Ly6E is a cell‑surface protein involved in tumor growth and immune evasion that is overexpressed across multiple solid tumor types, with limited expression in normal tissues. At AACR, researchers from Merck KGaA presented the preclinical characterization of M-7437, an anti-Ly6E ADC with a topoisomerase 1 (TOP1) inhibitor payload.

Shanghai Ailux Biotechnology Co. Ltd. and Ailux Inc. have presented preclinical data regarding the characterization of ALX-006, a 2+2 symmetric IgG1 PD‑1×VEGF bispecific antibody developed and designed for dual PD‑L1 and VEGF blockade as a cancer immunotherapeutic.

Akeso Pharmaceuticals Inc. has raised the bar for next-generation immuno-oncology, reporting more than 23 months median overall survival in pancreatic cancer with its PD-1/CTLA-4 bispecific antibody cadonilimab, as emerging competitors begin to post earlier signals across solid tumors at the American Association for Cancer Research annual meeting in San Diego April 17 to 22.

Researchers from Hangzhou DAC Biotechnology Co. Ltd. reported preclinical efficacy data for DXC-016, a next-generation, subcutaneously administered, dual-payload c-Met-targeting antibody-drug conjugate (ADC) derived from the DXA-016 anti-c-Met nanobody.

Tumor-associated calcium signal transducer 2 (TROP2) is a transmembrane glycoprotein involved in different signaling pathways that promote proliferation, migration and invasion of tumoral cells, and its overexpression is associated with poor prognosis in multiple cancer types. Astellas Pharma Inc. has developed a TROP2-targeting antibody-drug conjugate (ADC), ASP-2998, and recently presented preclinical data on the candidate.

CDKs are central regulators of cell-cycle progression in cancer, with resistance to CDK4/6 inhibitors frequently converging on CDK2 activation through cyclin E upregulation or CCNE1 amplification, supporting CDK2 inhibition as a strategy to restore cell-cycle control. Researchers from Novartis AG have revealed the preclinical profile of ECI-830, an oral bioavailable, highly selective ATP-competitive CDK2 inhibitor.

Homozygous deletion of methylthioadenosine phosphorylase (MTAP), present in ~15% of tumors, leads to accumulation of methylthioadenosine and partial inhibition of protein arginine methyltransferase 5 (PRMT5), creating a synthetic-lethal vulnerability that sensitizes tumors to PRMT5-targeted therapies. Researchers from Beone Medicines Ltd. presented preclinical efficacy data of BGB-58067, an MTA-cooperative PRMT5 inhibitor, in models of tumors with MTAP-deficiency.

An advantage of antibody-drug conjugates (ADCs) is that they allow targeted delivery of cytotoxic agents into tumors, thus improving the therapeutic index. Pfizer Inc. has developed a new ADC, PF-08046033, that contains auristatin S (AurS) as the cytotoxic payload and targets transmembrane glycoprotein NMB (GPNMB).