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Merck partners with Moderna to test KRas cancer vaccines in humans

The pair hopes to stimulate the immune system to tackle tumors bearing mutant KRas proteins, one of cancer’s toughest targets

by Ryan Cross
May 3, 2018

Merck & Co. is expanding its partnership with the mRNA company Moderna Therapeutics.

Under the deal, Merck will make a $125 million investment into Moderna. In addition, the big drug company will begin clinical tests of a Moderna cancer vaccine that stimulates the immune system to spot and destroy cancer cells with mutant versions of a protein called KRas—a perpetually tough target that has resided at the top of the cancer field’s most-wanted list for decades.

The deal is the latest for the closely watched Cambridge, Mass.-based biotech company, which just raised $500 million from private investors in February, placing its value at $7 billion. While many drug companies develop protein-based therapies, or small molecules that act on proteins, Moderna is making drugs from a different molecule called messenger RNA (mRNA).

A photo of Moderna CEO Stephane Bancel.
Credit: Moderna
Moderna CEO Stephane Bancel.

mRNA is the intermediary used to translate the genetic code of DNA into proteins in cells. For some of its therapies, Moderna will use mRNA to produce therapeutic proteins, but the majority of its current programs use mRNA to make vaccines for infectious diseases and cancer. When injected into the body, this mRNA is translated into bits of proteins that train the immune system to seek and destroy infected cells or tumors displaying similar proteins.

Merck was already collaborating with Moderna on personalized cancer vaccines, in which the vaccine’s mRNA is crafted uniquely to a person’s tumors. The duo began testing this approach in people with solid tumors in August 2017. The new collaboration uses a different vaccine to target tumors with specific mutant versions of a protein called KRas.

Drug hunters know KRas well. It’s a protein normally involved in controlling an array of cell behaviors, including cell division. Mutations in KRas can quickly spur unchecked growth and lead to cancer.

In fact, scientists estimate that 30% of all tumors contain KRas mutations. The number is as high as 90% for pancreatic cancers. Despite decades of drug development efforts to halt the protein’s cancer-promoting activity, there are no approved drugs that block KRas.

Moderna thinks the immune system can be recruited to help fight KRas where small-molecule drugs have failed. In 2016, researchers at the National Cancer Institute reported on discovering a person whose immune system developed a T-cell response to cancers with KRas (N. Engl. J. Med. 2016, DOI: 10.1056/nejmoa1609279). “That was really the watershed moment for the field,” says Tal Zaks, Moderna’s chief medical officer. Moderna’s vaccine encodes portions of the four most common KRas mutations, and people with any of those mutations might benefit from the therapy.

For Merck, the vaccine is another opportunity to expand the use of its marketed therapy Keytruda into more kinds of cancers, including pancreatic cancer, for which Keytruda currently doesn’t work.

Keytruda is already a multi-billion-dollar antibody immunotherapy that works for some cancers by unleashing the brakes on T cells’ tumor-targeting abilities. Hundreds of clinical trials are currently pairing Keytruda with other drugs in hopes of discovering combinations that help Keytruda work for more kinds of cancers.


Merck will pay for Phase I and II clinical trials using the KRas vaccine in combination with Keytruda. If Merck decides to continue into Phase III, Moderna will receive an undisclosed payment. The firms will split the profits if the vaccine is commercialized.

Moderna has three more programs that inject mRNA directly into tumors to help the immune system fight back. “But until we see human data, we are going to be cautious about doing more programs in immuno-oncology,” CEO Stéphane Bancel says. Moderna’s preclinical teams have many more immuno-oncology ideas “ready to go,” he adds, “but given that mRNA is a new technology, we need to not get ahead of ourselves.”


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