Overview
The development of oligonucleotide (ON) drugs such as antisense ONs and siRNAs has accelerated rapidly and is highly sought after, with increasing diversity in modalities and applications. The use of ONs has expanded from treating rare diseases to addressing more prevalent conditions, enabled by advances in chemistry and conjugation technologies that improve tissue targeting and reduce safety risks. While the long‑lasting effects of ONs offer major benefits in medical practice, rapid patient access is hampered by the lengthy first-in-human (FIH) trials needed to establish sufficient safety before demonstrating initial pharmacodynamic and early clinical effects.
While FIH experience with ONs has demonstrated favorable safety to date, the growing structural complexity of these molecules presents aspects that require closer consideration. This webinar will explore translational and clinical considerations for initiating FIH oligonucleotide studies, drawing on current literature and ICON’s experience. The objective is to provide early drug developers and the broader scientific community with practical guidance and insights to support the successful advancement of this promising drug class.
During this webinar we will discuss
- Translational considerations related to the pharmacokinetics, pharmacodynamics and toxicity of ON drugs.
Key aspects of first-in human study design, including assessments, study population, safety mitigation strategies (e.g., sentinel dosing, dose escalation and follow up periods) and the evaluation of immunogenicity and QT-prolongation.
Speakers:
Rüdiger Kaspera, Ph.D.
Rüdiger Kaspera, Ph.D. is a Clinical Pharmacologist within ICON’s Drug Development Solutions team. He provides consulting support to pharmaceutical companies from preclinical to registration, leveraging his clinical pharmacology and DMPK experienced from academia (University of Washington), industry (Novartis, Astellas, AstraZeneca) and consulting in support of a diversity of drug modalities for a range of therapeutic areas (oncology, metabolism, CNS, and other). He facilitates early clinical development strategies and projects in study designs, PK, PKPD and PBPK modelling, and regulatory support (EMA/FDA). He has co-authored 25+ publications.
Kamelia Mirdamadi, Ph.D.
Kamelia Mirdamadi, Ph.D. is a Clinical Pharmacologist within ICON’s Drug Development Solutions team, providing scientific leadership and strategic oversight across all stages of early drug development. Her consulting expertise spans the evaluation of preclinical and clinical data packages, as well as the design and review of early phase studies, including PK and PK/PD components and associated modelling. Prior to joining ICON, she worked as a research scientist in in‑vitro and in‑vivo pharmacology, preclinical toxico- and pharmaco-kinetics, drug metabolism and transport.
Thijs van Iersel, M.D
Thijs van Iersel, M.D. is a Clinical Pharmacologist within ICON’s Drug Development Solutions team. His previous roles include Principal Investigator, CRU Manager, Medical Director, global clinical development leader at Organon, and member of the Clinical Pharmacology team at AstraZeneca. He has engaged with major regulatory agencies—including the FDA, Health Canada, and PMDA (Japan)—and contributed to the EMA workshop on the draft revision of the first‑in‑human clinical trials guideline. He is the (co)‑author of more than 30 publications and is a patent holder (sugammadex.)
Target audience:
Non-clinical and clinical drug development, DMPK, clinical pharmacologist, toxicologist, translational scientists, oligonucleotide therapeutics drug developer, modelling and simulation scientists.