8:00 am Check-in & Morning Coffee
8:55 am Chair’s Opening Remarks
Shaping the Future of RNA-Targeted Therapeutics by Identifying Investment Trends & Forging Strategic Collaborations to Drive Novel Therapeutics to Patients
9:00 am Panel Discussion: Building Strategic Collaborations & Investment Pathways to Accelerate RNA-Targeted Drug Discovery Across Biotech & Pharma
Synopsis
• Discussing the importance of pharma-biotech-academic collaborations and what each sector can provide to successfully create RNA-targeted therapeutics
• How are large pharma and biotech companies structuring risk-sharing partnerships to access innovation and accelerate RNA-targeted therapeutic pipelines
• How can early-stage companies leverage academic collaborations, tool compound sharing and co development deals to validate targets and attract strategic capital
• What trends can be identified from recent investments, M&A activity and deal structures to inform future strategies in RNA therapeutics
9:45 am Advancing the Therapeutic Potential of Epitranscriptomics: Storm’s Firstin- Class METTL3 Inhibitor, STC-15
Synopsis
• Preclinical data demonstrates that modulating RNA methylation via METTL3 inhibition can enhance tumor sensitivity to treatment and impair resistance mechanisms
• Epitranscriptomic regulation produces durable changes to gene expression and the tumor microenvironment, suggesting anti-cancer efficacy through multiple mechanisms
• STC-15 clinical and translational data point to broad utility of METTL3 inhibition, enabling new treatment approaches across oncology indications
10:15 am Morning Break & Networking
Advancing RNA Target Selection & Functional Binder Design to Enable Reliable Modulation & Accelerate Therapeutic Discovery
11:00 am Panel Discussion: Selecting RNA Targets with Confidence to Maximize Therapeutic Impact & Enable Small Molecule Intervention
Synopsis
• What level of therapeutic effect biologically validates an RNA target and how can we ensure robust validation to uncover the RNA’s true therapeutic potential
• Which criteria should guide the selection of RNA targets to ensure compatibility with small molecule binding and downstream functional binder discovery
• What structural motifs or folding are indicative of a druggable RNA target and how can we reliably identify them during early discovery
11:45 am Conformation-Driven Biochemical Screening Approach Discovers Functional RNA Binders that Modulate Myc Translation In Cancer
Synopsis
• Discovering selective binders for translational regulatory elements in the Myc mRNA using Wayfinder’s highly quantitative HTS platform
• Validating functional activity and drug-like properties while reaching sub-micromolar potency via compound optimization
• Elucidating compound targeting profile and tumor-specific mechanism of action
12:15 pm Lunch Break & Networking
Targeting Structured RNA Motifs with Small Molecules to Enable Selective Functional Binders & Unlock New Therapeutic Frontiers
1:15 pm Small Molecules Modulate Stability of MALAT1 Substructures
Synopsis
• RNA-targeted libraries yield small molecule modulators of RNA conformation and function
• Oncogenic MALAT1 lncRNA contains ligandable substructures with putative function
• Tunable small molecules modulate MALAT1: protein interactions and lead to rapid degradation
1:45 pm Targeting HTT RNA & Translation for Allele-Selective Lowering of Mutant Huntington
Synopsis
• Validating HTT exon1 as a target for allele-selective targeting in HD
• Identifying and profiling of allele-preferential HTT RNA binding small molecules
• Exploring opportunities for targeting uORF regulatory mechanisms in HTT translation
2:15 pm Large-Scale Discovery of RNA Tertiary Structures & Disease Relevant RNA Targets
Synopsis
• RNA motifs with complex 3D structures are promising targets for small molecule therapeutics but are still very hard to find
• A new technology that identifies RNA tertiary structures, transcriptome-wide, typically with direct functional roles, will be presented
• Thousands of targetable sites likely exist across the human transcriptome
2:25 pm Afternoon Networking Break
Unlocking Peptide-Ribosome Complexes & Fungal RNA as Targets to Develop Novel Therapeutics Against Cancer & Infectious Diseases
3:15 pm Context-Dependent Translation Inhibition as a Novel Cancer Therapeutic Modality
Synopsis
• Leveraging structure-based drug design to inhibit the translation of historically undruggable oncology targets, including MYC, with orally dosed small molecules called interdictors
• Developing hetero-bifunctional molecules called Interdictors that bind to the ribosome and prevent protein synthesis by engaging with the linear nascent polypeptide as it is being made
• Combining techniques of in vitro biochemistry, ribosome profiling, structural biology and cellular biology, we characterize the context-selective activity of several tool interdictors and how they inhibit cancer cell proliferation
• Demonstrating robust efficacy in the MDA-MB-231 model for TNBC, establishing interdiction as a novel small molecule therapeutic modality for addressing historically difficult-to-treat cancers
3:45 pm Targeting Group I Introns with Small Molecules: Unlocking a New Antifungal Mechanism Through RNA Targeting
Synopsis
• Identifying self-splicing Group I introns as a novel RNA target in human-pathogenic fungi, such as Candida albicans, highlighting a unique RNA-targeting mechanism distinct from existing antifungal drugs
• Developing small molecule inhibitors through FRET-based high-throughput screening, followed by structure activity relationship (SAR) analysis and mechanistic insights guided by cryo-EM structural data
• Demonstrating potent cellular antifungal efficacy with low cytotoxicity, establishing RNA-targeting small molecules as a promising new class of antifungals