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Key Sessions

Firoz Antia

SPINRAZA (Nusinersen) Approval: CMC Strategies and Lessons Learned

Biogen

Muthiah (Mano) Manoharan, Ph.D.

RNAi Therapeutics in Human Disease

Alnylam Pharmaceuticals, Inc.

René Thürmer

Regulatory Authorities’ Views and Expectations for Oligonucleotides

BfArM - Federal Institute for Drugs and Medical Devices

Shai Erlich

Phase 2 Efficacy And Safety Results Of QPI-1002 (QPI), A Sirna Targeting p53, For Prevention Of Acute Kidney Injury (AKI) Following Cardiac Surgery (CS)

Quark Pharmaceuticals, Inc.

08:00 - 08:50 50 mins
Registration
08:50 - 09:00 10 mins
Chairperson's Opening Remarks
  • Troels Koch - VP & Head of Research, RNA Therapeutics, Roche Innovation Center Copenhagen, Denmark
more
09:00 - 09:35 35 mins
SPINRAZA (Nusinersen) Approval: CMC Strategies and Lessons Learned
  • Firoz Antia - Director, Antisense Oligonucleotide Process Development and Manufacturing, Biogen
more

Strategies for manufacturing and control, as well as CMC lessons learned from recent regulatory approval(s) of SPINRAZA (nusinersen) will be presented.

09:35 - 10:10 35 mins
RNAi Therapeutics in Human Disease
  • Muthiah (Mano) Manoharan, Ph.D. - Senior Vice President of Drug Discovery, Alnylam Pharmaceuticals, Inc.
more

Alnylam has advanced two delivery platforms for RNA interference (RNAi) based human therapeutics for liver-based disease molecular targets.  The first one is lipid nanoparticles (LNPs) formulation containing siRNAs used for intravenous administration. The second one, in which siRNAs are conjugated to trivalent GalNAc sugar to target asialoglycoprotein receptor (ASGPR) of hepatocytes are emerging as a potential new class of medicine supporting a broad clinical pipeline across multiple therapeutic targets by subcutaneous administration. Furthermore, we have been able to continuously optimize the siRNA chemical modifications and design resulting in the Enhanced Stabilization Chemistry (ESC) platform exhibiting improved efficacy and extended duration lasting for several months. Our progress and therapeutic applications will be presented.

10:10 - 10:45 35 mins
Regulatory Authorities’ Views and Expectations for Oligonucleotides
  • René Thürmer - Deputy Head, Unit Pharmaceutical Biotechnology, BfArM - Federal Institute for Drugs and Medical Devices
more

This presentation will provide an overview about the regulatory landscape for oligonucleotides. The presentation will address the control strategy for synthetic oligonucleotides.  Regulatory requirements for clinical trials and marketing authorisation applications will be highlighted. Experiences from recent regulatory submissions will be discussed. Since the early and open communication with Regulatory Agencies can significantly reduce time to market for a new drug product ways of interaction are exposed.

10:45 - 11:30 45 mins
Morning Coffee and Networking
11:30 - 12:00 30 mins
Delivery & R&D Strategies
Advances In Targeted Delivery Of Oligonucleotides Beyond The Liver
  • Shalini Andersson - Head of Drug Metabolism & Pharmacokinetics, Cardiovascular and Metabolic Diseases, AstraZeneca
more

AstraZeneca has in collaboration with IONIS Pharmaceuticals developed novel targeting approaches to enable specific delivery of oligonucleotide to cells other than hepatocytes and that are of interest in cardio-metabolic diseases. This talk will address some of the strategies and platforms developed to enable discovery and development of novel homing ligands that can be conjugated to antisense oligonucleotides for targeted delivery to pancreatic beta cells and that show efficient knock-down of genes in vitro and in vivo.

11:30 - 12:00 30 mins
Manufacturing and Scale Up Strategies
Improving Process Development in the Scale Up and Large Scale Manufacturing of Oligonucleotides
  • Doug Brooks - VP CMC, Miragen
more
12:00 - 12:30 30 mins
Delivery & R&D Strategies
Delivery of mRNA using Viromers®
  • Steffen Panzner - Managing Director, Lipocalyx GmbH
more
12:00 - 12:30 30 mins
Manufacturing and Scale Up Strategies
Update on AJIPHASE of Oligonucleotide Synthesis for Large Scale Manufacturing
  • Daisuke Takahashi - Senior Principal Researcher, Research Institute for Bioscience Products & Fine Chemicals, AJINOMOTO Co., Inc, Japan
more

We have reported the practical synthetic method AJIPHASE® which is a powerful tool for large scale manufacturing using solution-phase approach. The efficacy of AJIPHASE® has been proven with the successful synthesis of various oligonucleotides and with the same impurity profiles as it of solid-phase synthesis. This presentation will describe the technical updates on AJIPHASE® in detail and impurity analyses using some track records.

12:30 - 14:00 90 mins
Lunch
14:00 - 14:30 30 mins
Delivery & R&D Strategies
Peptide-PMO Conjugates For The Enhanced Delivery And Treatment Of Neuromuscular Diseases
  • Mike Gait - MRC Programme Leader, MRC Laboratory of Molecular Biology, Cambridge, UK
more

We developed over previous years a series of Arg-rich peptides called Pip as PMO conjugates for boosting activity in mouse models in targeting pre-mRNA in Duchenne muscular dystrophy (exon skipping) and spinal muscular atrophy (exon inclusion). Pip-PMOs showed more than 100 times the activity over naked PMO in muscles of the DMD mdx mouse, including heart. Considerable extension of life was seen following systemic injection of a Pip-PMO into SMA mouse pups as well as high exon inclusion in brain and spinal cord of adult mice, providing strong evidence for crossing of the blood-brain barrier. We have now developed 3 further novel Arg-rich peptide classes as PMO conjugates for DMD systemic treatment as well as one novel class for strong activity in SMA mouse brain and spinal cord following intravenous delivery. All these novel peptide classes (D-PEPs) maintain the activity of Pip-PMOs but show improved tolerability and they form the basis of our current aims to develop enhanced activity peptide-PMOs for clinical treatment of DMD and SMA, as well as for myotonic dystrophy.

14:00 - 14:30 30 mins
Manufacturing and Scale Up Strategies
The Journey of Alicaforsen towards Commercialisation – Manufacture and Treatment
  • Janette Thomas - Director of International Operations, Atlantic Healthcare plc
  • Mike Webb - Vice President, Manufacturing, Atlantic Healthcare plc
more

Atlantic Healthcare is an emerging trans-Atlantic pharmaceutical company with a core focus on gastrointestinal disorders including Inflammatory Bowel Disease (IBD). Atlantic’s lead product Alicaforsen enema is progressing through pivotal phase 3 clinical trial for the treatment of IBD, Pouchitis, due to read out 1H 2018. Alicaforsen is an antisense oligonucleotide, licensed from Ionis Pharmaceuticals, Inc., which provides the potential for the treatment of inflammation via multiple delivery formulations. Alicaforsen has been granted Orphan Drug designation by the FDA and EMA and a letter of Fast Track for the treatment of Pouchitis in recognition of the unmet medical need. The rolling NDA submission is underway with the non-clinical data section already submitted. Preparations for the CMC section, are well underway. The original API manufacturing process was developed over 12 years ago. Incorporating new approaches, Atlantic and Nitto Avecia have developed a new manufacturing process with process validation batches about to start. This presentation will describe the journey of alicaforsen through clinical and process development to provide an exciting new therapy for patients in need of a new treatment option for their condition.

14:30 - 15:00 30 mins
Delivery & R&D Strategies
COMPACT: A Public-Private Partnership to Develop Novel Delivery Systems for Biopharmaceuticals
  • Enrico Mastrobattista - dept. Pharmaceutics, Utrecht University, The Netherlands
more

COMPACT is a collaboration between pharmaceutical industry and academia sponsored by the EU Innovative Medicines Initiative to collectively work on the development of delivery strategies and systems for biopharmaceuticals as well as on the development of advanced models to study the transport of such delivery systems over biological barriers. In this presentation an overview will be given of the main activities and accomplishments of this consortium.

14:30 - 15:00 30 mins
Manufacturing and Scale Up Strategies
Sustainability of Oligonucleotide Processes
  • Anna Watson - Scientist (Process Engineer), Pharmaceutical Technology and Development, AstraZeneca, UK
more

This presentation will cover AstraZeneca’s definition of sustainability and how oligonucleotide manufacturing processes impact the environment. A comparison will be made to the environmental impacts of small molecule API manufacture. Finally, potential process development opportunities to improve the sustainability of oligonucleotide processes will be discussed.

15:00 - 15:30 30 mins
Delivery & R&D Strategies
Enhancing ASO Potency in Extra-Hepatic Tissues
  • Punit Seth - Vice President, Ionis Pharmaceuticals
more

Recent advances in targeted delivery have greatly enhanced the potency of oligonucleotide therapeutics for suppressing gene expression in hepatocytes. We have explored strategies to enhance potency of oligonucleotide therapeutics in extra-hepatic tissues such as muscle, endocrine organs and in lymphocytes, which will be presented.

15:00 - 15:30 30 mins
Manufacturing and Scale Up Strategies
Fully-Scalable, cGMP Production of Oligonucleotide-Containing Nanoparticles
  • Andreas Wagner - Head Liposome Technology, Polymun Scientific Immunbiologische Forschung GmbH
more

Polymun has unique know-how and technology for the development and manufacturing of liposomal formulations. Our proprietary crossflow injection technology is based on the solvent injection method and over the past 15 years it was used to formulate various nanoparticle formulations intended for clinical trials.

15:30 - 16:00 30 mins
Afternoon Coffee
16:00 - 16:30 30 mins
Delivery & R&D Strategies
How Phosphorothioate Oligonucleotides Traffic from the Endosome to the Cell Nucleus
  • Cy Stein - Professor of Medicine, Experimental Pharmacology, and Cellular and Molecular Biology, City Of Hope, USA
more

After internalisation into cells under the conditions of gymnosis (i.e., no transfection reagents or carriers), splice-switching oligonucleotides (SSOs) are often deeply trapped in cytoplasmic vesicular structures, and often only poorly perform their nuclear function. We have examined the formation of a protein/SSO complex that we believe traffics the SSO to the nucleus, and have identified two distinct, yet synergistic methods, for augmenting the nuclear localisation of an SSO after delivery by gymnosis.

16:00 - 16:30 30 mins
Manufacturing and Scale Up Strategies
Sequence Fidelity of Chemical Oligonucleotide Synthesis
  • Mario Jauker - Manufacturing and Process Characterisation Scientist, BioSpring GmbH
more
16:30 - 17:00 30 mins
Delivery & R&D Strategies
Pre-Clinical Development of a Novel Delivery System and MicroRNA Therapeutic Headed to the Clinic
  • Christian Marin-Muller - CEO, Speratum CR
more
16:30 - 17:00 30 mins
Manufacturing and Scale Up Strategies
Panel Discussion: Ensuring Raw Materials Supply Chain Quality for Oligonucleotides
  • Mike Webb - Vice President, Manufacturing, Atlantic Healthcare plc
  • Doug Brooks - VP CMC, Miragen
more
  • What control strategies are being used to ensure raw materials / starting materials quality?
  • What are critical and non-critical impurities?
  • Calculation strategies to calculate purity of APIs
  • How do suppliers ensure quality as larger batches are produced?
  • What are industry doing to ensure quality of starting materials? Are people doing their own testing as well as suppliers?
  • How to handle isomer impurities which can’t be detected in products?
  • Regulatory feedback on the quality control requirements for raw materials: What is excepted in terms of control of starting material and level of information included in the dossiers
17:00 - 17:35 35 mins
Phase 2 Efficacy And Safety Results Of QPI-1002 (QPI), A Sirna Targeting p53, For Prevention Of Acute Kidney Injury (AKI) Following Cardiac Surgery (CS)
  • Shai Erlich - President US Operations and Chief Medical Officer, Quark Pharmaceuticals, Inc.
more
17:35 - 19:00 85 mins
Drinks Reception in Exhibition Hall
19:00 - 22:00 180 mins
Coaches depart for Networking Dinner (you must collect your wristband during the Monring Coffee Break)
08:00 - 08:50

Registration

08:50 - 09:00

Chairperson's Opening Remarks

  • Troels Koch - VP & Head of Research, RNA Therapeutics, Roche Innovation Center Copenhagen, Denmark
more
09:00 - 09:35

SPINRAZA (Nusinersen) Approval: CMC Strategies and Lessons Learned

Strategies for manufacturing and control, as well as CMC lessons learned from recent regulatory approval(s) of SPINRAZA (nusinersen) will be presented.

  • Firoz Antia - Director, Antisense Oligonucleotide Process Development and Manufacturing, Biogen
more
09:35 - 10:10

RNAi Therapeutics in Human Disease

Alnylam has advanced two delivery platforms for RNA interference (RNAi) based human therapeutics for liver-based disease molecular targets.  The first one is lipid nanoparticles (LNPs) formulation containing siRNAs used for intravenous administration. The second one, in which siRNAs are conjugated to trivalent GalNAc sugar to target asialoglycoprotein receptor (ASGPR) of hepatocytes are emerging as a potential new class of medicine supporting a broad clinical pipeline across multiple therapeutic targets by subcutaneous administration. Furthermore, we have been able to continuously optimize the siRNA chemical modifications and design resulting in the Enhanced Stabilization Chemistry (ESC) platform exhibiting improved efficacy and extended duration lasting for several months. Our progress and therapeutic applications will be presented.

  • Muthiah (Mano) Manoharan, Ph.D. - Senior Vice President of Drug Discovery, Alnylam Pharmaceuticals, Inc.
more
10:10 - 10:45

Regulatory Authorities’ Views and Expectations for Oligonucleotides

This presentation will provide an overview about the regulatory landscape for oligonucleotides. The presentation will address the control strategy for synthetic oligonucleotides.  Regulatory requirements for clinical trials and marketing authorisation applications will be highlighted. Experiences from recent regulatory submissions will be discussed. Since the early and open communication with Regulatory Agencies can significantly reduce time to market for a new drug product ways of interaction are exposed.

  • René Thürmer - Deputy Head, Unit Pharmaceutical Biotechnology, BfArM - Federal Institute for Drugs and Medical Devices
more
10:45 - 11:30

Morning Coffee and Networking

Showing of Streams
12:30 - 14:00

Lunch

Showing of Streams
15:30 - 16:00

Afternoon Coffee

Showing of Streams
17:00 - 17:35

Phase 2 Efficacy And Safety Results Of QPI-1002 (QPI), A Sirna Targeting p53, For Prevention Of Acute Kidney Injury (AKI) Following Cardiac Surgery (CS)

  • Shai Erlich - President US Operations and Chief Medical Officer, Quark Pharmaceuticals, Inc.
more
17:35 - 19:00

Drinks Reception in Exhibition Hall

19:00 - 22:00

Coaches depart for Networking Dinner (you must collect your wristband during the Monring Coffee Break)