Challenges and Opportunities of RNA Therapeutics, A Roller Coaster from Discovery to Recovery I: Pioneering Patient-Centric RNA Therapeutics for Rare Diseases

Session Description

RNAs play a multifaceted role in cell biology, serving as messengers for protein synthesis, gene regulators, catalysts for chemical reactions, and modulators of other RNAs. This versatility has sparked significant interest in harnessing RNA for the treatment of rare diseases.

RNA therapies can be categorized into three main modalities: nucleic acid-targeting, protein-targeting, and protein-encoding. Nucleic acid-targeting RNA therapies, including single-stranded antisense oligonucleotides (ASOs) and double-stranded RNA interference (RNAi) molecules, have shown promise in rare disease treatment. Approved therapies include nusinersen, eteplirsen, patisiran, inotersen, givosiran, and vutrisiran, which target various rare genetic disorders. RNA aptamers, which modulate protein function, have also demonstrated efficacy, as exemplified by pegaptanib for age-related macular degeneration. mRNA-based therapies are being explored for personalized cancer vaccines, infectious disease vaccines, and protein-replacement therapy for rare conditions like haemophilia. Hybrid approaches, such as the "Silence and Replace" strategy, aim to combine gene silencing with protein encoding.

Despite the progress made, the major obstacle in RNA therapy remains the efficient delivery of RNA molecules to the target cells and tissues.

This session will focus on the clinical pharmacology aspects of RNA therapy development, with a patient-centered approach [1]. Considerable emphasis will be placed on exploring targeted therapies that leverage genetic profiling of patients to achieve precision medicine. Our distinguished panel of experts will offer an in-depth exploration of RNA therapies, imparting crucial insights gained from their experiences in industry, academia and regulatory, and delve into the latest developments and optimal strategies within the field.

Reference:
[1] M. Shahin and M. Rizk, Patient-centric Clinical Pharmacology: A Journey from Discovery to Recovery, CPT, 2024

Learning Objectives

1. Comprehend and gain deep understanding of the complex landscape of developing patient-centric RNA therapeutics, from the initial stages of discovery to the ultimate goal of recovery with emphasis on clinical pharmacology considerations.
2. Appreciate the revolutionary potential of RNA therapies as a paradigm-shifting approach in the management of rare diseases, offering a transformative shift from traditional treatment modalities.
3. Grasp the complex interplay between industry and regulatory stakeholders in the development of RNA therapies, encompassing the strategic, translational, and regulatory considerations that shape the trajectory of these innovative treatments.

Session Schedule

Introduction
Hazem Hassan, MS, PhD, RPh and Islam Younis, PhD

Unlocking the Potential of RNA Therapies: From Discovery to Recovery in Rare Diseases
Alexandre Sostelly, MSc, PhD

Revolutionizing RNA Therapeutics Development for Rare Diseases: The Emergence of Digital Twins as a Patient-Centric Approach
Chanchala Kaddi, PhD

Regulatory Insights: FDA's Perspective on Patient-Centric Development of RNA Therapies
Hobart Rogers, PharmD, PhD

Panel Discussion