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mRNA Therapeutics for Coronary artery disease

mRNA Therapeutics for Coronary artery disease

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mRNA Therapeutics for Coronary Artery Disease

Coronary heart disease (CAD) is the leading cause of death in the United States as the most common form of heart disease. Coronary heart disease contains stable angina, unstable angina, and myocardial infarction, whose common symptoms are chest pain and discomfort. CAD can cause a Myocardial infarction (heart attack) or heart failure because of damage to the heart or insufficient blood flow.

CAD can be cured by injecting new blood into the ischemic muscle, such as coronary bypass surgery or angioplasty techniques. However, these methods are not suitable for all patients.

Vascular endothelial growth factor A (VEGF-A) is a potent angiogenic factor that can facilitate the growth of blood vessels. Through partial tissue regeneration, local injection of mRNA encoding VEGF-A enhances the restoration of cardiac function.

Moderna and AstraZeneca are co-developing a locally-administered mRNA therapy (AZD8601) that encodes VEGF-A and promotes blood vessel growth. AZD8601 includes naked mRNA in a citrate saline-buffered solution (no lipid encapsulation).

In a phase 2a clinical trial, AZD8601 was administered directly into the myocardium of patients being treated with backup coronary artery bypass surgery. This Phase 2 clinical trial met its endpoints. But AstraZeneca excluded the drug from its Phase 2 treatment program in its quarterly review (PDF); Moderna, the collaborated company that developed AZD8601, also withdrew its candidate from the program.

In February 2023, AstraZeneca, in partnership with the University of Gothenburg, released in vitro and in vivo test data for LNP-encapsulated VEGF-A mRNA. It is shown that LNPs convert extracellular vesicles (EVs) into functional extensions of the therapeutic mRNA for cell-to-cell transport, where EVs deliver this mRNA differently than LNPs.

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Grade

Deliverables

Specification

Applications

non-GMP

Drug Substance, mRNA

0.1~10 mg (mRNA)

Preclinical research such as cell transfection, Analytical method development, Pre-stability studies, Formulation development

Drug Product, LNP-mRNA

GMP, Sterility

Drug Substance, mRNA

10 mg~70 g

Investigational new drug (IND), Clinical trial authorisation (CTA), Clinical trial supply, Biologic license application (BLA), Commercial supply

Drug Product, LNP-mRNA

5000 vials or pre-filled syringes/ cartridges

mRNA Therapeutics Pipelines for Coronary Artery Disease

Code Name

Target Protein

Indications

Manufacturer

Latest Stage

AZD8601

VEGF-A

Coronary artery disease (CAD)

Moderna and AstraZeneca

Phase II

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