 107.6
pertuzumab 10.11 10.62 8.91 9.96 -0.20 7.07 700.00 659.71 1.69 -0.49 0.00 0.13 8.60 8.84 78.5 75.5 31.4 136.4
pinatuzumab 9.22 10.03 8.83 9.78 0.59 6.47 800.00 659.56 2.49 5.15 0.01 0.15 8.77 9.25 79.0 70.1 130.6 140.5
polatuzumab 8.76 10.06 8.67 9.10 -1.00 3.87 1000.00 896.40 3.62 4.05 0.00 -0.03 8.26 8.56 74.0 69.9 225.1 197.2
ponezumab 10.50 10.89 9.00 9.94 -0.24 7.85 800.00 610.77 6.62 6.41 0.07 0.17 8.68 9.15 61.0 74.3 17.0 139.0
radretumab 9.51 10.63 8.69 9.76 3.38 8.15 900.00 632.46 3.29 3.12 0.13 0.19 8.86 9.74 77.0 72.0 151.2 162.0
ramucirumab 9.43 9.65 8.71 9.69 0.02 7.80 900.00 861.44 1.25 0.51 0.00 0.18 8.58 9.01 66.0 69.8 90.7 155.5
ranibizumab 12.14 11.27 18.06 10.59 7.93 6.22 300.00 550.57 3.14 3.07 0.00 0.11 10.06 9.41 65.0 72.3 41.4 163.8
reslizumab 9.82 10.25 8.90 9.72 1.74 5.62 700.00 668.74 2.02 0.85 0.23 0.13 8.86 9.04 75.5 73.7 191.6 113.5
rilotumumab 12.63 10.48 17.68 10.72 2.13 7.91 500.00 497.00 2.37 2.58 0.16 0.19 10.39 9.35 79.0 73.1 173.1 169.5
rituximab 10.80 10.32 9.11 10.03 2.13 8.22 700.00 604.43 2.93 4.23 0.38 0.23 10.15 9.31 69.0 68.9 164.1 150.1
robatumumab 9.51 9.95 8.97 9.72 29.65 7.99 0.00 715.57 8.25 4.62 0.27 0.21 9.75 9.43 80.0 72.7 117.1 146.3
romosozumab 9.18 10.09 8.65 9.90 -1.02 5.40 1000.00 779.21 1.47 1.81 0.00 0.03 8.43 8.88 76.0 70.0 227.7 186.4
sarilumab 8.99 8.50 8.69 8.65 1.11 6.00 900.00 887.80 2.17 0.47 0.00 0.04 8.71 8.13 64.0 70.8 181.8 138.6
secukinumab 11.39 12.05 8.91 11.73 -0.58 5.47 800.00 475.03 1.69 5.38 0.00 0.09 8.36 9.16 72.0 71.1 149.0 142.5
seribantumab 10.42 11.44 9.00 10.58 21.21 8.24 300.00 558.61 2.97 6.83 0.00 0.20 9.79 9.49 77.5 75.1 190.0 152.9
sifalimumab 9.65 10.03 8.77 9.66 2.10 8.20 800.00 623.33 2.50 2.40 0.06 0.22 9.02 9.46 67.0 69.7 158.6 153.7
siltuximab 11.00 10.57 12.08 10.02 2.64 7.34 600.00 587.60 1.55 1.92 0.00 0.16 9.42 9.14 64.5 68.7 95.7 122.4
simtuzumab 10.41 10.30 9.57 9.46 0.88 7.67 800.00 642.33 10.41 6.36 0.34 0.17 9.10 9.29 66.5 68.7 191.4 192.8
sirukumab 11.26 10.95 10.76 10.05 29.65 6.60 0.00 586.25 9.66 5.23 0.36 0.11 10.79 9.38 68.0 68.2 109.8 155.4
tabalumab 10.85 11.02 9.87 10.58 1.96 8.12 700.00 722.22 3.68 4.67 0.00 0.20 9.13 9.41 64.0 70.7 121.6 168.4
tanezumab 12.39 11.10 10.69 10.37 2.17 6.61 700.00 601.83 4.83 4.74 0.23 0.16 9.25 9.53 75.5 76.0 48.9 143.8
teplizumab 8.79 8.77 8.65 9.35 11.17 8.14 1000.00 851.00 3.84 4.23 0.31 0.20 9.36 8.36 64.5 67.6 150.9 133.5
tigatuzumab 10.02 10.08 8.73 9.70 5.49 8.18 700.00 805.62 1.70 5.41 0.13 0.20 8.70 9.50 64.5 71.1 179.0 163.0
tildrakizumab 11.08 11.07 9.87 10.40 0.81 7.34 600.00 554.25 1.77 3.06 0.00 0.18 8.73 9.48 77.5 71.0 181.9 109.5
tocilizumab 9.09 10.30 8.78 10.57 1.32 8.41 900.00 663.17 2.81 2.26 0.00 0.21 8.90 9.23 91.5 75.8 139.6 134.8
tovetumab 8.67 9.56 8.63 9.60 2.25 8.30 900.00 663.32 2.95 6.09 0.00 0.20 8.81 9.29 63.5 69.9 277.2 125.2
tralokinumab 10.26 9.68 8.99 9.52 4.81 6.85 800.00 544.83 2.32 4.14 0.16 0.16 8.80 9.69 63.0 68.9 121.4 159.5
trastuzumab 9.66 10.37 8.75 10.36 2.04 7.89 800.00 531.07 1.34 3.00 0.00 0.17 8.84 9.89 78.5 75.9 159.5 145.8
tremelimumab 11.56 11.11 19.32 11.01 29.65 7.37 0.00 512.14 1.97 5.85 0.15 0.19 11.24 9.50 75.0 69.3 229.6 160.3
urelumab 11.16 11.12 12.98 10.70 29.65 6.36 0.00 622.04 1.53 3.79 0.00 0.12 9.37 9.49 66.0 73.5 143.9 163.5
ustekinumab 8.78 9.47 8.64 8.68 0.42 6.80 1000.00 695.35 5.07 12.95 0.15 0.20 8.63 9.21 69.5 70.4 152.7 134.7
vedolizumab 10.94 10.19 12.31 9.71 0.39 4.62 600.00 633.02 1.58 3.02 0.00 0.12 8.99 9.26 80.5 72.5 221.8 148.2
veltuzumab 11.09 10.70 9.72 10.20 4.83 6.60 700.00 572.93 1.21 0.11 0.00 0.15 8.79 8.81 70.0 72.6 225.0 121.8
visilizumab 9.01 9.24 8.70 9.88 21.99 8.31 0.00 668.46 4.80 4.97 0.42 0.21 9.15 9.36 71.0 69.9 242.0 179.9
zalutumumab 9.34 9.39 8.74 10.08 -0.80 5.24 900.00 918.83 2.90 2.81 0.00 0.12 8.41 8.80 72.5 69.5 200.5 168.4
zanolimumab 9.59 9.76 8.77 9.30 1.46 7.89 700.00 828.68 1.46 1.07 0.13 0.19 8.61 9.51 80.5 72.2 116.4 168.5

Actual vs. Predicted High-Concentration Viscosity (150 mg/mL, N=44)

The table below details experimental cone-and-plate viscosity measurements at \(150\text{ mg/mL}\) (Act) alongside leave-one-out cross-validated predictions (Pred With Struct and Pred Seq Only) across all 44 clinical therapeutic antibodies from the Tomar et al. (2016) and Sharma et al. (2014) reference datasets.

Predictions are color-coded using the standardized absolute error normalized by the assay standard deviation (\(\sigma_{\text{viscosity}} = 23.05\text{ cP}\)):

  • Close Agreement: \(\text{Normalized Error} \le 0.5\,\sigma\) (\(|\text{Error}| \le 11.5\text{ cP}\))
  • Moderate Deviation: \(0.5\,\sigma < \text{Normalized Error} \le 1.0\,\sigma\) (\(11.5\text{ cP} < |\text{Error}| \le 23.0\text{ cP}\))
  • Outlier / High Deviation: \(\text{Normalized Error} > 1.0\,\sigma\) (\(|\text{Error}| > 23.0\text{ cP}\))
Antibody Actual (cP) Actual Risk Pred With Struct (cP) Pred Seq Only (cP) Predicted Risk
adalimumab 4.2 Low Risk 12.1 7.6 Low Risk
bavituximab 12.8 Low Risk 9.6 10.2 Low Risk
bevacizumab 7.5 Low Risk 18.7 21.2 Moderate
briakinumab 85.0 High Liability 20.8 22.5 Moderate
cetuximab 5.8 Low Risk 5.5 8.5 Low Risk
daratumumab 14.5 Low Risk 22.4 24.4 Moderate
denosumab 9.2 Low Risk 7.3 9.8 Low Risk
dupilumab 16.0 Moderate 32.2 32.9 High Liability
eculizumab 8.1 Low Risk 17.6 18.1 Moderate
efalizumab 6.4 Low Risk 24.0 22.2 Moderate
elotuzumab 11.2 Low Risk 19.6 20.3 Moderate
evolocumab 18.5 Moderate 13.8 17.3 Low Risk
golimumab 14.2 Low Risk 29.3 30.8 High Liability
guselkumab 12.0 Low Risk 21.5 23.1 Moderate
infliximab 115.0 High Liability 25.5 25.4 High Liability
ixekizumab 38.0 High Liability 39.9 36.1 High Liability
lebrikizumab 26.5 High Liability 24.5 17.7 Moderate
matuzumab 6.1 Low Risk 17.8 17.4 Moderate
mepolizumab 8.9 Low Risk 12.8 13.8 Low Risk
motavizumab 98.0 High Liability 21.5 20.1 Moderate
natalizumab 15.2 Moderate 18.6 19.5 Moderate
necitumumab 9.5 Low Risk 15.4 18.2 Moderate
nivolumab 7.8 Low Risk 18.1 13.2 Moderate
obinutuzumab 12.3 Low Risk 37.4 35.2 High Liability
ocrelizumab 6.8 Low Risk 17.3 19.5 Moderate
ofatumumab 10.5 Low Risk 8.2 11.4 Low Risk
omalizumab 18.0 Moderate 23.3 12.5 Moderate
palivizumab 7.2 Low Risk 20.7 16.0 Moderate
panitumumab 13.6 Low Risk 11.0 13.2 Low Risk
pembrolizumab 8.4 Low Risk 24.1 22.0 Moderate
pertuzumab 11.0 Low Risk 7.8 10.3 Low Risk
ranibizumab 5.2 Low Risk 19.1 21.4 Moderate
reslizumab 7.9 Low Risk 7.6 9.6 Low Risk
rituximab 9.1 Low Risk 17.0 19.1 Moderate
sarilumab 14.0 Low Risk 3.3 0.0 Low Risk
secukinumab 16.5 Moderate 23.6 25.0 Moderate
siltuximab 10.2 Low Risk 9.9 11.4 Low Risk
sirukumab 13.8 Low Risk 23.8 26.5 Moderate
tocilizumab 9.4 Low Risk 9.2 11.8 Low Risk
trastuzumab 6.5 Low Risk 7.6 8.9 Low Risk
tremelimumab 22.4 Moderate 22.1 23.8 Moderate
ustekinumab 11.6 Low Risk 21.7 24.2 Moderate
vedolizumab 15.0 Low Risk 19.1 18.4 Moderate
zalutumumab 8.2 Low Risk 11.5 5.1 Low Risk

Independent Zero-Shot Generalization: Ginkgo GDPa1 Benchmark (\(N=246\))

To test true out-of-distribution generalization without retraining, domain adaptation, or parameter fitting, AbLead's developability predictors were evaluated zero-shot against the 2025 Ginkgo Datapoints GDPa1 dataset (Arsiwala et al., mAbs, 2025), comprising \(N=246\) clinical and pre-clinical therapeutic antibodies assayed under automated high-throughput conditions:

Biophysical Assay Matching GDPa1 Assay N Zero-Shot Spearman ρ p-value Zero-Shot Pearson r Liability ROC-AUC (>90th %ile)
Hydrophobicity (HIC) HIC Retention Time 242 +0.468 \(1.51 \times 10^{-14}\) +0.387 0.724
Self-Association (AC-SINS) AC-SINS \(\Delta\lambda_\text{max}\) (pH 7.4) 242 +0.426 \(4.29 \times 10^{-12}\) +0.377 0.784
Colloidal Stability (SMAC) SMAC Retention Time 242 +0.381 \(8.53 \times 10^{-10}\) +0.207 0.716
Polyreactivity (PSR Score) Polyreactivity (Ova ELISA) 197 +0.525 \(2.33 \times 10^{-15}\) +0.438 0.804
Polyreactivity (PSR Score) Polyreactivity (CHO ELISA) 197 +0.349 \(5.14 \times 10^{-7}\) +0.290 0.615
Polyreactivity (BVP Score) Polyreactivity (Ova ELISA) 197 +0.376 \(5.13 \times 10^{-8}\) +0.260 0.654
Expression Titer HEK Titer 239 +0.027 0.681 -0.030 0.572
Thermostability (\(T_m\)) DSF \(T_{m1}\) 234 +0.031 0.637 +0.064 0.544

Ginkgo GDPa1 Zero-Shot 4-Quadrant Clinical Triage Benchmark

[!NOTE] Sequence-Only DeepSP Evaluation: All GDPa1 zero-shot predictions shown above were evaluated strictly using the Sequence-Only Model Pipeline (leveraging DeepSP convolutional spatial descriptors, language models, loop lengths, and electrostatics). Physical 3D structural homology modeling and structure-derived surface patch solvation potentials (SPH, SPP, SPN, SPCD) were not used.

Attribution & Non-Commercial Compliance Notice:
Zero-shot benchmark evaluation data is referenced from Arsiwala, A., et al., "A high-throughput platform for biophysical antibody developability assessment to enable AI/ML model training," mAbs 17, no. 1 (2025): 2593055 (DOI: 10.1080/19420862.2025.2593055), used under Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). AbLead model weights were not trained or parameterized on this dataset; GDPa1 serves exclusively as an independent, zero-shot external literature evaluation benchmark.