Session: Strategic Use of Surrogates and Transgenic Animal Models in General Toxicology and DART — A Case Study Approach
Chairs: C. K. Korgaonkar (Regeneron) & Smita Salian-Mehta (Gilead)
Many biotherapeutics show limited or no pharmacological activity in conventional nonclinical species because of target sequence divergence, which restricts the utility of standard rodent and non-human primate toxicology paradigms. Surrogate molecules and genetically engineered (transgenic/knock-in) animal models have become indispensable tools for characterizing on-target toxicity and reproductive and developmental risk when a pharmacologically relevant species is unavailable. This session draws on case studies from a variety of therapeutic areas and modalities to highlight the utility of surrogate and transgenic approaches in general toxicology and DART studies. The considerations involved in characterization of a surrogate or a transgenic model, the study designs, and any species-specific findings will be discussed. In addition, regulatory feedback from different health authorities will also be discussed. The session will conclude with Q&A and panel discussion.
Session: Advancing T Cell Engagers Beyond Oncology: Integrating Nonclinical Safety, Translational Science, and Clinical Pharmacology
Chairs: Kaushik Datta (Merck) & Kavita Raman (Amgen)
T cell engagers (TCEs) are an emerging therapeutic modality with potential to deliver transformative benefits beyond oncology, including autoimmune, infectious, neurodegenerative, and other non-oncology indications. However, TCE development remains largely guided by oncology experience, creating important gaps when this modality is applied to patient populations with distinct disease biology, risk tolerance, benefit–risk expectations, and long-term treatment needs. This session will examine key nonclinical, clinical pharmacology, and early clinical development considerations for advancing TCEs in non-oncology settings. Topics will include pharmacology-driven design and weight-of-evidence (WoE) approaches to support first-in-human (FIH)-enabling nonclinical safety packages; the relevance and limitations of animal models; and requirements for longer-term development, including chronic toxicity, DART, and carcinogenicity. The session will also address FIH starting-dose and dose-escalation strategies, step-up dosing, exposure–response assessment, biomarker selection, and mitigation of clinically important risks, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, cytopenias, and infection. The emphasis will be on WoE-based and model-informed drug development approaches that integrate nonclinical safety, translational science, and clinical pharmacology to propose a practical framework for responsible and efficient development of TCEs for non-oncology diseases.
Session: In silico and computational approaches for PK and tox assessments
Chairs: Samira Brooks (Amgen), Anh Diep (Surrozen), Jay Tibbitts (Gilead)
The rapid development in the capabilities and application of artificial intelligence and computational methods are transforming drug development. From molecule design to sample and data analysis to predictive pharmacology, companies are harnessing the power of these technologies to improve and streamline knowledge generation, data integration, and hypothesis generation. In this session, we’ll explore how these technologies are being applied to biotherapeutic discovery and nonclinical development, and what the future may hold for those working in these areas.
Session: Cell-Gene Therapy (TBD)
Chairs: Nick Buss (Lilly) & Jessican Lynch (J&J)
Breakout Sessions: The BioSafe Annual Meeting will feature several breakout sessions designed to foster small-group discussions on specific topics and areas of interest. Attendees will have the opportunity to select and participate in the sessions most relevant to them. Breakout topics will be finalized and shared soon!