Investment in mRNA Technology Is Driving Force for Moderna’s Vaccine Pipeline

Researchers have been studying mRNA for decades and it wasn’t until the COVID-19 pandemic where the platform found its greatest utility in vaccines. Moderna has been a leading company in research and development in this area. In its simplest terms, the company explains there are a few steps that can be done to address different diseases and viruses and the process can be replicated over and over again. The company explains that mRNA vaccines and therapies start with identifying a protein that is designed to prevent or treat a certain disease.¹ Their researchers then design an mRNA that carries instructions for this protein that could help the body fight infections or prevent diseases.¹

With this knowledge, Moderna has invested in this platform to address multiple diseases and viruses.

During Moderna’s Vaccines Day at the end of March, the company said its mRNA platform can transform the vaccine market because of the technology’s ability to develop candidates faster, combine vaccines, and can target difficult viral targets.

"We believe our mRNA platform disrupts the traditional vaccines market and as indicated in our Vaccines Day announcements, we expect to bring many more safe and effective vaccines to market," Moderna Chief Executive Officer Stéphane Bancel, said. "There is an opportunity for Moderna to positively impact public and global health, and with 31 active development programs, 19 of which are in the clinic, we expect to address several critical unmet medical needs with the power of our mRNA platform."

Moderna expects to be in a phase 1 trial this year for its influenza and COVID-19 combination vaccine, mRNA-1073. In terms of a long-term strategy, the company sees combination vaccines like mRNA-1073 being administered annually.

The company also said it was developing its mRNA-1230 vaccine to cover SARS-CoV-2, influenza, and respiratory syncytial virus (RSV) as well as another candidate, mRNA-1287, for endemic human coronaviruses.

In a wide-ranging interview with Contagion, Sunny Himansu, MBBS, DSM, associate director, ID Bacteriology, Infectious Diseases, Moderna, offers some insights into the mRNA platform, the role of mRNA therapies, and where they are with some of their investigational vaccines.

Contagion: In thinking about the mRNA platform, what is it about the technology that allows it to be developed for use against multiple disease targets?

Himansu: The mRNA platform is extremely versatile because it delivers instructions to the body to make proteins that can perform a wide range of functions. For example, mRNA vaccines train the body to fight infection by delivering the instructions to make key parts of specific pathogens, as we’ve done with our COVID-19 vaccine. Therapeutics based on the mRNA platform may help the body make a missing protein or replace a defective protein that leads to disease–among many possible applications. Many defects or targets that were beyond the reach of traditional modes of treatment may be amenable to treatment with mRNA-based therapies.

Moderna’s mRNA technology platform functions very much like an operating system on a computer, and each interchangeable mRNA sequence is like specific, interchangeable software. Today, we can create these vaccines and medicines rapidly and deliver them to the right place in the body with great efficiency. This will open up new ways to prevent and treat a wide variety of illnesses, from latent viral infections, to cancer, to rare diseases.

Contagion: Speaking of multiple targets, the company is developing a single combination vaccine to cover SARS-CoV-2, influenza, and RSV. Can you tell us when you will be in a phase 1 clinical trial for the investigational vaccine and do you see this as an annual vaccine given at the start of flu season?

Himansu: Our combination SARS-COV-2/Influenza/RSV vaccine (mRNA-1230) is currently in pre-clinical development. We are clinically testing the various “pieces” of this combination vaccine in parallel and have shown in pre-clinical mouse models that the combination vaccine induces a robust antibody response to all of the antigen components in mice. We look forward to progressing with a phase 1 program and aspire to administer this vaccine seasonally.

Contagion: Can you provide an overview of the 2 HIV vaccines Moderna has in development and how they target HIV?

Himansu: A protective HIV vaccine will likely need to produce broad neutralizing antibodies or bnAbs that can neutralize a wide range of HIV variants. Moderna is working with the leading experts in the HIV vaccine field to develop a vaccine regimen that will produce these antibodies in humans. Currently, we are optimizing different antigens in 2 different clinical studies.

The mRNA-1644 or G002 study is testing vaccine antigens that target B cells to produce broadly neutralizing antibodies (bNAbs). In study, we will sequentially administer 2 mRNA vaccines designed by a team of researchers at the International AIDS Vaccine Initiative and Scripps Research. These immunogens (antigens that elicit an immune response) are designed to promote the early maturation of specific types of B cells into cells that produce bNAbs against HIV.

The mRNA-1574 or HVTN302 study will test 3 different forms of mRNA encoded HIV env trimers, the only protein on the surface of the HIV virus required for entry into human cells. The goal of this trial is to identify the best trimer design that can be used in a future clinical study to elicit bnAbs through sequential vaccination of multiple antigens.

Contagion: Why the decision to pursue 2 vaccine strategies?

Himansu: Finding a protective HIV vaccine has been an elusive target; however, recent clinical studies have shown that bnAbs can be protective in humans. With the goal of designing a vaccine that elicits bnAbs by vaccination we are trying to strategically design clinical studies in parallel to answer test certain hypothesis that can ultimately accelerate the development of a successful candidate to the market

Contagion: During Moderna’s Vaccines Day, the company spoke of its mRNA design studio. Can you provide an overview of this and how it can be utilized with prospective outside partners?

Himansu: Our mRNA Design Studio is a proprietary, web-based software that enables rapid design of multiple mRNAs for research and testing within days. Our in-house suite can design mRNA geared towards any protein in the human genome, or novel or fusion “designer” proteins for various applications. Cloud-based computation then optimizes this sequence based on bioinformatics algorithms.

Finally, our digital ordering platform ensures the transmission of the sequences to our synthetic robots for mRNA productions. Moderna aims to use our Design Studio as an engine to accelerate both basic research and the search for novel drug candidates for clinical testing in partnership with scientists and biopharmaceutical stakeholders.

Contagion: In terms of your COVID-19 vaccine and the development of emerging variants, how would you characterize Moderna’s ability to update its vaccines to address new strains?

Himansu: One of the greatest advantages of our mRNA platform is the speed and efficiency with which we can integrate new mRNA sequences. We have already designed and integrated a new version of the COVID-19 vaccine for specificity to the Omicron variant mutations and we are testing it in Phase 2 booster studies in combination with our COVID-19 vaccine. Our platform will be able to rapidly respond to future emerging variants of concern with additional multi-valent boosters.

Contagion: Moderna has been using the mRNA platform to develop vaccines and has some therapeutics in early development, do you see the therapeutics side of the business as a vital part of the company?

Himansu: The elegance and adaptability of mRNA medicines makes them an ideal platform to harness the body’s own system for therapeutic approaches to key disease areas and is a critical goal for the company. To that end, we are developing therapeutic vaccines geared at the emerging field of immuno-oncology to produce personalized cancer vaccines that can help the patient’s immune system better recognize cancer cells as foreign and destroy them. Moderna also recognizes the need to address the over 7000 rare diseases that affect more than 300 million people worldwide with treatment options that are not currently available.

Finally, we are developing several potential mRNA therapeutics that have the potential to dampen autoimmune activation and help restore proper immune function in people afflicted with devastating autoimmune diseases.

This article originally appeared on ContagionLive.

Reference

1.The Power of mRNA. Moderna. Accessed May 15, 2022. https://www.modernatx.com/power-of-mrna/modernas-mrna-platform