C1C - Applications and Challenges of MIDD in Nucleic Acid therapies

Sunday, October 19, 2025

11:00 AM - 12:30 PM MDT

Location: Red Rock 8/9

Co-Chair(s)

Tao Niu, PhD (he/him/his)

Director, Quantitative Clinical Pharmacology
Sarepta Therapeutics, United States
Xiao Hu, PhD

President and Founder
Translational Consulting, L.L.C.
Chestnut Hill, Massachusetts, United States

Speaker(s)

Xiang Gao, PhD (he/him/his)

VP, Head of Pharmacokinetics and Clinical Pharmacology
Ionis Pharmaceuticals
Vista, California, United States
PZ

Peijuan Zhu, PhD

Senior Director, Clinical Pharmacology Lead
Intellia Therapeutics, New Jersey, United States

Panelist(s)

Daniel Kirouac, PhD

Vice President QSP
Metrum Research Group, United States

Disclosure(s):

Tao Niu, PhD: No financial relationships to disclose

Xiao S. Hu, PhD: No financial relationships to disclose

Peijuan Zhu, PhD: No relevant disclosure to display

Daniel Kirouac, PhD: No financial relationships to disclose

Description of session (include background & scientific importance): In recent years, nucleic acid (including antisense oligonucleotides, small interfering RNAs, mRNAs, and genome editing using CRISPR) have revolutionized the treatment landscape for numerous diseases, particularly for rare genetic diseases. Despite their promise, these novel modalities introduce unique pharmacokinetic (PK) and pharmacodynamic (PD) challenges not encountered in conventional therapeutics.
Model informed drug development (MIDD) has become a key driver in addressing these complexities, enabling robust modeling and simulation approaches that help guide dose selection, regimen optimization, and clinical trial design. However, each modality has distinct mechanisms of action, off‐target potential, and regulatory considerations—requiring tailored strategies for success.
This session will feature four speakers who will delve into the application of pharmacometrics for each of these modalities—ASOs, siRNAs, mRNAs, and CRISPR—highlighting methodologies, common pitfalls, and opportunities for accelerating development. By showcasing successes and lessons learned, the session will underscore how quantitative approaches can shape the future of these transformative therapies.

Learning Objectives:

Identify the unique PK/PD challenges inherent in ASOs, siRNAs, mRNAs, and genome editing with CRISPR therapy. Evaluate different pharmacometric and modeling strategies—including empirical, QSP, and/or PBPK—that address these challenges at various stages of drug development. Translate real‐world case studies to inform best practices for dose optimization, patient stratification, and trial design. Anticipate emerging regulatory and industry trends for quantitative approaches in these therapies, and understand how these frameworks can accelerate clinical impact.

Presentations:

11:00 AM - 11:20 AM MDT

Application and Challenges of Pharmacometrics in siRNAs
Speaker: Xiao S. Hu, PhD – Translational Consulting, L.L.C.
11:20 AM - 11:40 AM MDT

Application and Challenges of Pharmacometrics in Antisense Oligonucleotides
Speaker: Xiang Gao, PhD (he/him/his) – Ionis Pharmaceuticals
11:40 AM - 12:00 PM MDT

Clinical Pharmacology and Translational Considerations in the Development of CRISPR-Based Therapies
Speaker: Peijuan Zhu, PhD – Intellia Therapeutics
12:00 PM - 12:30 PM MDT

Panel - Applications and Challenges of MIDD in Nucleic Acid therapies
Panelist: Xiao S. Hu, PhD – Translational Consulting, L.L.C.
Panelist: Xiang Gao, PhD (he/him/his) – Ionis Pharmaceuticals
Panelist: Peijuan Zhu, PhD – Intellia Therapeutics
Panelist: Daniel Kirouac, PhD – Metrum Research Group