Chris Spivey is director of Industry Relations and Strategic Partnership, MJH Life Sciences.

Chris Spivey

PharmTech Europe discusses technology that enables the “democratization” of mRNA manufacturing with Scott Ripley, Cytiva.

Democratizing GMP Manufacturing for the New Therapeutic Pipeline

At the 11th International mRNA Health Conference in Berlin, Germany, held Oct. 29– Nov. 2, 2023, conversations on the show floor Illustrated the exuberance that a Nobel Prize confers on messenger RNA (mRNA) technology, while highlighting the molecular diversity challenges and opportunities new therapies create when entering the manufacturing process.

Many mRNA therapies and other types of genetic medicines in clinical development are designed to be delivered with the help of lipid nanoparticles. One such platform is Cytiva’s Precision Nanosystems NanoAssemblr microfluidic-based nanoparticle manufacturing platform, which enables the development of genetic medicines with potentially increased stability, efficacy, yield, and quality of non-viral genetic medicines, according to Scott Ripley, general manager, Nucleic Acid Therapeutics and Precision Nanosystems, Cytiva, in a discussion with 

® at the conference. Ripley was enthusiastic about this platform’s ability to “democratize” the good manufacturing practice (GMP) manufacturing aspects for advanced therapies, while managing to cope with the increased molecular diversity of the molecules being handled.

“For example,” Ripley says, “the mRNA platform is unique in that, on one end of the spectrum, it is vaccinating the planet, on the other end, it’s personalized cancer vaccines.”

All these must fit into the new GMP manufacturing ecosystem. The fact that the poster sessions in Berlin were plentiful and quite well attended gave attendees a window into what new approaches and angles are being tried and offered a glimpse as to what is in store for the future of medicines.

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PharmTech Europe discusses technology that enables the “democratization” of mRNA manufacturing with Scott Ripley, general manager, Nucleic Acid Therapeutics and Precision Nanosystems, Cytiva, at the 11th International mRNA Health Conference in Berlin, Germany.

In part two of an interview with Thomas Langenickel, he Langenickel highlights the challenges in developing mRNA th

mRNA Advances Allow Drug Development Focus on Rare Diseases (Part Two)

 at the leading scientific conference for the field, the 11th International mRNA Health Conference in Berlin, Germany, held Oct. 29– Nov. 2, 2023, with Thomas Langenickel, MD, chief medical officer at Ethris, a Germany-based biotechnology company specializing in next-generation RNA therapeutics and vaccines. In the second part of this interview Langenickel describes challenges with current pulmonary mRNA approaches.

The scientific and technical challenges lay in effectively managing stability through ambient temperature ranges, end-use stability and equal access throughout the supply chain, and the biological deployment conditions affecting ultimate biodistribution. Ethris has interim results on a technique to store lyophilized lipid nanoparticles (LNPs) at ambient temperatures successfully for up to six months. Mechanical stress (sheer forces) during manufacturing as well as shipping to and handling within the clinic (such as drawing drug product into the syringe) can create aggregation of LNPs or leakage of mRNA from the LNP. This can lead to increased immunogenicity, difficulties in nebulizing from clogging, and even batch failures during manufacturing itself.

Currently available vaccines injected into musculature show up in the brain, liver, spleen, and all major perfused organs, instead of more narrowly targeting, for example, lung tissue types. The Ethris manufacturing platform does not require high pressure liquid chromatography, which reduces costs but also some of the sheer forces mentioned earlier.

Langenickle has more than 15 years of experience in clinical development and translational medicine in cardiovascular and respiratory disease areas. He previously held the position of executive director and head of Respiratory Profiling at Novartis and served as medical director at Bristol-Myers Squibb.

In part two of an interview with Thomas Langenickel, MD, chief medical officer at Ethris, Langenickel highlights the challenges in developing mRNA therapeutics for pulmonary diseases.

Andy Geall, co-founder and chief development officer at Replicate Bioscience continues the discussion on the development history of mRNA therapeutics.

Discussing the Origins of the mRNA Therapeutics Field (Part Two)

 left off on describing the development of the commercial messenger RNA (mRNA) landscape, 2015 saw an anti-trust ruling which led Novartis’ vaccines division to sell assets to CSL rather than GSK. A subsequent related brain drain benefitted Moderna, as Boston, Mass., as a workplace, increasingly cemented its position as a life science cynosure. After interim steps at Avidity Biosciences (antibody short interfering RNA [siRNA] conjugates), consulting for the Bill & Melinda Gates Foundation, the Coalition for Epidemic Preparedness Innovations, Precision Nanosystems, and Verve Therapeutics, and conducting COVID-19 work, Andy Geall and Nathaniel Wang founded Replicate Bioscience, where Geall is co-founder and chief development officer. Geall and Wang’s platform works on next-generation self-replicating RNA (srRNA) vectors to amplify protein expression. srRNA’s self-limited replication unlocks new opportunities to treat many more patients across a broad range of diseases. In contrast to linear mRNA, this method requires minimal amounts of synthetic material to produce enough protein to obtain therapeutic efficacy. Replicate has a rabies vaccine in the clinic, with results due early in 2024. The company’s approach in oncology has an initial application for metastatic breast cancer, targeting the four known antigen mutation pathways, for a potentially generalized therapy.

In part two, Chris Spivey, editorial director for 

®, discussed messenger RNA (mRNA) advances and mRNA’s historical background with Geall, who also recently became inaugural chair of the board for the Alliance for mRNA Medicines (AMM). The interview was conducted at the 11th International mRNA Health Conference in Berlin, Germany, which was held Oct. 29–Nov. 2, 2023.

Chris Spivey, editorial director for Pharmaceutical Technology® discusses mRNA advances at the mRNA Health Conference in Berlin.

Thomas Langenickel of Ethris Discusses mRNA Advances

, discussed messenger RNA (mRNA) advances at the leading scientific conference for the field, the 11th International mRNA Health Conference in Berlin, Germany, which was held Oct. 29– Nov. 2, 2023, with Thomas Langenickel, MD, the chief medical officer at Ethris, a Germany-based biotechnology company specializing in next-generation RNA therapeutics and vaccines.

Langenickel has more than 15 years of experience in clinical development and translational medicine in cardiovascular and respiratory disease areas. He previously held the position of executive director and head of Respiratory Profiling at Novartis and served as medical director at Bristol-Myers Squibb. Ethris worked to create a new path from genes to therapeutic proteins through non-immunogenic mRNA (SNIM mRNA) and lipidoid nanoparticle (SNaP LNP) technology platforms. These can produce drug candidates with superior thermostability and resistance to mechanical manipulation and that are nebulizable at high throughput, without change in biophysical properties or potency.

During the conversation, Langenickel discusses the focus on rare lung diseases and advances made over the last few years with an approach not available via previous efforts. This obviates some of the biodistribution challenges. Also, various pharmacokinetics become more tractable alongside certain posttranslational modification issues, in particular during the manufacturing process of these therapies. For these respiratory viral infection applications, the host immune system is modulated. Clinical trial applications have been submitted and were awaiting approval at time of discussion. Regulatory challenges also came up as a common barrier for mRNA medicines, up to and including being considered a biologic in one geographic region versus a gene therapy in others. A call for more harmonization across geographies to build a clearer path for these products is considered an important step forward for increased commercial success.

A discussion with Thomas Langenickel, MD, chief medical officer at Ethris, shines a light on how advances made with mRNA technology are also advancing the industry’s ability to focus on treatment of rare diseases, such as rare lung diseases.

mRNA Advances Allow Drug Development Focus on Rare Diseases (Part One)

Andy Geall, co-founder and chief development officer at Replicate Bioscience, discusses the historical context and buildup of the mRNA therapeutics field.

Discussing the Origins of the mRNA Therapeutics Field

®, discussed messenger RNA (mRNA) advances and mRNA’s historical background with Andy Geall, co-founder and chief development officer at Replicate Bioscience, who also recently became inaugural chair of the board for the Alliance for mRNA Medicines (AMM). The interview was conducted at the 11th International mRNA Health Conference in Berlin, Germany, which was held Oct. 29– Nov. 2, 2023.

In this interview Geall discusses the origins of the buildup of an entire ecosystem for combining mRNA protein encoding medicines within lipid nanoparticles (LNPs) through initial funding provided jointly by the now prescient-looking Biomedical Advanced Research and Development Authority and Novartis.Based on work that had its origins in 2008, Geall, while at Novartis, published a 2014 paper that began: “Nucleic acid-based vaccines are being developed as a means to combine the positive attributes of both live-attenuated and subunit vaccines. Viral vectors and plasmid DNA vaccines have been extensively evaluated in human clinical trials and have been shown to be safe and immunogenic, although none have been licensed for human use. More recently, mRNA-based vaccine alternatives have emerged and might offer certain advantages over their DNA-based counterparts” (1).

1. Deering, R.P.; Kommareddy, S.; Ulmer, J.B.; Brito, L.A.; Geall, A.J. Nucleic Acid Vaccines: Prospects for Non-Viral Delivery of mRNA Vaccines. 

 (6), 885–899. DOI: 10.1517/17425247.2014.901308

Discussing the Origins of the mRNA Therapeutics Field (Part One)

, discussed messenger RNA (mRNA) advances and the background for the leading scientific conference for the field with host and co-organizer, CureVac CEO, Dr. Alexander Zehnder. Alexander joined CureVac as CEO in April 2023. He has held roles of increasing complexity and responsibility in the pharmaceutical industry for more than 20 years, across multiple business units and functional areas in Europe, the United States, and Japan.

Convinced that mRNA has unparalleled potential as a drug, CureVac has embarked on an exciting mission The CureVac method was developed from the cumulation of many years of work, research, and nucleotide analysis—all in the name of overcoming the instability of mRNA molecules. The company analyzed millions of naturally occurring sequences to develop insights into the endogenous RNA language. These findings enabled development of an extensive in-house nucleotide sequence library that allows assembling the various pieces of the mRNA puzzle for the desired therapeutic use without having to rely on additional chemical modifications in the RNA.

Each CureVac product can be thought of as a tailored molecular creation in which we customize the 5’ and 3’ untranslated regions and the open reading frame to ensure translation of the mRNA sequence produces the ideal levels of protein creation in the body. All the different parts of a CureVac-customized mRNA molecule create a packaged product specially optimized for different indications.

The International mRNA Health Conference took place in Berlin (and virtually) from October 31 to November 2, 2023. The event set the stage for academic mRNA experts, and those from industry, to discuss the rapidly advancing science and business of mRNA medicines.

The mRNA Health Conference provides participants with a platform for networking with experts, giving them an opportunity to learn more about developments in mRNA technology and to see scientific presentations by some of the most esteemed experts in the field. The event brings together over 900 attendees from leading pharma and biotech companies as well as academic institutions onsite in Berlin and virtual.

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Chris Spivey, editorial director for Pharmaceutical Technology®, discusses mRNA advances and the background for the leading scientific conference for the field, with host and co-organizer CureVac CEO Dr. Alexander Zehnder. 