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.
Oncopeptides AB announced May 11-12 it intends to submit a Type II variation application to the European Medicines Agency to expand the Pepaxti (melflufen) label to include third-line treatment of relapsed/refractory multiple myeloma. Pepaxti is one of two FDA-approved peptide-drug conjugates currently on market (the other being Novartis's 177Lu-dotatate Lutathera) and acts as a melphalan-flufenamide alkylating peptide that exploits aminopeptidase enzymes overexpressed in myeloma plasma cells to selectively release the cytotoxic payload inside tumor cells. The Pepaxti EMA label currently covers heavily pre-treated (≥4 prior lines) RRMM; the new third-line expansion submission would meaningfully extend the eligible population. The filing positions the PDC modality for a broader regulatory footprint as the broader peptide-drug-conjugate field heads into ASCO 2026.
Avacta Therapeutics's AVA6000, a fibroblast activation protein (FAP)-activated peptide-drug conjugate releasing doxorubicin selectively in the tumor microenvironment, will be presented at ASCO 2026 (Chicago, May 29-June 2) covering Phase Ia/Ib data in FAP-positive solid tumors with activity against salivary gland cancers — a rare cancer subset with no approved targeted therapies. The pre|CISION platform attaches a peptide tetrazolyl moiety that is cleaved by FAP, an enzyme overexpressed in cancer-associated fibroblasts and selectively present in the tumor stroma, allowing systemic dosing without the cardiotoxicity that limits free doxorubicin. AVA6000 joins Bicycle's nuzefatide pevedotin and Lilly's CRN09682 in the broader peptide-drug conjugate Phase 2/3 cohort.
ResearchAndMarkets published an April 21 PDC market landscape report counting six peptide-drug conjugates currently in Phase III trials and approximately 96 in development across the global pipeline. Lutathera remains the only FDA-approved PDC after Pepaxto's withdrawal, though Pepaxto retains EMA and MHRA approval. The report flags 34% year-over-year growth in clinical-trial registrations for peptide-based oncology compounds, with the majority targeting solid tumors previously considered peptide-resistant. Phase 2 ADC peptide-linker data released in early 2026 shows tumor-specific payload delivery rates above 85% — nearly double the 2023 benchmark — driven by the proteolytic-stability work that lets linker peptides survive serum peptidase degradation long enough to reach solid tumors.
Pfizer announced that data from more than 40 company-sponsored, investigator-sponsored, and collaborative research abstracts will appear at ASCO 2026 in Chicago (May 29–June 2). The slate spans Pfizer's diverse oncology pipeline including peptide-drug conjugate programs, bispecific T-cell engagers, and antibody-drug conjugates. Combined with previously announced ASCO 2026 acceptances from Bicycle Therapeutics, BriaCell, Greenwich LifeSciences, BioVaxys, and Immutep, the meeting is shaping up as the most peptide-and-immuno-conjugate-heavy ASCO in recent memory — building on the foundation laid at AACR 2026 in San Diego.
Mikhail Kolonin's group at UTHealth Houston published preclinical data showing BLMP6, a peptide identified through AI-guided modeling, selectively binds fibulin-4 — a protein highly expressed on metastatic triple-negative breast cancer cells — and not on noninvasive breast cancer or normal breast tissue. A BLMP6 conjugate carrying monomethyl auristatin E suppressed metastasis and improved survival in mouse models, and BLMP6-based fluorescent imaging probes successfully detected metastatic lesions. The paper, published in Molecular Therapy Oncology, identifies fibulin-4 as a new theranostic target.
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.