用于合理提名候选药物的全面临床前体内肿瘤学平台

Introduction: Robust in vivo pharmacology is critical to de-risk oncology drug candidates and guide translational decision-making. Evotec's integrated preclinical platform combines scientific and animal welfare expertise with AAALAC and My Green Lab accreditations to accelerate candidate nomination. Methods and Results: Leveraging multidisciplinary capabilities such as chemistry, early formulation, ADME/DMPK (LC-MS/MS), in vitro biology, and translational biomarker analysis is essential to support projects at any stage of drug discovery and whatever the therapeutic modality: small molecules, degraders, ADCs, antibodies, oligonucleotides, cell therapies, vaccines, and oncolytic viruses. Our extensive tumor model repertoire covers multiple cancer indications and includes CDX and syngeneic models implanted SC, orthotopically or as metastatic model in a variety of mice backgrounds, immunocompetent, immunosuppressed or humanized for the immune system. We describe here case studies illustrating flexible study designs that include:•Target validation with engineered cancer cells•PK/PD studies (single/repeated dosing)•Tolerability for chronic dosing derisking•Efficacy studies assessing anti-tumor activityReadouts encompass tumor growth inhibition, PK/PD correlation, target engagement, transcriptomics, proteomics, metabolomics, and tumor microenvironment characterization.In addition, deciphering the relationship between PK, PD markers modulation and antitumor efficacy is of great value to model and predict human dose. Experts at Evotec have access to several modeling and simulation softwares from PK, PK/PD, PBPK, statistical and mathematical analysis to optimize dosing for best efficacy while minimizing toxicity. Conclusion: Our platform enables tailored strategies that integrate PK/PD and biomarker-driven endpoints to optimize dosing and predict efficacy. Over 5 years, our multidisciplinary expertise delivered comprehensive in vivo solutions that accelerated oncology drug discovery with the nomination of nine preclinical drug candidates progressing in the clinic.