Catch fast clearance, aggregation, and immunogenicity before they kill your drug candidate.

Why polyreactivity drives clinical attrition

Polyreactive antibodies, those that bind structurally unrelated antigens through non-specific surface chemistry, exhibit accelerated serum clearance, elevated immunogenicity risk, self-association, and aggregation. Hötzel and colleagues showed that even modest polyreactivity correlates with poor pharmacokinetics in human subjects, and Jain et al.'s 2017 survey of 137 clinical-stage monoclonal antibodies established that polyreactivity scores correlate with progression through clinical development.

The biophysical liability is set by surface charge patches, hydrophobic residues, and non-specific affinity for membranes, nucleic acids, and abundant plasma proteins. Once a polyreactive lead enters lead optimization, the cost of catching it later, in pharmacokinetic (PK) studies, in toxicology, in early clinical, can be measured in months and millions.

Industry-standard methods are off-instrument and slow

Standard polyreactivity readouts are plate-based: PSR-ELISA on a soluble-membrane preparation, AC-SINS on aggregated antibody, BV-ELISA on baculovirus particles. Each consumes tens of micrograms of candidate per measurement, takes hours per plate, and runs on a different instrument than the target binding assay.

The result is that polyreactivity is measured after affinity ranking is complete, often after a lead candidate has been committed. The MACS® Matchmaker Polyreactivity Panel runs on the same chip and the same sample as your target binding kinetics, with the same fluidics and the same data export, in approximately 30 minutes per candidate.

Run the panel on every candidate alongside the target affinity measurement. Surface polyreactivity at the earliest selection point, before resources are committed to lead optimization. The Polyreactivity Index converts the multi-axis readout into a single quantitative number that can be paired directly with K_D in candidate-ranking tables.

Fc engineering, charge-patch removal, and CDR optimization can each shift the polyreactivity profile in unintended directions. The panel ranks engineered variants on the polyreactivity axis with the same within-chip statistics as the affinity measurement, in the same experiment.

Build the Polyreactivity Index into the standard developability data package alongside FcRn, target K_D, hydrophobic interaction chromatography, and self-interaction. Anchored to the Jain 2017 clinical-stage benchmark distribution, the PI gives a calibrated risk score that travels with the candidate into formulation and IND-enabling work.

Polyreactivity Essentials, 8-plex

The triage configuration. One ligand per major liability axis: Protein A/G as the Fc-capture positive control, dsDNA reference, human serum albumin, insulin, lysozyme, aminocardiolipin, aminoheparin, and polyclonal human IgG. 8 within-chip replicates per ligand for high-confidence statistics from a single experiment.

Built for the routine candidate-triage workflow at every discovery cycle. Drop polyreactive candidates early without consuming the material and the time of a full developability panel.

Polyreactivity Plus, 16-plex

The in-depth configuration. Adds parallel ligands per axis (BSA + HSA, ovalbumin + insulin, ssDNA + dsDNA), the antiphospholipid-syndrome autoantigen β2-glycoprotein I, lipopolysaccharide, transferrin, human IgM, and fibrinogen. 4 within-chip replicates per ligand, with the breadth needed for cross-axis liability mapping.

Built for the developability assessment that supports lead-nomination and IND-enabling work, where the breadth of axes resolves which liability is driving the score and informs targeted engineering.

Polyreactivity Essentials (8 ligands, one per major liability axis) for routine triage; Polyreactivity Plus (16 ligands, parallel axes plus β2-GPI, LPS, IgM, fibrinogen) for in-depth developability. Both run on the same instrument with the same protocol.

The Polyreactivity Index is the mean equilibrium response across non-control channels, normalized to the Protein A/G control. Three-tier thresholds (acceptable / orthogonal-confirm / liability) are anchored to the Jain et al. 2017 distribution of 137 clinical-stage monoclonal antibodies.

All ligands are conjugated through a single NHS amine-reactive chemistry to amine-modified DDI oligos. No aggregates, no soluble-membrane preparations, no carrier-protein hapten conjugates. Lot-to-lot reproducibility designed in.

The polyreactivity panel runs on the same MACS® Matchmaker chip and the same sample injection used for the target affinity assay. Polyreactivity moves into the discovery cycle instead of running parallel to it.

Coherent mass density at each ligand spot is a direct physical readout of bound mass, not a refractive-index proxy. The Polyreactivity Index is therefore a quantitative number rather than a relative semi-quantitative score.

The Protein A/G channel provides a per-injection Fc-capture quality control: absence of signal flags candidate or run failure before any PI is computed. 8 (Essentials) or 4 (Plus) within-chip replicates per ligand provide confidence intervals from a single experiment.