FOCUS DAY
Safety & Off-Target Toxicity Profiling
Tuesday, December 10
Join us for a dedicated day on key challenges including safety and off target toxicity that are currently holding back the field of RNA-targeting small molecules field. Through evaluating reliable preclinical models, safety margin considerations and off-target pharmacology, this day will provide you with actionable insights to fast-track successful translation of your preclinical pipelines into robust clinical candidates with higher rate of success.
8:30 am Check-in Opens & Light Breakfast
9:00 am Chair’s Opening Remarks
Rethinking Safety Testing for Small Molecules Targeting RNA for Improved Understanding of Off-Target Effects for Reduced Toxicity
9:15 am De-Risking Small Molecule Safety through Understanding the Small Molecule Toxicity & Off-Target Profiling Strategies for Advancing Safe & Efficacious Therapeutics
Synopsis
- Highlighting the safety and toxicity packages which are made to advance safe small molecules targeting RNA towards the patients in need
- Evaluating the safety window which is required for regulatory approval to fast-track RNA-targeting therapeutics towards the clinic
- Uncovering reliable preclinical models used to represent RNA targets and analyse small molecule safety
9:30 am Roundtable Discussion: Evaluating Regulators’ Views on Safety & Toxicity Testing to Streamline Preclinical Testing & Fast-Track RNA-Targeting Drug Approval
Synopsis
- What are regulators' thoughts on using animal models to showcase off-target effects and toxicity given their limited RNA conservation?
- What safety and toxicity tests are required to gain FDA approval for advancing into human clinical trials?
- Highlight specifications which are required to be met by RNA-targeting drugs to ensure regulatory approval
10:30 am Morning Break & Networking
Accomplishing Successful Translation Through Improved Preclinical Model Selection, Off-Target Understanding & Safety Testing to Advance Safe & Potent Small Molecules
11:30 am Utilizing RNA-Seq Data At-Scale to Improve the Translatability of mRNA Splicing Modulators
Synopsis
- Outlining the unique translational challenges in developing small molecule modulators of mRNA splicing
- Summarizing use of multi-dose RNA-seq experiments to identify potentially toxic off target liabilities for development candidates
- Summarizing use of multi-species RNA-seq data to improve animal model selection during preclinical research
12:00 pm Targeting RNA Genomes Small Molecules to Develop Retroviral Therapeutics
Synopsis
- Mechanisms for targeting small relevant mechanisms for cardiovascular indications
- Safety margins considerations for small molecules targeting RNA targets in CV diseases
- Improving small molecule design for greater efficacy to ensure therapeutic effect
12:30 pm Investigating RNA Off-Target Effects of FDA Approved Drugs to Understand Pharmacology
Synopsis
- Small molecule screening reveals many drug-like compounds bind to RNA
- Using AI/ML to understand that many FDA approved drugs have RNA binding potential
- Transcriptome-wide binding and functional analysis reveals the impact of RNA binding on off-target pharmacology
1:00 pm Lunch Break & Networking
Leveraging Strategies to Improve Human RNA Representation in Preclinical Models for More Reliable Translation of Small Molecule Drugs
2:00 pm Expert Led Breakout Session: Translating an RNA-Targeting Small Molecule from a Hit to a Human Using Novel Preclinical Modeling Strategies to Fast-Track Safe Therapeutics Towards Patients
Synopsis
A major challenge for the translation of safe RNA targeting therapeutics is understanding RNA conservation across different animal models. Disease causing RNA sequences can change from animal to animal, therefore, new and innovative approaches need to be developed to enable reliable pre-clinical testing for accelerating safe and efficacious therapeutics towards the patients in need.
During this interactive session, join forces with your peers to discuss different strategies for overcoming this challenge as well as uncovering novel and innovative approaches to preclinical modeling. Here are some questions to think about during this session:
- Are there ways to manipulate animal models to improve their representation of human RNA?
- Which models and screening methods are used to successfully translate a small molecule drug from hit discovery and into the clinic?
- How to ensure the animal models are representative of the mechanism which is occurring in humans?
- What new technologies have been developed to minimize the need to use animal models and more accurately represent humans?
- What are the opportunities and challenges of organoid and organ-on-chip models for advancing RNA-targeting drugs?