Infectious Diseases | Immuno-Oncology | Rare Diseases

 

We are also applying our mRNA technology to the emerging and highly promising field of immuno-oncology, also often referred to as immunotherapy. This therapeutic area involves harnessing the body’s immune system to identify and kill cancer cells in the same way the immune system identifies and targets infection from pathogens. 

Moderna’s Immuno-Oncology programs are currently focused on two main areas: therapeutic vaccines and intratumoral immuno-oncology therapeutics.

Therapeutic Vaccines – Personalized Cancer Vaccines

Moderna is creating an individualized, mRNA-based personalized cancer vaccine, mRNA-4157, to deliver one medicine for one patient at a time. Through next-generation sequencing, we identify mutations found on a patient’s cancer cells, called neoepitopes. Neoepitopes can help the immune system distinguish cancer cells from normal cells. Using algorithms developed by our in-house bioinformatics team, we predict 20 neoepitopes present on the patient’s cancer that should elicit the strongest immune response, based on unique characteristics of the patient’s immune system and particular mutations. We then create a vaccine that encodes for each of these mutations and load them onto a single mRNA molecule. 

Once injected into the patient, the vaccine should direct the patient’s cells to express the selected neoepitopes. In turn, this may help the patient’s immune system better recognize cancer cells as foreign and destroy them.

Leveraging our rapid cycle time, small-batch manufacturing technique and digital infrastructure, we plan to manufacture and supply each individually manufactured personalized cancer vaccine to patients within weeks.

mRNA-4157 also has the potential to enhance clinical outcomes associated with checkpoint inhibitor therapies. In 2016, Moderna and Merck formed a collaboration to develop mRNA-4157 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA.  A Phase 1 study evaluating the safety, tolerability, and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors and in combination with pembrolizumab in subjects with unresectable solid tumors (KEYNOTE-603) is now underway.

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Therapeutic Vaccines – KRAS Cancer Vaccine

We are also advancing a cancer vaccine that encodes for KRAS epitopes. KRAS is one of the most frequently mutated oncogenes in human cancer (approximately 30% of all cases). KRAS mutations are found principally in non-small cell lung cancer (NSCLC), colorectal cancer and pancreatic cancer, and are associated with worse outcomes. Hotspots of KRAS mutations are found in different tumor types and can serve as tumor rejection epitopes. Presentation of these epitopes to the immune system may elicit a robust anti-tumor response.

For this vaccine, we plan to include an mRNA that encodes for the four most commonly found KRAS mutations, which will cover most of the mutations that occur in NSCLC, colorectal cancer and pancreatic cancer.

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Intratumoral Immuno-Oncology Therapeutics

The cancer immunity cycle is highly complex; and we believe there are several points in this cycle where we may be able to intervene with mRNA intratumoral immunotherapies and, in combination with checkpoint inhibitors, more effectively unleash the immune system to target and kill cancer cells.

As a platform for creating immunotherapies, mRNA offers several potential advantages. mRNA makes proteins. The majority of the interactions between cancer cells and the immune system are regulated by proteins; either proteins that are secreted or those that remain on the surface of cells. As such, many components of immune-based treatment of cancer potentially can be impacted by mRNA. Because of the ability to get inside cells to direct protein expression, mRNA affords the opportunity to go after targets not previously druggable.  

In addition, mRNA can be leveraged to develop combinations of therapies, which may be an important key for overcoming treatment resistance for certain patients and delivering a powerful treatment punch to cancer. 

Finally, the use of mRNA immunotherapies permits a focused and powerful yet transient response, which may permit a highly regulatable and directed effect, mitigating unwanted systemic toxicity in a way similar to conventional drugs.

We are underway with a Phase 1 clinical study of our first intratumoral immuno-oncology therapeutic, and are advancing two additional intratumoral immuno-oncology therapeutics toward the clinic.

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