Cambridge Healthtech Institute’s Inaugural

Oligonucleotide CMC and Regulatory Strategies

Accelerating Product Development and Commercial Success

2019年3月26 - 27日


To complement our Discovery and Delivery conference, CHI is delighted to announce the launch of Oligonucleotide CMC and Regulatory Strategies as part of OPT Congress 2019. We bring together top scientists and executives from leading biotech and large pharma to share exclusive insights on CMC, manufacturing, analytical and regulatory advancements. Learn how to optimise your product development processes and speed up time to market.

Final Agenda


6:00 pm Dinner Short Course*

6:30-9:30 SC1: Examining the Safety and Toxicity of Nucleic Acid Therapeutics

Nucleic acid drugs continue to deliver on their promise to become a third therapeutic modality, besides small molecules and biologics. Several antisense oligonucleotide drugs have been on the market for some time, while the first RNAi approval was granted last year (2018). In addition, numerous mRNA and CRISPR therapeutic programs have entered clinical stages. Despite the common “nucleic acid” component, the mechanisms of action and of non-specific effects differ for each of these drug types.

Topics to be discussed include:

  • Different types of nucleic acid-based drugs
  • Mechanisms of actions and non-specific effects
  • Current approaches to address non-specific and potentially toxic effects

Aimed at both novice and advanced nucleic drug developers, the course will:

  • Introduce and explain the differences between various types of nucleic acids drugs
  • Summarize our current understanding of the origins of non-specific and potentially toxic effects
  • Provide certain directions as to how to minimize the potential toxic effects of nucleic acids drugs


Muthiah (Mano) Manoharan, PhD, Senior Vice President, Drug Discovery, Alnylam Pharmaceuticals

Dmitry Samarsky, PhD, CTO, Sirnaomics

Additional Instructors to be Announced

*Separate registration required.


7:00 am Registration and Morning Coffee


8:00 Welcome Remarks

Gemma Smith, Senior Conference Director, Cambridge Healthtech Institute

Chairperson’s Opening Remarks

Arthur Levin, PhD, Executive Vice President, Research and Development, Avidity Biosciences

RNA Targeting with Antisense Oligonucleotides: Present and Future

Richard S. Geary, PhD, Senior Vice President, Development, Ionis Pharmaceuticals

The number and chemical breadth of antisense oligonucleotide (ASO) medicines has rapidly grown in both clinical development and in market approvals. As the technology matures and innovations in delivery and increased safety margins are discovered, the ASOs currently in development are well balanced between rare and broad diseases. Some of the unique aspects associated with single strand ASO chemistry, distribution, cell uptake, clinical pharmacology and safety will be discussed as applied to clinical development examples and overall research progress.

8:45 RNAi Medicines in Hematology and Rare Diseases: The Silence Experience

David Horn Solomon, PhD, CEO, Silence Therapeutics

SLN124, a GalNAc-conjugated siRNA targeting hepatic TMPRSS6, reduces serum and tissue iron levels in a rodent model for hereditary hemochromatosis type 1, both as monotherapy and in combination with an oral iron chelator. SLN124 also demonstrates therapeutically relevant, dose-dependent and long-lasting effects on iron stores, erythropoiesis and anemia in an animal model for beta-thalassemia. The first-in-human study is planned to commence in 2019 in beta-thalassemia and myelodysplastic syndrome patients.

9:15 PANEL DISCUSSION: Bridging the Gap between Discovery, Development and Compliance

Moderator: Arthur Levin, PhD, Executive Vice President, Research and Development, Avidity Biosciences


Richard Geary, PhD, Senior Vice President, Development, Ionis Pharmaceuticals

Dmitry Samarsky, PhD, CTO, Sirnaomics

Lubo Nechev, PhD, Vice President, Process and Analytical Sciences, Alnylam Pharmaceuticals

10:00 Networking Coffee Break


10:45 Chairperson’s Opening Remarks

Marc Lemaitre, PhD, COO, Sirnaomics and ML Consult

10:50 FEATURED PRESENTATION: Developing the CMC Strategy for ONPATTRO™ (patisiran)

Lubo Nechev, PhD, Vice President Process and Analytical Sciences, Alnylam Pharmaceuticals

ONPATTRO (patisiran), the first RNA interference (RNAi) therapeutic approved in the United States and the European Union is targeting transthyretin (TTR) for the treatment of hereditary ATTR amyloidosis. Patisiran comprises a double stranded RNA API in a lipid nanoparticle formulation for intravenous administration. The presentation will discuss the development of the CMC strategy for patisiran from early stage to approval.

11:20 Stage 3 Continued Process Verification of Commercial Oligonucleotide Synthesis: Monitoring Strategy and Process Observations

Francis Ring, Assistant Director, Manufacturing & Operations, Ionis Pharmaceuticals

As more Oligonucleotide Therapies are approved, it is important to develop appropriate Continued Process Verification procedures, both to satisfy regulatory requirements and to inform future process development. Since 2010, across three compounds, Ionis has been performing validated solid-phase syntheses. The process data collection, analysis, and reporting strategy will be described, along with their evolution over time. Additionally, notable process trends and observations will be presented.

11:50 Enabling Rapid Start-Up with End-to-End Antisense Oligonucleotide Capability and Streamlined Business Processes

Sheron Branham, Associate Director, ASO Process Engineering and Manufacturing, Biogen

Biogen is the first innovator to internalize end-to-end ASO manufacturing capability while others have chosen to outsource. By vertically integrating their ASO supply chain, Biogen has been able to significantly reduce turnaround time and supply risk. The presentation will highlight how the facility and the business processes were designed to maximize flexibility and prepare for potential rapid growth in the future.

12:20 pm Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:50 Session Break

2:00 siRNA Case Study: Development and Implementation of Late Stage CMC Strategies

Vidhya Gopalakrishnan, PhD, Senior Vice President, Pharmaceutical Development, Quark Pharmaceuticals

2:30 Combining siRNA and Peptides for Improved Delivery – CMC Aspects

Marc Lemaitre, PhD, COO, Sirnaomics and ML_Consult

Branched peptides containing histidines and lysines (HK) have been shown to be effective carriers for DNA and siRNA. We will discuss the specific aspects of CMC for the development of such a product.

3:00 Refreshment Break in the Exhibit Hall with Poster Viewing

3:45 Sponsored Presentation (Opportunity Available)

4:15 CMO Outsourcing: An Integrated Approach

Joe DeCourcey, Head Manufacturing Science and Technology, Sarepta Therapeutics

4:45 CMC Challenges Associated with Oligonucleotide Products for Intravitreal Administration

Bianca Matthee, Vice President, Manufacturing & Pharmaceutics, ProQR Therapeutics

Oligonucleotide product design for intravitreal administration can be challenging from a formulation, analytical and manufacturing perspective. There are stringent specifications these products need to adhere to for the purpose of safely delivery the oligo into the eye. This presentation will elaborate on CMC challenges to overcome in manufacturing and will include some examples.

5:15 Welcome Reception in the Exhibit Hall with Poster Viewing

6:15 Dinner Short Course Registration*

6:30-9:30 SC2: Oligonucleotide-Based Drugs for Cancer Immunotherapy

Oligonucleotide-based therapies are now gaining attention as an alternative to antibody and small molecule-based therapies for cancer immunotherapy. In cancers where current treatment options are limited by efficacy and specificity, oligonucleotide-based drug modalities are offering a better alternative. This course will bring together experts who will share their perspectives on the opportunities and challenges underlying the generation of novel, more targeted and effective oligonucleotide-based therapies for cancer immunotherapy. Some topics that will be discussed include:

  • Modulating the tumor microenvironment using novel approaches and drug modalities
  • Emerging immuno-oncology targets (TLRs, STING, RIG-1 and more) for intervention using oligos
  • Preclinical and clinical evaluation of new immunomodulatory pathways and nucleic acids
  • Synthesis and delivery of oligonucleotides (siRNA, antisense, aptamers and others) for cancer immunotherapy


Shanthi Ganesh, PhD, Associate Director, Preclinical Oncology, Dicerna Pharmaceuticals, Inc.

Ekambar R. Kandimalla, PhD, CSO, Exicure, Inc.

Additional Instructors to be Announced

*Separate registration required.


8:00 am Breakfast Breakout Roundtable Discussions


9:15 Chairperson’s Opening Remarks

Paul Manley, President & Principal Consultant, Orvieto Consulting

9:20 Regulatory Expert to be Announced

9:50 Regulatory CMC Experience for OnpattroTM (patisiran), a First-in-Class siRNA Therapeutic

Samantha Gao-Sheridan, PhD, Senior Director, Regulatory Affairs CMC, Alnylam Pharmaceuticals

OnpattroTM (patisiran) became the first FDA/EMA-approved treatment of polyneuropathy caused by hereditary transthyretin-mediated amyloidosis (hATTR), and the first regulatory approval of a new class of drugs called small interfering ribonucleic acid (siRNA). CMC development of OnpattroTM involved extensive innovation, challenges due to complexity of the product (consisting of double-stranded siRNA and lipid components including novel excipients), and well-planned interactions with regulatory agencies. Regulatory CMC experience on Onpattro development and registration will be provided.

10:20 Sponsored Presentation (Opportunity Available)

10:50 Coffee Break in the Exhibit Hall with Poster Viewing

11:35 Strategies for Identity Testing of Oligonucleotide Therapeutics

Hong Jiang, Scientist II, Analytical Development, Biogen

Due to their polymeric nature and high molecular weight, establishing identity of oligonucleotide therapeutics is significantly more challenging compared to synthetic small molecules. The commonly accepted identity tests for small molecules, such as IR spectrum and retention time matching with a reference standard, are generally insufficient for identity confirmation of an oligonucleotide. In this presentation I will discuss various risk factors during the manufacturing process that can potentially lead to an oligonucleotide of an incorrect structure, along with currently available analytical methods that can detect certain structural changes and confirm the identity. A risk-based framework for the selection of identity tests and how it can be integrated into a robust control strategy will be proposed.

12:05 pm Regulatory Agency Questions and Learnings from Recent Commercial Submissions

Jennifer Franklin, Director, CMC Regulatory Affairs, Ionis Pharmaceuticals

Recent CMC questions received from global regulatory agencies for an antisense oligonucleotide drug will be detailed, along with a discussion of the response strategies that led to their successful resolution, and ultimately, to drug approval. Regulatory challenges and learnings from the review and approval process in the US, EU, and Canada will also be examined.

12:35 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

1:05 Dessert Break in the Exhibit Hall with Poster Viewing

2:00 Accelerating Pathway to Approval: Points to Consider in Conducting Productive Regulatory Interactions and Making Successful IND/CTA Submissions

Paul Manley, President & Principal Consultant, Orvieto Consulting

FDA and EU National Authorities have similar approaches to how they review and approve clinical trial applications, however key areas of difference need to be appreciated in order to achieve successful applications. This presentation provides advice for oligonucleotide companies covering: pre-submission dialogue, differences in application content and Regulatory Agency review approaches and commitments during and after trial completion.

2:30 PANEL DISCUSSION: How to Successfully Prepare for a Regulatory Submission and Overcome Common Hurdles

Panelists: Jennifer Franklin, Director, CMC Regulatory Affairs, Ionis Pharmaceuticals

Samantha Gao-Sheridan, Senior Director, Regulatory Affairs CMC, Alnylam Pharmaceuticals

Paul Manley, President & Principal Consultant, Orvieto Consulting

3:15 Refreshment Break in the Exhibit Hall with Poster Viewing


4:00 Examining the Results of Two New Analogues: Thiomorpholino and Phosphoramidimidate DNA

Marvin Caruthers, PhD, Distinguished Professor, University of Colorado

Case Study from GeneVant Sciences

Bo Rode Hansen, President & CSO, GeneVant Sciences

Implementing the Use of Antisense in the Brain

Jonathan Watts, PhD, Associate Professor, UMass Medical School

5:00 Close of Oligonucleotide CMC and Regulatory Strategies”

5:00 Dinner Short Course Registration*

5:30-8:30 SC3: CRISPR-Based Gene Editing for Targeted Therapies

While the challenges and risks associated with oligonucleotide therapies still remain, there is a new and better understanding of how genes can be effectively manipulated and delivered. With the rise of gene editing tools and enhanced knowledge of targeted delivery, these therapeutic modalities are once again being embraced with renewed hope and enthusiasm. This course helps you understand how gene editing – particularly the one enabled by the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system – works, and how it can be used to help develop targeted therapies with good efficacy and delivery.


Clifford Steer, MD, Professor of Medicine and Genetics, Cell Biology and Development; Director, Molecular Gastroenterology Program, University of Minnesota Medical School

Ciro Bonetti, PhD, Scientist, Regeneron Pharmaceuticals

Eric Kmiec, PhD, Director, Gene Editing Program and Senior Research Scientist, Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System

*Separate registration required.

* 活动内容有可能不事先告知作更动及调整。