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Key Sessions

Muthiah (Mano) Manoharan

RNAi Therapeutics in Human Disease

Alnylam Pharmaceuticals, Inc. USA

Matthew Stanton

Messenger RNA as a Novel Therapeutic Approach

Moderna Therapeutics, USA

08:00 08:50 (50 mins)

Main agenda

Registration and Morning Coffee

08:50 09:00 (10 mins)

Main agenda

Chairperson’s Opening Remarks

  • Fritz Eckstein, Max-Planck Institute for Experimental Medicine, Germany

09:00 09:40 (40 mins)

Main agenda

RNAi Therapeutics in Human Disease

This presentation will focus on advances in RNAi Therapeutics at Alnylam Pharmaceuticals based on our successful  hepatic delivery approaches. Specifically, this talk will address:

  • Chemically  modified siRNAs
  • LNP Platform 
  • Progress in siRNA-GalNAc Conjugate Platform for robust liver specific delivery and Reversir Technology
  • Examples of Clinical translation of ESC-siRNA-GalNAc conjugates in humans
  • Muthiah (Mano) Manoharan - Senior VP, Innovation Chemistry, Alnylam Pharmaceuticals, Inc. USA

09:40 10:20 (40 mins)

Main agenda

Thought Leader Discussion: Current and Future Opportunities for Oligonucleotide Therapeutics

  • Future trends and expectations for oligonucleotide development: Where is the market going?
  • Evaluating the uptake of oligonucleotide drugs in the marketplace
  • Strategies for increasing the scale of oligonucleotide production and future expectations
  • Developments in new manufacturing, new chemistries to increase manufacturing volumes
  • Dmitry Samarsky - CSO, Silence Therapeutics, Germany
  • Elena Feinstein - Chief Scientific Officer, Quark Pharmaceuticals, Israel
  • Matthew Stanton - VP, Head of Chemistry, Moderna Therapeutics, USA
  • Muthiah (Mano) Manoharan - Senior VP, Innovation Chemistry, Alnylam Pharmaceuticals, Inc. USA

10:20 11:00 (40 mins)

Main agenda

Morning Coffee and Networking

11:00 11:30 (30 mins)

Delivery, R&D Strategies, mRNA and Genome Editing

Improving the Delivery of Oligonucleotides via Conjugations - Feedback from Dicerna

  • Cheng Lai - Senior Director of Translational Biology, Dicerna Pharmaceuticals, USA

11:00 11:30 (30 mins)

Manufacturing and Scale Up Strategies

Manufacturing and Clinical Testing of Therapeutic Messenger RNAs

Messenger (m)RNA is increasingly investigated as a platform technology for multiple therapeutic applications. We are using mRNA to deliver the genetic information of antigens into professional antigen-presenting dendritic cells for immunotherapies against cancer. My presentation will cover GMP manufacturing of mRNA, preclinical testing including targeting of mRNA by suitable formulations as well as first experiences from our clinical program.

  • Andreas Kuhn - Vice President RNA Biochemistry & Manufacturing, BioNTech RNA Pharmaceuticals GmbH, Germany

11:30 12:00 (30 mins)

Delivery, R&D Strategies, mRNA and Genome Editing

Overcoming the Challenges and Lessons Learnt Across Delivery of Small and Large Nucleic Acids to Cancers

  • Formulation of siRNA vs plasmid 
  • mRNA delivery to tumours
  • Identification of key quality attributes and correlation to in vitro/in vivo efficacy
  • Key challenges for development and manufacturing therapeutics
  • Sanyogitta Puri - Associate Principal Scientist, Pharmaceutical Sciences, AstraZeneca ,UK

11:30 12:00 (30 mins)

Manufacturing and Scale Up Strategies

Pre-Validation through PPQ: Nitto Avecia's Approach to Process Validation of Oligonucleotide Manufacturing Processes

  • James O'Donnell - Principal Scientist , Nitto Denko Avecia Inc

12:00 12:30 (30 mins)

Manufacturing and Scale Up Strategies

Panel Discussion: Improving Process Development in the Scale Up and Large Scale Manufacturing of Oligonucleotides

  • Process improvement and scale up strategies for manufacturing oligonucleotide: How to create bigger batches?
  • How transfer from lab ideas to actual drug products
  • Capabilities and standard procedures to scale up oligonucleotides
  • Evaluating resins and linkers for oligonucleotides
  • Overcoming scale up issues in process development for oligonucleotides


  • Stefan Vonhoff - Vice President CMC , NOXXON Pharma AG, Germany
  • Piers Gaffney - Faculty of Engineering, Department of Chemical Engineering, Imperial College, UK

12:00 12:30 (30 mins)

Delivery, R&D Strategies, mRNA and Genome Editing

Targeting Oligonucleotides to the Cell Nucleus

We have determined the details of a major intracellular oligonucleotide transport pathway that is responsible for the translocation of phosphorothioate LNA gap mers from the cytoplasm to the nucleus.  Via manipulation of this pathway, we can increase the nuclear activity of a splice switching oligo delivered by gymnosis by approximately 10-fold.  The molecular determinants of this transport pathway and other factors that influence its activity will be discussed. 

  • Cy Stein - Professor & Chair & Clinical Research Deputy Director, City Of Hope, USA

12:30 13:00 (30 mins)

Main agenda

Novel Peptide-PMO Conjugates for the Treatment of Spinal Muscular Atrophy and Duchenne Muscular Dystrophy

Over the last few years we have developed a series of Arg-rich peptides called Pip as conjugates of PMO for enhanced activity in targeting pre-mRNA in Duchenne muscular dystrophy (exon skipping) and more recently spinal muscular atrophy (exon inclusion) via intravenous injection into mouse models of disease. We recently showed considerable extension of life following systemic injection of Pip6a-PMO into SMA mouse pups, and similar injection into adult SMA mice led to high exon inclusion in brain and spinal cord, providing strong evidence for crossing of the blood-brain barrier. We now describe a novel peptide class that when conjugated to PMO also leads to high exon inclusion in adult SMA mouse brain and spinal cord but where there is also evidence for lower potential toxicity.  Similarly, novel classes of peptides are also under development as PMO conjugates for DMD mouse delivery with prospects of lower toxicity than current Pip-PMO candidates.

  • Mike Gait - MRC Programme Leader, MRC Laboratory of Molecular Biology, Cambridge, UK

13:00 14:20 (80 mins)

Main agenda

Lunch and Networking Time

14:20 14:50 (30 mins)

Delivery, R&D Strategies, mRNA and Genome Editing

Selective Endogenous mRNA Up-Regulation using Single Stranded Oligonucleotides

RaNA is developing two distinct platforms. In first approach oligonucleotides are designed to bind target lncRNA to block its interaction with PRC2 leading to selective up-regulation of mRNA and protein. In second approach oligonucleotides are designed to bind UTR regions of target mRNA which leads to increase in half-life and up-regulation of mRNA and protein. The examples will be presented.

  • Balkrishen Bhat - Vice President, Chemistry, RaNA Therapeutics, USA

14:20 14:50 (30 mins)

Manufacturing and Scale Up Strategies

Guiding Oligonucleotide Formulations from Laboratory into Clinical Trials: Lessons Learnt from Development and Optimisation of Liposomal Formulations

The custom procedure to formulate an oligonucleotide into liposomes is to use a cationic or an amphoteric lipid in the liposome composition and to inject the lipid solution in the oligonucleotide solution at acidic environment. In this way, the positively charged lipid interacts with the negatively charged oligonucleotide and promotes the encapsulation of the oligonucleotide into the liposomes. Polymun Scientific has successfully transferred several laboratory-scale methods to large-scale production. Our well established proprietary crossflow injection technology used for the production of liposomes is a modification of the ethanol injection method described by Batzri and Korn in 1973 and it offers many advantages over other conventional methods used for the production of liposomes. All the process parameters are well-controlled and can be adjusted to result in a tailored liposomal product according to the specifications set by our clients. To reach robust and stable production of a new oligonucleotide formulation there are many factors to be considered and many crucial parameters to be optimized at the very early development phase. The main characteristic of all those parameters is that they should be cGMP compliant and fully scalable. This itself excludes many processing methods and makes the development process challenging. Some of the parameters that need optimization are process-related and some others are product-related. Process-related optimisation includes among others the choice of the appropriate solvents to overcome lipid insolubility issues, the minimisation of the chemical instability of the lipid components and the optimization of the process conditions to maximize the stability of the formulation during production. The process-related optimization is followed by the product-related optimization. Optimisation of the drug to lipid ratio and choice of the appropriate buffers are the major parameters which contribute to maximisation of the oligonucleotide yield in the final product. Besides development and optimization of the oligonucleotide formulation, analysis related to the formulated oligonucleotide is another challenging part. Often, issues related to the quantification of the lipid components and the oligonucleotide in the final product have to be solved. Our successful and long-term presence in the area of liposomal pharmaceuticals is reflected in several projects. By now, Polymun Scientific guided into Phase I clinical trials 12 projects one of which is currently in Phase II. Among those projects are injectable liposomal formulations, liposomal vaccines and topical formulations. With our current equipment and qualified processes we are capable of producing volumes ranging from several milliliters up to few hundred liters. Polymun is equipped with an automated filling line with capacity of 10000 vials and has the capacity to lyophilize liposomal products as there is planted a cGMP lyophilizer capable of lyophilizing 5000 vials per run.

  • Charalampos Koutsoulas - Scientific Project Leader, Polymun Scientific, Austria

14:50 15:20 (30 mins)

Manufacturing and Scale Up Strategies

Liquid Phase Oligonucleotide Synthesis with Membrane Separation for Efficient Large Scale Manufacturing

We introduce a liquid phase oligonucleotide synthesis (LPOS) strategy. After each chain extension membrane separation is used to purify the growing oligo. To enhance the separation, three oligos are linked to a central tri-star hub. This enables LPOS in standard chemical process plant; the technology is readily scaled; in-process reaction monitoring is facile; and building block usage is minimised. The process, and its technical and economic potential, will be described.

  • Piers Gaffney - Faculty of Engineering, Department of Chemical Engineering, Imperial College, UK

14:50 15:20 (30 mins)

Delivery, R&D Strategies, mRNA and Genome Editing

Messenger RNA as a Novel Therapeutic Approach

The contemplation of mRNA as a therapeutic platform has historically been shunned owing to challenges in oligonucleotide delivery and, maybe more importantly, the perceived shortcomings of mRNA with regard to stability and immunogenicity.  Significant advances in oligonucleotide delivery have been realized over the past decade thereby enabling mRNA therapeutics.  Recent discoveries in mRNA chemistry further enhance the attractiveness of this platform by eliminating innate immune activation and maximizing protein expression.  With these advances, mRNA is positioned to become an important new therapeutic modality.

  • Matthew Stanton - VP, Head of Chemistry, Moderna Therapeutics, USA

15:20 15:50 (30 mins)

Manufacturing and Scale Up Strategies

AJIPHASE®: Highly Practical Liquid Phase Technology for Large Scale Manufacturing of Oligonucleotides

A large quantity of oligonucleotides would be required in the near future according to progress of the current development of oligonucleotide therapeutics. Therefore, a practical synthetic method for large scale has been strongly needed. Recently, we have developed a novel liquid phase technology AJIPHASE® for DNA/RNA-type and morpholino-type oligonucleotide synthesis which can solve an issue of procurement in large scale. This presentation will describe a technical overview of AJIPHASE® technology and the latest result of large scale manufacturing.

  • Nobuhiro Yamanaka - In Charge of TIDES Business, Business Development Group, Bioproducts & Fine Chemicals Division, , AJINOMOTO Co., Inc.

15:20 15:50 (30 mins)

Delivery, R&D Strategies, mRNA and Genome Editing

Hepatic Gene Disruption In Vivo After Liposomal Delivery of Cas9 mRNA and Chemically Modified Guide RNAs

Co-delivery of guide RNA and mRNA coding for Cas9 offers the opportunity to achieve long lasting gene knockdown in vivo. Combining chemically stabilized guide RNA with transiently expressed Cas9 allows for efficient gene disruption whilst reducing the risk of off-target effects. We present data of persistent and therapeutically relevant protein knockdown in mice using liposomal delivery of Cas9 mRNA and chemically modified guide RNAs to liver.

  • Adrien Weingaertner - Group Leader mRNA Theraepeutics., Silence Therapeutics, Germany

15:50 16:20 (30 mins)

Main agenda

Afternoon Coffee and Networking Time

16:20 16:50 (30 mins)

Delivery, R&D Strategies, mRNA and Genome Editing

Probing the Relationship Between Endocytosis, Activity, and Receptor Capacity in Uptake of ASO Conjugates

ASGR mediated delivery of oligonucleotide therapeutics confers dramatic increases in potency for suppressing gene expression in hepatocytes. ASGR is a hetero-oligomeric receptor comprised of two subunits (ASGR1 and ASGR2). To determine the importance and relative abundance of each subunit towards enhancing ASO potency, we created cell lines which express these subunits individually or in combination. Our data suggest that the capacity of ASGR-mediated uptake is far in excess of that required for maximal activity of GalNAc-conjugated ASO therapeutics.  These results suggest there may be broad opportunity for targeting receptors with moderate expression levels to enhance ASO potency in other cell-types and tissues.

  • Michael Tanowitz - Senior Scientist, Ionis Pharmaceuticals, USA

16:20 16:50 (30 mins)

Manufacturing and Scale Up Strategies

Interactive Panel Discussion: Ensuring Raw Material Supply Chain Quality for Oligonucleotides

  • What control strategies are being used to ensure raw materials / starting materials quality?
  • Calculation strategies to calculate purity of APIs
  • How do suppliers ensure quality as larger batches are produced?
  • Regulatory feedback on the quality control requirements for raw materials
  • A Representative, ChemGenes Corporation
  • Stefan Vonhoff - Vice President CMC , NOXXON Pharma AG, Germany

16:50 17:20 (30 mins)

Delivery, R&D Strategies, mRNA and Genome Editing

Harnessing a Fundamental Innate Immune Defense Mechanism to Generate Effective Therapies: A Truly Novel Approach Entering Phase I in Oncology by Q1/2017

Rigontec is the leader in RIG-I targeting therapeutics. Rigontec’s proprietary agonists specifically activate RIG-I, inducing both immediate and long-term anti-tumour immunity and have proven substantial local and systemic tumour regression in several relevant in vivo models. The pioneering new technology will be presented and the progress to enter clinical development latest in Q1 2017 will be discussed.

  • Jörg Vollmer - Chief Scientific Officer, Rigontec, Germany and USA

17:30 20:40 (190 mins)

Main agenda

End of Conference Day Two, Networking Drinks followed by Dinner