Cambridge Healthtech Instituteの第2回年次会議
2023年8月16 - 17日、EDT（米国東部標準時）
Registration and Morning Coffee7:30 am
CHALLENGES AND OPPORTUNITIES
Public Perception of mRNA Therapies: The Patient Matters
Ben Locwin, Vice President, Project Solutions, Black Diamond
While over the past couple of decades, mRNA technology has advanced dramatically and provided one way out of the COVID-19 pandemic, at the same time public perception and favor has polarized, and strong and vocal holdouts have unequivocally affected general interest and uptake.
mRNA-BASED THERAPIES FOR ONCOLOGY AND OTHER INDICATIONS
Novel RNAs for Treating Cancer
Mark Kay, MD, PhD, Dennis Farrey Family Professor of Pediatrics and Genetics, Department of Pediatrics and Genetics, Stanford University
I will discuss a miRNA that has long been known to have anti-oncogenic properties and is derived from a long primary transcript, which we recently discovered has a separate tumor suppressor function. The role and anti-oncogenic mechanism by which this long non-coding RNA functions will be discussed. In addition, the therapeutic implications for therapeutic intervention will also be examined.
Sponsored Presentation (Opportunity Available)9:30 am
Coffee Break in the Exhibit Hall with Poster Viewing10:00 am
mRNA-BASED THERAPIES FOR ONCOLOGY (CONT.)
Next-Generation Self-Replicating RNA Vectors for Vaccines and Immunotherapies
Shigeki Miyake-Stoner, PhD, Director R&D & Head, Technology, Replicate Bioscience, Inc.
Self-replicating RNA (srRNA) technology has been enabled for vaccines, and requires lower doses than conventional mRNA, due to its ability to amplify in situ. Most srRNA approaches are derived from the same alphavirus backbone. Since viruses can differentially impact host cell mechanisms, we have explored alternate alphaviral vectors to assess their biological utility. We show that new synthetic srRNA vectors can enable us to build better next-generation therapies.
miRNA-Based Logic Circuits Encoded on Self-Amplifying RNA for Highly Specific Cancer Cell Classification
Ron Weiss, PhD, Professor, Biological Engineering, Massachusetts Institute of Technology
We developed self-amplifying RNA and modified RNA platforms into vectors capable of carrying synthetic circuitry payloads that can provide a variety of desirable dynamics. We also encoded miRNA target sites on our RNA vectors to provide for highly specific cell type classification. We are using this technology to create next-generation cancer immunotherapy RNA vectors capable of activating therapeutic payloads discriminately in cancer cells.
Applying an mRNA Vaccine Platform and New Developments to Next-Generation Products
Nicole Schiavone, PhD, Principal Scientist, Pfizer Inc.
The SARS-CoV-2 virus continues to evolve which presents the need to adapt and broaden protection provided by mRNA vaccines. This talk will highlight the importance of robust analytical methods to enable rapid mRNA vaccine development. It will also feature the application of Pfizer’s established mRNA analytical platform in combination with new developments to support next-generation products aimed at addressing the continuously changing viral landscape.
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:10 pm
Refreshment Break in the Exhibit Hall with Poster Viewing12:40 pm
CONSIDERATIONS FOR DEVELOPMENT OF mRNA VACCINES AND THERAPIES
Developing Dendritic Cell-Targeted mRNA Vaccines
Daryl Drummond, CSO, Akagera Medicines, Inc.
Akagera is developing ligand-targeted lipid nanoparticles encapsulating mRNA as vaccines against some of the world's most intractable infectious diseases. Here we describe our efforts to develop novel ionizable lipids to improve endosomal escape and pair them with small molecule lipid ligands to increase their uptake and subsequent expression in dendritic cells. This increased efficiency has significant potential impact on manufacturing capacity, cost of goods, tolerability, and flexibility to incorporate multiple mRNAs.
Combinational RNA Therapies and Novel Strategies for Multi-Cargo Distribution
Jay Sarkar, PhD, Visiting Scholar, Stanford University
The value of the RNA modality comes from its nature as a precise, versatile, and real-time instruction coding. Its initial use cases utilize a single action coding - for instance, for the production of a viral antigen component. However, more advanced applications are rapidly developing around coding entire instruction sets for combinational logic and benefit. The promise of such approaches will be discussed along with novel strategies for implementing them.
Presentation to be Announced2:45 pm
Refreshment Break in the Exhibit Hall with Poster Viewing3:00 pm
PLENARY KEYNOTE: LEADING TO TOMORROW'S ADVANCES
Current and Future Trends in Biomanufacturing of New Modalities
Konstantin B. Konstantinov, PhD, CTO, Codiak Biosciences
Using exosomes as an example, this presentation examines the current and future trends in biomanufacturing, and the technologies needed to manufacture emerging modalities at scale. Traditional biomanufacturing methods do not provide the industrialized, commercially scalable, highly efficient and reproducible manufacturing process essential for this new class of biotherapeutics- so we built it from the ground up.
The Digitalization of Biomanufacturing
Richard D. Braatz, PhD, Edwin R. Gilliland Professor, Chemical Engineering, Massachusetts Institute of Technology
A fully instrumented testbed is described for the end-to-end integrated and continuous manufacturing of monoclonal antibodies. The testbed consists of parallel bioreactors, simulated moving bed chromatography systems for capture and polishing, bespoke viral inactivation, and a MAST auto-sampling system. Experimental results are compared with a digital twin for continuous runs lasting 30 to 60 days each, which include variations in metabolites and glycosylation profiles in designed experiments. The increased consistency in the glycosylation profile of the monoclonal antibodies being produced is quantified when going from batch to semi-batch to perfusion mode, and when moving from start-up to quasi-steady conditions.
Networking Reception in the Exhibit Hall with Poster Viewing5:00 pm
Close of Day6:00 pm
Registration and Morning Coffee7:30 am
ANALYTICAL GUIDANCE AND TOOLS FOR mRNA VACCINES & THERAPIES
Biophysical Properties of mRNA
Alois Jungbauer, PhD, Professor & Head, Biotechnology, Institute of Bioprocess Science and Engineering, University of Natural Resources and Life Sciences (BOKU)
- The flexibility of mRNA is a challenge for chromatography separation
- Structural interconversion upon adsorption is more pronounced than observed with proteins
- How pure is pure for mRNA therapeutics and vaccines
mRNA Quality Assessment and USOP Guideline
John Cipollo, PhD, Senior Principal Scientist and Team Lead, USP
Following the rapid and successful deployment of mRNA vaccines during the COVID-19 pandemic, over 150 mRNA vaccines are in development, with further therapeutic applications in oncology, cardiovascular and genetic diseases. This presentation will provide an overview of USP updated guidelines based on stakeholder feedback and further assessment and qualification of analytical methods presented therein to address common quality attributes for mRNA products.
Coffee Break in the Exhibit Hall with Poster Viewing9:00 am
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 the breakout discussions page on the conference website for a complete listing of topics and descriptions.
ANALYTICAL GUIDANCE AND TOOLS FOR mRNA VACCINES & THERAPIES (CONT.)
High-Throughput mRNA Integrity Analysis and mRNA Fragment Characterization
Gaofei He, PhD, Principal Scientist, Pfizer Inc.
Ribonucleic acids (RNAs) have recently shown success in the vaccine space and promise as candidates for new therapeutics. For these large RNA molecules, RNA integrity is a key critical quality attribute (CQA) related to the translation of the intended RNA sequence. This quality attribute is tested and monitored for drug substance and drug product, both at manufacturing release and on stability. RNA integrity been assessed as a key quality attribute for optimization of the drug substance and drug product processes. This presentation discusses a capillary electrophoresis-based methodology to separate and resolve RNA of varied size and length.
mRNA Vaccines and Therapeutics: Development, Delivery, Safety, and Manufacturing
Trevor P. Castor, PhD, President & CEO, Aphios Corp.
Significant advances have been made over the last three decades in the development, delivery, safety and manufacturing of mRNA constructs for vaccines and therapeutics. This is evident from the tremendous contributions that mRNA vaccines have made in containing the COVID-19 pandemic. The goal of this presentation is to review and address fundamentals and unit operations for mRNA functionality, stability, delivery, safety and manufacturing. Within the context of this review, we will provide insights and novel technologies that may be helpful for furthering the development, delivery, safety and manufacturing of mRNA vaccines and therapeutics for infectious diseases, genetic disorders and cancers.
Sponsored Presentation (Opportunity Available)11:30 am
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:00 pm
Refreshment Break in the Exhibit Hall & Last Chance for Poster Viewing12:30 pm
LNPs & NOVEL DELIVERY SYSTEMS: FORMULATION, ANALYSIS, PROCESS DEVELOPMENT, AND DELIVERY
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.
Equilibrium and Stability Considerations in the Development and Manufacturing of Liposome and LNP Formulations
Christoph Brandenbusch, PhD, Assistant Professor, Bioprocess Separations & Biologics Formulation Development, TU Dortmund University, Germany
Liposome and LNP formulations have evolved as highly potent drug delivery systems. Recent literature gives valuable insights in developing and manufacturing these formulations, with focus mainly set on delivering different liposome and LNP compositions/sizes. This presentation will give some insight into thermodynamic equilibrium considerations, such as long-term (size) stability of liposomes and LNPs at various temperature, as well as equilibrium radius considerations in manufacturing liposomes and LNPs.
Considerations and Challenges in Early LNP Development for Non-Viral Gene Therapy
Yuefei Shen, PhD, Principal Scientist, CMC Drug Product Development, Sanofi
Lipid nanoparticle (LNP) technology, as currently one of the most promising and emerging technologies, shows the ability to deliver nucleic acid therapeutics for non-viral gene therapy (NVGT). Compared to intramuscular vaccine delivery, intravenous (i.v.) delivery of a LNP formulation for gene therapy shows unique challenges. An LNP formulation for gene therapy via i.v. may require different lipid and formulation design. Here, we will discuss the considerations and challenges in early LNP development and impact on tissue targeting for NVGT.
Networking Refreshment Break2:40 pm
LNPs & NOVEL DELIVERY SYSTEMS (CONT.)
Process Development Considerations for LNP Manufacturing
Amey Bandekar, PhD, Associate Director, Drug Product Development, Sanofi
In the development of LNP-based drug product, the choice of manufacturing technology is one of the key factors for success. The choice of technology can have a significant impact on the biophysical properties, structural characteristics, colloidal stability, and efficacy of the LNP. This study describes the impact of different manufacturing parameters and the scale-up consideration to enable successful LNP drug product manufacturing.
RNA Activation and Delivery
Nagy Habib, ChM, FRCS, Head of R&D and CMO, MiNA Therapeutics Ltd.
RNA activation in acquired and genetic diseases Small activating RNAs (saRNA) are double- stranded 21 nucleotide RNA that can target promoters or enhancers leading to mRNA upregulation. MTL-CEBPA is an investigative drug that resulted from the conjugation of saRNA CEBPA with NOV 340 lipsomes that targets tumour associated macrophages in order to alter favourably the tumour microenvironment. MTL-CEBPA has been administered safely in over 140 patients with advanced cancer and improved clinical outcome in a sub-set of patients when co-administered with TKI or check point inhibitor.
De-Risk mRNA Adduct Formation in Lipid Nanoparticle Formulation Intended for Glycogen Storage Disease Type-1a Using Analytical Tools
Close of Summit4:25 pm