Peptide-drug conjugates (PDCs) are the peptide analog of antibody-drug conjugates — a tumor-targeting peptide linked to a cytotoxic payload. The platform sits at the intersection of medicinal chemistry, peptide stability work, and ADC-style delivery.
Lead programs covered on this site: Bicycle Therapeutics' bicyclic peptide-toxin conjugates (BT5528 against EphA2, BT8009 against Nectin-4), Avacta's pre|CISION platform (AVA6103 with exatecan), Lirum's LX-101 against IGF-1R for Ewing sarcoma, and the broader academic peptide-payload work covered at AACR and ASCO. Several have followed ADC-style linker chemistry while keeping the peptide targeting moiety.
Stories here cover trial readouts, partnership deals, and the chemistry papers behind the platform. See #peptide-drug-conjugates for the alternate tag and #bicycle-therapeutics for the leading company.
A Nature paper from Liskiewicz, DiMarchi, Tschöp, Müller and colleagues introduces a unimolecular peptide-drug conjugate that combines a GLP-1R/GIPR co-agonist peptide with the pan-PPAR (α/γ/δ) agonist lanifibranor via a pH-sensitive linker. After receptor-mediated internalization, the linker cleaves and lanifibranor escapes to the nucleus to activate PPARs while the peptide moiety drives GLP-1R/GIPR signaling at the membrane. In obese, diabetic mice the conjugate produced greater weight loss and insulin sensitization than equimolar dosing of the unconjugated peptide and lanifibranor, without the typical PPAR-related cardiac and weight-gain safety signals.
Avacta Therapeutics presented April 21 data at AACR 2026 showing its FAP-enabled peptide-drug conjugate AVA6103, which delivers exatecan via the pre|CISION® platform, achieved a Tumor Selectivity Index three times higher than marketed ADC Enhertu in preclinical models, with tumor Cmax more than one log higher. AVA6103 entered the Phase 1 FOCUS-01 trial (NCT07454642) in March 2026 with initial clinical readout expected later this year.
A new market landscape report published April 21 projects the global peptide drug conjugate market will exceed $1.5 billion by 2031, with >14% CAGR and coverage of more than 50 peptide conjugates currently in clinical development. Commercial PDC benchmarks include Novartis's Lutathera and Pluvicto and Bicycle Therapeutics' nuzefatide pevedotin, with earlier-stage pipelines from Zymeworks, Bicycle, PeptiDream, and others.
Bicycle's EphA2-targeting bicyclic peptide-drug conjugate nuzefatide pevedotin (BT8009) at 6.5 mg/m² Q2W plus nivolumab achieved 40% confirmed ORR (4/10) in metastatic urothelial patients who had progressed on checkpoint inhibitors, and 100% (3/3) in MMAE-naive EphA2+ patients. No Grade ≥3 treatment-related adverse events of clinical interest. Presented at AACR 2026 on April 20.