SESSIONS TIDES Europe: Oligonucleotide and Peptide · robust identity or meaningful functional...

Workshop Moderator’s Opening Remarks

08:00 - 08:15Workshop 2: Analytical Strategies and Technologiesfor Peptide Therapeutics

Participants

Vivian Lindo - Associate Director, Analytical Sciences,AstraZeneca

Analytical Characterization Tools for PeptideTherapeutics Physical Stability


Participants

Ana Santos - Principal Scientist, Formulations,Principal Scientist, Formulations

Managing CMC Activities to AccelerateOligonucleotide Development andManufacturing

08:30 - 09:45Workshop 1: Managing CMC Activities to AccelerateOligonucleotide Development and Manufacturing

Workshop Description:

This half-day pore-conference workshop will addressearly to mid-phase drug development and related CMCfor oligonucleotide therapeutics. A detailed discussionon oligonucleotide therapeutics moving fromdiscovery to clinical trials will be presented in form ofcase studies. This includes strategies for early clinicalCMC development; early phase CMO work; GMPmanufacturing; and the regulatory framework aroundthese activities. Workshop attendees will be allowed15 minutes open discussion after each presentation todeepen or clarify the presentations.

Who should attend?

Anyone interested in early to mid-stage developmentof oligonucleotide therapeutics; Anyone interested inoutsourcing the manufacturing of oligonucleotidetherapeutics to a CMO / CRO. This includes R&DResearchers, Manufacturing Personnel, QualityAssurance, Project Management, BusinessDevelopment and Scientific Management.

Participants

Workshop Moderator:: Thomas Rupp - Owner &Principal, Thomas Rupp Consulting, Germany

Development and Validation of a PeptideBioassay


Developed and validated biological assays provide arobust identity or meaningful functional potencymeasure, and are increasingly requested for syntheticpeptides. Biological assays must be fit for a specifictarget, although many such assays have somecommon ground, such as statistical rigor to mitigatethe inherent variability of biological systems. Thispresentation discusses our experience with biologicalassays as GMP release tests, using a GLP-1 peptideagonist as an example.

Participants

Michael Postlethwaithe, Ph.D - Business DevelopmentManager, Bachem AG

Understanding the 3-D structures of a Peptideto Determine the Control Strategy forBiological Activity


A variety of analytical techniques were employed togain insight to the higher order structures of asynthetic peptide. Based on the understanding gained,regulatory insight and bioassay stability data, nobiological activity test was deemed necessary on thedrug product specification. This position has beenapproved by regulatory authorities.

Participants

Mark Drew - Business Programme Lead, AstraZeneca

Networking Refreshment Break

09:45 - 10:15

Managing CMC Activities to AccelerateOligonucleotide Development andManufacturing

10:15 - 12:00Workshop 1: Managing CMC Activities to AccelerateOligonucleotide Development and Manufacturing

Workshop Description:

This half-day pore-conference workshop will addressearly to mid-phase drug development and related CMCfor oligonucleotide therapeutics. A detailed discussionon oligonucleotide therapeutics moving fromdiscovery to clinical trials will be presented in form ofcase studies. This includes strategies for early clinicalCMC development; early phase CMO work; GMPmanufacturing; and the regulatory framework aroundthese activities. Workshop attendees will be allowed15 minutes open discussion after each presentation todeepen or clarify the presentations.

Who should attend?

Anyone interested in early to mid-stage developmentof oligonucleotide therapeutics; Anyone interested inoutsourcing the manufacturing of oligonucleotidetherapeutics to a CMO / CRO. This includes R&DResearchers, Manufacturing Personnel, QualityAssurance, Project Management, BusinessDevelopment and Scientific Management.

Participants

Thomas Rupp - Owner & Principal, Thomas RuppConsulting, Germany

Peptide Oligomers – Friends or Enemies?


Peptides offer enormous growth potential as futuretherapeutics and are recognized as being highlyselective and efficacious. Due to their size, theygenerally have flexible structures and many have apreference for self-assembly. We will present how toinvestigate peptide structures in liquid formulations,with a focus on the ability to self-assemble as bothstable structures and undesired higher orderaggregates.

Participants

Lise Giehm, Ph.D - Principal Scientist, Zealand PharmaA/S

Late Breaking Presentation


Panel Discussion with Workshop Speakers


SESSIONSOPTIONAL PRE-CONFERENCE WORKSHOPS - 12/11/2019

TIDES Europe: Oligonucleotide and PeptideTherapeutics

12-15 November 2019RAI Amsterdam

Amsterdam, Netherlands

+1-949-276-2634 lifesciences.knect365.com/tides-europe/ [email protected]

Close of Workshop

12:00 - 12:05


13:00 - 13:15Workshop 3: Drug Product Development Strategies forOligonucleotides and Peptides

Participants

Stefan Vonhoff - Vice President CMC, NOXXONPharma AG


13:00 - 13:15Workshop 4: Accelerating Oligonucleotide and PeptideDrug Development

Participants

Mimoun Ayoub, PhD - Director and Head of NorthAmerican and Emerging Markets, CordenPharmaInternational

Optimization of Novel Polymeric DeliveryVehicles by Chemical Evolution


Chemical evolution for optimizing synthetic drugdelivery carriers includes identification of deliverymotifs (e.g. artificial amino acids), their assembly intodefined sequences by solid phase synthesis, screeningand selection for a defined cargo (nucleic acid, protein,Cas9/sgRNA) followed by carrier sequence variationand next selection round.

Participants

Ernst Wagner, Ph.D. - Professor and Chair,Pharmaceutical Biotechnology,, Ludwig MaximilansUniversity

Stage Appropriate CMC Overview andRequirements for a Robust Dossier


Participants

Mimoun Ayoub, PhD - Director and Head of NorthAmerican and Emerging Markets, CordenPharmaInternational

Investigations into Disruptive DeliveryApproaches for LNA AntisenseOligonucleotides (ASO LNA)


Parenteral or intrathecal administration of antisenseoligonucleotides (ASO) have enabled treatment of liverand CNS based diseases, respectively, thanks to theinherent high exposure of the ASO in these tissues. Toextend the possible scope of indications to treat withASO, we looked at feasibility concepts to deliver ASOLNA into tissues where exposure with unformulatedASO LNA generally is insufficient for PD effect.

Participants

Dr. Michael Keller, Ph.D. - Senior Principal Scientist,pRED, pCMC, Roche

CMC Technical and Regulatory Strategies forDevelopment of Peptides and Oligonucleotides


Many factors guide the development pathways takento meet drug demands and the regulatoryrequirements of a peptide or oligonucleotide. Keyfactors include: Finance, Support, Clinical Phase,Geography. I will overview the factors that influenceCMC development of “tides” and strategies to keep theprogram successful when faced with obstacles.

Participants

Gary Musso, PhD - President, Musso and AssociatesLLC

Oligonucleotide Drug Product (Development)for (Ultra) Orphan Ophthalmic Diseases


Oligonucleotide drug product (DP) development for(ultra) orphan ophthalmic diseases can be challengingfrom a formulation, primary packaging andmanufacturing point of view. This presentation willelaborate on some of the challenges related tointravitreal (IVT) administered products, such asendotoxin and sub-visible particle specifications of DP.Also, considerations for dose accuracy, and the use of(prefilled) syringes will be discussed. Additionally, thispresentation will include the possibility of terminalsterilization for oligonucleotide-based products.

Participants

Vera Brinks - Director, Pharmaceutics, ProQRTherapeutics

Scale-up Peptide Manufacturing Case Study:Transition from Solid-phase to Liquid PhaseSynthesis


Participants

Bruce Morimoto, PhD - Vice President, DrugDevelopment Operations, Alkahest


14:45 - 15:15

Challenges for Peptides Drug Products at theInterface of Formulation, Primary Packagingand Application


Participants

Stephanie Lemoult, PhD - Senior Principal Scientist-Team Leader, Formulation, Lonza AG

Drug Product Development andIndustrialization for Peptides and Oligos: ACDMO Perspective


This presentation will provide a CDMO perspective onthe challenges, the requirements and the technologiesneeded for the successful formulation, processdevelopment and industrialization of oligonucleotideand peptide-based drug products.

Participants

Umberto Romeo - R&D Manager, Corden Pharma






Formulation Development and Device Optionsfor the Subcutaneous Injection of SpiegelmerDrug Product Solution


For pegylated oligonucleotides, concentration andviscosity of the drug product solution are keyparameters influencing the choice of devices suitablefor subcutaneous self-administration. Data from aformulation development study aiming to reduce theviscosity of the pegylated Spiegelmer solution will bepresented. Stability, compatibility and feasibility of theoptimized drug product solution were evaluated in arange of devices. Conclusions for the furtherdevelopment of the drug product/device combinationwill be discussed.

Participants

Stefan Vonhoff - Vice President CMC, NOXXONPharma AG





Panel Discussion with Workshop Speakers


Concluding Remarks and Discussion


Close of Workshops

17:00 - 17:05






TIME WORKSHOP 1: MANAGING CMC ACTIVITIES TOACCELERATE OLIGONUCLEOTIDE DEVELOPMENTAND MANUFACTURING

WORKSHOP 2: ANALYTICAL STRATEGIES ANDTECHNOLOGIES FOR PEPTIDE THERAPEUTICS

WORKSHOP 3: DRUG PRODUCT DEVELOPMENTSTRATEGIES FOR OLIGONUCLEOTIDES AND PEP-TIDES

WORKSHOP 4: ACCELERATING OLIGONU-CLEOTIDE AND PEPTIDE DRUG DEVELOPMENT

08:00 08:30 - Managing CMC Activities to AccelerateOligonucleotide Development and Manufactur-ing

08:00 - Workshop Moderator’s Opening Re-marks

08:15 - Analytical Characterization Tools forPeptide Therapeutics Physical Stability

08:45 - Development and Validation of a Pep-tide Bioassay

09:00 09:45 - Networking Refreshment Break 09:15 - Understanding the 3-D structures of aPeptide to Determine the Control Strategy forBiological Activity

09:45 - Networking Refreshment Break

09:45 - Networking Refreshment Break 09:45 - Networking Refreshment Break

10:00 10:15 - Managing CMC Activities to AccelerateOligonucleotide Development and Manufactur-ing

10:15 - Peptide Oligomers – Friends or Ene-mies?

10:45 - Late Breaking Presentation

11:00 11:15 - Panel Discussion with Workshop Speak-ers

12:00 12:00 - Close of Workshop 12:00 - Close of Workshop 12:00 - Close of Workshop 12:00 - Close of Workshop

13:00 13:00 - Workshop Moderator’s Opening Re-marks

13:15 - Optimization of Novel Polymeric Deliv-ery Vehicles by Chemical Evolution

13:45 - Investigations into Disruptive DeliveryApproaches for LNA Antisense Oligonu-cleotides (ASO LNA)

13:00 - Workshop Moderator’s Opening Re-marks

13:15 - Stage Appropriate CMC Overview andRequirements for a Robust Dossier

13:45 - CMC Technical and Regulatory Strate-gies for Development of Peptides and Oligonu-cleotides

SCHEDULEOPTIONAL PRE-CONFERENCE WORKSHOPS - 12/11/2019

TIDES Europe: Oligonucleotide and Peptide Therapeutics12-15 November 2019

RAI AmsterdamAmsterdam, Netherlands


TIME WORKSHOP 1: MANAGING CMC ACTIVITIES TOACCELERATE OLIGONUCLEOTIDE DEVELOPMENTAND MANUFACTURING

WORKSHOP 2: ANALYTICAL STRATEGIES ANDTECHNOLOGIES FOR PEPTIDE THERAPEUTICS

WORKSHOP 3: DRUG PRODUCT DEVELOPMENTSTRATEGIES FOR OLIGONUCLEOTIDES AND PEP-TIDES

WORKSHOP 4: ACCELERATING OLIGONU-CLEOTIDE AND PEPTIDE DRUG DEVELOPMENT

14:00 14:45 - Networking Refreshment Break 14:45 - Networking Refreshment Break 14:15 - Oligonucleotide Drug Product (Develop-ment) for (Ultra) Orphan Ophthalmic Diseases


14:15 - Scale-up Peptide Manufacturing CaseStudy: Transition from Solid-phase to LiquidPhase Synthesis


15:00 15:15 - Challenges for Peptides Drug Productsat the Interface of Formulation, Primary Packag-ing and Application

15:45 - Formulation Development and DeviceOptions for the Subcutaneous Injection ofSpiegelmer Drug Product Solution

15:15 - Drug Product Development and Industri-alization for Peptides and Oligos: A CDMO Per-spective


16:00 16:15 - Late Breaking Presentation

16:45 - Concluding Remarks and Discussion

16:15 - Panel Discussion with Workshop Speak-ers

17:00 17:00 - Close of Workshops 17:00 - Close of Workshops 17:00 - Close of Workshops 17:00 - Close of Workshops

SCHEDULEOPTIONAL PRE-CONFERENCE WORKSHOPS - 12/11/2019




Exhibit Viewing and Coffee in Poster andExhibit Hall

07:30 - 08:10

Chairperson's Remarks

08:10 - 08:15Keynote/Plenary Session

Opening the Central Nervous System for RNAi-based Modulation


RNAi enables simple and specific modulation of geneexpression when the chemical architecture supportingefficient in vivo delivery is defined. Using huntingtin –the causative gene in Huntington’s Disease – as amodel, we demonstrate that chemically engineeredsiRNAs induce potent protein silencing (> 99%) in allbrain regions tested one month post injection.Silencing persists for at least six months with thedegree of gene modulation correlating to the level ofthe guide strand tissue accumulation. Opening thecentral nervous system for RNAi-based modulation ofgene expression establishes a path toward thedevelopment of new cures for genetically definedneurodegenerative disorders.

Participants

Anastasia Khvorova, PhD - Professor, RNATherapeutics Institute and Program in MolecularMedicine, University of Massachusetts Medical School

Linkers for Peptide Conjugation


Conjugation, understood as the linking of twomoieties, which may be in the same or in a differentmolecule, is an effective chemistry approach to createnew entities with synergistic properties. The keyfactor is the linker. Herein, we will present severallinkers useful for the preparation of cyclic and branchpeptides and peptide and antibody drug conjugates aswell.

Participants

Fernando Albericio, PhD - Department of OrganicChemistry, University of Barcelona

Networking Refreshment Break in Poster andExhibit Hall


mRNA Vaccines and Therapeutics: FromPromise to Reality


Participants

Hari Pujar, PhD - Vice President, TechnicalDevelopment and Manufacturing, ModernaTherapeutics

Development of Delivery Systems forBiopharmaceuticals within the IMI COMPACTConsortium: Results and Lessons Learned


COMPACT, an IMI sponsored public-private partnershipbetween 23 academic groups, SMEs andpharmaceutical companies has collectively worked onthe delivery issues of biopharmaceuticals in the period2012-2017. Besides making and testing novel drugdelivery systems optimized to meet the demands forcrossing specific biological barriers (e.g. blood-brainbarrier, intestinal barrier, air-to-lung barrier as well asintracellular barriers), new tools and complex in vitromodels were developed. In this presentation, I willhighlight some of the achievements and discusslessons learned after 5 years COMPACT.

Participants

Enrico Mastrobattista, PhD - Professor ofPharmaceutical Biotechnology and Delivery, UtrechtUniversity

Antisense for a Billion People: TheDevelopment of RNA-based Therapy forElevated Lipoprotein(a)


Elevated Lp(a) (>50 mg/dL or >125 nmol/L) isestimated to be present in 1.4 billion people. ElevatedLp(a) is associated with cardiovascular disease andaortic stenosis. Due to its high plasma levels andhepatocyte origin, Lp(a) can only be effectivelytargeted by inhibiting its synthesis using RNAtherapeutics. The development of an antisensestrategy in reducing Lp(a) plasma levels will bereviewed from pre-clinical models to phase 3 clinicaltrials powered to evaluate cardiovascular eventreduction.

Participants

Sotirios Tsimikas, M.D. - Vice President of GlobalCardiovascular Development, Ionis Pharmaceuticals

Transition to Spotlight Presentation Rooms


Guiding RNA Formulations from Laboratoryinto Clinical Trials. Lessons Learned fromDevelopment and Optimization of LiposomalFormulations

12:00 - 12:30Sponsored Spotlight Presentation 1

Over the past few years liposomal drug preparationshave been increasingly used in clinical trials. Until now,several liposomal products have reached the market,many other formulations are still in the pipeline. For allthese products, simple, economic and GMP-conformproduction techniques and facilities are necessary.Here, several points to consider already at the stage ofprocess and product transfer to the CMO should belisted. Product development at early stage shouldimplement the use of high-quality raw materials,robust and stable product and process conditions androbust analytical methods. The whole system shouldbe implemented in a robust QA system. Furthermore,the production system should be designed to allowscalable and sterile manufacturing. In addition, itshould meet several requirements, such as simplicity,robustness and easy handling of sterilisationprocedures. Furthermore, the modified ethanolinjection technique itself is distinguished by mildpreparation conditions and the avoidance ofhazardous solvents and forces, which may disruptlipids as well as entrapped substances. Data will bepresented, which describe impact of processconditions on the generated particle size andhomogeneity. A few examples of drug products andrelated processes will be shown, where special focuswill be set on influencing particle size and sizedistribution by varying the process parameters of thePolymun liposome technology.

Participants

Andreas Wagner - Head of Liposome Technology,Polymun Scientific GmbH

ZEOsphere DRP Mixed-Mode forOligonucleotide Purification


Participants

Victoria Custodis - Team Leader R&D, Zeochem AG

Intertek Briefing


SESSIONSMAIN CONFERENCE DAY 1 - 13/11/2019




A Single-Use Solution to Bulk TrayLyophilization of Polypeptide andOligonucleotide Therapeutics


A recent survey of CMOs specializing in the synthesisand purification of polypeptide and oligonucleotidetherapeutics indicates that operator safety andelimination of stainless steel tray cleaning arepriorities for these manufacturers. These needs, aswell as others, will be discussed within the context ofbulk tray lyophilization. Information on a disposablesingle-use lyophilization tray, which provides bothisolation and containment of the contents in the tray,will be shared.

Participants

Scott Ross - Global Product Specialist, W.L. Gore &Associates

Networking Luncheon in Poster and ExhibitHall

12:30 - 13:50

Chairman’s Remarks

13:50 - 14:00Oligonucleotide Discovery, Preclinical and Clinical

Participants

Troels Koch, PhD - Vice President and Head ofResearch, RNA Therapeutics, Roche pRED, RocheInnovation Center Copenhagen


13:50 - 14:00Oligonucleotide Chemistry, Manufacturing andControls

Participants

Nadim Akhtar, PhD - Principal Scientist, AstraZeneca


13:50 - 14:00Peptide Discovery, Preclinical and Clinical

Participants

Rami Hannoush, PhD - Principal Scientist & GroupLeader, Genentech

Chairman's Remarks

13:50 - 14:00Peptide Chemistry, Manufacturing and Controls

Participants

Neil Thompson - Senior Director, BusinessDevelopment Europe, PolyPeptide Group

Machine Learning-guided Design of AntisenseOligonucleotides


Antisense oligonucleotides are particularly suited formachine learning-guided drug design. As oligomers,they can be easily represented digitally, and anypredicted sequence is straightforward to synthesizeusing standard phosphoramidite building blocks.Recent examples, enabled by careful organization andlabeling of preclinical datasets across multiplediscovery projects, will be presented.

Participants

Peter Hagedorn - Senior Principal Scientist, GroupLeader, Roche Innovation Center Copenhagen A/S

Characterization of Raw Materials for theManufacturing of Oligonucleotides


Raw materials are key sources for a number ofimpurites found in oligonucleotides. Therefore, thecontrol of raw materials and especially of potentialreactive or critial by-products are mandatory to obtaina high level of batch to batch reproducibility. Thispresentation will summarize general analyticalmethods for the characterization and control of rawmaterials. Moreover, it will focus on some reactivecomponents found in phosphoramidites as well as insome other raw materials.

Participants

Huseyin Ayguen - Chief Scientific Officer, BioSpring

Early Implementation of Appropriate Studies toIdentify Preclinical Liabilities is Key to Successin Peptide Drug Discovery


An appropriate screening strategy was implemented tosupport peptide drug discovery programs. Thispresentation will cover valuable studies necessary toaddress specific issues in peptide development suchas sub cutaneous and plasma metabolism with invitro/in vivo correlation to optimize bioavailability;potential peptide-induced pseudo-allergic reactions;immunogenicity and aggregation/oligomerizationtendencies.

Participants

Federica Orvieto - Senior Research Investigator,Peptide Chemistry, IRBM Science Park SPA

Gly-His Tag Acylation for N-terminal ChemicalModification of Proteins


Site-selective modification of proteins is highlydesirable for the controlled introduction of smallprobes like biotin or larger moieties such as PEG. Werecently reported the development of a new His tag,Gly-His3-6, for highly selective N-terminal acylation.New extensions of this method are presented. Finally,a new linker strategy for the synthesis of C-terminallypeptides and the use of automated high-performanceflash chromatography for the purification of thepeptides in this project will be discussed.

Participants

Knud Jensen, Ph.D - Professor, Department ofChemistry, University of Copenhagen

Novel Chemistries for RNAi Therapeutics


Participants

Muthiah (Mano) Manoharan, PhD - Senior VicePresident of Drug Discovery, Alnylam Pharmaceuticals,Inc.

Purge-based Risk Assessment for Solvent andSmall Molecule Impurities Generated duringOligonucleotide Manufacture


Through the European Pharmaceutical OligonucleotideConsortium, a team of companies is exploringopportunities and generating supporting data to justifythe exclusion of small molecule impurities andsolvents from release testing through the use of riskbased purge arguments. To support the theoreticalpurge arguments, spike and purge studies have beenperformed in different processes and by multiplecompanies.

Participants

Ben Andrews, Ph.D. - Scientific Investigator,GlaxoSmithKline





Developability and Preformulation of Peptides


When new peptide drug candidates are identified, it iskey to assess their suitability to be successfullydeveloped as stable drug products for the intendedroute of administration. An approach to assess andcompare several peptide drug candidates prior toentering Development from Research will be presentedand examples given.

Participants

Jette Boll - Senior Research Scientist, FerringPharmaceuticals

Improving Peptide Manufacturing and ProcessPerformance


Over the last few years, a multidisciplinaryorganization has been set up to better understand andcontrol peptide synthesis, merging the skills ofexperienced peptide chemists with the tools ofchemical engineers and the devices of advancedcontrol experts. These tools are combining decades ofexperience with a fundamental study of solid phasechemistry (modelling approach). The outcome of thisstudy is now put into practice and is combined withAdvanced Control Technologies, to offer a new way ofmanufacturing peptides.

Participants

Olivier Ludemann-Hombourger, PhD - Global DirectorInnovation and Strategy, PolyPeptide Group

Gap Modifications Improve Therapeutic Indexof Gapmer ASOs


Introducing chemical modifications in the DNA gap-region can enhance the therapeutic profile of gapmerASOs. Results from our comprehensive structureactivity relationships for evaluating gap-modificationsincluding controlling PS-chirality will be presented.

Participants

Michael Oestergaard - Research Fellow, IonisPharmaceuticals

Deeper Understanding of Separation of Nativeand Phosphorothioated Oligonucleotides andTheir Impurities Using Ion-pair Reversed PhaseChromatography


Separation of oligonucleotides were fundamentallystudied. Diastereomer separation was controlled bychoosing the right ion-pairing reagent and stationaryphase. Phosphorothioated oligonucleotides could bepurified at high purity and yield using appropriateconditions, due to the displacement of impurities.Here, the phenyl column showed better resultscompared to the alkyl columns.

Participants

Dr. Martin Enmark - Researcher, Karlstad University

Emerging Approaches in Peptide DrugDiscovery and Their Applications in TargetingProtein-Protein Interactions


This talk will describe our group's efforts indiscovering and optimizing peptide-based scaffoldsand will highlight some of the challenges and noveltechnologies for peptide lead identification anddevelopment. A case study on a peptide antagonistwith a unique mode of inhibition will be discussed.

Participants

Rami Hannoush, PhD - Principal Scientist & GroupLeader, Genentech

Ultra-fast Development and Optimization ofLarge-Scale Peptide Manufacturing Processes


This presentation will discuss data related to how wedevelop a manufacturing process in large scale byadapting a continuous approach and implementationof DoE and QbD enabling multivariate optimizations ina single manufacturing run. It will describe how we run30 large scale peptide manufacturing developmentruns in 4 weeks. The presentation will contain lots ofnovel experimental data with high scientific andregulatory impact, none of which has been presentedbefore.

Participants

Jens Bukrinski - Head of R&D, SB3000 Ltd.


15:30 - 16:00

Control of Backbone Stereochemistry Providesa New Dimension for the Optimization ofOligonucleotide Drug Candidates


Participants

Dr. Meiling Li - Scientist, Hoffmann-La Roche

Strategies for Identity Testing ofOligonucleotide Therapeutics


Due to their large size and polymeric nature,establishing identity of oligonucleotide therapeutics issignificantly more challenging compared to syntheticsmall molecules. Techniques such as molecularweight conformation and retention time matching thatare commonly employed and readily accepted forsmall molecules are generally deemed insufficient foridentity confirmation of the oligonucleotide. Thispresentation will discuss various risk factors duringmanufacturing process that can potentially lead to anoligonucleotide of an incorrect structure, along withcurrently available analytical methods that can detectdifferent structural changes. A risk-based frameworkfor the selection of identity tests and how it can beintegrated into a robust control strategy will beproposed.

Participants

Nadim Akhtar, PhD - Principal Scientist, AstraZeneca

Development of the Stable, Fast ActingGlucagon Analogue NN9513 for ClinicalTesting


The stable glucagon analogue NN9513 to be used in aprefilled ready-to-use device was developed. Nativeglucagon has poor physical and chemical stability somajor improvements of stability were required.Introduction of glutamic acid moieties on thesidechain of position 24 increased physical stabilitydramatically. Several amino acid substitutions wererequired to achieve the required chemical stability. Invitro and preclinical in vivo PK and PD data will also bepresented.

Participants

Jesper F. Lau, PhD - Scientific Director, ResearchChemistry, Novo Nordisk A/S





Development of New Multicolumn Processesand the Presentation of a New Concept with aSingle Column


Participants

Jose Paolo Mota - Professor, Chemical & BiochemicalEngineering, Universidade NOVA de Lisboa

Introduction of Non-chiral Phosphorodithioatesinto Locked Nucleic Acids


With the recent launches of chemically modifiedoligonucleotides, RNA therapeutics have clearlydemonstrated their medical benefit. Particularlyphosphorothioates have been extensively profiled andcover most of the clinically investigated entities.However the complexity of diastereoisomers haveresulted in the great challenges in understanding thePK/PD of stereomixed oligonucleotides. Introductionof non-chiral phosphorodithioates dramaticallyreduces the diastereomeric complexity. As we areconstantly developing our LNA platform, potential nextgeneration analogues have been identified, showingvery promising drug properties. Here we will report ourlatest observations of backbone modified LockedNucleic Acids with a particular focus on non-chiralphosphorodithioate modifications, including stereo-defined internucleoside linkages. Several strategieshow to rapidly identify highly potent one singlephosphorothioate LNA isomer will be discussed andmedicinal chemistry aspects highlighted, supported byrecent in vitro and in vivo data.

Participants

Dr. Chandra Vargeese, PhD - SVP, Head of DrugDiscovery, WAVE Life Sciences

Phase Appropriate Method ValidationStrategies for Antisense Oligonucleotides withAccelerated Product Development Timelines


Antisense oligonucleotides (ASOs) often target raredisease indications with unmet medical need leadingto expedited product development timelines.Balancing clinical phase-appropriate practices with therequirements of readiness for commercial licensurecan be challenging. An overall strategy for managinganalytical method validation over the productdevelopment lifecycle from R2D to commercial isproposed. Case studies for phase appropriateanalytical method validation of expedited programswill be presented.

Participants

Stacey Traviglia, Ph.D. - Associate Director, QCAnalytical Technology, Biogen

Outer Membrane Targeting Antibiotics(OMPTA): Preclinical and Clinical Developmentof a Novel Class of Antibiotics against Life-threatening Gram-negative Infections


The presentation will focus on the discovery anddevelopment of the OMPTA class of antibiotics totreat life-threatening Gram-negative infections.Murepavadin has entered phase III trials and is the firstrepresentative of the OMPTA class, whereaspreclinical stage POL7306 is a medium-spectrumantibiotic with potent activity against all WHO priority 1Gram-negative pathogens including MDR, XDR, andcolistin-resistant pathogens.

Participants

Dr. Anatol Luther - Head of Chemistry, Polyphor Ltd

Continuous Chromatography of SyntheticPeptides


The current modus operandi for the downstreamprocessing of synthetic peptides is reversed phasechromatography performed in batch mode.Multicolumn Countercurrent Solvent GradientPurification (MCSGP) is expected to be a disruptivetechnology for this very cost intensive part of syntheticpeptide manufacturing. Results from continuouspeptide purifications will be presented and comparedto traditional batch chromatography. Potentialimplementation strategies for this technology will bediscussed.

Participants

Ralf Eisenhuth, PhD - Process Manager TechnologyTransfer and Chromatography, Bachem AG

Secarna’s LNAplusTM ASOs for Treatment ofCancer and Kidney Disease


Secarna has developed a proprietary platform toidentify highly active and well-tolerated LNA-modifiedantisense oligonucleotides. Preclinical data will bepresented showing antitumor activity of ASOstargeting the immunosuppressive tumormicroenvironment. Furthermore, efficacy of ASOstargeting an endoplasmatic reticulum stress factor isshown in an in vivo model of diabetic nephropathy.

Participants

Dr. Frank Jaschinski - CSO, Secarna Pharmaceuticals

Panel Discussion with Session Speakers


Participants

Moderator:: Nadim Akhtar, PhD - Principal Scientist,AstraZeneca

Development of Novel Peptide Therapeutics


Participants

Efrat Halbfinger, PhD - Senior Director of Chemistry,BioLineRx Ltd.

Panel Discussion with Session Speakers


Participants

Neil Thompson - Senior Director, BusinessDevelopment Europe, PolyPeptide Group

Close of Sessions

18:00 - 18:05

Attendee Networking Reception Event at TheBoat House at Strandzuid

18:05 - 19:35





TIME KEYNOTE/PLENARYSESSION

OLIGONUCLEOTIDECHEMISTRY, MANU-FACTURING ANDCONTROLS

OLIGONUCLEOTIDEDISCOVERY, PRE-CLINICAL ANDCLINICAL

PEPTIDE CHEM-ISTRY, MANUFAC-TURING AND CON-TROLS

PEPTIDE DISCOV-ERY, PRECLINICALAND CLINICAL

SPONSORED SPOT-LIGHT PRESENTA-TION 1




07:00 07:30 - ExhibitViewing and Coffeein Poster and Ex-hibit Hall

07:30 - ExhibitViewing and Coffeein Poster and Ex-hibit Hall








08:00 08:10 - Chairper-son's Remarks

08:15 - Opening theCentral NervousSystem for RNAi-based Modulation

08:50 - Linkers forPeptide Conjuga-tion

09:00 09:25 - NetworkingRefreshment Breakin Poster and Ex-hibit Hall

SCHEDULEMAIN CONFERENCE DAY 1 - 13/11/2019













10:00 10:10 - mRNA Vac-cines and Thera-peutics: FromPromise to Reality

10:45 - Develop-ment of DeliverySystems for Bio-pharmaceuticalswithin the IMICOMPACT Consor-tium: Results andLessons Learned

11:00 11:20 - Antisensefor a Billion People:The Developmentof RNA-based Ther-apy for ElevatedLipoprotein(a)

11:55 - Transitionto Spotlight Pre-sentation Rooms














12:00 12:30 - NetworkingLuncheon in Posterand Exhibit Hall

12:30 - NetworkingLuncheon in Posterand Exhibit Hall




12:00 - GuidingRNA Formulationsfrom Laboratory in-to Clinical Trials.Lessons Learnedfrom Developmentand Optimizationof Liposomal For-mulations


12:00 - ZEOsphereDRP Mixed-Modefor OligonucleotidePurification


12:00 - IntertekBriefing


12:00 - A Single-Use Solution toBulk TrayLyophilization ofPolypeptide andOligonucleotideTherapeutics


13:00 13:50 - Chairper-son's Remarks

13:50 - Chairman’sRemarks

13:50 - Chairman'sRemarks

13:50 - Chairper-son's Remarks

14:00 14:00 - Characteri-zation of Raw Ma-terials for the Man-ufacturing ofOligonucleotides

14:30 - Purge-based Risk Assess-ment for Solventand Small Mole-cule ImpuritiesGenerated duringOligonucleotideManufacture

14:00 - MachineLearning-guidedDesign of Anti-sense Oligonu-cleotides

14:30 - NovelChemistries forRNAi Therapeutics

14:00 - Gly-His TagAcylation for N-terminal ChemicalModification ofProteins

14:30 - ImprovingPeptide Manufac-turing and ProcessPerformance

14:00 - Early Imple-mentation of Ap-propriate Studies toIdentify PreclinicalLiabilities is Key toSuccess in PeptideDrug Discovery

14:30 - Developa-bility and Preformu-lation of Peptides














15:00 15:30 - NetworkingRefreshment Breakin Poster and Ex-hibit Hall

15:00 - Deeper Un-derstanding of Sep-aration of Nativeand Phosphoroth-ioated Oligonu-cleotides and TheirImpurities UsingIon-pair ReversedPhase Chromatog-raphy

15:30 - NetworkingRefreshment Breakin Poster and Ex-hibit Hall

15:00 - Gap Modifi-cations ImproveTherapeutic Indexof Gapmer ASOs


15:00 - Ultra-fastDevelopment andOptimization ofLarge-Scale Pep-tide ManufacturingProcesses


15:00 - EmergingApproaches in Pep-tide Drug Discoveryand Their Applica-tions in TargetingProtein-Protein In-teractions






16:00 16:00 - Strategiesfor Identity Testingof OligonucleotideTherapeutics

16:30 - Phase Ap-propriate MethodValidation Strate-gies for AntisenseOligonucleotideswith AcceleratedProduct Develop-ment Timelines

16:00 - Control ofBackbone Stereo-chemistry Providesa New Dimensionfor the Optimiza-tion of Oligonu-cleotide Drug Can-didates

16:30 - Introduc-tion of Non-chiralPhospho-rodithioates intoLocked NucleicAcids

16:00 - Develop-ment of New Multi-column Processesand the Presenta-tion of a New Con-cept with a SingleColumn

16:30 - ContinuousChromatography ofSynthetic Peptides

16:00 - Develop-ment of the Stable,Fast ActingGlucagon AnalogueNN9513 for ClinicalTesting

16:30 - Outer Mem-brane Targeting An-tibiotics (OMPTA):Preclinical andClinical Develop-ment of a NovelClass of Antibioticsagainst Life-threatening Gram-negative Infections














17:00 17:00 - Panel Dis-cussion with Ses-sion Speakers

17:00 - Secarna’sLNAplusTM ASOsfor Treatment ofCancer and KidneyDisease

17:00 - Panel Dis-cussion with Ses-sion Speakers

17:00 - Develop-ment of Novel Pep-tide Therapeutics

18:00 18:00 - Close ofSessions

18:05 - AttendeeNetworking Recep-tion Event at TheBoat House atStrandzuid

18:00 - Close ofSessions




















Sponsored Breakfast Spotlight Presentation

08:00 - 08:40

Syngene Briefing



Global Development Programme of RG6042, anAntisense Oligonucleotide, for the Treatmentof Huntington’s Disease


RG6042 is an antisense oligonucleotide in clinicaldevelopment designed to lower HTT proteinproduction by selectively targeting HTT mRNA. In aPhase I/IIa study, RG6042 safely lowered CSF mutantHTT (mHTT) in early Huntington’s disease (HD),prompting Roche to begin a Global DevelopmentProgramme (GDP). Roche’s GDP will provide valuableinformation on the clinical benefit and safety ofRG6042, as well as further longitudinal evidence of thecausal role of mHTT in disease progression.

Participants

Scott Schobel - Associate Group Medical Director, F.Hoffman-La Roche Ltd.

Plants as Biofactories for Producing Peptide-based Pharmaceuticals


We are using crop plants as expression systems forthe production of pharmaceutically active cyclicpeptides. This presentation will give an overview onthe biosynthesis and applications of cyclic peptidesand describe the use of tobacco, Arabidopsis andpetunia plants in as vehicles for the production ofpeptide-based drug leads for cancer, cardiovasculardisease and pain.

Participants

David Craik, PhD - Professor of BiomolecularStructure, Institute for Molecular Bioscience, Universityof Queensland

Regulatory Quality and CMC Perspectives onmRNA Vaccines and Peptide VaccineAdjuvants


mRNA vaccines are an ever-increasing newsupplement to existing conventional vaccines. Theyare easy to manufacture, yet pose some CMCchallenges regarding functional characterization andstability. As expressed proteins and peptides arefrequently not sufficiently immunogenic bythemselves, adjuvants are needed in their formulation.Hence, Major CMC aspects for novel adjuvants will beaddressed.

Participants

Dr. Ralf Wagner - Head Section Viral Vaccines, Paul-Ehrlich-Institut


10:15 - 10:55

A Case Study of Concurrent Global RegulatoryFilings for Two Oligonucleotides

10:55 - 11:25Regulatory Strategies for Oligonucleotides andPeptides

A case study will be presented that compares thesubmitted module 3 content for two similaroligonucleotide drugs. Significant differences betweenthe dossiers will be detailed in combination withregulatory agency feedback relevant to thedifferences. An evaluation of the success of eachapproach will be presented, and how learnings fromthe case study may inform future filing strategies.

Participants

Jennifer Franklin - Director, CMC Regulatory Affairs,Ionis Pharmaceuticals

Experience with Early and Late Phase GlobalSubmissions of Oligonucleotide-basedProducts


Oligonucleotides are a relatively new class of drugswith the potential to treat a wide spectrum ofindications with a wide variety of therapeuticapproaches. The number of companies that includedoligonucleotides into their portfolio significantlyincreased in the last years, as well as the number ofapprovals of therapeutic medicines containingoligonucleotides. Most of these oligonucleotide-basedmedicines are approved in the major markets (EU, US,JP). However, there is still limited experience in termsof global regulatory expectations for this type ofproducts. We would like to present an overview of themajor topics that were raised from various HAs duringearly phase and late phase submissions.

Participants

Cinzia Gazziola - Technical Regulatory AffairsManager, Hoffmann-La Roche

Peptide Regulatory Strategies and Experiences


Speaker TBA

Participants

Peter Larsson - Global Director Regulatory Affairs,PolyPeptide Group







Mass-Production of Target RNA byMicroorganism


Recently, functional RNA and its application to nucleicacid-based drugs attract lots of attention. It isindispensable to produce the target RNA molecules ofinterest at low cost and in large-scale throughbiological production system. It seems that theconventional production of recombinant RNAs usingmainly E. coli are not sufficient in the productivity andthe stability of the production system that can copewith mass-production of recombinant RNA of interest.In this study, we have developed a fundamentalsystem of efficient production for target RNAmolecules in our microbial strain, Corynebacteriumglutamicum. Using the system, we will present somesuccessful instances of production of RNAs whichcould be active pharmaceutical ingredients for nucleicacid-drugs. Thus, our system will be able to serve asan efficient platform for preparation of RNAs ofinterest in large amounts.

Participants

Shuhei Hashiro - Research Scientist, Ajinomoto Co.,Inc.

Quantification of Selected Impurities inOligonucleotides


The quantification of oligonucleotide related impuritiesis commonly performed based on UV260nm. In somecases, the separation of certain impurities by liquidchromatography is not possible or the specificimpurity has no sufficient UV absorbance. To quantifyand monitor such impurities, alternative proceduresand detectors are needed. This presentation providesan overview of possible approaches to quantifyoligonucleotide related impurities, focusing especiallyon but not limited to the quantification by massspectrometry.

Participants

Huseyin Ayguen - Chief Scientific Officer, BioSpring

Precision Nanosystems Briefing


Changing the Tide in Peptides - PeptidePurification and Modification with Beylntic’sCatch-and-Release Technology


Peptide purification along the pharmaceutical valuechain becomes more and more challenging due torising demands for difficult peptides, chemical peptidemodification or high-throughput missions. Belyntic hastaken that challenge and has developed Peptide EasyClean (PEC), a novel Catch-and-Release technology forthe parallel purification of chemically synthesizedpeptides. As a truly orthogonal method tochromatography, PEC represents a new purificationtool for the difficult cases, while also allowing theconcurrent introduction of chemical modifications tothe peptides of interest.

Participants

Oliver Reimann, PhD - Co-Founder, Belyntic GmbH

Networking Luncheon in Poster and ExhibitHall

13:00 - 14:25

Co-Chairpersons' Remarks


Participants


Dmitry Samarsky, PhD - Chief Technology Officer,Sirnaomics



Participants





Participants

Bruce Morimoto, PhD - Vice President, DrugDevelopment Operations, Alkahest




14:25 - 14:30mRNA Therapeutics and CRISPR Therapeutics

Overcoming Extra- and Intracellular Barriers:Polymer-based mRNA Delivery Systems


Messenger RNA has long been considered toounstable to be a valuable tool for cell transfection. Thishas limited the interest in its application for a longtime. In recent years, however, it has become clear thatthere are ways to cope with this instability by showingthat complex formation with cationic lipids orpolymers provides effective protection of mRNAagainst degradation. CureVac has developed andoptimized its own versatile delivery platform (CureVacCarrier Molecule – CVCM), which can be tailored todeliver therapeutic mRNAs to different organs andtissues. We have established a broad range of in vitroand in vivo assays allowing the identification ofsuitable formulations for broad range of applications.Here we report on a panel of mRNA formulations,which were tested for their efficacy to transfect cells inthe lung and the eye.

Participants

Dr. Joanna Rejman - Associate Director Neurologicand Pulmonary Diseases, CureVac AG

Overcoming Extra- and Intracellular Barriers:Polymer-based mRNA Delivery Systems


Messenger RNA has long been considered toounstable to be a valuable tool for cell transfection. Thishas limited the interest in its application for a longtime. In recent years, however, it has become clear thatthere are ways to cope with this instability by showingthat complex formation with cationic lipids orpolymers provides effective protection of mRNAagainst degradation. CureVac has developed andoptimized its own versatile delivery platform (CureVacCarrier Molecule – CVCM), which can be tailored todeliver therapeutic mRNAs to different organs andtissues. We have established a broad range of in vitroand in vivo assays allowing the identification ofsuitable formulations for broad range of applications.Here we report on a panel of mRNA formulations,which were tested for their efficacy to transfect cells inthe lung and the eye.

Participants

Dr. Joanna Rejman - Associate Director Neurologicand Pulmonary Diseases, CureVac AG





Therapeutic Peptide Review and EmergingPeptide Science


This session will provide an overview of the peptidetherapeutic landscape, based on our comprehensivedataset of peptides that have entered human clinicalstudies. We will also highlight some emergingpeptides from Ferring’s discovery programs.

Participants

Michael Dunn - Senior Director, Ferring ResearchInstitute

APL-2 Drug Substance: Development of aCommercial Generation 2 Process


Participants

Najib Maslouh, PhD - Vice President of Manufacturing,Technical Operati, Apellis Pharmaceuticals

Inhibition and Degradation of Drug TargetsUsing bioPROTAC mRNAs – A Novel Approachwith Broad Therapeutic Potential


To tackle historically intractable targets, we arepursuing ‘bioPROTACs’, targeted-degradation fusionconstructs composed of I) mini-proteins/peptides withhigh-affinity against therapeutic targets linked to II)truncated E3 ligase receptors. Provided that the mini-protein’s binding affinity is below mid-nanomolar, itsfold and target interaction site is flexible with efficientdegradation achieved with monobodies, nanobodies,DARPins, αREPs and peptides. Similarly, there isflexibility for the truncated E3 protein with effectiveexamples across several E3 classes. Coupled withmRNA delivery, bioPROTACs have several distinctadvantages as a potential therapeutic modalityincluding inhibit & degrade pharmacology, specificityagainst post-translation modifications, leveraging ofdisease-relevant E3s, employment of tissue-specificmRNA self-destruct sequences, and the potential toboost neoantigens. So far, the bioPROTAC approachhas been broadly successful with active constructsagainst several targets with rapid and robustdegradation activity across multiple cell lines.Currently, we are working towards in vivo delivery ofbioPROTAC mRNAs via lipid nanoparticles.Prerequisite in vitro experiments with a bioPROTACagainst proliferating cell nuclear antigen (PCNA)showed robust degradation and proliferation/apoptoticeffects in a variety of cancer cell lines. Detailedstudies in HepG2 cells showed degradation of PCNA,just 4 hours post-dosing and with just 100 pM mRNA.

Participants

Anthony Partridge, PhD - Principal Scientist, EarlyDiscovery Pharmacology, Merck, Sharp & Dohme

Extra-hepatic Delivery


Alnylam Speaker TBA

Extra-hepatic Delivery


Alnylam Speaker TBA

Biopharmaceutical Properties ofPeptide:polyethylene Glycol SupramolecularAssemblies


We demonstrate non-covalent PEGylation of acylatedtherapeutic peptides as a strategy to circumventpotential loss of potency upon covalent conjugation,while maintaining a significant improvement insolubility, long term stability, and bioavailabilityfollowing subcutaneous injection. The approach isamenable to both liquid and solid state peptideformulation strategies. In silico molecular modelling ofthe complexation between acylated peptide and PEG-cholane has directed analytical method developmenttowards characterisation of physical quality attributessuch as peptide:PEG molar stoichiometry, structure,aggregation and fibrillation.

Participants

Christopher van der Walle - Director, Fellow,Biopharmaceutical Development, MedImmune Ltd.

Development of Long Contiguous OverlappingPeptides for Ultra-Fast Allergy Immunotherapy


Contiguous Overlapping Peptides (COPs) basedvaccine provide a novel tool for allergenimmunotherapy (AIT). COPs are long syntheticpeptides, reproducing fragments of the aminosequence of a selected major allergen(s). Thepresentation reviews the production, analysis,characterization and formulation of Bet v1 COP, themajor allergen in birch pollen.

Participants

Vanya Beltrami - VP, Head of Manufacturing, AnergisSA

TriMix Based mRNA Immunotherapies


TriMix, a mixture of mRNAs that encodes CD40L, CD70and caTLR4 has been specifically designed to enhancethe interaction of DCs with T cells. In combination withmRNA encoding tumor-associated antigens (TAAs),TriMix acts as an adjuvant that enhances the TAA-specific T cell response. The magnitude and functionalcharacteristics of T cell responses elicited by TriMixbased mRNA vaccines are governed by the complexinterplay between route of administration, the deliveryvehicle applied and the intrinsic properties of themRNA.

Participants

Stefaan De Koker, Ph.D - Non-clinical PrincipleScientist and site-Director, eTheRNA

Targeted Delivery of AntisenseOligonucleotides to Extra-hepatic Tissues


Previous work targeting liver hepatocytes has shownlarge enhancement in potency and multiple GalNAcconjugated ASOs are making their way through clinicaltrials. To expand of this success, we have investigatedvarious strategies to improve delivery and potency inextra-hepatic tissues. Herein will be discussedtargeting approaches and mechanisms of ASOdelivery to specific tissues.

Participants


Targeted Delivery of AntisenseOligonucleotides to Extra-hepatic Tissues


Previous work targeting liver hepatocytes has shownlarge enhancement in potency and multiple GalNAcconjugated ASOs are making their way through clinicaltrials. To expand of this success, we have investigatedvarious strategies to improve delivery and potency inextra-hepatic tissues. Herein will be discussedtargeting approaches and mechanisms of ASOdelivery to specific tissues.

Participants






Engineered Amphiphilic Peptides EnableDelivery of Protein and CRISPR Cargoes toCells


Among biologic cargoes, proteins offer promise butare limited by a lack of efficient delivery methods. Wedeveloped amphiphilic peptides that enable robustdelivery of proteins to cells by a simple co-incubation.These carrier peptides are optimized to deliverpeptides, antibodies and CRISPR ribonucleoproteincomplex to cells, including hard-to-modify NaturalKiller cells and airway epithelia.

Participants

David Guay, PhD - Research Director, FeldanTherapeutics

Peptide CMC Lessons Learned


Speaker TBA

mRNA Therapeutic Development


Participants

Dr. Amy Rabideau, Ph.D. - Senior Scientist, Moderna


16:00 - 16:30



Participants





Participants

Jurgen Machielse - Business Development DirectorSpherical Gels, Zeochem AG



Participants

Jurgen Machielse - Business Development DirectorSpherical Gels, Zeochem AG



Strategies for the Delivery of Nucleic AcidTherapeutics


Efficient delivery of nucleic acid therapeutics isessential to afford potent, safe products. Deliverystrategies differ depending on the nature of the nucleicacid payload and the intended therapeutic use. Thispresentation will review Genevants delivery platformsfor oligonucleotides and mRNA in hepatic andextrahepatic applications.

Participants

Peter Lutwyche, PhD - Chief Technology Officer,Genevant Sciences Corporation

Complete Enzyme Catalysed OligonucleotideSynthesis: From Single Nucleotides to FinalProduct


In order to address the challenges of large scaleoligonucleotide synthesis, namely scalability,sustainability and cost, we are developing an enzymecatalysed approach to oligonucleotide manufacture.Short oligonucleotides are synthesized from simple

nucleotide based starting materials using enzymes byadding nucleotides sequentially. The shortoligonucleotides are subsequently assembled in asingle templated convergent step to generate the finalproduct oligonucleotide. This assembly and productseparation eliminates all chromatography from theprocess. All processes are run in aqueous solutionimproving both scalability and sustainability. Theconvergent approach improves overall process yieldswhile the templating removes impurities such as ‘N-1’sequences from the final product.

Participants

Martin Olbrich, Ph.D - Process Chemist, F Hoffmann-La Roche Ltd.

When Upstream Meets DownstreamProcessing: It Takes Two to Have an EfficientManufacturing Process


Process development is often considered a stand-alone activity. This is not the case for most projects. Inthis presentation, Bachem will discuss processdevelopment in the context of new chemical entityprojects from phase I up to commercialization of thedrug substance.

Participants


When Upstream Meets DownstreamProcessing: It Takes Two to Have an EfficientManufacturing Process


Process development is often considered a stand-alone activity. This is not the case for most projects. Inthis presentation, Bachem will discuss processdevelopment in the context of new chemical entityprojects from phase I up to commercialization of thedrug substance.

Participants


Messenger RNA Therapeutics for PrimaryCiliary Dyskinesia


Primary ciliary dyskinesa (PCD) is a geneticallyheterogenous hereditary disease syndrom originatingfrom mutations in genes encoding proteins which areeither essential for ciliogenesis or are structural/functional parts of cilia. The dysfunction of motile ciliaresults in a reduced mucociliary clearance andconsequently recurrent lung infections, which can leadto chronic destructive lung disease withbronchiectasis and progressive lung failure.Challenges in pulmonary delivery of mRNA will bediscussed and proof of concept data for mRNAtranscript therapy for PCD will be presented.

Participants

Christian Plank, PhD - Chief Technology Officer, EthrisGmbH





Chemo-enzymatic Peptide Synthesis; PeptideChain Length Becomes Less Relevant


The peptiligase technology platform has beensuccessfully applied in the synthesis of medium sizedpeptide-based therapeutics like Exenatide, Thymosin-a1 and Liraglutide. It has been shown that synthesisyields could be improved by 20-30% compared toSPPS due to the enzymatic ligation strategy as well asanalytical technology. This presentation willsummarize the current status and will look forward tothe possibilities around large(r) peptide constructs.

Participants

Leendert van ven Bos - Chief Executive Officer,EnzyTag BV

Chemo-enzymatic Peptide Synthesis; PeptideChain Length Becomes Less Relevant


The peptiligase technology platform has beensuccessfully applied in the synthesis of medium sizedpeptide-based therapeutics like Exenatide, Thymosin-a1 and Liraglutide. It has been shown that synthesisyields could be improved by 20-30% compared toSPPS due to the enzymatic ligation strategy as well asanalytical technology. This presentation willsummarize the current status and will look forward tothe possibilities around large(r) peptide constructs.

Participants

Leendert van ven Bos - Chief Executive Officer,EnzyTag BV

Self Amplifying mRNA (SAM) Vaccines forRapid Response


Based on our accumulated experience on alphavirusvectors, we developed a self-amplifying (SAM) mRNAvaccine. Here we show that delivery of a 9 kb self-amplifying RNA encapsulated within an LNP oradsorbed to CNE substantially increased potencycompared to delivery of naked RNA, and hadcomparable or improved potency to more establishedvaccine approaches. This novel vaccine technologywas tested with genes encoding antigens from severalviral pathogens and found to elicit broad and potentimmune responses.

Participants

Derek O'Hagan - Head of Global Discovery Support &New Technologie, GSK Vaccines

Developing an Engineered ExosomeTherapeutics Platform


Exosomes have evolved to enable the transport oflarge and small macromolecules of variouscompositions across cellular barriers including theinner and outer cellular membranes. We havedeveloped the engEx platform, our proprietaryexosome engineering and manufacturing platform, toexpand upon the innate properties of exosomes todesign novel exosome therapeutics. Our engExplatform enables development of novel exosomeproduct candidates that are uniquely designed totarget cytoplasmic, nuclear or membrane signalingpathways throughout the body, with the goal ofdelivering potent signals to specific target cells. Wewill describe the development of initial engineeredexosome therapeutic, exoSTING, designed to elicitpotent anti-tumor immunity by selectively activatingtumor resident antigen presenting cells.

Participants

Sriram Sathy - Vice President Biology andTranslational Medicine, Codiak Biosciences

Process Improvement Strategies inOligonucleotide Development andManufacturing


Nitto Avecia Speaker TBA

Cost Efficient Peptide & OligonucleotidePurification via ZEOsphere DRP Mixed-ModeChromatography


The workshop will show the beneficial use ofZEOsphere DRP Mixed-Mode stationary phases in therepulsive-attractive mode compared to RP or IEXstationary phases on crude peptides andoligonucleotides. ZEOsphere DRP orthogonalinteraction is due to a better selectivity not only able toincrease purity, recovery and loading, but also todecrease the organic solvent usage. Real Peptide andOligonucleotide crude separation will be discussed.

Participants


Cost Efficient Peptide & OligonucleotidePurification via ZEOsphere DRP Mixed-ModeChromatography


The workshop will show the beneficial use ofZEOsphere DRP Mixed-Mode stationary phases in therepulsive-attractive mode compared to RP or IEXstationary phases on crude peptides andoligonucleotides. ZEOsphere DRP orthogonalinteraction is due to a better selectivity not only able toincrease purity, recovery and loading, but also todecrease the organic solvent usage. Real Peptide andOligonucleotide crude separation will be discussed.

Participants


Semi-automated Manufacturing of mRNANanoparticle Products for PersonalizedNeoantigen-specific Cancer Immunotherapy


Nanoparticle products comprising mRNA have beengaining attention for various therapeutic approachesincluding cancer immunotherapy, protein replacement,vaccination, and in vivo expression of therapeuticantibodies. For clinical development of such products,robust automated manufacturing processes andformulations suited for long-term stabilization of RNAnanoparticle are required. The presentation will dealwith BioNtech’s experiences during process andformulation development of a GMP compliantmanufacturing process for a personalized clinical trialwith a neoantigen-specific therapy using mRNA.

Participants

Sebastian Hörner - Head of Process Development,Formulation & Drug Development, BioNTech RNAPharmaceuticals GmbH

TANGO (Targeted Augmentation of NuclearGene Output) for the Treatment of GeneticDiseases


TANGO (Targeted Augmentation of Nuclear GeneOutput) is a novel technology which exploitsantisense-mediated modulation of pre-mRNA splicingto increase protein expression. TANGO preventsnaturally-occurring non-productive splicing events andincreases the generation of productive mRNA,resulting in an increase of full-length, fully-functionalprotein. We are applying TANGO to develop treatmentsfor autosomal dominant haploinsufficiencies.

Participants

Huw Nash, PhD - Chief Operating Officer and ChiefBusiness Officer, Stoke Therapeutics





GalNAc Cluster: Process Chemistry andRegulatory Considerations


Triantennary N-acetyl-D-galactosamine (GalNAc)clusters are well-established moieties for targetingoligonucleotide drugs to the liver by way of theasialoglycoprotein receptor (ASGPR). In this talk, thelatest process development for the manufacturingprocess of the triantennary GalNAc cluster ispresented. The knowledge generated on the origin andthe fate of process impurities, along with the robustmanufacturing process, provide key elements insupport of the GalNAc cluster as proposed regulatorystarting material.

Participants

David Tew - Senior Fellow, Glaxosmithkline MedicalReseach Centre

The Role of Membranes in (Pep)tide Synthesis:An Alternative Method of Addressing theSustainability Challenges in Synthesis andPurification


This presentation will give an overview, illustrated byexamples, of how membranes, and in particularmembranes stable to organic solvents, can bebeneficial in peptide and oligonucleotide synthesis.Examples will range from solvent exchange, topurification and reaction integrated membraneprocesses. Particular attention will be given to newmembrane developments being carried out within Vitoand how these can aid large scale production of tides.

Participants

Dominic Ormerod, Ph.D - Project Manager, ProcessIntensification, VITO

The Role of Membranes in (Pep)tide Synthesis:An Alternative Method of Addressing theSustainability Challenges in Synthesis andPurification


This presentation will give an overview, illustrated byexamples, of how membranes, and in particularmembranes stable to organic solvents, can bebeneficial in peptide and oligonucleotide synthesis.Examples will range from solvent exchange, topurification and reaction integrated membraneprocesses. Particular attention will be given to newmembrane developments being carried out within Vitoand how these can aid large scale production of tides.

Participants

Dominic Ormerod, Ph.D - Project Manager, ProcessIntensification, VITO

Regulatory View on mRNA Challenges in theContext of ATMP/Gene Therapy Guidelines


There are specific guidance’s for ATMP/Gene Therapyfrom EU CHMP and US FDA available. The challenge isthat mRNA constructs are not classical GeneTherapeutics and therefore the full applicability ofthese guidelines could be questioned. Thepresentation tries to outline pitfalls, challenges andopportunities for the CMC, nonclinical and clinicalareas by focusing on the most relevant guidances.

Participants

Otmar Pfaff - Vice President, Regulatory Affairs,CureVac AG

MicroRNAs - An Emerging Attractive DrugDiscovery Platform for TherapeuticIntervention in Oncology


MicroRNAs represent a class of small (18- to 28-nt),naturally-occuring non-coding RNA molecules whichplay major roles in normal and in pathological cellularprocesses, such as cell differentiation, cell cycleprogression, and apoptosis. Unlike antisenseoligonucleotides or siRNAs, microRNAs are able totarget multiple genes (100+) simultaneously, thusmodulating the expression of numerous proteins inkey biological pathways/networks.

Participants

Dr. Michel Janicot, Ph.D - Chief Development Officer,InteRNA Technologies



Close of Day

18:35 - 18:40





TIME KEYNOTE/PLE-NARY SESSION

OLIGONU-CLEOTIDECHEMISTRY,MANUFACTUR-ING AND CON-TROLS

OLIGONU-CLEOTIDE DIS-COVERY, PRE-CLINICAL ANDCLINICAL

PEPTIDE CHEM-ISTRY, MANU-FACTURINGAND CONTROLS

PEPTIDE DIS-COVERY, PRE-CLINICAL ANDCLINICAL

REGULATORYSTRATEGIESFOR OLIGONU-CLEOTIDES ANDPEPTIDES

SPONSOREDSPOTLIGHTPRESENTATION1




MRNA THERA-PEUTICS ANDCRISPR THERA-PEUTICS

08:00 08:00 - Spon-sored Break-fast SpotlightPresentation

08:40 - Chair-person's Re-marks

08:45 - GlobalDevelopmentProgramme ofRG6042, an An-tisenseOligonu-cleotide, for theTreatment ofHuntington’sDisease

08:00 - Spon-sored Break-fast SpotlightPresentation

























09:00 09:15 - Plantsas Biofactoriesfor ProducingPeptide-basedPharmaceuti-cals

09:45 - Regula-tory Qualityand CMC Per-spectives onmRNA Vac-cines and Pep-tide VaccineAdjuvants

10:00 10:15 - Net-working Re-freshmentBreak in Posterand Exhibit Hall

10:15 - Net-working Re-freshmentBreak in Posterand Exhibit Hall





10:55 - A CaseStudy of Con-current GlobalRegulatory Fil-ings for TwoOligonu-cleotides





















11:00 11:25 - Experi-ence with Earlyand Late PhaseGlobal Submis-sions ofOligonucleotide-based Prod-ucts

11:55 - PeptideRegulatoryStrategies andExperiences

12:00 12:25 - Transi-tion to Spot-light Presenta-tion Rooms

12:30 - Mass-Production ofTarget RNA byMicroorganism

12:30 - Quan-tification of Se-lected Impuri-ties in Oligonu-cleotides

12:30 - Preci-sion Nanosys-tems Briefing

12:30 - Chang-ing the Tide inPeptides - Pep-tide Purifica-tion and Modi-fication withBeylntic’sCatch-and-Release Tech-nology

13:00 13:00 - Net-working Lun-cheon inPoster and Ex-hibit Hall

13:00 - Net-working Lun-cheon inPoster and Ex-hibit Hall

























14:00 14:25 - Co-Chairpersons'Remarks

14:30 - Over-coming Extra-and Intracellu-lar Barriers:Polymer-basedmRNA DeliverySystems

14:25 - Co-Chairpersons'Remarks

14:30 - Over-coming Extra-and Intracellu-lar Barriers:Polymer-basedmRNA DeliverySystems


14:30 - APL-2Drug Sub-stance: Devel-opment of aCommercialGeneration 2Process


14:30 - Thera-peutic PeptideReview andEmerging Pep-tide Science


14:30 - Inhibi-tion and Degra-dation of DrugTargets UsingbioPROTACmRNAs – ANovel Ap-proach withBroad Thera-peutic Poten-tial
















15:00 15:00 - Extra-hepatic Deliv-ery

15:30 - Target-ed Delivery ofAntisenseOligonu-cleotides toExtra-hepaticTissues

15:00 - Extra-hepatic Deliv-ery

15:30 - Target-ed Delivery ofAntisenseOligonu-cleotides toExtra-hepaticTissues

15:00 - Devel-opment ofLong Contigu-ous Overlap-ping Peptidesfor Ultra-FastAllergy Im-munotherapy

15:30 - PeptideCMC LessonsLearned

15:00 - Bio-pharmaceuti-cal Propertiesof Pep-tide:polyethylene GlycolSupramolecu-lar Assemblies

15:30 - Engi-neered Am-phiphilic Pep-tides EnableDelivery of Pro-tein andCRISPR Car-goes to Cells

15:00 - TriMixBased mRNAImmunothera-pies

15:30 - mRNATherapeuticDevelopment
















16:00 16:00 - Net-working Re-freshmentBreak in Posterand Exhibit Hall


16:35 - Com-plete EnzymeCatalysedOligonu-cleotide Syn-thesis: FromSingle Nu-cleotides to Fi-nal Product


16:30 - Co-Chairpersons'Remarks

16:35 - Strate-gies for the De-livery of Nucle-ic Acid Thera-peutics


16:30 - Chair-man’s Remarks

16:35 - WhenUpstreamMeets Down-stream Pro-cessing: ItTakes Two toHave an Effi-cient Manufac-turing Process


16:30 - Chair-man’s Remarks

16:35 - WhenUpstreamMeets Down-stream Pro-cessing: ItTakes Two toHave an Effi-cient Manufac-turing Process








16:35 - Mes-senger RNATherapeuticsfor Primary Cil-iary Dyskinesia
















17:00 17:05 -Process Im-provementStrategies inOligonu-cleotide Devel-opment andManufacturing

17:35 - GalNAcCluster:Process Chem-istry and Regu-latory Consid-erations

17:05 - Devel-oping an Engi-neered Exo-some Thera-peutics Plat-form

17:35 - TANGO(Targeted Aug-mentation ofNuclear GeneOutput) for theTreatment ofGenetic Dis-eases

17:00 - Chemo-enzymatic Pep-tide Synthesis;Peptide ChainLength Be-comes LessRelevant

17:30 - Cost Ef-ficient Peptide& Oligonu-cleotide Purifi-cation viaZEOsphereDRP Mixed-Mode Chro-matography

17:00 - Chemo-enzymatic Pep-tide Synthesis;Peptide ChainLength Be-comes LessRelevant

17:30 - Cost Ef-ficient Peptide& Oligonu-cleotide Purifi-cation viaZEOsphereDRP Mixed-Mode Chro-matography

17:00 - SelfAmplifying mR-NA (SAM) Vac-cines for RapidResponse

17:30 - Semi-automatedManufacturingof mRNANanoparticleProducts forPersonalizedNeoantigen-specific CancerImmunothera-py
















18:00 18:35 - Closeof Day

18:05 - LateBreaking Pre-sentation

18:35 - Closeof Day

18:05 - MicroR-NAs - AnEmerging At-tractive DrugDiscovery Plat-form for Thera-peutic Interven-tion in Oncolo-gy

18:35 - Closeof Day

18:00 - TheRole of Mem-branes in(Pep)tide Syn-thesis: An Al-ternativeMethod of Ad-dressing theSustainabilityChallenges inSynthesis andPurification

18:35 - Closeof Day

18:00 - TheRole of Mem-branes in(Pep)tide Syn-thesis: An Al-ternativeMethod of Ad-dressing theSustainabilityChallenges inSynthesis andPurification

18:35 - Closeof Day

18:35 - Closeof Day

18:35 - Closeof Day

18:35 - Closeof Day

18:35 - Closeof Day

18:35 - Closeof Day

18:00 - Regula-tory View onmRNA Chal-lenges in theContext ofATMP/GeneTherapy Guide-lines

18:35 - Closeof Day





Sponsored Breakfast Spotlight Presentation

08:15 - 08:45

Chairman's Remarks


Chairman's Remarks


Participants

Yogesh Sanghvi, PhD - President, Rasayan Inc.

Chairman's Remarks


Chairman's Remarks


Chairman's Remarks


ApTOLL, A New Therapeutic Approach for theTreatment of Ischemic Stroke


ApTOLL is an aptamer designed to block TLR4, acrucial receptor involved in the inflammatory responsetriggered after ischemic stroke. Efficacy of ApTOLLhas been demonstrated in experimental models ofstroke and safety has been assessed in regulatoryassays. Phase I in healthy volunteers currentlyongoing.

Participants

Macarena Hernández-Jiménez - Chief ScientificOfficer, AptaTargets S.L.

Considerations for Ton-scale OligonucleotideManufacturing via Solid-phase synthesis,Preparing for the Future


Although there are new methodologies foroligonucleotide synthesis on the horizon (e.g. solution-phase synthesis), the tried and true approach for thepast 20 years has been a solid-phase route. In thisapproach, what will ton-scale production look like?What are likely failure modes and considerations notimmediately visible in current kilogram-scaleapplications.

Participants

Isaiah Cedillo - Director, Manufacturing & Operations,Ionis Pharmaceuticals

Development of Personal Neoantigen CancerVaccine NEO-PV-01


Neon Therapeutics, a clinical-stage immuno-oncologycompany developing neoantigen-based therapeutics,has pioneered a proprietary neoantigen platform todevelop a personal cancer vaccine, NEO-PV-01. Theneoantigen-targeting peptides in the vaccine areintended to engage the immune system to preciselyand selectively attack tumors. Our objective is tocreate and deepen anti-tumor immune responses andbroaden the range of cancers treatable via immuno-oncology approaches. Immune and clinical data fromour first clinical trial NT-001 will be summarized. Inaddition, the manufacturing process for NEO-PV-01will be discussed including the automated andscalable peptide production that we believe provideadvantages in both turnaround times andmanufacturing capacities.

Participants

Jesse Dong, PhD - Vice President, Peptide Chemistry,Neon Therapeutics




Participants





Participants






SiRNA therapeutics for Oncology: NewAvenues to Success


Immune Checkpoint (IC) inhibitors for HepatocellularCarcinoma (HCC) have only a low level of successsince an increase in TGFbeta around the tumorprevents T-cell penetration and activation. SilencingTGFbeta near the tumor demonstrated single agentactivity in HCC. In the presence of an IC antibody (anti-PDL1), it resulted in increased T-cell penetrationdeeper into the tumor. This presentation will outlinethe benefits of Sirnaomics vehicles for multiple siRNAdelivery and the steps being taken to drive theseinnovations to the clinic as cancer therapeutics.

Participants

David Evans, PhD - Co-Founder and CSO, Sirnaomics

Presentation Title TBA


Participants

Carl 'Charlie' Hitscherich - Global Head of ClinicalSupply Chain, Alnylam Pharmaceuticals

Individualized Neoantigen-specific Therapyagainst Cancer Using messenger RNA


One of the obviously biggest challenges in fightingcancer is that every patient has a unique cancer. Onereasonable approach to overcome this is to target theunique molecular signature of each cancer and toadapt treatment to the patient’s disease and immunesystem dynamics. To deliver the genetic informationof antigens into antigen-presenting dendritic cells ofthe immune system the mRNA platform technologyoffers plenty of new options. The presentation will dealwith conducting a clinical trial with a neoantigen-specific therapy using mRNA.

Participants

Dr. Christoph Kroener - Head of IVAC Mutanome LeadStructure, BioNTech AG




Participants





Participants


Inhibition of microRNA-155 as a TherapeuticStrategy for the Treatment of HematologicalMalignancies


microRNA-155 regulates the expression of multiplepathways implicated in oncology and itsoverexpression is an indicator of poor prognosis inseveral hematological malignancies and solid tumors.Clinical studies of cobomarsen, an inhibitor of

microRNA-155, in cutaneous T-cell lymphoma andadult T-cell leukemia/lymphoma suggest a potentialrole for cobomarsen in the treatment miR-155 elevatedhematological malignancies.

Participants

William Marshall, PhD - President and Chief ExecutiveOfficer, miRagen Therapeutics, Inc.

New Approaches in OligonucleotideManufacturing


Manufacturing large quantities of oligonucleotides fortherapeutic uses is a challenge. The batch modesolid-phase synthesis at a few kilogram scale is veryefficient. Scale-out of the process is technicallyfeasible, but challenging economically, becauserequires expensive equipment and facility that canaccommodate the large volume of solvents and waste.In this presentation, our efforts to solve some of theissues for large-scale manufacturing will be

discussed.

Participants

Xianglin Shi - Principal Scientist, Biogen

Delivering of Novel Cure: Unbridling the Powerof mRNA-based Medicines


As the first biotech company in China to focus onmRNA therapeutics, Stemirna strives to deliver novelcure for patients in the world. Taking advantage of itstwo innovative mRNA platforms – a comprehensivemRNA delivery platform and an IVT-mRNA synthesisplatform – Stemirna Therapeutics turns the patient’sbody into a drug factory that produces medicines foritself. Stemirna’s current pipeline include personalizedcancer vaccines and prophylactic vaccines forinfectious diseases.

Participants

Dr. Hangwen Li - Chairman and CEO, StemirnaTherapeutics




Participants









Participants



10:30 - 11:00

Clinical Development of CXCL12 Inhibiting L-RNA Aptamer NOX-A12 (Olaptesed Pegol)


The CXCL12-neutralizing, PEGylated L-RNA aptamer(Spiegelmer®) NOX-A12 was tested as monotherapyand in combination with the PD-1 checkpoint inhibitorpembrolizumab in a Phase 1/2 study in metastaticmicrosatellite-stable colorectal and pancreatic cancer.Pharmacodynamic effects on the tumormicroenvironment in response to the NOX-A12monotherapy and efficacy and safety data for thecombination with pembrolizumab as well as futureplans in these and additional indications will bepresented.

Participants

Dirk Eulberg - Vice President Project Management,NOXXON Pharma AG

Trinucleotide Phosphoramidites: Synthons forCodon-based Gene Synthesis and Blockmersfor Oligonucleotide Assembly


Trinucleotide synthons stand out as facilitating fullycontrolled randomization at any number and positionof codons of a given gene. We have been working onprotocols that give easy access to such trinucleotides(blockmers), which are also promising synthons forthe general assembly of oligonucleotides.

Participants

Sabine Muller - Professor, University of Greifswald

Applying New Imaging Modalities to the ADMEof ASO and Peptide Drugs


The ability to detect and quantify therapeutic ASOsand peptides is pivotal to their development as viabledrug candidates, especially when characterizing noveldelivery agents. Emerging tissue MS and non-invasiveoptical methodologies are providing new opportunitiesto accurately determine the ADME and efficacy ofthese macromolecular medicines.

Participants

Steve Hood - Director, Bioimaging and D@T,GlaxoSmithKline




Participants





Participants


The Oligonucleotide Agent BC 007 forNeutralization of Pathogenic AgonisticAutoantibodies Directed Against ß1-Adrenoceptors in Heart Failure Patients –Up-date with Very First Phase II Data


BC 007, a 15mer ssDNA sequence consisting of nineguanosine and six thymidine nucleosides neutralizesfunctional active pathogenic autoantibodies againstthe ß 1-adrenoceptor (ß 1-AAb) that are cause of heartfailure (HF) with high prevalence. Other autoantibodiesof this class against G-protein-coupled receptors(GPCR-AAb) and being associated with differentdiseases are also neutralized as already shown inGPCR-AAb positive elderly healthy volunteers(Phase-1, Part C). Phase-1 safety tests showed anexcellent tolerability, no clinically relevant side effects.Transient elevated aPTT to subclinical values,paralleling the infusion, were observed in somesubjects. BC 007 is rapidly metabolized unexpectedlyeven down to its nucleic bases degradation productsbeta-aminoisobutyric acid and uric acid, beginningshortly after start of infusion. BC 007 is now tested asthe first causative drug for patients with ß 1-AAbassociated heart failure. A two-arm randomized, open-label run-in phase (IIa) is currently investigating thetemporal persistence of the ß 1-AAb neutralization,safety and PK in chronic HF patients with reducedejection fraction, including twenty ß 1-AAb positive HFpatients and ten positive patients served as controls.Here the very first outcome data will be presented.

Participants

Dr. Johannes Müller - CEO and Founder, Berlin Cures





Nanostar Sieving for Liquid Phase Synthesis ofOligonucleotides


Solid phase synthesis offers rapid synthesis of oligosand is the dominant technology at present. Theattachment of the growing oligo to the solid phaseenables effective separation of molecular debrisduring the coupling cycle. However, it is difficult tomonitor the reaction progress, mass transferresistances inside the resin can make achievingcomplete reactions difficult, and when it’s time toincrease capacity, numbering out of synthesisers orscale up of packed beds is required. This talk willpresent Nanostar Sieving, an alternative approach inwhich two or more growing oligos are linked to a hubmolecule, forming a high molecular weight, macro-molecular nanostar. This nanostar is soluble, and isreadily separated from molecular debris using asolvent stable nanofiltration membrane. The couplingcycles are carried out entirely in the liquid phase, withdiafiltration to remove debris at each coupling anddeprotection step. This allows further building block orother reagents to be added at each cycle, if anyincomplete reaction is detected, and generallypromotes a high degree of in-line quality control usinguPLC-MS and other analytical techniques. Thesynthesis of a 2'-methyl RNA phosphorothioate 20 mersequence using this approach at the 10-20 mmol(50-100 g) scale will be discussed, and the high purityof the crude material produced by Nanostar Sievingcompared to the purity obtained by solid phasesynthesis with similar excesses of phosphoramidites.Scale-up from the 1-2 g scale to the 50-100g scale hasbeen achieved with spiral wound membrane modules,and will be described with an approximate economiccomparison made with solid phase synthesis.

Participants

Andrew Livingston - Professor of ChemicalEngineering, Imperial College London

Targeted Drug Delivery to the CNS andPeripheral Tissues Using the VECTrans®Innovative Technology


Initially designed to enhance the transport across theBlood-Brain Barrier (BBB), the VECTrans® technologydeveloped by VECT-HORUS promotes the delivery ofdrugs through vectors targeting specific receptorsexpressed at the BBB or in specific peripheral organsor tumours. The technology will be exemplified withsmall organic or large protein payloads.

Participants

Dr. Guillaume Jacquot, Ph.D - Translational ResearchManager, Vect-Horus




Participants





Participants



12:00 - 12:05

Sponsored Spotlight Presentations

12:05 - 12:35

Networking Luncheon

12:35 - 13:40











Clinical Development of Tivanisiran, A siRNAfor the Treatment of Dry Eye Disease


Tivanisiran is a siRNA inhibitor of the TransientReceptor Potential cation channel subfamily Vmember 1 (TRPV1) synthesis designed to reducesigns and symptoms of dry eye disease. Previousphase 2 trials identified the most effective dose oftivanisiran (1.125%) that has been tested in new phase3 study. Sylentis will present topline results of phase 3trial with updates on the clinical development oftivanisiran.

Participants

Anne-Marie Bleau - Clinical Operations Manager,Sylentis

Clinical Development of Tivanisiran, A siRNAfor the Treatment of Dry Eye Disease


Tivanisiran is a siRNA inhibitor of the TransientReceptor Potential cation channel subfamily Vmember 1 (TRPV1) synthesis designed to reducesigns and symptoms of dry eye disease. Previousphase 2 trials identified the most effective dose oftivanisiran (1.125%) that has been tested in new phase3 study. Sylentis will present topline results of phase 3trial with updates on the clinical development oftivanisiran.

Participants

Anne-Marie Bleau - Clinical Operations Manager,Sylentis





Control Strategies and Analytical Test Methodsfor Peptide-Conjugates


Peptide conjugates constitute a promising andgrowing class of peptide therapeutics. They require aspecific set of analytical test methods to fullycharacterize the manufacturing process, itsintermediates and the final drug substance. Typically,the physical and chemical properties of the drugsubstances are substantially influenced or dominatedby the properties of the conjugate. E.g. when a proteinis conjugated to a peptide, biomolecular test methodsare best suited, while PEGylated peptides requireanalytical test methods that adequately characterizethe polymeric moiety. In addition, the determination ofthe degree of conjugation and the identification andstructural elucidation of peptide related impurities inthe drug substance are important for accuratecharacterization. We will present data from casestudies, and discuss challenges during development ofassay and purity methods while applying differentchromatographic and MS techniques.

Participants

Silvan Rihm - Group Leader QC, Bachem AG

Control Strategies and Analytical Test Methodsfor Peptide-Conjugates


Peptide conjugates constitute a promising andgrowing class of peptide therapeutics. They require aspecific set of analytical test methods to fullycharacterize the manufacturing process, itsintermediates and the final drug substance. Typically,the physical and chemical properties of the drugsubstances are substantially influenced or dominatedby the properties of the conjugate. E.g. when a proteinis conjugated to a peptide, biomolecular test methodsare best suited, while PEGylated peptides requireanalytical test methods that adequately characterizethe polymeric moiety. In addition, the determination ofthe degree of conjugation and the identification andstructural elucidation of peptide related impurities inthe drug substance are important for accuratecharacterization. We will present data from casestudies, and discuss challenges during development ofassay and purity methods while applying differentchromatographic and MS techniques.

Participants

Silvan Rihm - Group Leader QC, Bachem AG

Strategies for Translocation Reduction duringCRISPR/Cas Multiplexing


We have developed and characterized multiplestrategies with which to reduce rearrangementfrequencies. We observed that multi-gene editing witha CRISPR-Cas9 and CRISPR-Cas12a (Cpf1)combination reduced translocation frequenciescompared to multiplexing with only CRISPR-Cas9.Taken together, for the development of T cell-basedmedicines, these data suggest that CRISPR-Cas12a isboth robust, specific, and capable of reducing genomicrearrangements when making multiple gene editscompared to the CRISPR-Cas9 system alone.

Participants

John Zuris - Scientist III, Editas Medicine

Breakthrough Treatment with Twice a YearShots to Prevent Heart Attacks and Strokes:Inclisiran Is a New Class of CholesterolLowering Drugs


Cardiovascular disease is the world’s leading killer.Treatments with statins and PCSK9 mAbs areconstrained by poor adherence. Inclisiran is in PhaseIII trials of twice-annual injections to lower LDL-C. Ifapproved, inclisiran may help in millions of patients.We review challenges and progress, manufacturingtons of this siRNA.

Participants

John Richards - SVP and Head of PharmaceuticalDevelopment, The Medicines Company

Breakthrough Treatment with Twice a YearShots to Prevent Heart Attacks and Strokes:Inclisiran Is a New Class of CholesterolLowering Drugs


Cardiovascular disease is the world’s leading killer.Treatments with statins and PCSK9 mAbs areconstrained by poor adherence. Inclisiran is in PhaseIII trials of twice-annual injections to lower LDL-C. Ifapproved, inclisiran may help in millions of patients.We review challenges and progress, manufacturingtons of this siRNA.

Participants

John Richards - SVP and Head of PharmaceuticalDevelopment, The Medicines Company

From Homebrewing to Peptide Chemistry


In this lecture, we would like to share with the peptidecommunity our efforts in the quest of efficientmethods and tools for the large-scale production ofpeptides as drugs. The tool that we are going todisclose is not used currently in the manufacture ofpeptides and we are convinced that it will be inspiringfor any peptide chemist.

Participants

John Lopez - Fellow, Chemical R&D, Novartis AG

From Homebrewing to Peptide Chemistry


In this lecture, we would like to share with the peptidecommunity our efforts in the quest of efficientmethods and tools for the large-scale production ofpeptides as drugs. The tool that we are going todisclose is not used currently in the manufacture ofpeptides and we are convinced that it will be inspiringfor any peptide chemist.

Participants

John Lopez - Fellow, Chemical R&D, Novartis AG

Highly Efficient Gene Knockdown of MouseLiver Genes Via Base Editing Using Non-viralDelivery of CRISPR-Cas9 Base Editors


Base editing is a new category of genome editing. Itenables precise, programmable conversion of singlenucleotides in the mammalian genome without cuttingDNA. Using a lipid nanoparticle-mediated deliverysystem, we report highly efficient disruption of mouseliver genes via introduction of a stop codon throughprecise base editing.

Participants

Dr. Francine Gregoire - VP, Liver Diseases, BeamTherapeutics

Givosiran Phase 3 Data and Next Steps


Alnylam Clinical Speaker TBA

Givosiran Phase 3 Data and Next Steps


Alnylam Clinical Speaker TBA









Investigation of Lipid Nanoparticle FormulationOptimisations across Nucleic acid-basedModalities


Lipid nanoparticles are the most advanced clinicallydeveloped delivery system for nucleic acids. Many ofthese systems were first developed for siRNA,however in recent times there has been increasinginterest in other nucleic acid-based modalities, inparticular, mRNA and CRISPR-based gene editingwhich can be delivered via a DNA, mRNA/gRNAcomplex or ribonucleoprotein/gRNA complex. Thesemodalities have a different mode of action andphysicochemical properties. Here we present a seriesof formulation process and composition optimisationof LNP based systems and compare how they performacross different modalities. We find that LNP basedsystems effectively delivery a range of differentphysicochemical distinct cargo, highlighting theversatility of this platform as an intracellular deliverysystem. We also see specific optimisations arerequired to optimise depending on the cargo, providinginsights into how to best optimise LNP based systemsfor a specific application.

Participants

Lili Cui - Senior Formulation Scientist, Pharm Sci,Astrazeneca

Close of TIDES Europe 2019








Nanocarrier for CRISPR Gene Editing andmRNA-mediated Tumor Suppressor Rescue


DivInCell has designed a peptide-based nanocarrierthat can potently deliver active CRISPR/CAS andmRNA in primary cell lines and in various tissues invivo. We demonstrated that our proprietary nanocarrierpromotes in vivo delivery CRISPR/Cas, leading to arobust editing of a selected target gene in specificorgans or in tumors. This delivery technology wassuccessfully applied in clinically relevant systems forCRISPR PCSK9 gene editing as well as for mRNA-mediated tumor suppressor rescue in pancreatic andovarian cancers.

Gilles Divita, Ph.D., Chief Executive Officer, DivincellSAS, France

Participants

Gilles Divita - CEO, Divincell SAS







TIME OLIGONUCLEOTIDE CHEMISTRY, MAN-UFACTURING AND CONTROLS

OLIGONUCLEOTIDE DISCOVERY, PRE-CLINICAL AND CLINICAL

PEPTIDE CHEMISTRY, MANUFACTUR-ING AND CONTROLS

PEPTIDE DISCOVERY, PRECLINICALAND CLINICAL

MRNA THERAPEUTICS AND CRISPRTHERAPEUTICS

08:00 08:15 - Sponsored Breakfast Spot-light Presentation

08:55 - Chairman's Remarks

08:15 - Sponsored Breakfast Spot-light Presentation








09:00 09:00 - Considerations for Ton-scaleOligonucleotide Manufacturing viaSolid-phase synthesis, Preparing forthe Future

09:30 - Presentation Title TBA

09:00 - ApTOLL, A New TherapeuticApproach for the Treatment of Is-chemic Stroke

09:30 - SiRNA therapeutics for Oncol-ogy: New Avenues to Success

09:00 - Development of PersonalNeoantigen Cancer Vaccine NEO-PV-01

09:30 - Individualized Neoantigen-specific Therapy against Cancer Us-ing messenger RNA





10:00 10:00 - New Approaches in Oligonu-cleotide Manufacturing

10:30 - Networking RefreshmentBreak

10:00 - Inhibition of microRNA-155 asa Therapeutic Strategy for the Treat-ment of Hematological Malignancies


10:00 - Delivering of Novel Cure: Un-bridling the Power of mRNA-basedMedicines






11:00 11:00 - Trinucleotide Phospho-ramidites: Synthons for Codon-basedGene Synthesis and Blockmers forOligonucleotide Assembly

11:30 - Nanostar Sieving for LiquidPhase Synthesis of Oligonucleotides

11:00 - Clinical Development of CX-CL12 Inhibiting L-RNA Aptamer NOX-A12 (Olaptesed Pegol)

11:30 - The Oligonucleotide Agent BC007 for Neutralization of PathogenicAgonistic Autoantibodies DirectedAgainst ß 1-Adrenoceptors in HeartFailure Patients – Up-date with VeryFirst Phase II Data

11:00 - Applying New Imaging Modal-ities to the ADME of ASO and PeptideDrugs

11:30 - Targeted Drug Delivery to theCNS and Peripheral Tissues Using theVECTrans® Innovative Technology





12:00 12:00 - Transition to Spotlight Pre-sentation Rooms

12:05 - Sponsored Spotlight Presen-tations

12:35 - Networking Luncheon

12:00 - Transition to Spotlight Pre-sentation Rooms
















TIME OLIGONUCLEOTIDE CHEMISTRY, MAN-UFACTURING AND CONTROLS

OLIGONUCLEOTIDE DISCOVERY, PRE-CLINICAL AND CLINICAL

PEPTIDE CHEMISTRY, MANUFACTUR-ING AND CONTROLS

PEPTIDE DISCOVERY, PRECLINICALAND CLINICAL

MRNA THERAPEUTICS AND CRISPRTHERAPEUTICS

13:00 13:40 - Chairperson's Remarks

13:45 - Clinical Development ofTivanisiran, A siRNA for the Treat-ment of Dry Eye Disease

13:40 - Chairperson's Remarks

13:45 - Clinical Development ofTivanisiran, A siRNA for the Treat-ment of Dry Eye Disease


13:45 - Control Strategies and Analyt-ical Test Methods for Peptide-Conjugates


13:45 - Control Strategies and Analyt-ical Test Methods for Peptide-Conjugates


13:45 - Strategies for TranslocationReduction during CRISPR/Cas Multi-plexing

14:00 14:15 - Breakthrough Treatment withTwice a Year Shots to Prevent HeartAttacks and Strokes: Inclisiran Is aNew Class of Cholesterol LoweringDrugs

14:45 - Givosiran Phase 3 Data andNext Steps

14:50 - Close of TIDES Europe 2019

14:15 - Breakthrough Treatment withTwice a Year Shots to Prevent HeartAttacks and Strokes: Inclisiran Is aNew Class of Cholesterol LoweringDrugs

14:45 - Givosiran Phase 3 Data andNext Steps


14:15 - From Homebrewing to Pep-tide Chemistry


14:15 - From Homebrewing to Pep-tide Chemistry


14:15 - Highly Efficient Gene Knock-down of Mouse Liver Genes Via BaseEditing Using Non-viral Delivery ofCRISPR-Cas9 Base Editors

14:45 - Investigation of LipidNanoparticle Formulation Optimisa-tions across Nucleic acid-basedModalities

15:00 15:15 - Close of TIDES Europe 2019 15:15 - Close of TIDES Europe 2019 15:15 - Nanocarrier for CRISPR GeneEditing and mRNA-mediated TumorSuppressor Rescue






SESSIONS TIDES Europe: Oligonucleotide and Peptide · robust identity or meaningful functional...

Documents

Transcript of SESSIONS TIDES Europe: Oligonucleotide and Peptide · robust identity or meaningful functional...