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Nov 08
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09:00 - 09:10

Chairperson’s Opening Remarks

  • Bill Marshall - CEO, MiRagen Therapeutics, USA
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Showing of Streams
10:30 - 11:30

Morning Coffee and Networking

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Showing of Streams
13:00 - 14:15

Lunch and Networking

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Showing of Streams
15:45 - 16:15

Afternoon Coffee and Networking

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Showing of Streams
17:15 - 17:20
End of Day 3

End of Day 3

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09:00 - 09:10 10 mins
Chairperson’s Opening Remarks
  • Bill Marshall - CEO, MiRagen Therapeutics, USA
09:10 - 09:50 40 mins
Info
Opening Keynote Plenary Session
DCR-PHXC: Successful Translation of RNAi from Bench to Clinic
  • Ralf Rosskamp, MD - Chief Medical Officer, Dicerna Pharmaceuticals
  • Bob Brown, PhD - Chief Scientific Officer, Senior Vice President, Research, Dicerna Pharmaceuticals

DCR-PHXC is an investigational drug targeting LDHA, which catalyzes the formation of oxalate from glyoxylate in the terminal step of hepatic oxalate production. LDHA suppression in murine PH1 and PH2 models reduces urinary oxalate, suggesting that DCR-PHXC has the potential to treat all 3 genetically defined forms of Primary Hyperoxaluria (PH). These results translated into PH1 and PH2 patients in a Phase 1 study. Most patients reached normal or near-normal urinary oxalate excretion after one dose of DCR-PHXC.

09:50 - 10:30 40 mins
Info
Opening Keynote Plenary Session
RNA Interference for Mass Markets: Groundbreaking Therapy for Cardiovascular Disease Brings Manufacturing Challenges
  • Clive Meanwell - Chief Executive Officer, The Medicines Company

Short interfering RNA is rapidly emerging as a platform for new drugs. Most siRNA development compounds are aimed at rare diseases. One exception is inclisiran, an siRNA PCSK9 synthesis inhibitor in phase III trials to lower potentially harmful LDL-cholesterol. Phase II studies showed impressive effects with infrequent dosing and apposite safety data. Inclisiran aims at global markets in which tens of millions of patients need better protection against heart attacks and strokes. The opportunity to delay first heart attack or stroke by 30 years and to reduce recurrence by 30% with just one or two “flu shots” per year is ahead.

10:30 - 11:30 60 mins
Morning Coffee and Networking
11:30 - 12:00 30 mins
Info
TRACK 1: Non-Clinical, Preclinical and Clinical Development
The Dose Makes All the Difference: Impact of Targeted Delivery on Appearance and Therapeutic Margins for the Typical 2’-MOE ASO Class Effects.
  • Scott Henry, PhD, D.A.B. - Vice President of Nonclinical Development, Ionis Pharmaceuticals, Inc.



11:30 - 12:00 30 mins
TRACK 2: CMC and Analytical Method Development Strategies
Future State of Collaborations for Oligonucleotides
  • Rachel Orr - Enablement Manager, GlaxoSmithKline R&D
12:00 - 12:30 30 mins
Info
TRACK 1: Non-Clinical, Preclinical and Clinical Development
In Vitro And In Vivo Assessment Of Human Specific Oligonucleotides For Duchenne Muscular Dystrophy
  • Pietro Spitali - Assistant Professor, Leiden University Medical Center

Duchenne muscular dystrophy is caused by protein truncating mutations, often out-of-frame deletions, which can often be corrected by exon skipping. I will present how we assess human specific oligonucleotides in vitro and in vivo and how the use of humanized mouse models can support and bridge the gap between preclinical and clinical development.

12:00 - 12:30 30 mins
Info
TRACK 2: CMC and Analytical Method Development Strategies
Impurity qualification strategy for antisense oligonucleotides
  • Yannick Fillon - Senior Scientist, Biogen

Toxicology studies for antisense oligonucleotides are critical to establish control limits on drug substance impurities. This talk will describe how we evolved from separate impurity qualification toxicology studies with several test articles, to using a single engineered batch containing sufficient levels of all relevant impurities for the IND enabling tox study itself, circumventing the need for additional studies later in the program.

12:30 - 13:00 30 mins
Info
TRACK 1: Non-Clinical, Preclinical and Clinical Development
Polypeptide nanoparticles for tissue specific siRNA delivery for therapeutics
  • David Evans - CSO, Sirnaomics

HKP is a polypeptide with proven efficacy and safety in delivering siRNAs for therapeutic use. Without modification it demonstrates targeting to stellate cells and hepatocytes in the liver - allowing use of siRNA therapies focused on this organ.

This talk will discuss utility of targeting and the steps we are taking to identify and validate optimal targets to allow uptake into cells of interest.

12:30 - 13:00 30 mins
Info
TRACK 2: CMC and Analytical Method Development Strategies
Screening for Success - Selectivity Drives Method Development
  • Brian M Kile - Principal Scientist, Nitto Avecia Inc.

Oligonucleotide Therapeutics (ONTs) have become increasingly complex over recent years due primarily to an influx of exotic ONT conjugations and backbone modifications.  Current analysis techniques for purity/impurity profiling during manufacture, release, and for stability testing rely on traditional approaches of high fidelity chromatographic separation combined with UV detection.  Iterative improvements in column technologies and mobile phase additives have increased the defensibility and applicability of this approach.  However, there are significant time penalties associated with the development of analytical methods to support the manufacture of novel ONTs.  Chromatographic selectivity, in particular, is a critical method attribute that should be studied early on in the development process.  High throughput method screening at Avecia facilitates data-driven identification of method selectivity drivers.  A single screening sequence is used to assess selectivity impacts from column stationary phase, organic modifier, and ion pairing reagent.  Screening can be performed on drug substance, development samples, or material spiked with known critical impurities to provide a comprehensive assessment of selectivity.  Screening approaches decrease overall development time through the use of standardized platforms and data driven decision making to quickly assess selectivity critical parameters. The reports can be used as a starting point for full scale method development or as a standalone assessment for early phase molecules.

13:00 - 14:15 75 mins
Lunch and Networking
14:15 - 14:45 30 mins
TRACK 1: Non-Clinical, Preclinical and Clinical Development
Preclinical and Clinical Updates on Oligonucleotides
  • Bill Marshall - CEO, MiRagen Therapeutics, USA
14:15 - 14:45 30 mins
Info
TRACK 2: CMC and Analytical Method Development Strategies
Oligonucleotides: absolute quantification and P=O/P=S ratio in a single ICP-MS/MS run
  • Philippe De Raeve - Scientific Director, Quality Assistance

Oligonucleotide quantification by UV on basis of a calculated absorption coefficient lacks accuracy due to inaccuracy of the predicted coefficient and potential bias from other UV absorbing molecules.

A sensitive method was developed to determine the phosphorus content by ICP-MS, after microwave digestion of the sample: accurate quantification of oligonucleotide can then be obtained, knowing the fixed stoichiometry of phosphorus in the sample.

Sulfur may also be measured in the same run, allowing the simultaneous accurate determination of the P=O/P=S ratio, a very important parameter for the characterization of therapeutic phosphorothioates, that can only be measured by  31P-NMR, a technique not readily available in pharmaceutical labs.

14:45 - 15:15 30 mins
TRACK 1: Non-Clinical, Preclinical and Clinical Development
Childhood Blindness due to a Photoreceptor Cilium Defect Treated with an Intravitreal Antisense Oligonucleotide (QR-110)
  • Pete Adamson - Sr VP Ophthalmology, ProQR Therapeutics
14:45 - 15:15 30 mins
TRACK 2: CMC and Analytical Method Development Strategies
Control and Qualification of Impurities for Oligonucleotides
  • Nadim Akhtar - Principal Scientist, AstraZeneca
15:15 - 15:45 30 mins
Info
TRACK 1: Non-Clinical, Preclinical and Clinical Development
Asymmetric siRNA Targeting Fibrotic and Ocular Disorders
  • Sun Woo Hong - Director, OliX Pharmaceuticals

OLX10010, an anti-fibrotic cell-penetrating asymmetric siRNA (cp-asiRNA) targeting connective tissue growth factor (CTGF), effectively reduces target gene expression as well as expression of fibrotic markers in animal model study. Preclinical as well as clinical study update of OLX10010 in anti-skin scar will be presented. In addition to skin scar, OLX10010 has a potential to be developed as therapeutics targeting various fibrotic disorders. We will present preclinical study data of OLX10010 in other fibrotic diseases in lung and eye, such as idiopathic pulmonary fibrosis (IPF) and subretinal fibrosis.

15:15 - 15:45 30 mins
Info
TRACK 2: CMC and Analytical Method Development Strategies
Oligonucleotide Characterisation by NMR and Consideration of Orthogonal Techniques
  • Thomas Brown - Senior Scientist - Oligonucleotides, Intertek Pharmaceutical Services

An overview of NMR techniques for Oligonucleotide analysis, including a discussion on how NMR can be used in place of more conventional techniques for melting temperature calculation, the challenges presented by NMR and a reflection on regulatory aspects.

15:45 - 16:15 30 mins
Afternoon Coffee and Networking
16:15 - 16:45 30 mins
Info
TRACK 1: Non-Clinical, Preclinical and Clinical Development
Spherical Nucleic Acids and Their Use in Treatment of Disease
  • David Giljohann - CEO, Exicure

Spherical Nucleic Acids, or SNAs, are 3-dimensional confirmations of DNA or RNA wherein the architecture unlocks the potential of therapeutic oligonucleotides in a wide range of cells and tissues. SNA constructs overcome one of the most difficult obstacles to nucleic acid therapeutics: safe and effective delivery into cells and tissues. SNA constructs exhibit unparalleled transfection efficiency into numerous cell and tissue types including the skin without carriers or transfection agents. Moreover, SNAs can be used as potent immunotherapeutic agents for the treatment of cancer or infectious disease. Updates on their application in clinical will be presented.

16:15 - 16:45 30 mins
Info
TRACK 2: CMC and Analytical Method Development Strategies
Evaluating the impact of sterilization on oligonucleotide based drug products
  • Erik van der Hage, PhD - Director Analytical Development & Quality Control, ProQR Therapeutics

Erik van der Hage and Vera Brinks

Sterile medicinal products can be sterilized in two ways, either via terminal methods on the product in its final container or via aseptic processing.

Recent studies on oligonucleotide based drug products evaluated the effects that different sterilization methods have on product quality. Physical and chemical properties such as rheology, color formation, particle formation, and degradation of the active ingredient were studied. The latest results and insights will be presented.

17:15 - 17:20 5 mins
End of Day 3