Moderna Announces First Patient Enrolled in Phase 1/2 Study of mRNA-3704 for Methylmalonic Acidemia
mRNA-3704 is Moderna’s first rare disease program to enter clinical studies
“This study will provide important information about the potential of an mRNA approach to replace the deficient enzyme in patients with MMA, which currently has no approved medical therapy or investigational medicines that address the underlying cause,” said
mRNA-3704 has been granted Fast Track, Orphan Drug, and Rare Pediatric Disease designation by the
About the Phase 1/2 Study
The Phase 1/2 open-label study is designed to evaluate the safety and tolerability of up to four ascending dose levels of mRNA-3704 administered via intravenous infusion in patients one year and older with isolated methylmalonic acidemia due to methylmalonyl-CoA mutase (hMUT) deficiency with elevated plasma methylmalonic acid, a key metabolite that accumulates in the disorder. Upon establishment of a dose with acceptable safety and pharmacodynamic effect, additional patients will be enrolled in a dose expansion stage to allow for further characterization of the safety and pharmacodynamics of mRNA-3704. Patients in both stages of the study will participate in a pre-dosing observational period, followed by a treatment period and a follow-up period after withdrawal of treatment.
mRNA-3704 is designed to instruct the body to restore the missing or dysfunctional proteins that cause MMA. mRNA-3704 consists of mRNA encoding human MUT, the mitochondrial enzyme commonly deficient in MMA, encapsulated within Moderna’s proprietary lipid nanoparticle (LNP). Preclinical data have demonstrated that repeat systemic dosing of mRNA-3704 enabled liver expression of functional hMUT in mouse models of MMA, significantly improving survival and weight gain.1 Repeat dosing did not increase markers of liver toxicity or inflammation.1 mRNA-3704 uses the same proprietary LNP formulation as the Company’s antibody against chikungunya virus (mRNA-1944) and propionic acidemia (mRNA-3927) programs.
About Methylmalonic Acidemia (MMA)
Methylmalonic acidemia is a rare, life-threatening, inherited metabolic disorder that is most commonly (approximately 60% of cases) caused by a deficiency in the mitochondrial enzyme methylmalonic-CoA mutase (MUT). This deficiency can lead to metabolic crises due to a toxic buildup of acids in the body. As a result, MMA is associated with significant mortality and morbidity, and there are no approved therapies. Standard of care includes dietary and palliative measures. Currently, liver or combined liver and kidney transplant is the only effective treatment.
About Moderna’s Systemic Intracellular Modality
Moderna’s systemic intracellular therapeutics modality was designed to achieve a therapeutic effect in one or more tissues or cell types by producing proteins encoded by mRNA inside the cell, either located in the cytosol or specific organelles, like the mitochondria. The goal of this modality is to provide intracellular proteins, such as intracellular enzymes and organelle-specific proteins, as safe, tolerable and efficacious therapies.
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended, including, without limitation, statements regarding the Company’s plans for the Phase 1/2 study of mRNA-3704, including its intent to begin dosing the patient who has entered the observational study and plans for additional enrollment; and statements regarding plans for Moderna’s development candidates and Moderna’s strategy, business plans and focus. The words “may,” “will,” “could,” “would,” “should,” “expect,” “plan,” “anticipate,” “intend,” “believe,” “estimate,” “predict,” “project,” “potential,” “continue,” “target” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Any forward-looking statements in this press release are based on management’s current expectations and beliefs and are subject to a number of risks, uncertainties and important factors that may cause actual events or results to differ materially from those expressed or implied by any forward-looking statements contained in this press release, including, without limitation, uncertainties related to the ability of the Company to enroll patients in its rare disease clinical trials and the risk of unexpected safety events related to the first rare disease clinical study. These and other risks and uncertainties are described in greater detail in the section entitled “Risk Factors” in Moderna’s most recent Annual Report on Form 10-K filed with the
1 An et al. Systemic messenger RNA therapy as a treatment for methylmalonic acidemia. Cell Reports. 2017; 21(12): 3548-3558.
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