Moderna Reviews Clinical Trial Programs Across Portfolio at 2022 R&D Day

Interim data from Phase 1/2 propionic acidemia (PA) multi-dose Paramount trial shows mRNA-3927 was well-tolerated to date, with encouraging early signs of potential for clinical benefit

Interim data from Phase 1/2 glycogen storage disease 1a (GSD1a) single-dose Ba1ance trial shows mRNA-3745 was well tolerated to date, with encouraging early signs of potential for clinical benefit

Moderna announces a new development candidate, mRNA-3139, for ornithine transcarbamylase (OTC) deficiency, a rare genetic disorder

Phase 3 clinical trial of RSV vaccine, mRNA-1345, has enrolled more than 24,000 of the 34,000-participant target

Phase 3 immunogenicity and safety study of flu vaccine, mRNA-1010, is fully enrolled; Company to pursue accelerated approval pathway in 2023

Company is on track to report data from its Phase 2 personalized cancer vaccine (PCV) study in 4Q 2022

CAMBRIDGE, MA / ACCESSWIRE / September 8, 2022 / Moderna, Inc. (NASDAQ:MRNA), a biotechnology company pioneering messenger RNA (mRNA) therapeutics and vaccines, today announced advances across its portfolio of mRNA programs presented at the Company's annual R&D Day.

"We continue to make significant progress in accelerating our pipeline. Our Phase 3 flu and RSV clinical trials are rapidly advancing toward completion. We are seeing early clinical benefits in two rare disease programs and we expect to report on data from our personalized cancer vaccine trial later this year," said Stéphane Bancel, Chief Executive Officer of Moderna. "As a reflection of the Company's growth and progress, we are preparing for multiple product launches globally."

Updates and recent progress include:

mRNA Therapeutics

Rare Diseases: Proof-of-Concept Studies

Propionic Acidemia: Propionic acidemia (PA) is a rare and severe metabolic disorder. PA is characterized by a deficiency of propionyl-CoA carboxylase, an enzyme involved in the breakdown of proteins, certain fatty acids, and other substances. This deficiency leads to the build-up of toxic compounds that can cause serious health problems like repeating episodes of life-threatening metabolic crises and damage to the brain, nervous system, and heart. There is no approved pharmacologic therapy for PA.

• Moderna's mRNA therapy for PA, mRNA-3927, encodes for two proteins that can help the body make the missing enzyme that is absent in PA patients. The Phase 1/2 Paramount clinical trial, evaluating the safety and pharmacology of mRNA-3927, is actively enrolling PA patients.
• Several critical milestones have been reached in the trial. Over 120 repeated intravenous doses have been administered to 10 patients. So far, mRNA-3927 is well-tolerated at the doses tested. To date, there has been no dose-limiting toxicity, discontinuations due to safety, or drug-related serious adverse safety events. Three of the ten study participants have been dosed with over one year of continuous treatment.
• All eligible participants have decided to continue with treatment by participating in the Open Label Extension Study.
• PA is characterized by recurrent life-threatening metabolic decompensation events (MDEs) which are clinical crises that occur when there is a build-up of toxic metabolites. Due to the objective and disease-defining nature of MDEs, regulators have provided initial support for MDE as a clinically meaningful, preferred primary clinical endpoint for development.
• Based on preliminary data, there was a decrease in the number of MDEs post-mRNA-3927 treatment. The trial will continue with testing the next dose level (0.6 mg/kg IV every two weeks).

Glycogen Storage Disease 1a: Glycogen Storage Disease 1a (GSD1a) is a rare, inherited metabolic disorder. GSD1a is caused by a deficiency of an enzyme called glucose 6-phosphatase (G6Pase-α). G6Pase-α is critical for the release of glucose in the blood, and is needed to maintain normal blood sugar levels. Patients with GSD1a may have life-threatening events when their blood sugar levels are too low. They may also experience long-term liver complications, possibly including cancer. There are no approved pharmacologic therapies for GSD1a.

• Young children with GSD1a require tube feeding at night and life-long regular blood glucose monitoring with strict adherence to a special diet of frequent feedings (every 4-6 hours) and uncooked or modified cornstarch. Taking care of GSD1a patients places a significant burden on family members.
• Participants have been dosed in Moderna's Phase 1/2 Ba1ance trial that is evaluating a GSD1a therapeutic candidate, mRNA-3745. This study is the first to evaluate the safety, tolerability, and pharmacology of a single intravenous dose of mRNA-3745 in adult participants with GSD1a.
• Early data on safety and pharmacodynamics are consistent and encouraging. In two patients, intravenous infusion of mRNA-3745 was well tolerated to date, and showed extension of fast duration and normalization of glucose during fast.
• Enrollment and safety evaluations are continuing, with initial data expected in 2023.

Methylmalonic acidemia: PA and methylmalonic acidemia (MMA) share similar biology and disease pathology (deficiency of an enzyme in the propionate pathway) with subsequent accumulation of toxic metabolites. MMA is a rare genetic disease with significant morbidity and mortality caused by a deficiency in an enzyme called methylmalonyl-CoA mutase (MUT). MMA mostly affects children, and there is no approved pharmacologic therapy. Long-term complications of MMA can include problems with neurocognitive function, slower growth, and heart, kidney, and blood problems.

• The first two groups of patients are fully enrolled in Moderna's Landmark Study, a Phase 1/2 clinical trial to evaluate the safety and pharmacology of mRNA-3705 for MMA. mRNA-3705 is designed to instruct the body to restore the missing or dysfunctional proteins that cause MMA. Moderna is recruiting participants in the United Kingdom, Canada, and the U.S. Initial data from the trial are expected by 2023.

Rare Disease: New Development Candidate

Leveraging data and learnings from the rare disease program, Moderna announces a new development candidate, mRNA-3139, for ornithine transcarbamylase (OTC) deficiency. mRNA-3139 uses the same lipid nanoparticles (LNP) as in Moderna's GSD1a program and is the Company's sixth rare disease candidate.

OTC deficiency is a rare genetic condition characterized by complete or partial lack of the OTC enzyme, resulting in ammonia build-up in the blood. The clinical presentation of OTC deficiency is very heterogeneous, with more severe symptoms including seizures, enlarged liver, and respiratory difficulty. For more severe or non-responsive cases that progress towards liver failure, treatment may include liver transplantation.

Late-Stage Respiratory Vaccines

COVID-19 Boosters

• Moderna has launched two vaccine boosters to meet different needs across the largest markets: mRNA-1273.214 and mRNA-1273.222.
• mRNA-1273.214 is a COVID-19 bivalent booster vaccine that targets both the original strain of SARS-CoV-2 and the Omicron variant of concern (BA.1). Clinical trials demonstrated that this booster vaccine increased the immune response against the more recent Omicron strains (BA.4 and BA.5). They found the results to be similar regardless of prior infection status or age.
• Moderna developed mRNA-1273.222 in accordance with guidance from the U.S. FDA to develop a booster vaccine targeting the Omicron BA.4 and BA.5 variants, combined with mRNA-1273. A Phase 2/3 clinical trial for mRNA-1273.222 is currently underway and fully enrolled.
• Moderna has rapidly scaled manufacturing of COVID-19 boosters and began delivery of doses in August.

Seasonal Influenza Vaccine Program: Influenza, which occurs seasonally, causes respiratory illnesses and places a substantial burden on healthcare systems. Worldwide, the influenza virus leads to 3-5 million cases of severe illness and 290,000-650,000 influenza-related respiratory deaths annually. About 8% of the US population experiences symptoms from influenza each year, with 140,000-710,000 hospitalizations and 12,000-52,000 deaths per year.

• mRNA-1010 is a vaccine candidate that encodes for hemagglutinin (HA) glycoproteins of the four influenza strains recommended by the World Health Organization (WHO) for the prevention of influenza. HA is a major influenza surface glycoprotein that is considered an important target to generate broad protection against influenza and is the primary target of currently available influenza vaccines. A Phase 3 immunogenicity and safety study of mRNA-1010 in the Southern Hemisphere is fully enrolled (~6,000 participants). Initial regulatory feedback supports an accelerated pathway for approval.
• Moderna is also preparing to launch a Phase 3 efficacy trial in the Northern Hemisphere to demonstrate superior effectiveness of mRNA-1010 against a currently licensed seasonal influenza vaccine.

Respiratory Syncytial Virus Vaccine Program: Respiratory syncytial virus (RSV) causes a substantial disease burden in older adults aged 65 years and older. There are approximately 177,000 RSV-related hospitalizations in adults 65 and older in the U.S. each year and approximately 14,000 RSV-related deaths. Globally, there are more than 1.5 million episodes of acute respiratory tract infection related to RSV each year.

• Moderna's pivotal Phase 3 placebo-controlled clinical trial of mRNA-1345, an RSV vaccine, will evaluate its effectiveness in older adults (adults 60 years of age and older); so far, the trial has enrolled more than 24,000 of the anticipated 34,000 participants. The study has been designed to provide an efficacy readout in the 2022-2023 winter season.
• Since RSV also causes a significant disease burden in children, mRNA-1345 is being tested in an ongoing Phase 1 trial in pediatric populations.

Combination Respiratory Vaccines

In addition to single-agent vaccines, the Company is progressing several combination respiratory vaccines, including a fully enrolled Phase 1/2 trial testing mRNA-1073 targeting SARS-CoV-2 and influenza. Clinical trials for mRNA-1230, targeting SARS-CoV-2, influenza, and RSV are expected to be initiated this year.

Late-Stage Latent Vaccine: CMV Trials

Cytomegalovirus Vaccine Program: Cytomegalovirus (CMV), a type of latent herpes virus, is the most common cause of infection that occurs before birth worldwide and is responsible for more than $1 billion in annual healthcare costs. CMV can cause long-term health problems in infected infants, such as hearing loss, vision impairment, cerebral palsy, learning disabilities, and decreased muscle strength and coordination.

• Moderna's CMV vaccine candidate, mRNA-1647, comprises six mRNAs encoding two antigens in one vaccine and is designed to protect against CMV infection. mRNA-1647 is being evaluated in the Phase 3 CMVictory trial to prevent congenital CMV. To date, more than 40% of anticipated participants are enrolled. The study will determine the efficacy, safety, and immunogenicity of mRNA-1647 against CMV infection in women ages 16-40 years. Enrollment is ongoing in the U.S. and internationally.
• In addition to congenital infection, CMV has a major impact on morbidity and mortality in transplant patients. CMV is a frequent complication after transplantation since the ability to fight infection after transplant is decreased. Moderna is planning to test mRNA-1647 in a randomized, placebo-controlled, study to evaluate the efficacy, safety, and immunogenicity of mRNA-1647 in patients who have undergone a high-risk stem cell transplant.

Personalized Cancer Vaccine

• Personalized cancer vaccines (PCV) target an individual patient's unique tumor mutations to selectively treat their cancer. Moderna's PCV program is being developed in collaboration with Merck.
• mRNA-4157 is a PCV candidate designed to stimulate an immune response by boosting T cells, which are believed to be necessary for a curative cancer therapy. Moderna's Phase 2 clinical trial will determine if mRNA-4157 in combination with KEYTRUDA®, an approved cancer therapy, can improve recurrence-free survival (at 12 months) in patients with resected melanoma at high risk of recurrence, compared to KEYTRUDA alone. KEYTRUDA was selected as the comparator in the trial because it is considered the standard of care for high-risk melanoma patients.
• The Phase 2 trial is fully enrolled and primary data are expected in 4Q 2022.

Commercial Preparation

• As Moderna's pipeline advances, preparations are underway for multiple vaccine launches globally between 2023-2026. Commercial priorities include planning for the 2023 endemic COVID-19 market, expanding into respiratory vaccine markets with single-agent and combination vaccines for RSV, influenza, and COVID-19, preparing for a possible CMV vaccine launch, and entering the therapeutics market.
• Moderna to pursue accelerated pathway for potential approval of the flu vaccine (mRNA-1010) in 2023.
• Moderna continues to invest in building global manufacturing capabilities to support multiple product launches, including seasonal updates and different product formulations.

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: clinical trends in Moderna's Phase 1/2 PA trial; Moderna's pursuit of an accelerated approval pathway for mRNA-1010 and the timing of potential approval; the timing of data from Moderna's trials of its product candidates targeting PCV, MMA,GSD1a and RSV; the initiation of clinical trials for mRNA-1230, targeting SARS-CoV-2, influenza and RSV; Moderna's commercial priorities; the timing of future product launches; Moderna's manufacturing capabilities; and the timing of delivery of COVID-19 boosters. 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 Annual Report on Form 10-K for the fiscal year ended December 31, 2021 and Quarterly Report on Form 10-Q for the quarterly period ended March 31, 2022, each 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, R&D Communications
617-899-3991
MaryBeth.Woodin@modernatx.com

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

SOURCE: Moderna,Inc.