Main Conference Day 2
- Yogesh Sanghvi, PhD - President, Rasayan Inc.
- Keith Cronce - Chief Operating Officer, Fluid Air, A Division of Spraying Systems
Site-specific chemical modification of mRNAs can improve their translation efficiency and stability. Therefore, it is desirable to develop a complete chemical synthesis method for chemically modified mRNA. The key step in the synthesis of eukaryotic mRNA is a chemical reaction in which a cap structure is introduced to the chemically synthesized RNA strand. we have developed a capping reaction that proceeds rapidly and quantitatively and synthesized series of chemically modified mRNAs.
- Hiroshi Abe, PhD - Professor, Department of Chemistry, Graduate School, Nagoya University
This presentation will provide clinical development updates on two innovative nucleic acid therapeutic programs: TUG1-targeting antisense oligonucleotide for recurrent glioblastoma and Runx1 mRNA therapy for knee osteoarthritis, showcasing the versatility of nucleic acid medicine across diverse therapeutic areas and highlighting recent clinical milestones and future development strategies.
- Shiro Akinaga, PhD - President and CEO, NANO MRNA, Co., Ltd.
This talk will summarize the preclinical validation and clinical translation of mRNA therapeutics for protein replacement. Non-clinical studies confirm robust expression and stability across multiple species. The data collectively demonstrate the flexibility of the mRNA platform to encode diverse therapeutic proteins, supporting rapid advancement toward scalable, precision-driven treatments.
- Pad Chivukula, PhD - Chief Scientific Officer and COO, Arcturus Therapeutics
- Yogesh Sanghvi, PhD - President, Rasayan Inc.
The shift from IV to SC administration in biologics has enhanced patient convenience and healthcare efficiency. Similarly, oligonucleotide therapies are expected to adopt SC routes, overcoming challenges like injection volume and viscosity with advanced formulation technologies. This presentation discusses these strategies, inspired by biologics, and briefly explores macromolecule oral delivery as the ultimate user-friendly solution. The intended audience includes professionals involved in oligonucleotide formulation development, researchers exploring or offering novel SC formulation technologies for oligonucleotides, and healthcare providers interested in transitioning from IV to SC administration.
- Tomoya Takenaka, PhD - Principal Scientist, Drug Product and Device Development, Takeda Pharmaceutical Company
Non-covalent RNA complexes such as siRNA duplexes are a commercially established continuously evolving class of oligonucleotide therapeutics, with many novel formats and modification patterns currently under development. The non-covalent nature of these duplexes merits unique considerations for both analytical and formulation development in comparison to their single-stranded oligonucleotide therapeutic counterparts. Using UV-Vis absorbance measurements, thermal melting temperature analyses, and chromatography experiments, we explore the impact of siRNA concentration, solvent type and concentration, and salt type and concentration on siRNA duplex absorbance measurements and thermal melt data, and highlight the extent to which the hyperchromicity effect plays a role in these measurements, illuminating the stability of siRNA duplexes under various conditions. Additionally, we evaluate rapid-screening differential scanning calorimetry DSC (RS-DSC) as a novel instrument towards siRNA duplex analysis in a low-volume, high-throughput format, circumventing the limitations of traditional DSC and enabling parallel thermal stability analysis of high-concentration siRNA drug product formulations. We demonstrate the utility of this instrumentation for the comprehensive thermal analysis of therapeutic siRNA duplexes in multiple different contexts relevant to drug discovery and development, including: formulation screening, analytical sample preparation, and simulated in vivo administration. RS-DSC is a powerful, label-free technique that directly measures heat capacity changes associated with siRNA duplex unfolding, providing quantitative thermodynamic parameters such as melting temperature (Tm), enthalpy change (ΔH), and heat capacity. By characterizing subtle stability differences induced by various relevant formulation components, analytical methods, and administration via different routes, we highlight the flexibility of this method for evaluating the stability of siRNA across various critical stages of drug development. These experiments showcase the criticality of both UV-Vis and RS-DSC thermal analysis techniques for therapeutic oligonucleotide development, and provide a roadmap for how these techniques can be used in the development of chemistry, manufacturing, and controls (CMC) strategies for formulation development, analytical development, quality control, in-vivo stability prediction, and beyond.
- Molly Blevins, PhD - Principal Scientist, Genentech
For technical leads advancing oligonucleotide therapeutics, purification strategies are central to ensuring product quality and regulatory alignment. Agilent’s scientific team has developed scalable approaches that support high-resolution separation and consistent impurity profiles across diverse oligo formats. These capabilities help reduce risk, streamline process development, and enable confident progression from early-stage development through commercial manufacturing.
- Alun Garner - Business Development Manager, Nucleic Acid Solutions Division, Agilent Technologies
- Yogesh Sanghvi, PhD - President, Rasayan Inc.
Following purification, oligonucleotide processes often use UF/DF step to formulate their API for subsequent lyophilization (solid API). A better understanding of the UF/DF operation reveals this step can do more including enabling manufacturing flexibility to make either a liquid API or a more efficient lyophilized API process. Here we describe learnings from in depth UF/DF studies that provide improved process control and productivity that we believe Regulators will find acceptable.
- Robert Gronke, PhD - Senior Principal Scientist, Biogen, Inc
The increased complexity of oligonucleotide leads to the usage of new building blocks and raw materials in manufacturing of oligonucleotide for clinical application. This leads to inevitable challenges in qualification of the vendors as well as qualification of the raw materials used in the production process. Examples will be presented including potential solutions that would help overcome these challenges.
- Long Ma, PhD - CEO and Chief Scientist, Orilife Biotech
- Ved Srivastava, PhD - CTO, Perpetual Medicines
Protein-protein interactions, and in particular Transcription Factors (TFs), remain compelling drug targets, yet are often intractable to small molecules and inaccessible to larger biologics. Peptides occupy an attractive middle ground if they can become suitable ordered for target engagement. We utilize intracellular peptide library screening approaches to identify selective peptide-based inhibitors that can functionally antagonize TFs. There are two major novelties to our approach: i) our Transcription Block Survival (TBS) peptide-library screening platform in which TF consensus sites are placed directly into the coding region of an essential gene. Subsequent TF binding within the gene directly blocks gene transcription leading to cell death under selective conditions. Cell survival is therefore only possible if antagonists bind to the TF, but more importantly can prevent it from binding to its consensus sequence, thus shutting down TF function. TBS is an entirely tag-free genotype-to-phenotype approach, selecting desirable attributes such as high solubility, target specificity, biostability and low toxicity within the complex environment of the cell. TBS facilitates rapid library screening to accelerate identification of therapeutically valuable sequences. ii) concomitant deployment of cell penetrating crosslinkers. These enter cells to post-translationally constrain every library member into conformations not possible via genetic encoding alone, to select only those in which crosslinking translates into improve target antagonism. Screening ultra-structured biostable peptide libraries, where entire libraries are constrained during the search is highly desirable as it prevents a slow and costly retrospective trial-and-error search for beneficial crosslinkers, positions, and sequences. Using several different exemplars, I will discuss how library-derived constrained peptide antagonists are derived and discuss their characterization using a range of biophysical and cancer cell-based assays.
- Jody Mason, PhD - Professor of Biochemistry, University of Bath
- David Craik, PhD - Professor of Biomolecular Structure, University of Queensland
Targeting GPCRs for disease therapy has proven problematic with many drugs exhibiting off target side effects due to lack of receptor selectivity. We have targeted the cannabinoid GPCR CB2R with libraries of stabilized and constrained peptides, called Selektides. We describe here our work on discovery and functional characterization of candidate receptor antagonists with an emphasis on functional experimental design and receptor selectivity determination. Progress in development of an IND ready Selektide for IBD treatment will be described.
- David O'Connell, PhD - Professor, School of Biomolecular & Biomedical Science, University College Dublin
As demand, volume, and structural complexity of oligonucleotide therapeutics grows, new technologies are required to address increasing environmental, cost, and efficiency concerns in the manufacture of these drugs. Fragment-based enzymatic ligation (EL) is emerging as a synthetic approach that captures benefits of well-established solid phase synthesis of short fragments with the specificity of biocatalysis for direct assembly of oligonucleotide duplexes. This talk will describe key drivers for the development of EL processes, control strategy advantages, and learnings from scale up to kilogram quantities under cGMP conditions.
- Scott May, PhD - VP of Chemistry, Synthetic Molecule Design & Development, Eli Lilly and Company
- Arne Berthelmann - Senior Director Oligonucleotide R&D, Bachem AG
- Masafumi Iwamoto, PhD - Associate Director of Technology and Innovation, Nitto Denko Avecia
This presentation shares key lessons from building a CMC program for a therapeutic oligonucleotide that progressed to Phase 3. Focused on the realities of small biotech, it offers practical insights into analytical, manufacturing, and regulatory strategy, highlighting how to make smart, resource-conscious decisions from early development through late-stage milestones.
- Pablo Lores Lareo, PhD - CMC Director, Sylentis
Please join your fellow attendees in the exhibit hall for an evening of networking while enjoying beverages and appetizers.
This presentation outlines the design of mRNA display libraries featuring diverse chemical properties and scaffolds for the initial identification of peptide hits with high affinity and specificity for targets. We discuss strategies for constrained peptides to develop viable, orally available therapeutics, along with future advancements in therapeutic peptides.
- Haruaki Kurasaki, PhD - Director, Medicinal Chemistry, PeptiDream
A robust peptide therapeutics discovery platform has been developed using approximately 500 venom peptides as scaffolds. The platform leverages both phage and yeast surface display technologies. The libraries were designed with machine learning model that can rapidly predict key-residue determinants for peptide foldability. Additionally, a fast and cost-effective affinity maturation workflow has been enabled through machine learning, leading to the identification of potent and stable leads against targets of interest from this venom platform.
- Yingnan Zhang, PhD - Senior Principal Scientific Manager, Genentech
- Kerry Blanchard, MD, PhD - CEO, Chairman and Founder, Perpetual Medicines
Please join your fellow attendees in the exhibit hall for an evening of networking while enjoying beverages and appetizers.