1. First-in-class/Best-in-class: The Core of Differentiated Competition

RevMed’s RMC-5127 is a first-in-class, orally bioavailable, non-covalent tri-complex inhibitor selectively targeting RAS(ON)G12V, designed for RAS-addicted cancers. AbbVie disclosed ABBV-969 is a dual-targeting STEAP1/PSMA ADC carrying a cell-permeable TOPi payload, aimed at treating metastatic castration-resistant prostate cancer (mCRPC). Novartis presented FXX489 (177Lu-NNS309), a HER2-targeted radioligand therapy with best-in-class potential [3]. ABP-102/CT-P72, co-developed by Abpro and Celltrion, is a tetravalent bispecific HER2 x CD3 T-cell engager that demonstrates potent and highly selective tumor-killing activity [4]. These four drug candidates represent differentiated breakthroughs across mechanisms of action, novel targets, and delivery strategies, underscoring the strategic importance of competitive differentiation.

References:

[1] Cancer Res 15 March 2024; 84 (6_Supplement): 3340.

[2] Annals of Oncology, Volume 35, S1000-S1001.

[3] https://clinicaltrials.gov/study/NCT06562192?intr=NCT06562192&rank=1

[4] https://investor.abpro.co/news-releases/news-release-details/abpro-and-celltrion-unveil-preclinical-data-abp-102ct-p72-aacr

2. Targeted Therapies for Previously "Undruggable" Targets: RAS, WRN

Significant progress has been made in targeting traditionally undruggable targets such as KRAS and WRN, reshaping the landscape of precision oncology. Amgen’s AMG 410 is a pan-KRAS inhibitor demonstrating strong tumor-suppressing effects across various mutation models. AstraZeneca disclosed AZD0022, a selective KRAS(G12D) inhibitor, exhibits favorable membrane permeability and dose-dependent anti-tumor activity. GSK and IDEAYA’s GSK4418959 selectively targets WRN helicase, showing best-in-class potential in MSI-H tumors. Together, these programs highlight parallel strategies, target focus, and resistance mechanism-informed development.

References:

[1] IAACR; 2025. Abstract nr ND02.

[2] AACR; 2025. Abstract nr 841 / 29.

[3] https://ir.ideayabio.com/2025-03-26-IDEAYA-Announces-Oral-Presentation-at-the-New-Drugs-on-the-Horizon-Series-at-AACR-2025-for-IDE275-GSK959-,-a-Phase-1-Werner-Helicase-Inhibitor

3. Targeted Protein Degradation: PROTAC & Molecular glue

Targeted protein degradation continues to advance with diverse mechanisms: Genentech reported GDC-2992 is an orally bioavailable PROTAC that effectively degrades the androgen receptor (AR), showing strong efficacy in prostate cancer models. BMS’s BMS-986449 is a molecular glue degrader that reprograms Cereblon to selectively degrade transcription factors Helios and Eos, offering new therapeutic opportunities for advanced solid tumors.

References:

[1] AACR; 2025. Abstract nr ND02.

[2] AACR; 2025. Abstract nr 2249/20.

4. Antibody-Based Therapies

This meeting emphasized innovation in immuno-oncology focused on precision and safety: Roche’s bispecific antibody RO7567132 restricts LTBR activation to the tumor microenvironment, promoting tertiary lymphoid structure (TLS) formation while minimizing systemic toxicity. Bayer’s BAY 3547926 is an α-particle radiotherapeutic that delivers its payload via tumor-targeted mechanisms, inducing irreparable DNA damage in tumor cells. Merck’s M0324 is a conditional CD40 agonist activated in MUC-1–overexpressing tumors, aiming to enhance anti-tumor immunity while reducing systemic immune-related adverse effects.

References:

[1] AACR; 2025. Abstract nr ND08.

[2] AACR; 2025. Abstract nr ND09.

[3] AACR; 2025. Abstract nr ND12.

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