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8:00am - 8:25am

Registration and Coffee

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Showing of Streams
12:15pm - 12:20pm
Transition to Spotlight Presentation Rooms

Transition to Spotlight Presentation Rooms

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

Networking Luncheon in Poster and Exhibit Hall

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Showing of Streams
3:30pm - 3:35pm
Close of TIDES Conference

Close of TIDES Conference

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8:00am - 8:25am 25 mins
Registration and Coffee
8:25am - 8:30am 5 mins
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
Chairperson's Remarks
  • Paul Metz - Principal Consultant, Metz Biotechnology Consulting, LLC
8:25am - 8:30am 5 mins
Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
Chairperson's Remarks
  • Chairperson Claus Rentel, PhD - Executive Director, Analytical Development/QC, Ionis Pharmaceuticals, Inc.
8:25am - 8:30am 5 mins
Track 3: Peptide Chemistry, Manufacturing and Controls
Chairperson's Remarks
  • Chairperson Trishul Shah, MS - Director Business Development, PolyPeptide Laboratories Inc.
8:25am - 8:30am 5 mins
Track 4: Peptide Discovery, Preclinical and Clinical
Chairperson's Remarks
  • Chairperson Trishul Shah, MS - Director Business Development, PolyPeptide Laboratories Inc.
8:25am - 8:30am 5 mins
Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
Chairperson's Remarks
  • Chairperson Arthur Levin, PhD - Executive Vice President, R&D, Avidity Biosciences LLC
8:30am - 9:00am 30 mins
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
HEPLISAV-B Path to Approval
  • Randall Hyer, MD, PhD - Vice President, Clinical Development and Medical Affairs, Head, Drug Safety and Pharmacovigilance, Dynavax Technologies Corporation
8:30am - 9:00am 30 mins
Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
Transfer of Analytical Methods for DNA and MOE Phosphoramidites from LC-Ion Trap to LC-QTOF Mass Spectrometry
  • Kyeong Eun Jung, PhD - Senior Vice President, Head of Oligo and R&D Division, ST Pharm
8:30am - 8:50am 20 mins
Info
Track 3: Peptide Chemistry, Manufacturing and Controls
Registration of Generic Peptide Drug Substances, Where Are the Challenges and How Should These Be Approached?
  • Peter Larsson - Global Director Regulatory Affairs, PolyPeptide Laboratories AB

The regulatory landscape for generic peptide drug substances is evolving. What used to be seen as relatively straightforward from the CMC point of view might today be a complex and more resource and competence demanding exercise fully comparable with that of a new chemical entity. The development is driven by new guidelines and higher expectations from both authorities and customers. Also, new challenges and opportunities come with more complex peptides, sometimes manufactured by recombinant technology, going out of patent. The presentation will share PolyPeptide Group’s experience with today’s regulatory environment and discuss how to address it.

8:30am - 8:50am 20 mins
Info
Track 4: Peptide Discovery, Preclinical and Clinical
Registration of Generic Peptide Drug Substances, Where Are the Challenges and How Should These Be Approached?
  • Peter Larsson - Global Director Regulatory Affairs, PolyPeptide Laboratories AB

The regulatory landscape for generic peptide drug substances is evolving. What used to be seen as relatively straightforward from the CMC point of view might today be a complex and more resource and competence demanding exercise fully comparable with that of a new chemical entity. The development is driven by new guidelines and higher expectations from both authorities and customers. Also, new challenges and opportunities come with more complex peptides, sometimes manufactured by recombinant technology, going out of patent. The presentation will share PolyPeptide Group’s experience with today’s regulatory environment and discuss how to address it.

8:30am - 9:00am 30 mins
Info
Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
Development of Cellular Therapies Using CRISPR
  • Vic Myer, PhD - Chief Technology Officer, Editas Medicine

This talk will cover the technical advancements enabling efficient editing of primary human cells for development of autologous cell therapies.

8:50am - 9:10am 20 mins
Info
Track 3: Peptide Chemistry, Manufacturing and Controls
Opportunities and Challenges of the FDA Draft Guidance ANDAs for Certain Highly Purified Synthetic Peptide Drug Products That Refer to Listed Drugs of rDNA Origin
  • Gerhard Haas, PhD - Vice President, Quality Assurance and Regulatory Affairs, Bachem AG

This new FDA draft guidance opens the door for generic synthetic peptides referencing a marketed drug product of rDNA origin. The draft guidance will be discussed with respect to opportunities, technical limitations and possible improvements based on public comments obtained.

8:50am - 9:10am 20 mins
Info
Track 4: Peptide Discovery, Preclinical and Clinical
Opportunities and Challenges of the FDA Draft Guidance ANDAs for Certain Highly Purified Synthetic Drug Products That Refer to Listed Drugs of rDNA Origin
  • Gerhard Haas, PhD - Vice President, Quality Assurance and Regulatory Affairs, Bachem AG

This new FDA draft guidance opens the door for generic synthetic peptides referencing a marketed drug product of rDNA origin. The draft guidance will be discussed with respect to opportunities, technical limitations and possible improvements based on public comments obtained.

9:00am - 9:30am 30 mins
Info
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
Temporary Inhibition of P53 for Tissue Protection: From Therapeutic Concept to Prevention of Acute Kidney Injury in Humans following Kidney Transplantation and Cardiac Surgery
  • Elena Feinstein, MD, PhD - Chief Scientific Officer, Quark Pharmaceuticals

Although therapeutic inhibition of the master tumor suppressor p53 is counterintuitive, its temporary inhibition for tissue protection under conditions of genotoxic and/or oxidative stress was proven to be not only safe but also efficient. Efficacy of siRNA targeting p53 was demonstrated in numerous animal models. Clinical POC was achieved in two large (>300 patients each) multicenter double-blinded placebo-controlled Phase 2 trials studying efficacy of the p53-targeting siRNA drug QPI-1002 in prevention of delayed graft function following kidney transplantation and prevention of acute kidney injury following cardiac surgery.

9:00am - 9:30am 30 mins
Info
Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
Development of a Platform Impurity Characterization Method for RNAi Therapeutics
  • Bo Pang, PhD - Associate Director, Analytical Development, Alnylam Pharmaceuticals

This presentation will focus on the development and implementation of a characterization method for impurities detected by denaturing ion exchange chromatography of RNAi therapeutics. The method involves a two-dimensional chromatography approach with separation by ion pair reversed phase chromatography and mass spectrometric identification in second dimension. The practical aspects and the application of the method for conjugated and non-conjugated siRNAs will be discussed.

9:00am - 9:30am 30 mins
Info
Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
Enhancing the Versatility of CRISPR Genome Editing
  • Benjamin Kleinstiver, PhD - Pathology Instructor, Massachusetts General Hospital

Notwithstanding the limitations of their inherent properties, genome editing nucleases have become ubiquitous as research reagents. To broaden their utility, we have developed engineered CRISPR nucleases with improved activity, safety, and targeting range. These novel enzymes improve the prospects of CRISPR technologies for genome, epigenome, and base editing applications.

9:10am - 9:30am 20 mins
Track 3: Peptide Chemistry, Manufacturing and Controls
Assays for Evaluating RLD and Generic Peptide Drugs In Silico and In Vitro in Preparation for ANDA
  • Annie De Groot, MD - Founder, CEO and CSO, Epivax, Inc.
9:10am - 9:30am 20 mins
Track 4: Peptide Discovery, Preclinical and Clinical
Assays for Evaluating RLD and Generic Peptide Drugs In Silico and In Vitro in Preparation for ANDA
  • Annie De Groot, MD - Founder, CEO and CSO, Epivax, Inc.
9:30am - 10:00am 30 mins
Info
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
Novel Chemical Modifications for Improving Pharmacological Function of siRNAs
  • Muthiah (Mano) Manoharan, PhD - Senior Vice President of Drug Discovery, Alnylam Pharmaceuticals, Inc.

This presentation will focus on our recent publications from 2016 and 2017.

9:30am - 10:00am 30 mins
Info
Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
Assay Determination by Mass Spectrometry for Oligonucleotide Therapeutics
  • Mark Madsen, PhD - Assistant Director, Analytical Development & Quality Control, Ionis Pharmaceuticals

Antisense oligonucleotide drugs typically contain product-related impurities that are difficult to resolve chromatographically from the parent oligonucleotide. The presence of these co-eluting impurities hinders the process of determining assay for oligonucleotides based on chromatographic separation alone. An Ion Pair-HPLC-UV-MS assay method using a mass spectroscopy based purity assessment of the main chromatographic peak can be used to quantitate the co-eluting impurities and accurately measure assay for oligonucleotides, but due to the complexity of the IP-HPLC-UV-MS method a more straightforward measure of assay was desired. Therefore, we developed a highly selective electrospray ionization mass spectrometry-based (ESI-MS) assay method that does not rely on separation of the product from its related impurities, rather the oligonucleotide concentration is measured directly from the ESI-MS signal. This method utilizes an internal standard that is co-sprayed with the analyte to compensate for the drift commonly associated with mass spectrometry based quantitation. The internal standard correction enables the method to achieve excellent linearity (R2 = 0.995 from 70 to 130% of the expected sample concentration), repeatability (RSD = 0.5%), intermediate precision (0.6%), and accuracy (measured assay values consistently within 2% of expected). Since this method relies solely on the specificity of the mass spectrometer with no requirement for chromatographic separation of the parent oligonucleotide from product-related impurities, this procedure should be applicable to a wide variety of oligonucleotide therapeutics regardless of chemistry or nucleotide modifications.

9:30am - 10:00am 30 mins
Track 3: Peptide Chemistry, Manufacturing and Controls
Panel Discussion
  • Moderator Trishul Shah, MS - Director Business Development, PolyPeptide Laboratories Inc.
9:30am - 10:00am 30 mins
Track 4: Peptide Discovery, Preclinical and Clinical
Panel Discussion
  • Trishul Shah, MS - Director Business Development, PolyPeptide Laboratories Inc.
9:30am - 10:00am 30 mins
Info
Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
Heavily Modified Guides for SpyCas9-mediated Genome Editing
  • Jonathan Watts, PhD - Associate Professor, RNA Therapeutics Institute, University of Massachusetts Medical School

Chemical modification will likely be necessary for in vivo applications of CRISPR-Cas9-based genome editing. We have identified several heavily-modified versions of crRNA and tracrRNA that are more potent than their unmodified counterparts. In addition, we describe fully chemically modified crRNAs and tracrRNAs (containing no 2'-OH groups) that are functional in human cells.

10:00am - 10:45am 45 mins
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
Networking Refreshment Break in Poster and Exhibit Hall
10:00am - 10:45am 45 mins
Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
Networking Refreshment Break in Poster and Exhibit Hall
10:00am - 10:45am 45 mins
Track 3: Peptide Chemistry, Manufacturing and Controls
Networking Refreshment Break in Poster and Exhibit Hall
10:00am - 10:45am 45 mins
Track 4: Peptide Discovery, Preclinical and Clinical
Networking Refreshment Break in Poster and Exhibit Hall
10:00am - 10:45am 45 mins
Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
Networking Refreshment Break in Poster and Exhibit Hall
10:45am - 11:15am 30 mins
Info
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
Advanced GalNAc-siRNA Platform and Its Therapeutic Applications
  • Torsten Hoffmann, Ph.D. - Chief Scientific Officer, Silence Therapeutics

Silence Therapeutics harnesses the power of RNAi interference (RNAi) to downregulate disease-causing genes. We use GalNAc (N-acetylgalactosamine) moieties to deliver the RNAi triggers (siRNA) directly to the liver hepatocytes. Numerous disorders are associated with expression of various genes in hepatocytes. We will describe how we apply our advanced GalNAc-siRNA platform to build a comprehensive therapeutic pipeline.

10:45am - 11:15am 30 mins
Info
Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
Improving Specificity of Reverse-Phase Analytical Purity Methods for Oligonucleotides
  • Jonathan Neidigh, PhD - Analytical Development Group Leader, Nitto Avecia

Reverse phase analytical methods for oligonucleotides increasingly use triethylamine (TEA) and 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) in mobile phases with C18 columns as first demonstrated by Appfel and colleagues in 1997. The increased use of HFIP-containing mobile phases in analytical methods mirrors the popularity of phosphorothioate modified oligonucleotides and the compatibility of HFIP with mass spectrometry detectors. While the primary literature explores the use of HFIP and amines besides TEA for mass spectrometry detection, the effect of these changes on chromatographic performance is less understood. Furthermore, the emphasis of published reverse phase methods containing HFIP has been to improve the chromatographic resolution of oligonucleotides that differ in length. Analytical methods used to control the manufacturing process and release oligonucleotides, in contrast, need specificity for impurities that differ by length or hydrophobicity from the desired drug substance. As the diversity of oligonucleotide modifications continues to increase, a corresponding expansion in method options is often needed to meet the required analytical specificity. Recent experiences with column chemistries besides C18 and ion-pairing amines other than TEA will be presented to highlight additional options available to achieve the desired analytical specificity.

10:45am - 11:15am 30 mins
Track 3: Peptide Chemistry, Manufacturing and Controls
Bachem’s Experience with the Registration of Peptide APIs in Japan
  • Valeska Kreibich, PhD - Specialist Regulatory Affairs, Bachem AG
10:45am - 11:15am 30 mins
Track 4: Peptide Discovery, Preclinical and Clinical
Bachem’s Experience with the Registration of Peptide APIs in Japan
  • Valeska Kreibich, PhD - Specialist Regulatory Affairs, Bachem AG
10:45am - 11:15am 30 mins
Info
Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
RNA Activation in NASH, Liver Failure and Hepatocellular Carcinoma
  • Nagy Habib, MD - Head of R&D, MiNA Therapeutics Ltd.

Small activating RNAs (saRNAs) are designed to selectively up-regulate therapeutic proteins by recruiting endogenous transcriptional complexes to a target gene, leading to increased expression of naturally processed mRNA. Transcription factor C/EBPα (CCAAT/enhancer-binding protein alpha) is a leucine zipper protein which acts as a master regulator of liver homeostasis and multiple oncogenic processes including cell cycle control, proliferation and angiogenesis. MTL-CEBPA comprises a double stranded RNA payload (CEBPA-51) formulated inside a SMARTICLES® liposomal nanoparticle to specifically target the CEBPA gene. In vitro transfection of CEBPA-51 in Hepatocellular carcinoma (HCC) cell lines leads to up-regulation of CEBPA mRNA, CEBPA protein and inhibition of tumor cell growth. In vivo MTL-CEBPA treatment in a diethylnitrosamine induced rat model of cirrhotic HCC leads to up-regulation of CEBPA mRNA and 80-90% inhibition of tumor growth accompanied by improved liver function. MTL-CEBPA has shown therapeutic activity, including disease regression and improved survival, in a range of other liver disease models including high fat diet, MCD diet, CCl4 liver fibrosis and cirrhosis and liver regeneration models. Increased levels (2 fold) of CEBPA mRNA have been seen in the liver in these models post treatment with MTL-CEBPA. Based on this encouraging preclinical data a Phase 1 trial (standard 3+3 dose escalation study) in patients with HCC or secondary liver cancers has been initiated (Clinical trial information: NCT02716012). MTL-CEBPA is administered as a 1-hr IV infusion on Day 1, 8 and 15 of a 28-day cycle. RECIST tumor response is assessed after every 2 cycles. The primary objective is to determine safety and tolerability; secondary objectives include PK, PD, liver function improvement and anti-tumor activity. Initial findings have confirmed target engagement in the clinic by comparing CEBPA mRNA levels in patient white blood cells before and after administration of MTL-CEBPA. Early clinical results are encouraging. RNA activation can be applied to most of our genome. Therefore, with suitable delivery systems new therapeutic avenues could be explored.

11:15am - 11:45am 30 mins
Info
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
New Drug Discovery Concepts for LNA Therapeutics
  • Troels Koch, PhD - Vice President and Head of Research, RNA Therapeutics, Roche pRED, Roche Innovation Center Copenhagen

Oligonucleotide drug discovery is experiencing significant change, and is shifting from paradigms based primarily upon sequence diversity, towards exploiting compound diversity: Small structural alterations can greatly affect the pharmacological properties of oligonucleotides, and even stereo definition of single phosphorothioate internucleoside linkages (PS) are pharmacological determinants of LNA oligonucleotides. Strategies for identifying improved lead compounds from diastereoisomeric PS mixtures will be illustrated. Our latest modelling and preclinical data show that new opportunities for LNA oligonucleotide drug discovery are enabled when collective sets of diversity parameters are exploited.

11:15am - 11:45am 30 mins
Info
Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
Separation of Composite Impurities of Oligonucleotides
  • Claus Rentel, PhD - Executive Director, Analytical Development/QC, Ionis Pharmaceuticals, Inc.

A screening of different alkylamines, with and without auxiliary modifiers, was performed to investigate their capacity for the separation of impurities in oligonucleotide drugs. Optimal chromatographic conditions for ion pair-reversed phase HPLC were obtained permitting the separation of individual components of composite impurities such as n-1, N3-(2-cyanoethyl)thymine (CNET), deaminated and 3-(2-oxopropyl)imidazopyrimidinone (OPC) impurities.

11:15am - 11:45am 30 mins
Info
Track 3: Peptide Chemistry, Manufacturing and Controls
Automated Flow Peptide Synthesis: Toward Amide Bonds at Nature’s Pace
  • Bradley Pentelute, PhD - Professor, Chemistry, Massachusetts Institute of Technology

Here we describe a rapid flow solid phase peptide synthesis methodology that enables incorporation of an amino acid residue in 40 seconds with amide-bond formation taking only 7 seconds. To demonstrate the broad applicability of this method, it was employed to synthesize hundreds of peptides and proteins.

11:15am - 11:45am 30 mins
Info
Track 4: Peptide Discovery, Preclinical and Clinical
Automated Flow Peptide Synthesis: Toward Amide Bonds at Nature’s Pace
  • Bradley Pentelute, PhD - Professor, Chemistry, Massachusetts Institute of Technology

Here we describe a rapid flow solid phase peptide synthesis methodology that enables incorporation of an amino acid residue in 40 seconds with amide-bond formation taking only 7 seconds. To demonstrate the broad applicability of this method, it was employed to synthesize hundreds of peptides and proteins.

11:15am - 11:45am 30 mins
Info
Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
Antisense Control of RNA Splicing to Treat Genetic Diseases
  • Huw Nash, PhD - Chief Operating Officer and Chief Business Officer, Stoke Therapeutics

Most human genetic diseases are due to loss or reduction of function of a single gene, and currently approved therapeutic strategies are unable to treat most of these inherited deficiencies. Stoke Therapeutics is developing first-in-class medicines to treat such monogenic diseases by leveraging antisense oligonucleotides to increase target protein expression through control of RNA splicing.

11:45am - 12:15pm 30 mins
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
Inhibition of Difficult to Drug Tumor Cell and Immuno-Oncology Targets with Next Generation Antisense
  • A. Robert MacLeod, PhD - Vice President, Onccology and Exploratory Discovery, Ionis Pharmaceuticals
11:45am - 12:15pm 30 mins
Info
Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
Development of a Robust Analytical Control Strategy for the Manufacture of Liquid Oligonucleotide Products
  • Jessica Stolee, PhD - Senior Scientist, Biogen

The control strategy includes the development and implementation of novel methods for ASO analysis, including process analytical technologies, moving the control points upstream, phase appropriate validation of the analytical methods, minimizing redundant testing, and setting specifications for a liquid oligonucleotide product. Where appropriate, Biogen's experience with the regulatory authorities will also be included.

11:45am - 12:15pm 30 mins
Info
Track 3: Peptide Chemistry, Manufacturing and Controls
Considerations in the Development and Implementation of Analytical Methods for Understanding and Controlling the Chemical and Physical Stability of Formulated Synthetic Peptides and Oligonucleotides
  • Paul Walsh, PhD - Principal Scientist, Merck Research Labs

Formulated peptides and oligonucleotides such as sterile liquids combined with administration devices such as multi-use pens have numerous challenges including the chemical and physical stability of the active ingredient.  The analytical tools used to characterize these aspects of the molecule during formulation development and clinical use will be covered.

11:45am - 12:15pm 30 mins
Info
Track 4: Peptide Discovery, Preclinical and Clinical
Considerations in the Development and Implementation of Analytical Methods for Understanding and Controlling the Chemical and Physical Stability of Formulated Synthetic Peptides and Oligonucleotides
  • Paul Walsh, PhD - Principal Scientist, Merck Research Labs

Formulated peptides and oligonucleotides such as sterile liquids combined with administration devices such as multi-use pens have numerous challenges including the chemical and physical stability of the active ingredient.  The analytical tools used to characterize these aspects of the molecule during formulation development and clinical use will be covered.

11:45am - 12:15pm 30 mins
Info
Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
Axiomer® Technology: Therapeutic Oligonucleotides for Directing Site-specific A-to-I Editing by Endogenous ADAR Enzymes
  • Antti Aalto, PhD - Senior Scientist, ProQR Therapeutics

The Axiomer® technology achieves targeted A-to-I editing (effectively an A-to-G change) on RNA, thus enabling the reversal of therapeutically relevant G-to-A mutations. Editing is directed by Editing OligoNucleotides (EONs) which contain specific patterns of chemical modifications that enable recruitment of the endogenous editing enzymes, ADARs, in a highly site-selective manner.

12:15pm - 12:20pm 5 mins
Transition to Spotlight Presentation Rooms
12:20pm - 12:50pm 30 mins
Info
Oligonucleotide Downstream Optimization for Large Scale Manufacturing
  • Amanda Lewis, MSc - Senior Chemist, Oligonucleotide Division, Corden Pharma


The current aqueous downstream purification process used in oligonucleotide manufacturing is limited by Tangential Flow Filtration (TFF) and Lyophilizer capacity.  During diafiltration with water the TFF membranes lose flux as the salt is removed and the product is concentrated.  The point at which the TFF flux approaches zero as the product is concentrated is somewhat compound dependent, however, typical oligonucleotide concentrations are in the range of 50 grams/Liter.  At Corden Pharma Colorado we have developed a process that utilizes Sodium Acetate during the diafiltration stage of TFF and allows for the concentration of Oligonucleotide in the range of 150 – 300 grams/Liter.  After TFF the Oligonucleotide is ethanol precipitated and reconstituted in water for lyophilization.  This process change substantially increases the throughput of both the TFF and the lyophilizer.  Bench scale experiments with supporting analytical data along with a detailed process comparison will be presented.


12:20pm - 12:50pm 30 mins
Info
Analytical Challenges in the Characterisation of Therapeutic Oligonucleotides
  • Speaker Jordi Trafach - Characterisation Manager, Intertek Pharmaceutical Services
12:20pm - 12:50pm 30 mins
Info
Sumitomo's Approach for Large-Scale Synthesis of Long RNA Oligos
  • Akihiro Sakata - Senior Research Scientist, Sumitomo Chemical Co., Ltd.

In this presentation, our approach for synthesizing long RNAs with high purity will be presented. And examples of (1) successful large scale GMP production of 53mer RNA and (2) chemical synthesis of tracrRNAs and sgRNAs with high purity are reported. Our amidites enable the highly efficient synthesis of long RNA oligos, particularly over 50 mer.

12:50pm - 1:55pm 65 mins
Networking Luncheon in Poster and Exhibit Hall
1:55pm - 2:00pm 5 mins
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
Chairperson's Remarks
  • Paul Metz - Principal Consultant, Metz Biotechnology Consulting, LLC
1:55pm - 2:00pm 5 mins
Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
Chairperson's Remarks
  • Chairperson Mimoun Ayoub, PhD - Director and Head of North American and Emerging Markets, CordenPharma International
1:55pm - 2:00pm 5 mins
Track 3: Peptide Chemistry, Manufacturing and Controls
Chairperson's Remarks
  • Chairperson Mimoun Ayoub, PhD - Director and Head of North American and Emerging Markets, CordenPharma International
1:55pm - 2:00pm 5 mins
Track 4: Peptide Discovery, Preclinical and Clinical
Chairperson’s Remarks
  • Bruce Morimoto, PhD - Vice President, Scientific Affairs, Celerion, Inc.
1:55pm - 2:00pm 5 mins
Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
Chairperson's Remarks
  • Stephen Spagnol, PhD - Senior Scientist, Sterile Formulation Sciences, Merck Research Laboratories
2:00pm - 2:30pm 30 mins
Info
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
Effects on Lp(a), Oxidized Phospholipids and Monocyte Inflammation by Antisense Oligonucleotides Targeting Apolipoprotein(a)
  • Nicholas Viney - Executive Director, Clinical Development, Ionis Pharmaceuticals

The preclinical and clinical data in this presentation, represent the evolution of antisense oligonucleotide therapy targeting hepatic apolipoprotein(a) [apo(a)] mRNA. Preclinical data in transgenic animal models successfully predicted significant lowering of lipoprotein(a) [Lp(a)] in humans using the 2' MOE-Gapmer, IONIS-APO(a)Rx. The reductions in Lp(a) in the clinic, were also associated with significant reductions in proinflammatory oxidized phospholipids. We also demonstrated that the promigratory behavior of circulating monocytes to endothelial cells in participants with elevated Lp(a) concentrations was significantly reduced when participants were on the drug, whereas monocytes regained their promigratory phenotype as the drug wore off. Preclinical experiments had further predicted that IONIS-APO(a)-LRx, a Ligand Conjugated Antisense Oligonucleotide (LICA) using the same base sequence conjugated to N-acetyl galactosamine, would be a novel method to inhibit apo(a) with superior potency for reducing Lp(a) and its associated oxidized phospholipids. The GalNAc3 conjugation and the additional modifications in IONIS-APO(a)-LRx resulted in a more than 30-times higher potency in humans with a mean of 92·4% reduction (up to 99% in some) in Lp(a) concentrations, as well as enhanced tolerability. Overall, these data validate antisense-mediated targeting of apo(a) mRNA as the most potent and specific therapy to lower Lp(a) and provide a compelling rationale to test clinical hypotheses.

2:00pm - 2:30pm 30 mins
Info
Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
Microbial Aspects of Oligonucleotide Solutions
  • Julie Ma, PhD - Associate Director, Pharmaceutical Development, Ionis Pharmaceuticals

This presentation will discuss the characteristics of microbial growth in oligonucleotide solutions. These data include growth promotion studies in high concentration oligonucleotide solutions, water activity data, and drug product manufacturing bulk solution bioburden data. Additionally, the value of the data will be highlighted with a case study in a sterility failure investigation on stability where these data were used to support that this result was likely a false positive during the sterility test.

2:00pm - 2:30pm 30 mins
Info
Track 3: Peptide Chemistry, Manufacturing and Controls
Microbial Aspects of Oligonucleotide Solutions
  • Julie Ma, PhD - Associate Director, Pharmaceutical Development, Ionis Pharmaceuticals

This presentation will discuss the characteristics of microbial growth in oligonucleotide solutions. These data include growth promotion studies in high concentration oligonucleotide solutions, water activity data, and drug product manufacturing bulk solution bioburden data. Additionally, the value of the data will be highlighted with a case study in a sterility failure investigation on stability where these data were used to support that this result was likely a false positive during the sterility test.

2:00pm - 2:30pm 30 mins
Info
Track 4: Peptide Discovery, Preclinical and Clinical
Design and Development of a Novel Peptide-centric Drug Delivery System
  • Sheauyu Teddy Hsu, PhD - Managing Director, Adepthera

Therapeutic proteins and peptides are generally administered parenterally. Due to sensitivity to proteolysis and renal clearance, many peptide therapeutics need continuous administration or frequent doses of injections to achieve efficacy, leading to inconvenience and discomfort to patients. To overcome this obstacle, conjugation or fusion to polyethylene glycol (PEG), fatty acids, albumin, antibodies and unstructured proteins such as XTEN and PAS have been developed to extend the half-life of peptide drug candidates. Among them, pegylation was one of the first modifications shown to extend the circulating half-life by increasing the molecular mass of peptide moiety. Likewise, fusion to Fc, albumin, or other large proteins extends the half-life of peptides by increasing the size of the fusion product. By contrast, lipidation extends the circulating half-life of peptides indirectly through non-covalent interactions with albumin and other serum proteins. These modifications have led to the approval of lipidated GLP-1 (liraglutide), GLP-1R agonist-Fc fusion (dulaglutide) and GLP-1R agonist-albumin fusion (albiglutide). Techniques employing slow-release carriers, including oil suspension, crystal particle suspension, liposomes and biocompatible hydrogels such as PLGA polymers, have also been used to improve the pharmacokinetics, dosage accuracy, patient compliance, and efficacy of peptide therapeutics. However, most of these sustained-release techniques are associated with select disadvantages. For example, the support materials may elicit immunogenic responses, and may not degrade after administration (e.g., PEG and silicone). In addition, these formulations frequently require complex fabrication and manufacturing processes. Therefore, alternative techniques that can further improve the delivery and efficacy of peptide therapeutics are much needed. To improve the development of peptide therapeutics, we have developed a unique peptide-centric formulation that can greatly increase the bioavailability of therapeutics and has a minimum immunogenic footprint. In this presentation, we will discuss the discovery and design of this novel peptide-centric drug delivery system as well as its applications in peptide drug development.

2:00pm - 2:30pm 30 mins
Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
Development of New Lipid Nanoparticles for mRNA-based Therapeutics
  • Kerry Benenato, PhD - Director, Chemistry, Moderna Therapeutics
2:30pm - 3:00pm 30 mins
Info
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
Antibody-Olignonucleotide Conjugates (AOC): Exploiting Cell Surface Receptors for Directed Delivery and Uptake of siRNA
  • Arthur Levin, PhD - Executive Vice President, R&D, Avidity Biosciences LLC

Delivery remains a key limitation to the use of oligonucleotide-based therapeutics. Uptake of oligonucleotides is limited by their high molecular weights and hydrophilicity, independent of whether the oligonucleotide works through siRNA, antisense or splice switching mechanisms. It is now known that siRNA and antisense molecules conjugated to GalNAc bind to and are internalized by the asialoglycoprotein receptor on hepatocytes, and recent data demonstrate receptor-mediated uptake increases the efficacy of the GalNAc-conjugated oligonucleotides up to 30-fold. Although there are multiple diseases of hepatocellular origin, effective delivery of oligonucleotides to a larger repertoire of cell types would enable oligonucleotide technologies to be applied more broadly and effectively across a range of diseases. Antibody-drug conjugates (ADCs) have been successfully developed using tumor-targeting monoclonal antibodies (mAbs) to deliver small molecule payloads of oncolytic drugs to tumor cells. Building on that knowledge and combining mAb targeting with siRNA and antisense technologies, we have generated antibody-oligonucleotide conjugates (AOCs). AOCs are stable and can circulate intact in plasma for days. The delivery of the oligonucleotide payload is driven by antibody binding to cell surface receptors, and thus it is possible to get cell-selective uptake. Using AOC technology, we have demonstrated reductions in target mRNA concentrations after systemic administration in cell types that include tumor, liver, muscle, heart and immune cells. Protein reduction, phenotypic changes and functional changes as well as RISC loading all correlate with mRNA knockdown. Selection of cell-specific antibodies, improved siRNA optimization and further advances in antibody technologies and linker strategies are extending the promise of the AOC as a platform.

2:30pm - 3:00pm 30 mins
Info
Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
STP705: Combining Peptides and Oligonucleotides in a Nanoparticle Drug Product
  • Marc Lemaître, PhD - Chief Operating Officer / Principal, Sirnaomics, Inc. / ML Consult

STP705 is a nanoparticle drug product consisting of 2 siRNA and 1 peptide. This product combines several challenges regarding CMC and offers a nice insight on both peptides and oligonucleotides manufacturing challenges. The presentation intends to cover typical topics in a CMC IND submission

2:30pm - 3:00pm 30 mins
Info
Track 3: Peptide Chemistry, Manufacturing and Controls
STP705: Combining Peptides and Oligonucleotides in a Nanoparticle Drug Product
  • Marc Lemaître, PhD - Chief Operating Officer / Principal, Sirnaomics, Inc. / ML Consult

STP705 is a nanoparticle drug product consisting of 2 siRNA and 1 peptide. This product combines several challenges regarding CMC and offers a nice insight on both peptides and oligonucleotides manufacturing challenges. The presentation intends to cover typical topics in a CMC IND submission

2:30pm - 3:00pm 30 mins
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Track 4: Peptide Discovery, Preclinical and Clinical
PASylation: the Biological Alternative to PEGylation
  • Lars Friedrich - Scientist, XL-protein GmbH

PASylation® technology comprises the conjugation – via genetic fusion or chemical coupling – of peptides, proteins and small molecule drugs, with natively disordered biosynthetic polypeptides made of the small L-amino acids Pro, Ala and/or Ser. PAS sequences are highly soluble in physiological solution and exhibit an expanded hydrodynamic volume, leading to retarded kidney filtration and drastically prolonged pharmacokinetics. PAS (poly)peptides are metabolized after cellular uptake, thus side effects such as organ accumulation or vacuolation can be avoided. This presentation will focus on fundamental concepts of PASylation and will highlight recent advances in preclinical applications.

2:30pm - 3:00pm 30 mins
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Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
Progress in the Delivery of mRNA Therapeutics
  • Kim Askew, PhD - Director, Pharmacology, Translate Bio


The potential to deliver an intact mRNA to provide an absent or deficient protein was recognized years ago. But the progress using this strategy, however, has been slow, hampered in part by the difficult hurdle of delivering the intact mRNA to the tissues or cells of interest. We will present progress on two development programs for mRNA therapies directed to two different tissues of interest. One development program is focused on the challenge of demonstrating efficient delivery of cystic fibrosis transmembrane conductance regulator mRNA to lung tissue. A second development program is focused on the challenge of delivering ornithine transcarbamylase mRNA to liver tissue.

3:00pm - 3:30pm 30 mins
Track 1: Oligonucleotide Discovery, Preclinical and Clinical
Some Chemical Insights of Delivery Utilizing GalNAc-siRNA Conjugates
  • Kallanthottathil G. Rajeev, PhD - Senior Director, Chemistry, Alnylam Pharmaceuticals
3:00pm - 3:30pm 30 mins
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Track 2: Oligonucleotide Chemistry, Manufacturing and Controls
Statistical Models for Predicting the Long-Term Storage of Peptide Drug Products Using Accelerated Stability
  • Jameson Bothe, PhD - Associate Principal Scientist, Analytical Sciences, Merck & Co.

Development of robust peptide formulations with desirable long-term chemical and physical stability under short timelines is challenging from a formulation and analytical standpoint. Here we investigate the use of Monte Carlo and Bootstrap statistical methods to make robust predictions of long term chemical stability using short term accelerated stability data.

3:00pm - 3:30pm 30 mins
Info
Track 3: Peptide Chemistry, Manufacturing and Controls
Statistical Models for Predicting the Long-Term Storage of Peptide Drug Products Using Accelerated Stability
  • Jameson Bothe, PhD - Associate Principal Scientist, Analytical Sciences, Merck & Co.

Development of robust peptide formulations with desirable long-term chemical and physical stability under short timelines is challenging from a formulation and analytical standpoint. Here we investigate the use of Monte Carlo and Bootstrap statistical methods to make robust predictions of long term chemical stability using short term accelerated stability data.

3:00pm - 3:30pm 30 mins
Track 4: Peptide Discovery, Preclinical and Clinical
Design and Development of a Glucose-Responsive Insulin Formulation
  • Christopher Rhodes, PhD - President and CEO, Drug Delivery Experts and Chief Technology Officer, Sensulin LLC
3:00pm - 3:30pm 30 mins
Info
Track 5: mRNA, CRISPR and Hot Topics in Oligonucleotides
Optimizing mRNA Therapeutics
  • Patrick Baumhof, PhD - Vice President, Formulation & Delivery, CureVac AG


Messenger RNA based therapeutics offer the unique potential for product specific optimization to enable a tailored therapy for different diseases. The optimization does not only comprise the sequence and structure of mRNA but also the delivery system, that has to be adapted for each tissue in order to enable mRNA expression.

3:30pm - 3:35pm 5 mins
Close of TIDES Conference