Acuitas is developing lipid nanoparticulate systems (LNP) that allow efficient delivery and expression of mRNA. Through internal research and multiple industry and academic collaborations, Acuitas is enabling mRNA in a broad range of therapeutic areas. The most advanced therapeutic application is as prophylactic vaccines against infectious disease. Results from collaborations demonstrating the ability of mRNA-LNP vaccines to protect against infectious diseases will be shown. Further, clinical translation of our mRNA-LNP as a prophylactic vaccine against SARS-CoV2 will be presented.

Speaker:

Ying Tam, Ph.D.
Chief Scientific Officer
Acuitas Therapeutics, Inc.

A new purification approach starting from E.Coli all through to mRNA production is presented here. This new approach integrates a pDNA linearisation step before polishing (removal of linear and open circular isoforms) of plasmid DNA. The polishing step, placed after enzymatic linearisation, purifies linear pDNA from enzyme and other unwanted process impurities. The linearised plasmid DNA is then used in IVT for production of mRNA. Fast in-process analytics allows for transcription numbers well above 100 in a reproducible manner.

This approach further introduces mRNA purification tools for improved contaminant removal. The altered sequence of purification and linearisation reduces the overall number of purification steps required, improves recoveries, while the complete process results in extra low protein impurity and very efficient dsRNA removal.

The participants would get insight into the mRNA production steps, their optimisation and tools to allow for robust process. The analytical tools to allow for safe products will be highlighted.

Speaker:

Ales Strancar, PhD
BIA Separations d.o.o.

ARCT-021 is a self-transcribing and replicating RNA (STARR^TM) technology based vaccine expressing the SARS-CoV-2 spike glycoprotein. Preclinical data showing immunogenicity of vaccines in rodents and NHPs will be presented. These results include results from challenge studies in both species and also 2nd generation vaccine cross neutralization results against spike glycoproteins from variants of concern (VOC).

Speaker:

Sean Sullivan
Executive Director, Process Development
Arcturus Therapeutics

This presentation will describe a collaboration between Merck and Moderna to develop a vaccine targeting Respiratory Syncytial Virus (RSV). The value of mRNA as a tool to enable rapid antigen screening in a discovery vaccine program will be demonstrated. Preclinical data showing the immunogenicity of the vaccines in rodents and NHPs will be shown, as will immunogenicity data from the Phase 1 study with the selected vaccine.

Speaker:

Amy Espeseth, Ph.D.
Executive Director, Infectious Diseases and Vaccines Discovery
Merck

The COVID-19 pandemic has driven development and introduction of new vaccines with unprecedented speed. The evolution of mRNA vaccine technology has also increased global demand for manufacturing capacity as governments race to vaccinate their populations. As we race to meet today’s challenges, we must also look ahead: how will new variants affect demand for vaccines or boosters? How will mRNA vaccine technology evolve? Responding to future changes will require flexibility to pivot or adapt to a mutating virus.

In this presentation, we will discuss strategies for rapid manufacturing using a flexible, end-to-end platform approach and pre-designed modular manufacturing environments. We will also address multiproduct manufacturing, outsourcing processes vs keeping them in house, and logistical challenges.

Speaker:

Katarina Stenklo
Enterprise Solutions Commercial Activation Leader
Cytiva

Understand the manufacturing benefits of IVT synthesis using CleanCap Cap1 analogs for highly functional mRNA as shown in mice. Co-transcriptional capping with state-of-the-art analogs saves cost on enzymes and reduces manufacturing hours while maintaining activity in vivo. Saving time through optimized minimal step processing of mRNA improves quality of full-length products, a critical aspect when working with long molecules.

Speaker:

Jordana M Henderson, MS
Scientist
Trilink

Lipid nanoparticles (LNPs) are the leading vehicles for mRNA therapies as the approved SARS-CoV-2 vaccines. In order to design safe and effective LNPs, we investigated their structure in the absence and presence of proteins using high resolution techniques as small angle neutron scattering. Apolipoprotein E shows high binding affinity towards LNPs and induces lipid redistribution. These findings are relevant to understand cellular mechanisms involved in LNP delivery as endosomal escape.

Speaker:

Marianna Yanez Arteta, Ph.D.
Associate Principal Scientist
AstraZeneca

Key CMC information on the critical quality attributes and corresponding justification of acceptance criteria has yet to be formally established in regulatory guidance for mRNA.

In this presentation, we describe how advanced "superhero" analytics to characterize DNA templates and RNA transcripts can be deployed to build effective quality control with a focus on the Fantastic Four - Capping efficiency, sequencing, Poly-A Tail, Residual dsRNA - as core considerations to support CMC.

Speakers:

Ashleigh Wake
Business Development Director, UK
Intertek Pharmaceutical Services