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7:30am - 7:45am

Registration and Coffee

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Showing of Streams
10:00am - 10:45am

Networking Refreshment Break in Poster and Exhibit Hall

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Showing of Streams
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12:50pm - 1:55pm

Networking Luncheon in Poster and Exhibit Hall

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Showing of Streams
3:30pm - 4:15pm

Networking Refreshment Break in Poster and Exhibit Hall

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Showing of Streams
5:45pm - 6:45pm

Networking Refreshment Break in Poster and Exhibit Hall

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7:30am - 7:45am 15 mins
Registration and Coffee
7:45am - 8:15am 30 mins
Info
Breakfast Spotlight Presentations 1
Cost Efficient Peptide Purification via ZEOsphere DRP Mixed-Mode Chromatography
  • Timothy O'Mara - Sales Manager, Itochu Chemicals America, Inc.

The presentation will show the beneficial use of ZEOsphere DRP Mixed-Mode stationary phases for the separation of charged molecules like peptides. ZEOsphere DRP orthogonal interaction is due to a better selectivity not only able to increase purity, recovery and loading, but also to decrease the organic solvent usage. Real peptide crude separations will be shown, including production cost-efficiency data.

7:45am - 8:15am 30 mins
Info
Breakfast Spotlight Presentations 2
Lessons Learned from Liposomal Products and Processes – Chemistry, Manufacturing and Controls
  • Andreas Wagner - Head of Liposome Technology, Polymun Scientific GmbH

Polymun Scientific GmbH is a private Austrian company, located in Klosterneuburg, offering contract development and manufacturing of biopharmaceuticals as well as development and production of liposomal formulations. Its patented liposome technology allows efficient manufacturing of constantly high quality in small and large scale. Polymun is an FDA- and EMEA-certified manufacturer conducting several own R&D projects. For more information, please visit www.polymun.com

7:45am - 8:15am 30 mins
Info
Breakfast Spotlight Presentations 3
LGC’s Approach Towards Preclinical and Clinical Development of Oligonucleotide Therapeutics: Covering the Value Chain from Lead ID to Phase 1 Supply
  • Hans-Peter Vornlocher, PhD - Managing Director Research, LGC Axolabs
  • Juergen Mueller, PhD - Commercial and Strategic Development Director, LGC Axolabs Biosearch
8:25am - 8:30am 5 mins
Oligonucleotide Discovery, Preclinical and Clinical
Chairwoman’s Remarks
  • Shuling Guo, PhD - Vice President, Antisense Drug Discovery, Ionis Pharmaceuticals, Inc.
8:25am - 8:30am 5 mins
Oligonucleotide Chemistry Manufacturing and Controls
Chairman’s Remarks
  • Doug Brooks, PhD - Consultant, Matapalo Pharma Consulting Services
8:25am - 8:30am 5 mins
Peptide Discovery, Preclinical and Clinical
Chairman’s Remarks
  • Waleed Danho, PhD - Consultant, Danho & Associates
8:25am - 8:30am 5 mins
Peptide Chemistry Manufacturing and Controls
Chairman’s Remarks
  • Alex Fassler, PhD - COO, Bachem Holdings AG
8:30am - 9:00am 30 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
Human Genetics Moves from Clinic to Bench and Back: Develop Antisense Therapies for Inherited Diseases
  • Shuling Guo, PhD - Vice President, Antisense Drug Discovery, Ionis Pharmaceuticals, Inc.

Genome-wide association studies provide insights into the culprit genetic changes for many inherited diseases. Antisense technology, which provides a direct route from genetic sequence to therapy, offers the potential to deliver personalized medicine in such diseases. Here I will discuss our efforts in developing novel antisense therapies for genetic diseases.

8:30am - 9:00am 30 mins
Info
Oligonucleotide Chemistry Manufacturing and Controls
Industrial Scale Manufacture of 2-cyanoethyl-N,N,N′,N′-tetraisopropylphosphorodiamidite (Phos reagent)
  • Gary Woodward, PhD - Senior Research Fellow, Solvay Solutions UK Ltd

Phos Reagent, a key phosphorus intermediate for phosphoramidites, is moving through a key industrialisation phase to support market growth; the use of Phos Reagent in multiple API developments now means that it is required at multi tonne scale. Previous manufacture has been substantially kilo-lab based and has concentrated on development and control of impurities derived from raw materials and the manufacturing process. These impurities will be described. In particular, it is important that any industrialised process can deliver Phos Reagent with long term stability at room temperature. Development of a robust process will be described, which has been safely and reliably scaled to deliver consistent, high purity Phos Reagent at the industrial scale required for the phosphoramidite market. Solvay's manufacture process will be outlined.

8:30am - 9:00am 30 mins
Info
Peptide Discovery, Preclinical and Clinical
Genetically Encoded Selection of Novel Cyclic and Bicyclic Architectures
  • Ratmir Derda, PhD - Associate Professor, Department of Chemistry, University of Alberta

The talk will describe genetically-encoded (GE) platform for discovery of macrocyclic and macrobicyclic peptides synthesized by aqueous late-stage functionalization of readily-available libraries of peptides displayed on phage. The structure of these chemical post-translational modifications can be encoded in the genome of phage using silent encoding technology. The resulting phage displayed libraries of "unnatural" macro(bi)cyclic peptides could be used to target either proteins or cells and tissues; the latter targets are difficult to address with DNA/RNA or bead-based libraries. Expanded chemical space offers value-added properties such as stability to aggressive protease environment and incorporation of unnatural chemotypes that are known to increase bioavailability.

8:30am - 9:00am 30 mins
Info
Peptide Chemistry Manufacturing and Controls
CMC Development Concept for Synthetic Peptides
  • Tanja Huth, PhD - Group Leader QA/RA Project Management, Bachem AG

Bachem’s modular concept for CMC development is based on experience with a wide range of customers (virtual to big Pharma). The concept covers the complete API life cycle and will be presented with emphasis on milestones and deliverables commensurate to the clinical development phases.

9:00am - 9:30am 30 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
Targeted Delivery of Oligonucleotides to Muscle with Antibody Oligo conjugates.
  • Arthur Levin, PhD - Executive Vice President, R&D, Avidity Biosciences LLC

Avidity Biosciences has developed novel technology for delivering oligonucleotide payloads to multiple tissues using antibody oligonucleotide conjugates (AOCs). This presentation will focus on recent data demonstrating pharmacologic activity of payloads to muscle for the treatment of rare muscle diseases. The properties of these AOCs make them attractive therapeutic agents. With this application, oligonucleotide agents can be delivered to multiple target sites. The technology has now been demonstrated with multiple payloads in multiple species.

9:00am - 9:30am 30 mins
Info
Oligonucleotide Chemistry Manufacturing and Controls
Increasing Yields and Reducing Waste in Oligonucleotide Manufacture
  • Anna Watson - Senior Scientist & Process Engineer, AstraZeneca, UK

Oligonucleotide processing is expensive and generates disproportionate waste compared to small molecule processing but must operate in a competitive environment. This presentation will assess a typical oligonucleotide manufacturing process to identify opportunities where process yield and recovery can be increased to minimize costs and reduce waste. It will include an in-depth mass balance over the process focusing on the target compound to rank the potential for unit operations to increase yield, and how these opportunities might be realized. The environmental metric Process Mass Intensity will be exemplified to fingerprint waste generation throughout the process and demonstrate the positive impact that increasing the yield will have on the environment.

9:00am - 9:30am 30 mins
Info
Peptide Discovery, Preclinical and Clinical
Chemoenzymatic Synthesis of Macrocycles
  • David Craik, PhD - Professor of Biomolecular Structure, Institute for Molecular Bioscience, University of Queensland

Macrocyclic peptides have attracted much attention recently as leads and scaffolds in peptide-based drug design. This presentation will describe the use of peptide ligases for the chemo-enzymatic synthesis of a wide range of peptide substrates of pharmaceutical relevance. I will focus on asparaginyl endopeptidases from plants as efficient tools for the cyclisation of peptides.

9:00am - 9:30am 30 mins
Info
Peptide Chemistry Manufacturing and Controls
Supply Chain and CMC Considerations during Development of Lumicell’s Cleavable PEGylated Peptide-dye Conjugate for Fluorescence Guided Surgery
  • Daniel Harris, PhD - Director of Drug Manufacturing, Lumicell

The complex structure of the LUM015 imaging agent presents unique supply chain and quality challenges. We combined several different control strategies and coordinated between several vendors in order to leverage specialized expertise and manage quality and supply chain risk.

9:30am - 10:00am 30 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
Development of microRNA Therapeutics
  • Aimee Jackson, PhD - Vice President of Research, miRagen Therapeutics

microRNAs are small non-coding RNAs that modulate biological processes through regulation of gene networks.  Aberrant regulation of microRNA expression and function has been linked to numerous disease processes.  Modulation of microRNA activity has the potential to restore homeostasis to gene expression networks to provide therapeutic benefit.  A key challenge associated with development of microRNA-based therapeutics has been the identification of translational pharmacodynamic biomarkers to establish PK/PD relationships and inform therapeutic dosing.  We will discuss strategies we have used to address these challenges in clinical and preclinical development of microRNA therapeutics.

9:30am - 10:00am 30 mins
Info
Oligonucleotide Chemistry Manufacturing and Controls
Development of A Novel Method for Manufacturing A Single-stranded Long-chain RNA Oligomer, Which Is An Active Pharmaceutical Ingredient of TRK-250
  • Hideaki Inada - Senior Research Associate, Toray Industries Inc

An efficient and generally applicable synthetic method will be described to provide single-stranded long-chain RNA oligomers at high yield. A single-stranded long-chain RNA oligomer of 51 bases and 2 proline derivatives, TRK-250 in phase 1 clinical study, selectively suppress expression of the transforming growth factor-β1 (TGF-β1) protein, a key growth factor involved in lung fibrosis, through sequence-specific gene silencing. Most nucleic acid medicines are 20-30mer oligonucleotides and are manufactured almost exclusively using solid-phase synthesis. However, if long-chain RNA oligomers were synthesized with common TBDMS phosphoramidite, using this method, a high yield could be not expected. Therefore, a special amidite having a ribose 2’-OH protecting group that is different from that of TBDMS is needed to synthesize long-chain RNA oligomers with high yield, which increases cost. The purpose of this study is to develop a method for manufacturing single-stranded long-chain RNA oligomers without using a special phosphoramidite. First, two short single-stranded RNA oligomers, which span the target single-stranded long-chain RNA oligomer, were synthesized by a common solid-phase synthesis method with TBDMS phosphoramidite. Next, these two short single-stranded RNA oligomers were annealed and ligated using a catalytic amount of RNA ligase. We have accomplished the synthesis of TRK-250 in more than 95% purity and more than a 90% ligation yield. This novel enzymatic ligation method enables the production of many single-stranded long-chain RNA oligomers at a high purity and in high yield at a lower cost compared to that of common methods.

9:30am - 10:00am 30 mins
Info
Peptide Discovery, Preclinical and Clinical
The Power of Isoacyl Chemistry: Its Application to Insulin and Glucagon
  • Fa Liu, PhD - Director of Discovery Chemistry, Novo Nordisk Research Center Seattle

Isoacyl bonds can offer considerable advantages when substituted as part of a peptide backbone. This approach has been validated both as a synthetic technique, one particularly useful in overcoming aggregation and poor solubility, as well as a prodrug strategy exemplified in HIV-protease inhibitors. In exploring next generation diabetes therapies, we have successfully applied isoacyl chemistry to synthetic problems as well as to the design of drug candidates. Our initial effort involved incorporation of isoacyl dipeptides into insulin A and B-chains which enabled a highly efficient route to this historically challenging target. We subsequently successfully adapted this approach to other members of the insulin superfamily, notably to relaxin 2 and insulin-like peptide 5. These synthetic routes have been instrumental in facilitating the discovery of novel analogs and potential clinical candidates. Inspired by the insulin precedent, we utilized the isoacyl element in the design of soluble glucagon analogs which are stable in conventional liquid formulations but rapidly revert to native glucagon under physiological conditions. Taken together these examples highlight the versatility and impact of the isoacyl principle on peptide chemistry and drug discovery.

9:30am - 10:00am 30 mins
Info
Peptide Chemistry Manufacturing and Controls
APL-2 Drug Substance: Strategic Dual-sourcing of a PEG-ylated Peptide during Late Stage Clinical Development
  • Najib Maslouh, PhD - Vice President of Manufacturing, Technical Operati, Apellis Pharmaceuticals

APL-2 Drug Substance is a PEG-ylated peptide manufactured under cGMP for use in Phase 2 and Phase 3 clinical trials. Strategic dual sourcing of large scale batches to meet current clinical and future demands will be presented.

10:00am - 10:45am 45 mins
Networking Refreshment Break in Poster and Exhibit Hall
10:45am - 11:15am 30 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
Overcoming the Hurdle of Subcutaneous Delivery of mRNA in LNP to Enable Treatment of Chronic Diseases
  • Shalini Andersson, PhD - Senior Director and Head of New Therapeutic Modalities, AstraZeneca

mRNA-based therapeutics have the potential to address a wide variety of genetic diseases requiring protein replacement therapy or for regenerative approaches. However, a major challenge to making mRNA-based therapies a reality is the access to efficient delivery vehicle with acceptable tolerability profile for chronic dosing. We report the development of functionalized LNPs for use in vivo that are tolerable for subcutaneous administration of mRNA and enable expression of the therapeutic protein required for treatment of disease.

10:45am - 11:15am 30 mins
Info
Oligonucleotide Chemistry Manufacturing and Controls
Enzyme Catalysed Assembly of Oligonucleotides
  • David Tew - Senior Fellow, Glaxosmithkline Medical Reseach Centre

Although solid phase phosphoramidite based chemistry is a well-controlled and high yielding process for manufacturing oligonucleotides, the multiple rounds of iterative synthesis ultimately erode overall yields and purity. We have developed an enzyme catalysed process where multiple short oligonucleotides are brought together in a single convergent assembly step to generate the final product oligonucleotide. This assembly process provides the opportunity to use unpurified short oligonucleotides and the elimination of chromatography from the overall process. Both overall process yield and product purity are significantly improved compared to standard solid phase synthesis. Notably, product related impurities such as ‘N-1’ sequences are eliminated from the final product.

10:45am - 11:15am 30 mins
Info
Peptide Discovery, Preclinical and Clinical
An Appropriate Screening Funnel at An Early Stage of Peptide Discovery is Key to Success: An Overview
  • Stefania Colarusso - Senior Research Scientist, IRBM Science Park SPA

The use an appropriate screening funnel to correctly drive the SAR since the early stage of a project can have a deep impact is speeding up the development of peptide therapeutics. This presentation will show details of the repertoire of assays necessary to address specific issues such as sub cutaneous and plasma metabolism with in vitro/in vivo correlation to optimize bioavailability; potential peptide-induced pseudo-allergic reactions; immunogenicity; oligomerization and aggregation tendencies.

10:45am - 11:15am 30 mins
Info
Peptide Chemistry Manufacturing and Controls
Introducing Green and Sustainable Chemistry in Liquid Phase Peptide Manufacturing Processes
  • El Djouhar Rekaï, PhD - Head of Development & Manufacturing Process, PolyPeptide Group

The challenge for the pharmaceutical industry is to find ways to develop and manufacture APIs based on environmentally-friendly and efficient processes. The selection of solvents and excess of reagents, together with process design including solvent recycling/VOC emission control are emphasized with the objective to minimize the production of wastes/gas emission while being operationally safe and economical. We will describe an overview of the PolyPeptide Group approach for setting environmentally-friendly, safe and cost-effective processes in liquid phase peptide synthesis. Case studies of successful process development to reach improved green processes will be highlighted.

10:45am - 10:50am 5 mins
mRNA Therapeutics and CRISPR Therapeutics
Co-Chairwomens' Remarks
  • Cecilia Fernández, PhD - Director, Platform Development, Editas Medicine
  • Rubina Parmar, PhD - Director, Chemistry, Intellia Therapeutics
10:50am - 11:15am 25 mins
Info
mRNA Therapeutics and CRISPR Therapeutics
CRISPR/Cas Lipid Nanoparticle Formulations Optimized for Delivery and In Vivo Gene Editing
  • Christopher Cheng, PhD - Associate Director Formulation Technology Development, Casebia Therapeutics

Lipid nanoparticles (LNPs) are a robust and effective technology for delivering nucleic acids to the liver, including multi-component systems that use both mRNA and gRNA for gene editing. However, typical mRNAs used for expressing Cas9 are complex with large RNA payloads. Here we have engineered a library of novel Cas9 nucleases (smCas9) with improved performance compared to other Cas9 endonucleases, such as SpCas9, when formulated as mRNA into LNPs. We believe that the small size (~3.5 kb) of smCas9 mRNA confers a packaging advantage into LNPs compared to SpCas9 mRNA (~4.4 kb). When evaluated in vivo in rodent, numerous smCas9-LNPs showed comparable or higher editing efficiency to SpCas9-LNPs—even at equimolar doses. Toward understanding the mechanism for these LNP delivery improvements, cryoTEM analysis of smCas9-LNPs showed improved LNP morphology and physicochemical characteristics, which suggest a better quality LNP formulation with smaller payloads. Interestingly, smCas9-LNPs also showed enhanced particle stability compared to SpCas9-LNPs; smCas9-LNPs were less prone to aggregation over time and retained in vivo potency significantly longer than SpCas9-LNPs. Over the same storage conditions, a ~70% drop in editing efficiency was observed with SpCas9-LNPs whereas a potency drop as low as ~20% was observed with smCas9-LNPs. Overall, these novel smCas9-LNPs represent an improved CRISPR/Cas delivery system with potent in vivo gene editing performance and enhanced particle stability

11:15am - 11:45am 30 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
Small Activating RNAs – An Innovative Platform for Gene Activation
  • David Blakey, PhD - Chief Scientific Officer, MiNA Therapeutics

Small activating RNAs are short double strand oligonucleotides that lead to specific upregulation of target mRNA and protein. Pre-clinical in vitro and in vivo examples will be presented to illustrate the versatility of this approach for gene activation.

11:15am - 11:45am 30 mins
Info
Oligonucleotide Chemistry Manufacturing and Controls
Applications of Hydrophilic Interaction Chromatography (HILIC) to Oligonucleotides
  • Zach Parsons, PhD - Research Scientist II, Nitto Denko Avecia, Inc.

Hydrophilic interaction chromatography (HILIC) is a variant of normal phase chromatography which has traditionally garnered far less attention than reverse phase methods for oligonucleotide separations. Critically, HILIC offers differential selectivity to that of ion pair reverse-phase (IPRP) methods for oligonucleotides and conjugates thereof, and HILIC mobile phases are typically comprised of volatile components, thus retaining MS compatibility. As structures of oligonucleotide therapeutics (ONTs) have recently exploded in complexity due to modifications to the oligo backbone, sugar, and nucleobase moieties, as well as the introduction of oligonucleotide conjugates, analytical methods are increasingly challenged to deliver target specificity. Achieving target specificity is critical for purity/impurity profiling in process control, material release, and sample stability applications. Furthermore, in some instances, ‘traditional’ IPRP methods may not be suitable to achieve target specificity due to properties intrinsic to an ONT structure. In such cases, HILIC represents a particularly powerful alternative to IPRP chromatography. This work provides insight from such a case, where IPRP methods failed to achieve target specificity due to the unusually hydrophobic character of an ONT and related impurities, but separation by the HILIC mechanism was successful. Additionally, these efforts aimed at better understanding of the fundamental retention and separation mechanisms that are operative during HILIC-based separations of ONTs and related impurities

11:15am - 11:45am 30 mins
Info
Peptide Discovery, Preclinical and Clinical
Epitope Targeted Protein Catalyzed Capture Agents
  • Heather Agnew, PhD - Vice President R&D Operations, Indi Molecular

Protein catalyzed capture agents (PCCs) are synthetic, macrocyclic peptides designed to bind to specific regions (epitopes) of protein targets with antibody-like performance. Applications range from displacing antibody-dominated techniques in both biological tools and in vitro diagnostics settings, to groundbreaking potential advances in molecular imaging and targeted therapeutics. A key strategy element is in situ click chemistry, which directs the selection of macrocyclic peptides that recognize a chosen site on a protein surface with high affinity and specificity while retaining the stability and chemical accessibility of synthetic compounds. Approaches for engineering cell permeability and for designing bivalent ligands are currently being explored. Because they are chemical constructs, PCCs are amenable to medicinal chemistry optimization and may be efficiently and selectively modified with radioisotopes, therapeutic functionalities, or other labels during the discovery process.

11:15am - 11:45am 30 mins
Info
Peptide Chemistry Manufacturing and Controls
Building Enzymatically Degradable Tissue Scaffolds with Thiol-ene Photo-click Polymer Chemistry: Development of Peptide Linkers for Biological Functionality, Chemical Reactivity, and Manufacturing Stability
  • Peter Mariner, PhD - Director of Wound Healing, Mosaic Biosciences

Mosaic Biosciences employs a proprietary photo-click chemistry to create degradable polymer matrices that can serve as provisional tissue scaffolds when placed into wound environments. A critical aspect of these polymer networks is that they are rationally designed, by the incorporation of enzymatically degradable peptide linkers, to break down and be replaced as cells from the surrounding tissues infiltrate the scaffold and deposit new tissue. The selection of appropriate peptide linkers relies on balancing peptide properties relating to biological functionality, chemical reactivity, and manufacturing stability. Sequence selection starts with identifying cleavage recognition sites that will render the final network susceptible to degradation to enzymes commonly found in wound environments (plasmin, matrix metalloproteinases, elastases, etc.). Amino acids that participate in Mosaic’s thiol-ene reactions are then added to the sequence to functionalize the peptide for matrix polymerizations. When solubility and stability issues are encountered, sequence modifications can be employed that make these peptide linkers suitable for scaled manufacturing and use in these polymer systems.

11:15am - 12:15pm 60 mins
mRNA Therapeutics and CRISPR Therapeutics
Panel Discussion: Optimizing Lipid Nanoparticles (LNPs) for Liver Delivery of CRISPR/Cas9
  • Manmohan Singh, PhD - VP, Pharmaceutical Sciences and Delivery Technology, Beam Therapeutics
11:45am - 12:15pm 30 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
Recent Progress in the Use of Targeted-Augmentation of Nuclear Gene Output (TANGO) for the Treatment of Genetic Diseases
  • Charles Allerson - Vice President Chemistry, Stoke Therapeutics

Stoke is developing antisense oligonucleotides that can be used to increase gene expression for the treatment of genetic diseases.  One such disease, Dravet Syndrome, is caused by mutations in the SCN1A gene which lead to haploinsufficiency of the voltage-gated sodium channel subunit NaV1.1.  We have identified oligonucleotides that significantly increase SCN1A mRNA and NaV1.1 protein in vivo and demonstrate robust efficacy in a mouse model of Dravet Syndrome.

11:45am - 12:15pm 30 mins
Info
Oligonucleotide Chemistry Manufacturing and Controls
Purge-based Risk Assessment for Solvent and Small Molecule Impurities Generated during Oligonucleotide Synthesis
  • Robert Gronke, PhD - Senior Principal Scientist, Technical Development, Biogen, Inc
  • Ben Andrews, Ph.D. - Scientific Investigator, GlaxoSmithKline

Through the European Pharmaceutical Oligonucleotide Consortium, a team of companies is exploring opportunities to justify the exclusion of small molecule impurities and solvents from release testing through the use of risk-based purge arguments. To support the theoretical purge arguments, spike and purge studies have been performed in different processes and by multiple companies.

11:45am - 12:15pm 30 mins
Peptide Discovery, Preclinical and Clinical
Challenges and Emerging Approaches in Peptide Phage Display and Its Application in Targeting Stem Cell Receptors
  • Rami Hannoush, PhD - Principal Scientist & Group Leader, Genentech
11:45am - 12:15pm 30 mins
Info
Peptide Chemistry Manufacturing and Controls
Drug Substance Dual Sourcing: a CMC Opportunity during Manufacturing Process Validation
  • Marc Constant, PharmD - Senior Director, CMC, NoNO Inc.

Too often during Drug Development, dual sourcing is considered a nice to have and a post approval change. Introducing a second manufacturing site in the CMC validation strategy is an opportunity to effectively prepare the drug substance supply chain incorporating technology transfer principles, risk and knowledge management and comparability studies to facilitate the review of the New Drug Application. But when is it appropriate to introduce the second site and what approaches should be considered? Should a complete validation data package be available? Should a comparability protocol be considered? And what about the associated Global Quality Control Strategy? Are differences acceptable between the 2 sites? What is the acceptable data submission package? These questions will be discussed in the context of our CMC drug substance development and validation strategy.

12:20pm - 12:50pm 30 mins
Info
Spotlight Presentations 1
Manufacturing of Oligonucleotide API Using Nucleotide Blockmers
  • Masanori Kataoka, Ph.D. - Chief Technical Officer, Shikoku Nucleic Acid Chemistry (S-NAC)

We have developed the new synthetic method for therapeutic oligonucleotides using segmental nucleotide units. Several-mers nucleotides were synthesized separatory and the target sequence was built via solution or solid phase synthesis. It can reduce time, cost and manpower on synthetic and purification steps and improve the yield and purity of desired products. We can introduce innovative manufacturing route of oligonucleotides.

12:20pm - 12:50pm 30 mins
Info
Spotlight Presentations 2
Comparison of Purification Strategy in Oligonucleotide API Manufacture: Chromatography and Desalting Processes
  • Kyeong Eun Jung, PhD - Senior Vice President Head of Oligo and R&D Division, ST Pharm

In order to determine a robust production route design, process efficiency and purity of oligonucleotide API are evaluated with different chromatographic methods including reverser-phase and anion exchange media. The following downstream processes such as desalting and concentration steps are also explored by applying ultrafiltration and precipitation technology. The overall production yield and impurity profiles of final oligonucleotides are to be compared in selection of production processes.

12:20pm - 12:50pm 30 mins
Info
Spotlight Presentations 3
Thermo Fisher Scientific Spotlight Presentation
12:20pm - 12:50pm 30 mins
Info
Spotlight Presentations 4
Hongene Scientific Briefing Presentation
12:50pm - 1:55pm 65 mins
Networking Luncheon in Poster and Exhibit Hall
1:55pm - 2:20pm 25 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
Reinventing Oligonucleotide Synthesis
  • Phil Baran, PhD - Professor, Scripps Research Institute

The 1955 demonstration by Lord Todd that dinucleotides could be constructed using P(V)-based chemistry was rapidly discarded with the advent of Carruthers pioneering phosphoramidate platform. This discovery revolutionized the field and enabled much of what we take for granted today in the oligonucleotide world. Our lab has been interested in reinvestigating whether the native P(V)-based chemistry that Nature uses in her approach has any place in mainstream oligonucleotide synthesis. This talk will focus on our latest strides in this area of inquiry.

1:55pm - 2:00pm 5 mins
Oligonucleotide Chemistry Manufacturing and Controls
Chairman’s Remarks
  • Claus Rentel, PhD - Executive Director, Analytical Development/QC, Ionis Pharmaceuticals, Inc.
1:55pm - 2:00pm 5 mins
Peptide Discovery, Preclinical and Clinical
Chairman’s Remarks
  • Rami Hannoush, PhD - Principal Scientist & Group Leader, Genentech
1:55pm - 2:00pm 5 mins
Peptide Chemistry Manufacturing and Controls
Chairman’s Remarks
1:55pm - 2:00pm 5 mins
Drug Delivery Innovations and Strategies
Chairman’s Remarks
  • Stephen Spagnol, PhD - Senior Scientist, Sterile Formulation Sciences, Johnson & Johnson
1:55pm - 2:00pm 5 mins
mRNA Therapeutics and CRISPR Therapeutics
Chairman's Remarks
2:00pm - 2:30pm 30 mins
Info
Oligonucleotide Chemistry Manufacturing and Controls
High Resolution Mass Spectrometry Enabled Sensitive Impurity Profiling and Structural Characterization of Oligonucleotides
  • Kui Yang, PhD - Chemist, CDER, US FDA

Comprehensive impurity analysis in synthetic oligonucleotides will be presented. The strategies to enhance analytical sensitivity of low-level oligonucleotide impurities include high resolution mass spectrometry coupled with chemical derivatization to modify charges, optimized modes of chromatography to balance separation and ion suppression, and ion mobility to add an additional dimension of separation.

2:00pm - 2:30pm 30 mins
Info
Peptide Discovery, Preclinical and Clinical
Peptide Drug Products: Formulation Development and Process Characterization to Inform Control Strategies
  • Suzanne D'Addio, PhD - Associate Principal Scientist, Merck & Co., Inc

The diversity of molecular properties and therapeutic sites of action for approved peptide products has resulted in peptides being formulated into a wide variety of drug product images, which include standard parenteral forms like solutions and lyophilized powders, complex parenteral formulations like combination products and sustained release formulations, and alternative routes of delivery including oral capsules and nasal sprays. Due to their intermediate size relative to small molecules and larger biologics, peptides exhibit assorted liabilities during formulation development and manufacturing related to their amino acid sequences, intended dosage form, and manufacturing process train. There is a growing appreciation across industry for the unique physical and chemical stability risks associated with traditional parenteral solution and lyophilized formulations. Excipients often can impact multiple drug product formulation attributes, sometimes in unpredictable ways, necessitating appropriate formulation characterization and data-driven decision making throughout development. This presentation will review the application of Quality by Design principles to the design and development of robust drug product formulations and manufacturing processes, including identifying and assessing quality risks in order to inform the design of process characterization studies and control strategies.

2:00pm - 2:30pm 30 mins
Info
Peptide Chemistry Manufacturing and Controls
New Engineering Tools for Peptide Synthesis: Prediction, Control and Automation to Boost Process Performances
  • Olivier Ludemann-Hombourger, PhD - Global Director Innovation and Strategy, PolyPeptide Group

This presentation will discuss the outcome of our latest innovation activities in both USP and DSP and show the impact on the process performance, the manufacturing cost and the process robustness.

2:00pm - 2:30pm 30 mins
Info
Drug Delivery Innovations and Strategies
Polymeric Architecture Affects Cellular and in vivo Delivery of Nucleic Acids and Genome Editing
  • Theresa Reineke, PhD - Distinguished McKnight University Professor, University of Minnesota

Polymers that assemble with nucleic acids into nanocomplexes (polyplexes) are have been widely examined for many fundamental biological and applied biomedical applications.  However, understanding the binding, encapsulation, and intracellular transport mechanisms and in vivo efficacy of these vehicles remains a major hurdle in their effective usage and translation. Here in, the synthesis and characterization of several cationic polymer vehicles will be presented that vary in charge density, hydrophilic composition (such as the presence of carbohydrates), architecture, and functionality. We show that polymer structure impacts the ability of the vehicle to bind and compact nucleic acids into polyplexes. We have performed extensive studies on various polymer structures to understand their in vitro/ex vivo (primary fibroblasts and induced pluripotent stem cells) and in vivo (mouse liver) performance as a function of polymer structure. We show that cellular and in vivo transgene delivery, expression, and toxicity is highly affected by polymer structure. In addition, polymer structure played a large role for in vivo tissue specific pDNA delivery to the mouse liver. The cellular internalization, trafficking pathways, and intracellular organelle colocalization were also highly affected by vehicle structure. We conclude that the presence and type of carbohydrates displayed on the polymeric vehicle determine in vivo delivery efficacy to the mouse liver and improve ex vivo delivery of CRISPR-Cas9. 

2:00pm - 2:30pm 30 mins
Info
mRNA Therapeutics and CRISPR Therapeutics
Successful Millimole gRNA Production & Highly Resolving Purity Test Methods
  • Joe Guiles, PhD - Head of Development, Agilent Technologies, Inc.

As CRISPR gene editing moves into the clinic from the research bench there is a need to bring forward scalable high-quality manufacturing and testing capability. This talk will focus on considerations that Agilent is using for achieving this goal and recent outcomes toward it. Including deca-millimole scale production outcome and interesting resolution properties of chromatographic purity methods.

2:20pm - 2:45pm 25 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
Biomimetic Chemistry of RNAi Therapeutics
  • Muthiah (Mano) Manoharan, PhD - Senior Vice President of Drug Discovery, Alnylam Pharmaceuticals, Inc.

The role of chemical modifications in translating the natural process of RNA interference (RNAi) to human therapeutics will be illustrated by using known modifications and novel chemical modifications. These modifications provide metabolic stability, cellular delivery, potency, safety and specificity to RNAi medicine.

2:30pm - 3:00pm 30 mins
Info
Oligonucleotide Chemistry Manufacturing and Controls
An Ion-Pair HPLC-UV-MS Methodology for Quality Control Analysis of Oligonucleotide Therapeutics
  • Carolyn Mazzitelli, PhD - Associate Director, Ionis Pharmaceuticals

An approach for testing oligonucleotide therapeutics in a quality control laboratory that employs ion-pair high performance liquid chromatography with UV and mass spectrometric detection (IP-HPLC-UV-MS) will be presented. In addition to summarizing the development and validation of the method, the recommended best-practices for implementing the method and approaches for troubleshooting common challenges will be covered. Finally, a comparison of the IP-HPLC-UV-MS method to alternative approaches will also be discussed.

2:30pm - 3:00pm 30 mins
Info
Peptide Discovery, Preclinical and Clinical
Development of Synthetic D-proteins

Speaker TBA, Reflexion Pharmaceuticals

2:30pm - 3:00pm 30 mins
Info
Peptide Chemistry Manufacturing and Controls
Commercial Manufacturing of Disulfide-Rich Peptides
  • Michael Pennington, PhD - Chief Scientific Officer, AmbioPharm Inc.

Peptides without some type of stabilizing element exist as an equilibrium between multiple conformational states. One of the principal means of stabilizing peptides in nature has been different cyclization motifs. The most common of these motifs is the disulfide bond. Peptides with less than 60 residues with multiple disulfide bonds are often referred to as “disulfide-rich peptides” (DRP). Examples of these peptides which have entered into clinical development and ultimately to commercially approved drug products include: insulin (multiple analogs), ziconotide (ω-conotoxin) , aprotinin (bovine pancreatic trypsin inhibitor), linaclotide I(heat-stable enterotoxin, plecanatide (Glu4-uroguanylin). Numerous other DRPs are in clinical development. These include: dalazatide (ShK peptide analog), tozuleristide (dye-labeled chlorotoxin), hepcidin and α-conotoxin RgIA. Commercial manufacturing of these peptide API’s requires a combination of a robust synthetic production which may involve total SPPS or a combination of hybrid methods as well as an optimized folding procedure to generate the desired disulfide bonding pattern. Ambiopharm’s approach to manufacturing of several examples of DRPs will be provided.

2:30pm - 3:00pm 30 mins
Drug Delivery Innovations and Strategies
Characterizing Lipid Nanoparticle Function to Inform on mRNA Vaccine Design
  • Marian Gindy, PhD - Executive Director, Pharmaceutical Sciences, Merck Research Laboratories
2:30pm - 3:00pm 30 mins
Info
mRNA Therapeutics and CRISPR Therapeutics
High Fidelity Chemically Synthesized Guide RNA for CRISPR Applications: Synthesis, Processing and Purity Analysis
  • John Walker II, PhD - Director of Chemistry Research, Synthego

Inconsistencies in guide RNA purity can significantly influence editing outcomes, and therefore differences between manufacturers or batch-to-batch variances should be accurately described and measured. We will discuss the chemical synthesis and processing of high-fidelity, full-length guide RNA. In addition, we describe the use of IP-HPLC and ESI-MS to provide quantitative and qualitative information on the synthesized guide RNA.

2:45pm - 3:10pm 25 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
Enhancing Therapeutic Profile of ASOs Using Gap-modifications
  • Punit Seth, PhD - Vice President, Medicinal Chemistry, Ionis Pharmaceuticals

Introducing chemical modifications in the DNA gap-region can enhance the therapeutic profile of gapmer ASOs. Results from our comprehensive structure activity relationships for evaluating gap-modifications including controlling PS-chirality will be presented.

3:00pm - 3:30pm 30 mins
Info
Oligonucleotide Chemistry Manufacturing and Controls
Selectivity in Ion-pairing Reversed Phase Liquid Chromatography of Oligonucleotides
  • Brian Trammell, PhD - Principal Scientist, Nitto Denko Avecia, Inc.

The selectivity of ion-pairing reversed phase liquid chromatographic separations is a complex subject with significant implications for the in-process, release and stability testing of oligonucleotide therapeutics.  Ion-pairing reversed phase chromatographic separations of oligonucleotides must separate the expected impurities inherent to the synthesis process, maintain compatibility with mass spectrometric detection and provide adequate separation and detection of possible degradants.  In this presentation, we will review and discuss a focused set of important chromatographic method variables explored to develop selective ion-pairing reversed phase methods for oligonucleotides.  

3:00pm - 3:30pm 30 mins
Info
Peptide Discovery, Preclinical and Clinical
Long-Acting Human Growth Hormone Analogue Somapacitan by non-Covalent Albumin Binding
  • Henrik Sune Ramírez-Andersen - Scientific Director, Novo Nordisk A/S

Identification of somapacitan, a long acting human growth hormone (hGH) analogue based on reversible non-covalent albumin binding was achieved using positional cysteine scan in combination with different albumin binders. In vitro and in vivo profiling provided the basis for establishing position L101C in hGH as the most optimal conjugation position when both sufficient receptor binding and half-life extension was to be attained.

3:00pm - 3:30pm 30 mins
Info
Peptide Chemistry Manufacturing and Controls
Peptide Manufacturing Scale-up Considerations
  • Robert Topping, PhD - Distinguished Scientist, Development Synthetic Chemistry, Corden Pharma Colorado

Peptide development and scale-up requires analysis of many different considerations: linear SPPS vs. solution phase vs. hybrid syntheses; protection group and coupling agent strategies; chromatography conditions; lyophilization vs. precipitation, etc. CordenPharma has made a business of assessing and resolving these issues as they apply to various peptide products at manufacturing scale. We will present the pros and cons of the types of decisions that need to be addressed to help you and your organization prepare for the scale-up phase of your program.

3:00pm - 3:30pm 30 mins
Info
Drug Delivery Innovations and Strategies
Optimization of Novel Polymeric Delivery Vehicles by Chemical Evolution
  • Ernst Wagner, Ph.D. - Professor and Chair, Pharmaceutical Biotechnology,, Ludwig Maximilans University

Chemical evolution for optimizing synthetic drug delivery carriers includes identification of delivery motifs (e.g. artificial amino acids), their assembly into defined sequences by solid phase synthesis, screening and selection for a defined cargo (nucleic acid, protein, Cas9/sgRNA) followed by carrier sequence variation and next selection round.

3:00pm - 3:30pm 30 mins
mRNA Therapeutics and CRISPR Therapeutics
Evaluating Genome Editing Specificity with CRIPSR/CAS9 and CPF1
  • Eugenio Marco, PhD - Senior Scientist, Computational Biology, Editas Medicine
3:10pm - 3:30pm 20 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
From Stereopurity to Precision Medicine: Optimizing the Properties of Antisense Nucleic Acid Therapeutics
  • Chandra Vargeese, Ph.D - SVP, Head of Drug Discovery, WAVE Life Sciences

Wave Life Sciences has developed proprietary synthetic chemistry and manufacturing capabilities that we are using to design and produce stereopure antisense oligonucleotides (ASOs) for patients with serious, genetically defined disease. In our evaluation of ASOs that promote RNase H-mediated activity or exon-skipping activity, we have explored the relationships among sequence space, chemical modification and backbone stereochemistry to optimize their pharmacological properties. We have discovered a relationship between the molecular configuration of our ASOs and their activity. We will present data from multiple programs that illustrate how our chemistry platform allows us to optimize ASOs for mechanism (e.g., gene knockdown or splicing), properties in vitro and in vivo, and distribution to an array of tissues.

3:30pm - 4:15pm 45 mins
Networking Refreshment Break in Poster and Exhibit Hall
4:15pm - 4:35pm 20 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
From Rectal Solution to Oral Capsule: Life Cycle Management of Cobitolimod, a Novel Immunomodulatory Oligonucleotide for Local Treatment of Active Ulcerative Colitis.
  • Christine Dieterich Johansson, Ph.D. - Senior Project Manager CMC and Pre-clinical, InDex Pharmaceuticals

Cobitolimod as a rectal solution is undergoing a randomized, double-blind and placebo-controlled phase IIb study in patients with moderate to severe active ulcerative colitis. As a follow-on product, InDex has developed a pH-sensitive oral capsule for colon-targeted delivery of cobitolimod.

4:15pm - 4:45pm 30 mins
Info
Oligonucleotide Chemistry Manufacturing and Controls
Control of Impurities for siRNA Therapeutics
  • Matthias Kretschmer, PhD - Senior Director Analytical Sciences, Alnylam Pharmaceuticals

This presentation will explain the general approach for control of impurities for siRNA therapeutics. Control of impurities for Onpattro, the first approved siRNA therapeutic, follows a tiered approach using manufacturing stage appropriate methods designed for individual single strands, siRNA (duplex) drug substance and final (lipid nano particle) drug product. Based on the quality attributes tested, methods are of orthogonal nature and assess impurities both as specified groups as well as individually.

4:15pm - 4:45pm 30 mins
Info
Peptide Discovery, Preclinical and Clinical
Reimagining Drug Discovery: How Artificial Intelligence Can Balance the Return on Research Investment and Fuel New Peptide Discoveries
  • Nora Khaldi, PhD - Founder and Chief Scientific Officer, Nuritas Ltd.

Nuritas was established in 2014 to revolutionise the discovery of new bioactive peptides with increased chance of preventing and/or modifying diseases in current areas of medical unmet need. Nuritas is a hybrid TechBio preclinical discovery company, that converges the power of artificial intelligence and traditional ‘omic’ sciences to discover entirely new and patentable bioactive peptides across a range of disease areas in combination with industry partners. Nora will discuss the benefits of artificial intelligence with real practical case studies that demonstrate that AI can deliver new bioactive drugs that exhibit desired bioactive properties in man at significantly reduced cost and time.

4:15pm - 4:45pm 30 mins
Info
Peptide Chemistry Manufacturing and Controls
Reimagining Drug Discovery: How Artificial Intelligence Can Balance the Return on Research Investment and Fuel New Peptide Discoveries
  • Nora Khaldi, PhD - Founder and Chief Scientific Officer, Nuritas Ltd.

Nuritas was established in 2014 to revolutionise the discovery of new bioactive peptides with increased chance of preventing and/or modifying diseases in current areas of medical unmet need. Nuritas is a hybrid TechBio preclinical discovery company, that converges the power of artificial intelligence and traditional ‘omic’ sciences to discover entirely new and patentable bioactive peptides across a range of disease areas in combination with industry partners. Nora will discuss the benefits of artificial intelligence with real practical case studies that demonstrate that AI can deliver new bioactive drugs that exhibit desired bioactive properties in man at significantly reduced cost and time.

4:15pm - 4:45pm 30 mins
Info
Drug Delivery Innovations and Strategies
mRNA Vaccination with Charge-altering Releasable Transporters Elicits Human T cell Responses and Cures Established Tumors in Mice
  • Robert Waymouth, PhD - Robert Eckles Swain Professor of Chemistry, Stanford University

We report a new class of delivery vectors (Charge Altering Releasable Transporters, CARTs) that complex, protect, deliver and dynamically release mRNA and pDNA in cells and animals. Selective and efficient uptake into lymphocytes and can be used to generate an immune response that can cure mice with established tumors.

4:15pm - 4:45pm 30 mins
Info
mRNA Therapeutics and CRISPR Therapeutics
Novel Cas12a mutants with improved activity and expanded PAM recognition domains.
  • Mark Behlke, M.D., Ph.D. - Chief Scientific Officer, Integrated DNA Technologies, Inc.

Cas12a (Cpf1) is a Class 2 CRISPR-Cas endonuclease with a T-rich PAM recognition domain (TTTV) whose utility has been limited by variable cleavage efficiency across all predicted PAM sites.  We report here an As Cas12a mutant with markedly improved cleavage efficiency and an expanded PAM recognition domain of TTTN.

4:35pm - 5:00pm 25 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
Preclinical and Clinical Development of AST-008, A Toll-like Receptor Agonist 9 Spherical Nucleic Acid for Immuno-oncology Applications
  • Weston Daniel , PhD - Senior Director of Program Management, Exicure, Inc.

Exicure, Inc. is developing a toll-like receptor 9 (TLR9) agonist oligonucleotide-containing nanoparticle called AST-008. Drug discovery and development efforts by Exicure revolve around the use of spherical nucleic acid (SNA) constructs, which are 3-dimensional arrangements of oligonucleotides where the nucleic acids are densely packed and radially oriented. When arranging oligonucleotides in this way, properties arise that are distinct from “linear” oligonucleotides (i.e., oligonucleotides not arranged in the SNA format). Most importantly, oligonucleotides arranged in the SNA geometry exhibit increased cellular uptake when compared to linear nucleic acids. A Phase 1 clinical trial of AST-008 in healthy volunteers indicated that AST-008 did not elicit dose limiting toxicity, was well tolerated, produced a dose dependent T-helper 1 type cytokine response, and activated natural killer and T cells. This presentation will describe the development of AST-008, the non-clinical toxicology program and results, the Phase 1 clinical trial and its results, and the ongoing Phase 1b/2 trial.

4:45pm - 5:15pm 30 mins
Info
Oligonucleotide Chemistry Manufacturing and Controls
Experiences as Commercial Release Lab for Oligonucleotides
  • Susann Rosmus, PhD - Head of Quality Management, BioSpring GmbH


This talk will focus on BioSpring´s experience as a release lab for a commercialized oligonucleotide. It will cover our experience with FDA-inspections, drug product release methods (especially LC-MS) and  further requirements.

4:45pm - 5:15pm 30 mins
Info
Peptide Discovery, Preclinical and Clinical
The Orally Available Clinical Stage All-D-enantiomeric Peptide PRI-002 Reverses Cognition Deficits and Decelerates the Neurodegeneration Phenotype in Transgenic Alzheimer’s Disease Mouse Models
  • Dieter Willbold, Ph.D. - Director, ICS-6 Structural Biochemistry, Forschungszentrum Jülich, Germany

PRI-002 proved to eliminate already formed, toxic Aβ oligomers and to reverse cognitive deficits even in old-aged transgenic Alzheimer’s disease (AD) mice with full blown pathology and deficits, even by oral administration. PRI-002 is fully blood-brain-barrier penetrable and demonstrated successful target engagement. I will summarize successful in vivo proof-of-concept in four treatment studies in three different transgenic animal models in three different laboratories. I will report first clinical data for PRI-002.

4:45pm - 5:15pm 30 mins
Info
Peptide Chemistry Manufacturing and Controls
The Orally Available Clinical Stage All-D-enantiomeric Peptide PRI-002 Reverses Cognition Deficits and Decelerates the Neurodegeneration Phenotype in Transgenic Alzheimer’s Disease Mouse Models
  • Dieter Willbold, Ph.D. - Director, ICS-6 Structural Biochemistry, Forschungszentrum Jülich, Germany

PRI-002 proved to eliminate already formed, toxic Aβ oligomers and to reverse cognitive deficits even in old-aged transgenic Alzheimer’s disease (AD) mice with full blown pathology and deficits, even by oral administration. PRI-002 is fully blood-brain-barrier penetrable and demonstrated successful target engagement. I will summarize successful in vivo proof-of-concept in four treatment studies in three different transgenic animal models in three different laboratories. I will report first clinical data for PRI-002.

4:45pm - 5:15pm 30 mins
Info
Drug Delivery Innovations and Strategies
Rapidly Identifying Nanoparticles for Non-hepatocyte RNA Delivery by Testing Thousands in vivo Using DNA Barcodes
  • James Dahlman, PhD - Assistant Professor, Biomedical Engineering, Georgia Institute of Technology and Emory Medical School

Chemists can design thousands of nanoparticles to deliver RNA. However, after nanoparticles are synthesized, they are tested with in vitro systems without a liver, kidney, spleen, immune system, pulsatile blood flow, or other factors that affect nanoparticle delivery in vivo. To test thousands of nanoparticles in vivo, we designed a series of increasingly advanced DNA barcoding platforms. We can quantify how over 200 nanoparticles functionally deliver mRNA or siRNA into up to 30 cells from a single mouse. Since 2016, we have generated nearly 200,000 in vivo drug delivery data points, and developed a customized bioinformatics pipeline to iteratively ‘evolve’ nanoparticles that target new cell types in the spleen, liver, and bone marrow.

4:45pm - 5:15pm 30 mins
Info
mRNA Therapeutics and CRISPR Therapeutics
sgRNA Plate-Based Synthesis For In Vitro CRISPR Screening
  • Michelle Young, PhD - Senior Scientist, Intellia Therapeutics

Chemically synthesized 100mer single guide RNAs (sgRNAs) have demonstrated superior editing in comparison to two-piece crRNA-tracrRNA complexes and in vitro transcription derived guides. Here we present the development of high-throughput plate-based synthesis of sgRNAs with improved sequence quality and fidelity, for in vitro screening efforts.

5:00pm - 5:25pm 25 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
Intrathecal Delivery of siRNA Conjugates Leads to Robust and Durable Silencing in the Central Nervous System
  • Stuart Milstein, PhD - Associate Director, Alnylam Pharmaceuticals

Diseases of the CNS represent some of the highest unmet medical need and greatest therapeutic challenges, though accessing this tissue effectively has been a challenge. Our recent work, with conjugated, stable siRNAs enables intrathecal delivery that yields robust silencing across CNS. We demonstrate that a single IT dose of conjugated siRNA in rats and NHP leads to sustained silencing of target transcripts throughout the brain and spinal cord.

5:15pm - 5:45pm 30 mins
Oligonucleotide Chemistry Manufacturing and Controls
Late Breaking Presentation
5:15pm - 5:45pm 30 mins
Peptide Discovery, Preclinical and Clinical
Progress in the Development of Peptide Therapeutics for Unmet Medical Needs
  • Mark Smythe, PhD - Founder and Vice President, Protagonist Therapeutics
5:15pm - 5:45pm 30 mins
Peptide Chemistry Manufacturing and Controls
Progress in the Development of Peptide Therapeutics for Unmet Medical Needs
  • Mark Smythe, PhD - Founder and Vice President, Protagonist Therapeutics
5:15pm - 5:45pm 30 mins
Info
Drug Delivery Innovations and Strategies
Characterizing the Therapeutic Application of messenger RNA-lipid Nanoparticles
  • Ying Tam, Ph.D. - Chief Scientific Officer, Acuitas Therapeutics, Inc.

Acuitas is developing lipid nanoparticle systems (LNP) to efficiently deliver and express mRNA via different routes of administration. Recent studies have developed a deeper understanding of immune activation, a primary clinical safety factor, including detailed cytokine/chemokine expression profiles for various payloads. We are also exploring other strategies including systemic mRNA-LNP expression after local administration to achieve the convenience of subcutaneous administration while still providing efficient liver expression and targeted mRNA-LNP systems.

5:15pm - 5:45pm 30 mins
Info
mRNA Therapeutics and CRISPR Therapeutics
Synthesis and Characterization of High Purity gRNAs for CRISPR-based Therapeutics
  • Stacy Capehart, PhD - Scientist II, Editas Medicine

In RNA synthesis, errors are introduced to the desired sequence at each coupling step. These errors propagate as the synthesis proceeds, negatively effecting the 5’ fidelity for guide RNAs (gRNAs). In this talk, we describe our approach to producing gRNAs with high sequence fidelity in the 5’ region of the gRNA. We will discuss the synthesis, construction, and characterization of high purity gRNAs for use in CRISPR-based therapeutics.

5:25pm - 5:45pm 20 mins
Info
Oligonucleotide Discovery, Preclinical and Clinical
DTx Pharma: Leveraging Fatty Acids as Targeting Ligands to Enable Delivery of RNA Medicines Beyond the Liver
  • Arthur Suckow, PhD - CEO and CSO, DTx Pharma

The biggest obstacle limiting the expansion of RNA as a therapeutic class is delivery--cells do not effectively take up siRNA and siRNAs are rapidly cleared by the kidney and liver following systemic administration. DTx technology leverages lipidation, the covalent conjugation of fatty acids to siRNA, to address these challenges. These fatty acids serve as targeting ligands that potently promote cellular uptake and markedly enhance pharmacokinetics to safely and effectively enable the activity of RNA medicines in tissues beyond the liver.

5:45pm - 6:45pm 60 mins
Networking Refreshment Break in Poster and Exhibit Hall