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 (PCVs)

Moderna is advancing mRNA-based personalized cancer vaccines (PCVs), applying our mRNA vaccine and manufacturing technologies to the field of cancer vaccines, and building on advances in recent years in the field of immuno-oncology.

Under our existing collaboration with Merck to develop personalized cancer vaccines (PCVs), we will evaluate mRNA-4157 in combination with Merck’s anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). We will identify neoepitopes present in a patient’s tumor and then create an mRNA-based PCV encoding for approximately 20 neoepitopes. When injected into the patient, the mRNA-based PCV will 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 eradicate them. mRNA-4157 also has the potential to enhance clinical outcomes associated with checkpoint inhibitor therapies.

Rapid Cycle Time, Small-Batch Manufacturing and Digital Infrastructure

Moderna’s demonstrated engineering and process capability enables the synthesis of more than 1,000 unique mRNAs per month via our automated, in-house productions systems. By leveraging this rapid cycle time, small-batch manufacturing technique and Moderna’s digital infrastructure, we believe we will be able to manufacture and supply cancer vaccines tailored to an individual patient’s cancer within weeks.

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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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“Each patient’s cancer is different, so it is logical to customize cancer therapy for each patient. It’s been shown that patients who are most responsive to immunotherapies, like KEYTRUDA, are those who have tumors expressing higher numbers of neoantigens. Our mRNA technology and digital infrastructure will enable us to rapidly manufacture cancer vaccines encoding for neoantigens unique to each patient’s cancer, which may improve the ability of their immune system to do its job. The ultimate goal is improved outcomes for patients.”

-Ted Ashburn, M.D., Ph.D., Head of Development, Oncology