NEO-811 targets ARNT (HIF-1β), an “undruggable” transcription factor, with a molecular glue degrader to suppresses downstream transcriptional activity. It has shown potent single-agent activity in ccRCC and is currently in Phase 1/2 (NCT07300241)^[1]. TNG961 is a first-in-class oral bioavailable molecular glue that degrades HBS1L, offering a novel therapeutic strategy for FOCAD-deficient tumors and is marching its way toward clinical development^[2]. TRI-611 is a CNS-penetrant, highly potent and selective molecular glue degrader for ALK. It is now being evaluated in a phase 1/2 clinical trial (NCT07491497) for ALK⁺ NSCLC^[3]. AMX-883 is a novel and orally bioavailable BRD9 degrader that acts via the DCAF16 E3 ligase rather than cereblon or VHL. With promising tolerability and efficacy data in preclinical studies, AMX-883 is advancing toward clinical trials^[4].

Two notable small-molecule inhibitors are ECI830 (Novartis) and CID-078 (CirclePharma), both with favorable safety profile and oral availability. ECI830 is a potent, selective ATP-binding CDK2 inhibitor that exhibits strong antiproliferative activity in CCNE1-amplified tumors and demonstrates synergistic effects in HR⁺/HER2⁻ breast cancer models. It is currently undergoing a Phase 1/2 clinical trial (NCT06726148)^[5]. CID-078 is a first-in-class macrocycle inhibitor that blocks cyclin A/B-RxL substrate interactions. It demonstrates robust anti-tumor activity across multiple E2F-driven tumor models in vivo. CID-078 is currently being evaluated in a Phase 1 clinical trial（NCT06577987) in patients with advanced solid tumors including SCLC, sarcoma, and other RB1-altered or E2F-hyperactive cancers^[6].

AZD8359 (AstraZeneca) is a novel CD8-biased T cell engager designed to deliver a wider therapeutic window in prostate cancer and is currently in Phase 1/2 (NCT07529717). Preclinical studies have showed preferential CD8⁺ T cells activation over CD4⁺ T cells, with a fourfold increase observed in vitro. In vivo studies have demonstrated strong antitumor activity and complete tumor regressions in both STEAP2⁺ 22Rv1 subcutaneous and C4-2 intratibial xenograft models^[7]. IPN01203 (Ipsen) is a first-in-class T cell activator (TCA) presented at AACR 2026, showcasing its unique mode of action by selectively activating Vβ6/Vβ10 T cells through the TCR and IL-15R pathways. This specific activation enhances their capacity to recognize and target tumors^[8].

EPI-326 (EpiBiologics) is a mutation-independent EGFR-degrading bispecific antibody capable of eliminating both wild-type and mutated EGFR in tumors while sparing normal tissue. A Phase 1 clinical trial (NCT07462377) is currently underway^[9]. E-688/HLX316 (Palleon Pharmaceuticals) is an engineered human sialidase fused to an anti-B7-H3 nanobody. In both in vitro and in vivo studies, this design markedly enhanced the depth, duration and efficacy of tumor sialidolysis while maintaining desired safety profile^[10].

AstraZeneca’s CD30 ADC is a dual-payload ADC combines the clinically validated microtubule inhibitor MMAE with a proprietary topoisomerase 1 inhibitor (Top1i), using non-natural amino acid conjugation technology. In the classic xenograft model of Hodgkin lymphoma (L428), a single intravenous injection of the CD30 dpADC achieved 92.5% tumor growth inhibition (TGI) at 2.4 mg/kg and 76.5% TGI at 1.2 mg/kg. In the anaplastic large cell lymphoma (ALCL) xenograft model (DEL), a single dose of CD30 dpADC achieved complete tumor regression at doses as low as 0.6 mg/kg^[11]. JNJ-89862175(J&J Innovative Medicine) is an ADC targeting ENPP3, which is highly expressed in multiple solid tumors but with restricted expression in normal tissues. It has demonstrated good tolerability and pharmacokinetic profiles in non-human primates and is currently in Phase I clinical trials (NCT07223125)^[12].