Cambridge Healthtech Instituteの第8回年次会議

Oligonucleotide Discovery and Delivery
(オリゴヌクレオチドの発見とデリバリー)

設計、デリバリー、性能の最適化

2023年3月13 - 14日、EDT(米国東部標準時)

Cambridge Healthtech Instituteの「オリゴヌクレオチドの発見とデリバリー」会議では、新しい化学、新規のデリバリーメカニズム、最も重要な前臨床および臨床の進歩に関する詳細なセッションにより、発見、化学、デリバリーの最前線における最新の戦略を明らかにします。業界や学界の専門家が、アンチセンス、RNA、GalNAc、アプタマー、コンジュゲート、その他の新しいモダリティに関する詳細なケーススタディを提供し、次世代の標的オリゴヌクレオチド医薬への道を切り開きます。

3月13日(月)

Main Conference Registration9:15 am

Welcome Remarks by Conference Organizer10:40 am

GalNAc-RNAi THERAPEUTIC PLATFORM
GalNAc-RNAi医薬プラットフォーム

10:50 am

Chairperson's Opening Remarks

Chandra Vargeese, PhD, CTO & Head, Platform Discovery Sciences, WAVE Life Sciences

10:55 am FEATURED PRESENTATION:

GalAhead: A Novel Therapeutic GalNAc-RNAi Platform to Downregulate Single and Multiple Genes

Dmitry Samarsky, PhD, CTO, Sirnaomics

Sirnaomics has developed a proprietary GalNAc-RNAi therapeutic platform, GalAhead, comprising two key technological components - mxRNA (miniaturized RNAi triggers) and muRNA (multi-unit RNAi triggers). mxRNAs are composed of single ~30 nt long oligonucleotides to downregulate individual genes, while muRNA molecules are comprised of multiple oligonucleotides (2 or more) to simultaneously silence two or more targets. We will present data validating these two technologies both in vivo and in vitro, as well as a progress report on quickly expending GalAhead therapeutic pipeline.

TRANSLATION TO THE CLINIC
臨床への移行

11:25 am

Impact of Phosphoryl Guanidine on Oligonucleotide Pharmacology: Translation to the Clinic

Chandra Vargeese, PhD, CTO & Head, Platform Discovery Sciences, WAVE Life Sciences

We have applied phosphoryl guanidine backbone chemistry (PN chemistry) to oligonucleotides. Similar to the phosphorothioate (PS) backbone, PN is a chiral modification, so we apply it as part of our stereopure platform. The application of PN chemistry has improved the pharmacological properties of our stereopure molecules in preclinical studies across oligonucleotide modalities. Early data from our ongoing clinical trials suggests these improved pharmacological properties are translating into the clinic.

11:55 am

FORCE Platform for Delivery of Oligonucleotides for the Treatment of DM1 and DMD: Moving from Bench to Clinic with DYNE-101 and DYNE-251

Oxana Beskrovnaya, PhD, CSO, Dyne Therapeutics

The FORCE platform is a novel technology that harnesses the natural expression of TfR1 on muscle cells for targeted delivery of rationally designed therapeutics with the goal of addressing the underlying cause of rare genetic muscle diseases. Data from Duchenne muscular dystrophy (DMD) and myotonic dystrophy type 1 (DM1) preclinical models demonstrate that administration of DYNE-251 and DYNE-101, respectively, results in delivery of oligonucleotides directly to cardiac and skeletal muscle. DYNE-251 and DYNE-101 are expected to begin patient dosing in Phase I/II clinical trials in mid-2022.

Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:25 pm

Grand Opening Dessert Break in the Exhibit Hall with Poster Viewing12:55 pm

RECENT ADVANCES WITH RNAs
RNAによる最近の進歩

1:35 pm

Chairperson's Remarks

Dmitry Samarsky, PhD, CTO, Sirnaomics

1:40 pm

FEATURED PRESENTATION: Finding the Needle in the miRNA Haystack: Rethinking the miRNA Discovery Platform

David Corey, PhD, Professor, Department of Pharmacology, UT Southwestern

Human miRNAs have the potential to be versatile agents for regulating gene expression. Connecting a miRNA first to recognition of mRNA sequences and then to control of specific cellular functions is more difficult than has been widely assumed, slowing therapeutic applications. Here I describe approaches to find out when and where miRNAs are most likely to play important roles in disease.

2:10 pm

Expanding Oligonucleotide Target Space through RNA Editing

Paloma H. Giangrande, PhD, Vice President, Platform and Discovery Sciences Biology, Wave Life Sciences

We have developed AIMers, A-to-I RNA base editing oligonucleotides that engage endogenous ADAR enzymes to edit RNA sequences with high efficiency and specificity. Our first RNA editing program was launched to correct a disease-causing, protein-coding mutation in SERPINA1 mRNA. RNA editing is a versatile technology, with enormous opportunity to address diseases with unmet need. We will provide an update on our preclinical efforts to expand the target space for this new technology, including modulating protein-protein interactions and upregulating gene expression.

Sponsored Presentation (Opportunity Available)2:40 pm

Refreshment Break in the Exhibit Hall with Poster Viewing3:10 pm

PLENARY SESSION
プレナリーセッション

3:50 pm

Plenary Chairperson's Remarks

Dmitry Samarsky, PhD, CTO, Sirnaomics

3:55 pm PLENARY PRESENTATION:

Biological Studies with Thiomorpholino Oligonucleotides

Marvin Caruthers, PhD, Distinguished Professor, University of Colorado

Currently underway are more than 20 biological studies focused on the use of thiomorpholino oligonucleotides (TMOs) as a therapeutic drug for the treatment of various genetic diseases. These collaborations are being carried out with cells in culture and several have progressed to studies in mouse models. Without exception, TMOs are more active than any other analogue tested and, in one case, a TMO is active under conditions where the 2'-MOE analogue is toxic to mice in the same treatment group.

4:25 pm PLENARY PRESENTATION:

Advances in CRISPR Genome Editing for Therapeutics Application

Rubina Parmar, PhD, Vice President, Chemistry & Delivery Sciences, Intellia Therapeutics, Inc.

At Intellia, we are building a full-spectrum genome editing company. We are deploying the industry's broadest and deepest toolbox, including novel editing and delivery solutions, to harness the immense power of CRISPR-based technologies for in vivo and ex vivo therapeutic applications, each with the potential to revolutionize the future of medicine. In this presentation, we will share the advances in the therapeutic application of CRISPR/Cas9 for genome editing.

4:55 pm PLENARY PRESENTATION:

Recent Developments in Oligo Conjugates

Arthur Levin, PhD, CSO, Avidity Biosciences

The promise of oligonucleotide therapeutics is to use Watson-Crick-Franklin base-pairing rules to design drugs directly and rationally based on genomic information. Until recently, that promise has remained elusive because of cell barriers to oligonucleotide uptake. Receptor-mediated uptake through bioconjugation oligonucleotides has changed that. Avidity's AOC technology uses monoclonal antibodies to cell surface proteins that are internalized in order to facilitate the functional delivery of oligonucleotide therapeutics into a broad range of cell and tissue types. 

Welcome Reception in the Exhibit Hall with Poster Viewing5:25 pm

Close of Day6:25 pm

3月14日(火)

Registration and Morning Coffee7:45 am

RECENT ADVANCES WITH RNAs
RNAによる最近の進歩

8:30 am

Chairperson's Remarks

Leo Ziqing Qian, PhD, Co-Founder & Vice President, Discovery Research, Entrada Therapeutics

8:35 am

Asymmetric siRNA Therapeutics Targeting Skin, Eye, and Liver Diseases

Dong-Ki Lee, PhD, CEO, OliX Pharmaceuticals

RNAi therapeutics has potential to target a variety of disease indications by targeting hepatic as well as extra-hepatic target genes. To achieve this goal, the development of optimal delivery methods for each target organ is essential. We have successfully established lipid-conjugated asymmetric siRNA (asiRNA) targeting skin and ocular tissues, to develop therapeutic programs against hypertrophic scar, androgenic alopecia, and age-related macular degeneration. We also established GalNAcTang, our own GalNAc-based liver targeting strategy to tackle diseases such as HBV and NASH. Preclinical and clinical updates on each program will be presented.

9:05 am

Development of Stem-Loop RNA Oligonucleotide Therapeutics

Radhakrishnan Iyer, PhD, CSO, RIGImmunce, Inc.

RIGImmune is developing a new class of RNA oligonucleotides that activate the innate immune sensor RIG-I. The lead compound is being developed as a pan-viral agent and for immuno-oncology.

Sponsored Presentation (Opportunity Available)9:35 am

10:05 amBreakout Discussions

Breakout discussions provide an opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Please visit Breakout Discussions for a complete listing of topics and descriptions.

IN-PERSON BREAKOUT DISCUSSION:

Integrating Innovative Technologies into Oligo Therapeutics Discovery and Delivery

June Park, PhD, CEO, siRNAgen Therapeutics

  • What are emerging innovative technologies in oligo R&D, focusing on in particular:
    - AI/machine learning
    - Delivery strategies
    - Safety screening
  • Challenges in the adoption and implementation of innovative technologies
  • Strategies to keep up with the rapidly evolving field
  • What's next in oligo discovery and delivery innovation?

Coffee Break in the Exhibit Hall with Poster Viewing10:50 am

11:30 am

GalNac-RNA for the Lung - Targeted Oligonucleotide Therapy for Respiratory Diseases

Thomas Frischmuth, PhD, CEO, rnatics

rnatics has developed first-in-class, macrophage-specific delivery technology for targeted RNA therapeutics. Cell surface receptors naturally present in high density on macrophages enable the targeted delivery to tissue resident macrophages through tailored carbohydrate ligands. The achievement of specific and efficient delivery to macrophages is a breakthrough technology that enables access to multiple tissues previously not accessible to RNA therapeutics. The most advanced drug candidate, RCS-21, is in development for the treatment of severe cases of COVID-19. RCS-21 is delivered by inhalation and addresses the macrophage-mediated lung damage following a SARS-CoV-2 infection. We aim to start clinical trials in 2023.

OPTIMIZING DESIGN, DELIVERY, AND PERFORMANCE
設計、デリバリー、性能の最適化

12:00 pm FEATURED PRESENTATION:

Robust Gene Silencing in the Brain and Lung

Jonathan Watts, PhD, Associate Professor, RNA Therapeutics Institute, University of Massachusetts Chan Medical School

Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:30 pm

Session Break1:00 pm

1:40 pm

Chairperson's Remarks

Leo Ziqing Qian, PhD, Co-Founder & Vice President, Discovery Research, Entrada Therapeutics

1:45 pm

Endosomal Escape Vehicle-Oligonucleotide Conjugates for the Targeted Upregulation and Downregulation of Gene Expression

Leo Ziqing Qian, PhD, Co-Founder & Vice President, Discovery Research, Entrada Therapeutics

We have developed a novel oligonucleotide delivery platform by conjugation with Entrada's proprietary Endosomal Escape Vehicle (EEV) technology, a class of cyclic peptides designed to facilitate intracellular delivery and endosomal escape. Preclinical studies in several disease models have confirmed the significant therapeutic potential of this approach and demonstrated that the EEV platform can serve as a general and highly efficient delivery technology for the targeted delivery of therapeutic oligonucleotides.

DEEP LEARNING AND ADVANCED COMPUTATIONAL APPROACHES
深層学習と高性能コンピューターによるアプローチ

2:15 pm

Using Computation to Enhance Target ID in RNAi Drug Discovery

James Longden, PhD, Head, Discovery Biology, e therapeutics plc

e-therapeutics ("ETX") combines data, computation and biology to discover and develop RNAi medicines at speed. The company generates mechanistic network biology models, then analyzes these networks to interrogate disease process complexity, test therapeutic hypotheses, identify novel drug targets, and then design nucleotide sequences. ETX has built a comprehensive knowledgebase of proprietary and public hepatocyte-relevant data that it mines using deep learning and then employs proprietary GalNAc-siRNA technology to target hepatocytes in the liver.

Refreshment Break in the Exhibit Hall. Last Chance for Poster Viewing2:45 pm

PLENARY SESSION
プレナリーセッション

3:15 pm

Plenary Chairperson's Remarks

Jonathan Watts, PhD, Associate Professor, RNA Therapeutics Institute, University of Massachusetts Chan Medical School

3:20 pm PLENARY PRESENTATION:

Nucleic Acid Delivery Systems for RNA Therapy and Genome Editing

Daniel Anderson, PhD, Professor, Chemical Engineering, Massachusetts Institute of Technology

Here we describe our work developing nanoformulations for RNA therapy and genome editing. Libraries of degradable polymers and lipid-like materials have been synthesized, formulated, and screened for their ability to deliver RNA payloads inside cells. These nanoformulations facilitate in vivo delivery to a range of tissues and can enable targeted gene suppression with siRNA, gene expression with mRNA, or even permanent genetic editing using the CRISPR/Cas9 system.

3:50 pm PLENARY PRESENTATION:

Advances in Chemistry Made RNAi Therapeutics Possible

Mano Manoharan, PhD, Distinguished Scientist & Senior Vice President, Innovation Chemistry, Alnylam Pharmaceuticals

For siRNAs, chemical modifications are necessary to regulate metabolic stability, potency (through effects on the interaction with the Ago2 enzyme and the targeted mRNA strand), and safety (impacted by metabolites and on-target specificity). We have evaluated numerous chemical modifications beyond the standard 2'-O-methyl, 2'-fluoro, and phosphorothioate linkages. These include backbone chiral phosphorothioates, glycol nucleic acids, altriol nucleic acids, gem 2'-deoxy-2'-α-F-2'-β-C-methyl, 5'-morpholino, and amino-oxy click chemistry (AOCC) mediated conjugates. Furthermore, novel spatial architectures like circular siRNAs have also been evaluated. This presentation will summarize how chemistry has made possible the currently exciting world of RNAi therapeutics.

4:20 pm PLENARY PRESENTATION:

Development of mRNA-Based Vaccines

Steve Pascolo, PhD, Senior Scientist, University Hospital of Zurich; Founder & CEO, Miescher Pharma GmbH

The safety and efficacy of mRNA-based vaccines was evidenced during the COVID-19 pandemic: less than one year after the publication of the sequence of SARS-CoV-2, mRNA vaccines against COVID-19 were approved. More mRNA vaccines (against infectious diseases and cancer) are in clinical developments and are expected to be approved in the coming years. New mRNA formats (circular, replicating) and formulations (lipoplexes and polyplexes) are also being tested to further improve mRNA vaccines. I will present the past, present and future of mRNA vaccines.

Close of Conference4:50 pm

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OLIGO DISCOVERY AND DELIVERY