Skip to main content
ISOP ACoP 2025 Annual Conference Main banner
ViewAttendees 3
Symposium

General Pharmacometrics

C3C - Envisioning the Future Landscape of Quantitative Pharmacology and MIDD for Next-Generation RNA Therapeutics

Monday, October 20, 2025
2:00 PM - 3:30 PM MDT
Location: Red Rock 8/9

Disclosure(s):
Vivaswath S. Ayyar, PhD: No relevant disclosure to display
Wei Gao, PhD: No financial relationships to disclose
Zheng Yang, PhD: No relevant disclosure to display
Devam A. Desai, M.S.: No financial relationships to disclose
Kenji Miyazawa, PhD: No financial relationships to disclose

Description of session (include background & scientific importance): Recent breakthroughs in RNA therapeutics have revolutionized drug development by enabling precise modulation of disease-related proteins. RNA interference (RNAi) via small interfering RNA (siRNA) and antisense oligonucleotides (ASO) silences target mRNA, preventing protein synthesis. Conversely, mRNA-based therapies and vaccines introduce functional proteins, while CRISPR-based approaches enable gene editing. While several RNA therapeutics—primarily for hepatic targets—have been approved, advances in RNA engineering, lipid nanoparticle delivery, and conjugation strategies have enhanced pharmacokinetics (PK) and pharmacodynamics (PD), enabling potent and durable effects beyond the liver.

Despite progress, key challenges persist in quantitative pharmacology assessments, limiting model-informed drug development (MIDD):
1. Complex ADME controlling systemic PK profiles – transient plasma exposure with prolonged tissue residence.
2. Diverse mechanisms-of-action – RISC and RNaseH-mediated RNAi, ribosomal translation, and CRISPR editing introduce distinct PD complexities.
3. Intracellular rate-limiting steps – nonlinear and time-dependent pathways (e.g., receptor-mediated uptake, endolysosomal processing) complicate dose-exposure-response predictions.
4. Current gaps in experimental paradigms – there is urgent need for optimal experiments studies and measurements which offer the quantitative, mechanistic, and translational insights needed to advance MIDD of RNA therapeutics.

This symposium will showcase cutting-edge experimental and quantitative methodologies addressing these challenges. Experts from industry and academia will discuss advances spanning discovery, delivery, mechanistic modeling, and clinical development. Integrated perspectives needed to advance quantitative pharmacology to optimize next-gen RNA therapeutics will be offered. An engaging panel discussion will highlight how data/knowledge-driven insights can serve as a critical inflection point, accelerating MIDD and shaping the future of RNA therapeutics and related emerging modalities.

Learning Objectives:

  • 1. Clarify the evolving landscape of RNA therapeutics, including diverse modalities, mechanisms-of-action, and translational challenges. 2. Identify key quantitative pharmacology considerations unique to oligonucleotides and mRNA-based vaccines and therapies and their implications for clinical development. 3. Examine and illustrate through ongoing basic, translational, and clinical research how novel experimental and computational tools generate critical data/knowledge/evidence-driven insights that fill current knowledge gaps to advance MIDD for these novel RNA-based modalities. 4. Exemplify how integrated experimental and mechanistic modeling approaches will continue harnessing emerging insights from discovery, delivery, and clinical pharmacology to advance MIDD for the next generation of RNA-based medicines.

Presentations:

  • 2:00 PM - 2:20 PM MDT
    ADME Attributes of siRNAs and Translational PK/PD Approaches

    Speaker: Zheng Yang, PhD – Excelsius LLC.

  • 2:20 PM - 2:40 PM MDT
    Systems modelling for gene-based therapies

    Speaker: Devam A. Desai, M.S. – Center of Pharmacometrics and Systems Pharmacology, University of Florida, Orlando, FL

  • 2:40 PM - 3:00 PM MDT
    Developing physiologically based PK (PBPK) models to facilitate LNP based mRNA therapeutics development

    Speaker: Kenji Miyazawa, PhD (he/him/his) – Moderna, Inc.

  • 3:00 PM - 3:30 PM MDT
    Panel - Envisioning the Future Landscape of Quantitative Pharmacology and MIDD for Next-Generation RNA Therapeutics

    Panelist: Zheng Yang, PhD – Excelsius LLC.

    Panelist: Rodrigo Cristofoletti, PhD – University of Florida

    Panelist: Kenji Miyazawa, PhD (he/him/his) – Moderna, Inc.

    Panelist: Jiawei Zhou, PhD (she/her/hers) – UNC-Chapel Hill