Cambridge Healthtech Institute’s Inaugural

Applications of mRNA Therapeutics

Unlocking the Potential of Innovative Therapies

March 13-14, 2024



In the wake of the remarkable development and success of mRNA vaccines during the COVID-19 pandemic, myriad companies are now exploring the potential of mRNA-based vaccines and therapeutics in various indications. Promising pipeline developments are underway in areas such as oncology, infectious diseases, and chronic conditions. Join CHI's Inaugural conference on the Applications of mRNA Therapeutics for a comprehensive overview of the latest industry and academia advancements, remaining challenges, and where the field is heading next.

Tuesday, March 12

Registration Open12:00 pm

Recommended Short Course*5:30 pm

SC1: Safety & Toxicity of Nucleic Acids

*Separate registration required. See short course page for details.

Wednesday, March 13

Registration and Morning Coffee7:00 am

Organizer's Welcome Remarks8:30 am

INNOVATIONS IN MANUFACTURING DRIVING NEW APPLICATIONS

8:40 am

Chairperson's Remarks

Craig Martin, PhD, Professor, Chemistry, University of Massachusetts, Amherst

8:45 am FEATURED PRESENTATION:

Flow Manufacturing of mRNA Free of dsRNA, DNA, and Protein—Before Purification

Craig Martin, PhD, Professor, Chemistry, University of Massachusetts, Amherst

Functional immobilization of RNA polymerase to promoter DNA, with function coupling of the pair to a solid support, allows the direct manufacturing of RNA free of both protein and DNA. It also largely eliminates formation of dsRNA and allows for much higher yields of RNA per DNA and enzyme. Synthesized reporter mRNAs show significantly reduced innate immune response and higher expression of mRNA transfected into cells—before any downstream purification. Benefits include elimination of dsRNA, freedom from protein/DNA contamination, and purity at synthesis.

9:15 am

Innovating and Digitalising mRNA Vaccine and Therapeutics Production Platform Processes

Zoltán Kis, PhD, Associate Professor, Chemical and Biological Engineering, The University of Sheffield

To reach the full potential of the disease-agnostic RNA platform, we are developing a set of synergistic technologies consisting of continuous manufacturing processes (continuous enzymatic RNA synthesis, continuous downstream purification, and continuous lipid nanoparticle formulation), analytical technologies, computer models, and bespoke software. These technologies are co-developed under a patient-centric Quality by Digital Design (QbDD) framework to obtain a multi-product design space with CQAs as a function of CPPs, and aid process automation. By combining the QbDD framework with the RNA platform, vaccines and therapeutics can be developed and mass-produced faster against a wide range of diseases at low cost.

9:45 am

Continuous Purification Methods for the Rapid Manufacture of mRNA-Based Products

Harris Makatsoris, PhD, Professor, Sustainable Manufacturing Systems, Kings College London

Our work is focusing on ensuring the equitable access to RNA based vaccines by everyone, everywhere. This vision is underpinned by the creation of flexible manufacturing networks comprising autonomous and multipurpose RNA manufacturing and discovery nodes in any geography. In this talk, a brief overview of the BiaB technology will be given, focusing then on our purification methods and our Quality-By-Design framework with examples.

10:15 am

Prospects and Challenges in Sterile Filtration of mRNA-Lipid Nanoparticles

Kevork Oliver Messerian, Graduate Research Assistant, Penn State University

mRNA-based vaccines use lipid nanoparticles (LNPs) to ensure mRNA delivery for effective protein translation. However, the large size and unique behavior of the LNPs create significant challenges in the design and implementation of the sterile filtration step. Filter capacities can be significantly smaller than those for traditional biotherapeutics, and the fouling behavior does not follow traditional mechanisms. The results provide important insights into the mechanisms controlling sterile filtration of LNPs.

Grand Opening Coffee Break in the Exhibit Hall with Poster Viewing10:45 am

NOVEL PLATFORMS FOR mRNA CANDIDATES

11:35 am

Developing Synthetic DNA Template (SDT)-Based Platforms for the Fast in vitro Transcription, Screening, and Validation of mRNA-Therapeutic Candidates

Lorenzo Franceschini, PhD, Postdoctoral Researcher, Laboratory of Molecular & Cellular Therapy, Vrije Universiteit Brussel; Visiting Scholar, Miller School of Medicine Microbiology & Immunology, Miami University

A rapid, flexible, and affordable mRNA manufacturing workflow is necessary to unlock the full potential of mRNA therapeutics. mRNA transcription relies on the rigid sequence design of constructs obtained by laborious bacterial cloning and time-consuming plasmid preparation. Here, we introduce a synthetic DNA template (SDT)-based platform, allowing cost, and time-efficient production of mRNA molecules encoding different protein candidates for therapeutic evaluation, enabling applications such as T cell receptor (TCR) screening, and neoantigen immunogenicity validation directly from tumor patients. The presentation will cover therapeutic evaluation, immunogenicity investigation, and mRNA molecular characterisation.

12:05 pm

Programming mRNA for Cancer Immunotherapy

Prashant Nambiar, DVM, PhD, MBA, Senior Vice President, R&D, Strand Therapeutics

Immunotherapy, particularly mRNA therapeutics, is redefining cancer treatment by harnessing the body's immune system to target cancer cells. These therapies, delivering tumor-specific antigens or immune modulators via mRNA, are enhancing immune recognition and attack on cancer cells. However, challenges like limited patient response due to inadequate T cell activation in the tumor microenvironment persist. Addressing this, we present STX-001, a novel synthetic self-replicating mRNA technology for intratumoral delivery. It provides sustained IL-12 cytokine expression, specifically within the tumor microenvironment, improving T cell recruitment and activity. STX-001 exemplifies the next step in personalized immunotherapy, combining the precision and adaptability of mRNA therapeutics to overcome existing immunotherapy limitations.

Please attend a sponsored lunch in either Seaport A (Oligonucleotide Discovery and Delivery) or Seaport BC (mRNA Design & Delivery)12:35 pm

2:00 pm

Creating an mRNA Vaccine Manufacturing Platform for Hands-on Training

Baley Reeves, PhD, Interim Director, National Center for Therapeutics Manufacturing (NCTM)

The National Center for Therapeutics Manufacturing (NCTM) partnered with the Biomedical Advanced Research and Development Authority (BARDA), Pfizer, the US Pharmacopeia (USP), and other solution providers to develop the first commercial-scale, hands-on training course for mRNA vaccine production in the US. This presentation will give an overview of the company-agnostic, in-house platform process that was developed for the production of mRNA-LNPs, beginning with pDNA production and continuing through bulk filling/freezing.

2:30 pm

ADAR Mediated RNA Editing Platform Development for Broad Applications

Shanhu Hu, PhD, Director, Platform Biology, Korro Bio Inc.

This presentation focuses on the strategy we take at Korro Bio on building a platform that harnesses the body’s natural RNA editing machinery, ADAR (Adenosine deaminases acting on RNA) mediated RNA editing, to treat previously untreatable diseases and the potential of this platform in broad applications.

Refreshment Break in the Exhibit Hall with Poster Viewing3:00 pm

PLENARY KEYNOTE SESSION

3:40 pmOrganizer's Welcome Remarks
3:45 pm

Plenary Chairperson's Remarks

Jim Weterings, PhD, Vice President Research, RNA Therapeutics & Delivery, Sirnaomics

3:50 pm

Biomimetic Chemistry of RNA Therapeutics

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

Achieving success in RNA therapeutics depends on proper understanding of mechanisms of nature. In stages of discovery, delivery, and development of RNA-based therapeutics we follow and mimic many natural processes. We will illustrate this concept by taking several key steps of molecular mechanisms involved and examples of medicines which are either approved or in clinical development.

4:20 pm

Applications for mRNA Therapeutics: Immunological Issues and Considerations

Arthur Krieg, MD, Adjunct Professor, University of Massachusetts, Chan School of Medicine

From an immunological perspective, there are 3 distinct categories of mRNA therapeutics, including: 1. Protein expression mRNAs (including e.g., enzyme replacement, antibody expression, gene editing with encoded programmable nuclease), wherein any immune activation is highly undesirable; 2. Infectious disease mRNA vaccines such as COVID (immune activation desirable to induce neutralizing antibodies); and 3. Cancer mRNA vaccines (immune activation desirable to induce CD8+ T cells able to kill tumors). Achieving these distinct immune effects requires intentional design of the mRNA and delivery system, which will be reviewed.

Welcome Reception in the Exhibit Hall with Poster Viewing4:50 pm

Close of Day5:50 pm

Thursday, March 14

Registration and Morning Coffee8:00 am

PLENARY KEYNOTE SESSION

8:30 amOrganizer's Welcome Remarks
8:35 am

Plenary Chairperson's Remarks

Paloma Giangrande, PhD, CTO, Eleven Therapeutics

8:40 am

Realizing the Promise of in vivo CRISPR Therapeutics

Sean Burns, PhD, VP Disease Biology, Intellia Therapeutics Inc.

NTLA-2001 is an investigational CRISPR-based therapy being evaluated in a Phase 1, two-part, open-label study in adults with hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) or with cardiomyopathy (ATTR-CM). NTLA-2002 is being developed for hereditary angioedema (HAE), designed to knock out the KLKB1 gene in the liver with the potential to permanently reduce total plasma kallikrein protein and activity, a key mediator of the disease. NTLA-2002 is being evaluated in a Phase 1/2 study in adults with Type I or Type II HAE. Preclinical and clinical data for both programs will be presented.  

9:10 am

Harnessing RNA Metabolism for Precision RNA Therapeutics

Jeffery M. Coller, PhD, Bloomberg Distinguished Professor of RNA Biology and Therapeutics, Johns Hopkins University

We have created a therapeutic technique that enhances mRNA translation. This technology has numerous clinical applications and works by binding to mRNA and improving translation. The approach offers key benefits: it is disease-modifying, restoring normal protein levels; it is mutation agnostic; it can be tailored to precisely control expression, reducing the risk of overexpression; and lastly, it is applicable across indications and highly versatile.

Coffee Break in the Exhibit Hall with Poster Viewing9:40 am

mRNA VACCINES

10:30 am

Chairperson's Remarks

Gilles Besin, PhD, CSO, Orbital Therapeutics

10:35 am

sa-mRNA Vaccine Development

Raveen Rathnasinghe, PhD, Investigator, Virology and Biocontainment, Seqirus

A/H2N3 influenza has posed a particular pandemic threat. Self-amplifying mRNA (sa-mRNA) vaccine emerges as the counter measurement. We evaluated sa-mRNA A/H2N3 vaccine designs, including codon optimization and co-expression of neuraminidase (NA), in addition to hemagglutinin (HA). Mouse studies showed robust neutralizing antibody and CMI responses to both HA and NA, and strong cross-reactivity to another A/H2N3 virus, demonstrating the sa-mRNA pandemic vaccine as the effective approach for pandemic preparation.

11:05 am

Design and Optimization of a VLP-Forming mRNA Vaccine for HIV-1

Paolo Lusso, MD, PhD, Chief, Senior Investigator, Viral Pathogenesis Section, NIAID, NIH

A multiclade env+gag+pro mRNA vaccine capable of producing virus-like particles (VLP) in vivo induced broad-spectrum neutralization, albeit at low titers, and partial protection in nonhuman primates. Is an HIV-1 vaccine feasible? Why is it so challenging to develop an HIV-1 vaccine? Why is mRNA especially suited as a vehicle for an HIV-1 vaccine? What are the requirements for the induction of broadly neutralizing antibodies? Is protection from HIV-1 possible without the induction of broadly neutralizing antibodies?

Enjoy Lunch on Your Own11:35 am

1:00 pm

mRNA Therapy Corrects Defective Glutathione Metabolism and Restores Ureagenesis in Preclinical Argininosuccinic Aciduria

Patrick Finn, PhD, Vice President, Rare Disease Research & Preclinical Development, Moderna Inc

1:30 pm

Introducing circRNA Vaccine Platform as Novel Alternative to RNA Vaccine

Gilles Besin, PhD, CSO, Orbital Therapeutics

Since the discovery of circular RNA, a new class of single-stranded RNA, their biogenesis, regulation, and function have been rapidly characterized, allowing for better understanding and their adoption as new tools for therapeutic applications. With the development of biotechnology and molecular medicine, circRNAs have been engineered as a novel class of RNA therapeutics. In the field of vaccines, compared to linear mRNA vaccines, mRNA vaccines offer an improved approach to RNA-based vaccination with increased stability, simplicity of manufacture, and scalability.

2:00 pm

A Versatile Technology Platform for Next Generation mRNA Vaccines and Therapeutics

Heinrich Haas, PhD, NeoVac

In order to exploit the potential of mRNA technology for pharmaceutical application, tailored delivery systems are required. NeoVac has a pioneering 2.0 LNP Platform for superior delivery of RNA payloads for vaccines and therapeutic intervention, such as treatment for metabolic diseases, oncology treatments, genetic diseases, and others, based on novel, proprietary lipids. The technology allows to one specifically target different organs and to modulate immunogenicity according to the intended intervention. Here we present first data to underline the potential of our new technology.

INTERACTIVE BREAKOUT DISCUSSIONS

2:30 pmInteractive Breakout Discussions

Interactive Breakout Discussions are informal, moderated, small-group discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator(s) who keeps the discussion on track and the group engaged.  To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Breakout Discussion page for a complete listing of topics and descriptions.

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

mRNA THERAPEUTICS FOR NON-ONCOLOGY INDICATIONS

3:45 pm

Modified mRNA Therapeutics for Cardiovascular Diseases

Ajit Magadum, PhD, Associate Scientist, Lewis Katz School of Medicine, Temple University

Modified mRNA (modRNA) technology, lauded for its triumphs in COVID-19 vaccine development, is emerging as a promising strategy against cardiovascular diseases (CVD). With 19.1 million global deaths in 2020 and a prevalence of 620 million, CVD demands innovative solutions. Despite medical strides, the lack of a cure intensifies public health concerns. My presentation spotlights our work on modRNA therapies fostering cardiac regeneration and combating cardiac fibrosis, hypertrophy, and cell death in CVD animal models. We also showcase our cell-specific modRNA expression platforms, contributing to evolving modRNA therapeutic landscapes for CVD.

4:15 pm

Targeted LNP-mRNA for Developing the Next Generation of mRNA-based Therapeutics

Hamideh Parhiz, PharmD, PhD, Research Assistant Professor, Infectious Diseases, University of Pennsylvania

In vivo cellular reprogramming via targeted delivery of RNA-based therapeutics to selective cells could be highly valuable. In this talk, I will discuss some of our recent efforts in developing targeted mRNA therapeutics for non-oncology indications.

Close of Conference4:45 pm






Call For Papers