AACR2026 reports 12 new drugs: degraders targeting HIF-1β, HBS1L, ALK and BRD9; T cell engagers against STEAP2 and Vβ6; biologics modulating EGFR and B7-H3; a CDK2 inhibitor; ADCs for CD30 and ENPP3; and a cyclin interaction inhibitor for solid and hematologic tumors in early clinical trials.
WO2026073816 - engineered CD27 extracellular domains with modified sequences to enhance CD70 binding, stability, and resistance to proteolysis for CAR-T use. Targeting aberrant CD70 on tumors, these ligand-based domains improve affinity and persistence, overcoming instability of native CD27 CARs.
WO2026069278 antibody-based degraders targeting CD123 (IL-3Rα) to eliminate CD123+ cells via receptor degradation. For AML, BPDCN and MDS, it proposes a non-cytotoxic, PROTAC-like strategy that may reduce toxicity while bypassing antigen persistence and overcoming limits of ADCs and bispecifics.
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Asymmetric bispecific ADCs use knob-into-hole Fc heterodimers for site-specific, reproducible conjugation of two distinct payloads. This enables precise DAR and composition control, overcoming stochastic heterogeneity, limited payload positioning, and efficacy-toxicity trade-offs.
Activity cliffs are pairs of highly similar molecules (e.g., ECFP4, Tanimoto ≥0.90) with ≥10-fold potency differences (~1 log), revealing sharp SAR discontinuities. They expose key structural drivers but challenge ML models assuming smoothness, causing overconfident yet inaccurate predictions.
Etripamil is a first-in-class, short-acting intranasal L-type calcium-channel blocker for acute paroxysmal supraventricular tachycardia. Self-administered, it inhibits AV nodal calcium currents to terminate AVNRT/AVRT, enabling rapid out-of-hospital control and reducing reliance on IV therapy.
RAS therapies face resistance from secondary mutations blocking Switch-II inhibitors and cyclophilin-A glues. K. Tran designed 10-mer peptides mimicking NS1 FG-loop that bind the α4-α5-β6 allosteric site of H/KRAS, disrupting signaling across mutations, with structural validation & Cys118 targeting.
WO2026068513 - bispecific antibody binding α-synuclein protofibrils and human TfR1 to enable brain delivery via receptor-mediated transcytosis for PD and DLB. Targeting a protease-like TfR1 epitope avoids ferritin interference, reducing iron homeostasis and safety risks while preserving efficacy.
WO2026068504 RBC-based enzyme delivery uses antibody/nanobody–enzyme conjugates to anchor therapeutic enzymes onto erythrocyte surfaces, extending circulation time, improving pharmacokinetics. Targeting glycophorin A enables stable, specific binding while preserving RBC integrity & enzyme activity.
WO2026068519 pH-sensitive antibody targeting the protease-like domain of human TfR1 to enhance BBB transcytosis of biologics. It binds strongly at physiological pH and weakly in endosomes, promoting release, while avoiding apical-domain interactions, reducing iron-related hematologic toxicity risks.
WO2026068449 describes ASAPs: affibody-like binders built from two short alpha helices forming a PNA-stabilized coiled-coil. PNA placement preserves binding surfaces and enables reversible, switchable affinity via nucleic-acid control, yielding small, programmable, antibody-mimetic therapeutics.
WO2026064598 outlines bifunctional fusion macromolecules that selectively bind and clear anti-ADAMTS13 autoantibodies in immune TTP. By linking ADAMTS13 antigen domains to receptor-targeting elements, they enable rapid, specific antibody removal while sparing normal immunity versus plasma exchange.
Covalent-induced drug conjugates target KRAS G12C, linking a selective covalent binder to a tubulin inhibitor payload. This molecule strategy intracellular, mutation-specific delivery of cytotoxic agents, aiming to enhance efficacy, reduce off-target toxicity, overcome resistance to KRAS inhibitors.
WO2026062043 describes multispecific fusion proteins enabling conditional activation of TNFRSF receptors (CD40, 4-1BB, OX40) via TRAF2 signalling. Modular antibody-derived scaffolds restrict activity to target sites, reducing systemic toxicity and improving manufacturability.
WO2026052513 describes antibody-drug conjugates targeting FLT3 (CD135) in blood malignancies AML. FLT3-ITD drives constitutive signaling and poor prognosis. The ADC approach delivers cytotoxics selectively to leukemic cells, aiming to overcome resistance and limited durability of kinase inhibitors.
WO2026061104 describes PROTAC-based SARDs that link an AR ligand to an E3 ligase binder (e.g., cereblon), driving ubiquitination and proteasomal AR degradation. This overcomes resistance (e.g., AR-V7) in castration-resistant prostate cancer.
[Credit: Gan & Lee Pharmaceutical]
PROTACs drive targeted protein degradation via catalytic, event-driven mechanisms, overcoming undruggable targets and resistance. Reliance on CRBN/VHL (>90%) limits efficacy and safety. New E3 ligases, screening methods, and reversible ligands expand selectivity and therapeutic potential.
WO2026060136 describes bispecific antibodies that eliminate autoreactive B cells by targeting IGHV-defined clonotypes, especially IGHV4-34 (9G4). Unlike broad depletion or CAR-T, this approach spares normal B cells, reducing infection risk while removing key pathogenic clones in autoimmune disease.
Patent WO2026059389 describes engineered multi-domain fusion proteins targeting CD300 receptors to reprogram myeloid cells. By favoring activating CD300c signaling over inhibitory CD300a/f pathways, they enhance cytokine release, antigen presentation, and phagocytosis, countering TME lipid axis.
Efflux ratio best predicts oral PROTAC absorption, unlike chameleonicity. Active uptake and transporter saturation may influence PK and BBB penetration. Caco-2 limitations require validation. PROTAC guidelines are context-specific; improved models and assays are needed for compound selection.
WO2026060187 describes bispecific antibody-drug conjugates targeting CDH17 plus tumour antigens (EGFR, HER2, TROP2) in GI cancers. binding enables avidity-driven selectivity, improves heterogeneity coverage, and reduces antigen escape while delivering cytotoxic payloads with preserved Fc properties.
WO2026060117 antibodies targeting TL1A and OSMR to treat chronic inflammatory diseases. Dual blockade of TL1A-DR3 and OSM/IL-31-OSMR pathways reduces T-cell activation, cytokine signaling, fibrosis and tissue damage, offering superior efficacy over single-target therapies.
[Credit: Mirador Therap]
WO2026058155 describes monoclonal antibodies targeting IL-31 and bispecific IL-31/IL-13 format to treat inflammatory diseases like atopic dermatitis. By blocking complementary Th2 cytokine pathways these agents aim to improve itch, inflammation, and outcomes beyond current single-target therapies.
WO2026057723 describes bispecific antibodies targeting Claudin-1 and EGFR to overcome resistance to anti-EGFR therapies. By dual binding, they inhibit signaling, enhance tumor targeting, and address KRAS/BRAF-driven escape, EMT, and invasiveness across multiple cancers.
BCR-ABL1 inhibitors transformed CML/Ph+ ALL therapy. Imatinib binds inactive ABL (DFG-out) but is mutation-sensitive. Dasatinib binds active form, higher potency, less selective. Nilotinib improves affinity yet misses T315I. Bosutinib targets SRC/ABL, better safety, limited T315I efficacy.
WO2026055788 describes bombesin-derived peptides targeting GRPR, a GPCR overexpressed in cancers. These radioligands support PET/SPECT imaging (68Ga,18F,64Cu) and therapy (177Lu, alpha emitters). Improved stability and lower pancreatic uptake enhance theranostic precision in oncology settings.
WO2026039642 anti-MSLN ADCs targeting membrane-proximal epitopes to overcome soluble MSLN interference. Optimised antibodies show improved binding, internalisation, and tumour targeting. Conjugated with cleavable cytotoxic payloads, they demonstrate strong xenograft efficacy.
[Credit: Ardeagen Corp]
Pimicotinib is an oral, selective CSF-1R inhibitor for TGCT, under NDA review in China. It targets CSF-1 signaling, blocking PI3K-AKT, MAPK-ERK, and JAK-STAT pathways, reducing immunosuppressive macrophages and enhancing T-cell activity, enabling tumor shrinkage in unresectable or recurrent disease.
WO2026047782 describes antibody abEC1.1 targeting extracellular domains of connexin hemichannels (Cx26 Cx30 Cx32) to treat gliomas and tumor-related epilepsy. It inhibits ATP release and Ca2+ signaling, reduces proliferation markers, modulates microglia, and improves survival in preclinical models.