Technological Solution Sets to Create Medicines
At Moderna, we combine elements of our mRNA platform into distinct approaches to address diseases. We call these approaches modalities. A modality is a technological solution set that can be deployed to create a family of medicines for different diseases within one therapeutic area, and often across therapeutic areas.
Infectious Diseases / Viral Vaccines
Vaccines work by mimicking an infection from a known pathogen, such as a virus, without causing disease. They teach the immune system to recognize antigens, which are parts of pathogens. Current vaccines introduce antigens to the body as weakened or inactivated pathogens or as selected protein antigens produced recombinantly in cells in bioreactors.
With our vaccine approach, we deliver mRNA encoding for one or more viral antigenic proteins to the body’s cells. The mRNA directs the cells to produce and express the antigenic proteins, either secreted or on the cell surface, much like a native infection would do but without the ability to cause disease or spread. As a result, the body’s immune system responds as if the actual virus is present. The immune system produces antibodies that have the potential to neutralize the virus and prevent infection in the event the vaccinated person is exposed to the virus in the future.
Moderna has eight infectious disease vaccine development candidates.
Personalized Cancer Vaccines
We also developing mRNA-based personalized cancer vaccines to prime the immune system to recognize cancer cells and mount a strong, tailored response to each individual patient’s cancer. Utilizing our mRNA vaccine technology, we encode a patient’s specific neoantigens, or unique mutations present in that specific patient’s tumor. When injected into a patient, the vaccine is designed to elicit a specific immune response that can recognize and destroy cancer cells.
Moderna has a development candidate, mRNA-4157, to develop personalized cancer vaccines.
We utilize this modality when we want to direct the localized expression of one or more proteins in targeted tissue but do not want to generate systemic expression of a protein. Certain proteins are potent and/or may have toxic or off-target effects if expressed throughout the body. However, when directly injected into targeted tissue – for example, into a tumor – the desired benefit of the protein can be concentrated in that specific tissue.
Intratumoral injection leading to localized expression of therapeutic proteins may open the opportunity to go after new targets to treat cancer, including those where the associated therapeutic potential historically has been limited by either the inability to access these targets or by systemic toxicities.
As another application of this modality, local tissue injection of VEGF-A mRNA may potentially lead to the creation of more blood vessels and improved blood supply. Using mRNA to initiate a strong, local and transient surge of VEGF-A expression could help overcome challenges associated with previous approaches to regulate VEGF-A in tissues. One day, this approach could provide a unique regenerative treatment option for patients with heart failure or after a heart attack, as well as for diabetic wound healing and other ischemic vascular diseases.
Moderna has three localized therapeutic development candidates, two in immuno-oncology and one in cardiovascular disease.
Certain proteins can have systemic effects after being secreted from cells where they are produced. One example is antibodies, which are a key component of the immune system. Antibodies bind to and inhibit specific targets and, when used as drugs, that activity can be harnessed for therapeutic effect.
Moderna is using its modality of systemic intravenous (IV) delivery of mRNA to stimulate the body’s cells to produce specific antibodies that can bind to cellular targets or targets on infectious pathogens.
Our first application of the IV systemic modality is advancing the discovery of a combination of mRNA-based antibody therapeutics to help prevent human immunodeficiency virus (HIV) infection through a partnership with the Bill & Melinda Gates Foundation. By triggering the production of several neutralizing antibodies, it may be possible to prevent HIV infection.
Moderna is in the discovery phase with the IV systemic therapeutic modality.
Many diseases are caused by defects or deficits in proteins that function inside or on the surface membranes of cells. Existing methods of protein-based therapy do not generally allow for proteins to reach the intracellular space or to be inserted onto the surface of cells. Therefore, they are unable to replace the defective or missing disease-causing proteins within cells.
A large number of diseases, including many rare genetic diseases, are caused by defects or deficits in proteins expressed by liver cells. By delivering mRNA drugs intravenously (IV) to the liver, we can potentially stimulate production of therapeutic proteins in ways that cannot be achieved with other technologies.
Moderna is in the discovery phase with the IV liver therapeutics modality.
Through our collaboration with Vertex, we are pursuing the potential of delivering mRNA to the lungs (via inhaled delivery) to trigger the cells to produce a functional cystic fibrosis transmembrane conductance regulator (CFTR) protein, which is known to be defective in people with cystic fibrosis (CF). With this modality, mRNA would be used as a drug to direct cells in the lung to produce functional CFTR proteins. There are more than 1,900 known mutations in the CFTR gene. An mRNA-based approach could be applicable to any person with CF regardless of a person’s specific CFTR mutations.
CFTR represents our first exploration of this modality, where we are in the discovery phase. It could potentially lead to treatments for other pulmonary diseases in which mRNA could be delivered to the lung to direct cells to produce therapeutic proteins.