CAMBRIDGE, MA / ACCESSWIRE / April 3, 2024 / Moderna, Inc. (NASDAQ:MRNA) today announced that interim data for a first-in-human, phase 1/2, open-label, dose optimization study and extension study, evaluating the safety and efficacy of mRNA-3927, an investigational mRNA therapy for propionic acidemia (PA), has been published in Nature.

"We are excited to share the first published clinical data utilizing an mRNA therapy for intracellular protein replacement," said Kyle Holen, M.D., Moderna's Senior Vice President and Head of Development, Therapeutics and Oncology. "PA is a rare, inherited metabolic disorder that results from the body's inability to process certain parts of proteins and lipids due to a specific enzyme deficiency. For people with PA, harmful amounts of toxic metabolites can build up in the body and lead to metabolic decompensation events (MDEs) and multisystemic complications. These interim data indicate early signs of potential clinical benefit with mRNA-3927, and importantly also demonstrate that mRNA-3927 has infrequent treatment-limiting side effects. I'm particularly proud of these results given that there are currently no therapeutic treatments approved for patients with this disease."

The ongoing global Phase 1/2 clinical trial (ClinicalTrials.gov Identifier: NCT04159103) is a multicenter, open-label study designed to assess the safety, pharmacodynamics, and pharmacokinetics of mRNA-3927 in participants aged one year and older with genetically confirmed PA. Data from the study was previously presented at the 2023 American Society of Gene & Cell Therapy (ASGCT) Annual Meeting.

As of the latest data cut (May 31, 2023), 16 participants received investigational therapy mRNA-3927 across five cohorts as part of the dose optimization and extension studies. Of these, 12 participants completed the study and enrolled in the open-label extension study. Over 340 intravenous doses were administered, accounting for over 15 person-years of treatment.

To date, mRNA-3927 has been well tolerated in participants at the doses administered, with no dose-limiting toxicities observed. Fifteen participants reported treatment-emergent adverse events (TEAEs), while nine participants experienced drug-related TEAEs. Serious adverse events (SAEs) were reported in eight participants. Most SAEs were related to PA and unrelated to mRNA-3927. Five participants had mild infusion-related (IRR) TEAEs; however, most events occurred at the first doses. A reduction in the number of MDEs was observed. The relative risk for MDEs was reduced by 70% during the treatment period of the dose optimization study. No MDEs were observed with higher doses of mRNA-3927.

Additional participants are now being enrolled into the study as part of a dose expansion phase to allow for further characterization of the efficacy, safety, and pharmacodynamic activity of mRNA-3927.

About Propionic Acidemia

Propionic acidemia is a rare, serious, inherited metabolic disorder with significant morbidity and mortality, affecting one in 100,000-150,000 individuals worldwide. PA is caused by pathogenic variants in the propionyl-coenzyme A carboxylase (PCC) α or β subunits (PCCA and PCCB genes, respectively), leading to PCC deficiency and subsequent accumulation of toxic metabolites. PA is characterized by recurrent life-threatening MDEs and multisystemic complications. Some of the most common multisystemic complications include neurological manifestations, cardiomyopathy, arrhythmia, growth retardation, recurrent pancreatitis, bone marrow suppression, and predisposition to infection. Long-term, insults by toxic metabolites cause multiorgan complications and are correlated with recurrent MDEs.

Currently, there are no effective therapies for PA that target the underlying root cause of the disease.

About mRNA-3927

mRNA-3927 is a novel, IV-administered, lipid nanoparticle (LNP)-encapsulated dual investigational mRNA therapy that encodes for PCCA and PCCB subunit proteins to restore functional PCC enzyme activity in the liver. By encoding for the PCC enzyme, mRNA-3927 has the potential to replace a missing or dysfunctional enzyme.

About Moderna

Moderna is a leader in the creation of the field of mRNA medicine. Through the advancement of mRNA technology, Moderna is reimagining how medicines are made and transforming how we treat and prevent disease for everyone. By working at the intersection of science, technology and health for more than a decade, the company has developed medicines at unprecedented speed and efficiency, including one of the earliest and most effective COVID-19 vaccines.

Moderna's mRNA platform has enabled the development of therapeutics and vaccines for infectious diseases, immuno-oncology, rare diseases and autoimmune diseases. With a unique culture and a global team driven by the Moderna values and mindsets to responsibly change the future of human health, Moderna strives to deliver the greatest possible impact to people through mRNA medicines. For more information about Moderna, please visit modernatx.com and connect with us on X (formerly Twitter), Facebook, Instagram, YouTube and LinkedIn.

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 potential clinical benefits of mRNA-3927 for the treatment of propionic acidemia; the safety and tolerability of mRNA-3927; and plans for future clinical studies of mRNA-3927. 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, 2023, 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.

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