Moderna continues to expand its mRNA platform for a range of additional clinical applications and routes of administration including a modality for lung delivery

Moderna's 5^th Annual Science and Technology Day presentations highlight continued focus, safety and innovation of our intramuscular lipid nanoparticles (LNPs) delivery system in vaccines

CAMBRIDGE, MA / ACCESSWIRE / May 17, 2022 / Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messengerRNA (mRNA) therapeutics and vaccines, today announced new research findings as part of the Company's fifth annual Science and Technology Day. Moderna continues to highlight investments in the expansion of the utility of the mRNA platform, characterization of the Company's vaccines, biodistribution of vaccines, and using clinical data to predict vaccine dosing.

"Science and Technology Day gives us an opportunity to showcase our leadership in mRNA medicines. Having continuously invested in our mRNA platform for more than 10 years, Moderna is well-positioned to continue bringing innovative medicines to the world through next-generation technology, research and manufacturing. I'm particularly excited about the advances that our more than 700 experienced platform research scientists have made in delivering medicines to the lungs and intramuscularly for vaccines, and am confident that the financial resources and expertise Moderna has will ensure Moderna remains as the world leader in mRNA," said Stéphane Bancel, Chief Executive Officer of Moderna.

Expansion of the utility of the mRNA platform

Multiple biological barriers must be overcome to deliver mRNA medicines and maximize their clinical potential. In most cases, the effective delivery of mRNA-based medicines is enabled by encapsulating the mRNA in tiny lipid (fat) droplets, known as lipid nanoparticles (LNPs) in order to protect it against degradation and facilitate uptake by cells. Moderna announces advances in developing numerous proprietary LNPs, each suited to target different cell types and optimized for different routes of administration. Moderna has invested in the development of LNPs for systemic, intramuscular, intratumoral, and pulmonary delivery of mRNA.

With Moderna's focus on respiratory diseases, the Company has invested in designing mRNA delivery systems tailored to targeting pulmonary disease. For pulmonary applications, delivery of mRNA medicines directly to the lungs by inhalation is the preferred method of administration in order to maximize the concentration of the medicine locally in the lung. Moderna researchers have developed a new LNP formulation that addresses many of the challenges associated with lung delivery of mRNA. This pulmonary LNP formulation is delivered by inhalation, uses multiple lipids, and is able to target specific areas of the lung. Moderna's optimization of pulmonary delivery of mRNA provides opportunities to address a range of unmet medical needs.

Moderna is collaborating with Vertex to deliver mRNA directly to the lungs via aerosolization to enable production of a functional cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein. CFTR is an important target for treatment because it is a defect in the CFTR gene that leads to buildup of thick mucus in the airways, chronic lung infections, inflammation and eventual respiratory failure. To date, the companies have completed IND studies that are supportive of advancing to clinical development. Vertex expects to submit an IND for this program in the second half of this year. In a second collaboration, the companies are collaborating to develop a portfolio of mRNA CF treatments, through the discovery and development of novel LNPs and mRNAs for the delivery of gene-editing therapies for the treatment of CF.

Characterizing Moderna's mRNA

mRNA is inherently unstable, but with continued investments in innovative science, Moderna researchers have developed a detailed understanding of the reactions that drive instability and lead to mRNA inactivation and degradation. mRNA stability has practical implications for product storage and shelf-life.

In addition to known chemical reactions that contribute to mRNA instability upon storage of product, Moderna researchers have identified and elucidated another mechanism that leads to a loss in mRNA activity: the formation of lipid-mRNA complexes, known as adducts. Since mRNA must be intact to be translated, adduct formation renders mRNA untranslatable, leading to a decrease in the expression of the proteins needed to treat or prevent disease.

In addition to the clinical benefits of stabilizing mRNA integrity, manufacturing protocols that limit the formation of lipid-mRNA adducts can improve product shelf-life. It thus remains critical to ensure robust analytical methods and stringent manufacturing controls to ensure mRNA stability and high activity in LNP delivery systems. Moderna's adduct formation research has led to the development of manufacturing processes designed to identify and mitigate lipid-driven impurities that would otherwise disrupt mRNA translation and reduce product shelf-life. As a result, new manufacturing controls have resulted in improved shelf-life, improved product activity, and higher storage temperatures.

With hundreds of millions of COVID-19 vaccines administered, numerous observational studies and in-depth animal research, current data supports the safety of vaccination relative to fertility, pregnancy, and breastfeeding. In addition to examination of real-world and observational data, Moderna reviewed guidelines from several health agencies, including the United States Centers for Disease Control and Prevention (CDC), the United Kingdom (UK) Health Security Agency, the European Medicines Agency (EMA)'s COVID-19 Task Force (ETF), the UK Joint Committee on Vaccination and Immunisation (JCVI). Taken together, current data supports the safety of COVID-19 vaccination for pregnant or breastfeeding women and suggests no safety concerns in regard to fertility. Currently there is no evidence that COVID-19 vaccines cause fertility problems in women or men. Observational data from vaccinated pregnant women has not shown an increase in adverse pregnancy outcomes and no increased risk for miscarriage has been seen.

Observational data from women who were breastfeeding after COVID-19 vaccination have not shown a risk for adverse effects in breastfed newborns/infants. As per the CDC, COVID-19 vaccination is recommended for people who are pregnant, breastfeeding, trying to get pregnant now, or might become pregnant in the future.

Biodistribution of Moderna's vaccine

To further characterize Moderna's IM vaccines, biodistribution studies were conducted to demonstrate where mRNA goes in the body after injection. Studies demonstrate that injected mRNA remains predominantly at the injection site and in nearby draining lymph nodes. Furthermore, consistent with its transient nature, mRNA is undetectable in the body 5 days after injection, with minimal mRNA detectable after only 3 days.

Using Clinical Data to Predict Vaccine Dosing

Selecting an optimal dose for new vaccine candidates is important in reaching maximal vaccine efficacy at a desirable safety level. Well-informed decisions about dose selection can reduce the development time and expense for new candidates. Moderna presented an immunostimulatory/immunodynamic (IS/ID) modeling approach that simulates immune response by vaccination (IS) and the resulting measured immune response dynamics (ID). The model was developed, tested and shown to be effective using data from Moderna's cytomegalovirus (CMV; mRNA-1647) and COVID (mRNA-1273) vaccines.

With the goal of maximizing immunogenicity and reducing risk of adverse reactions, Moderna will apply the model to support dose selection for upcoming clinical studies.

Science Day Webcast Information

Moderna will host its annual Science and Technology Day for analysts and investors at 9:00 a.m. ET on May 17. A live webcast will be available under the "Events and Presentations" in the Investors section of the Moderna website at investors.modernatx.com. A replay of the webcast will be archived on Moderna's website for one year following the presentation.

About Moderna

In over 10 years since its inception, Moderna has transformed from a research-stage company advancing programs in the field of messenger RNA (mRNA), to an enterprise with a diverse clinical portfolio of vaccines and therapeutics across seven modalities, a broad intellectual property portfolio in areas including mRNA and lipid nanoparticle formulation, and an integrated manufacturing plant that allows for rapid clinical and commercial production at scale. Moderna maintains alliances with a broad range of domestic and overseas government and commercial collaborators, which has allowed for the pursuit of both groundbreaking science and rapid scaling of manufacturing. Most recently, Moderna's capabilities have come together to allow the authorized use and approval of one of the earliest and most effective vaccines against the COVID-19 pandemic.

Moderna's mRNA platform builds on continuous advances in basic and applied mRNA science, delivery technology and manufacturing, and has allowed the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases, cardiovascular diseases and auto-immune diseases. Moderna has been named a top biopharmaceutical employer by Science for the past seven years. To learn more, visit www.modernatx.com.

Forward-Looking Statements

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including statements regarding: the Company's ability to continue to introduce new mRNA medicines; the ability to delivery mRNA medicine for pulmonary applications through the lungs; the Company's leadership position in developing mRNA medicines; the ability to address multiple diseases, including cystic fibrosis, through pulmonary LNPs and to engage in gene-editing; the timing for a potential IND application by Vertex; the safety of pulmonary mRNA delivery; the ability of the Company's platform to achieve greater stability, including at refrigerator temperatures, for its medicines; the safety of the Company's medicines for pregnant and breastfeeding women and the absence of any adverse impact on fertility of men or women; the rate of degradation for mRNA medicine once in the body; and the Company's ability to predict dose levels for efficacy and safety. In some cases, forward-looking statements can be identified by terminology such as "will," "may," "should," "could," "expects," "intends," "plans," "aims," "anticipates," "believes," "estimates," "predicts," "potential," "continue," or the negative of these terms or other comparable terminology, although not all forward-looking statements contain these words. The forward-looking statements in this press release are neither promises nor guarantees, and you should not place undue reliance on these forward-looking statements because they involve known and unknown risks, uncertainties, and other factors, many of which are beyond Moderna's control and which could cause actual results to differ materially from those expressed or implied by these forward-looking statements. These risks, uncertainties, and other factors include, among others, those risks and uncertainties described under the heading "Risk Factors" in Moderna's most recent Annual Report on Form 10-K filed with the U.S. Securities and Exchange Commission (SEC) and in subsequent filings made by Moderna with the SEC, which are available on the SEC's website at www.sec.gov . Except as required by law, Moderna disclaims any intention or responsibility for updating or revising any forward-looking statements contained in this press release in the event of new information, future developments or otherwise. These forward-looking statements are based on Moderna's current expectations and speak only as of the date of this press release.

Moderna Contacts

Media:
Mary Beth Woodin
Senior Director, Communications
617-899-3991
Mary.BethWoodin@modernatx.com

Investors:
Lavina Talukdar
Senior Vice President & Head of Investor Relations
617-209-5834
Lavina.Talukdar@modernatx.com

SOURCE: Moderna,Inc.