CAMBRIDGE, Mass. & KENILWORTH, N.J.—The saying goes that you can never have too much of a good thing, and that seems to be the prevailing opinion for Merck (known as MSD outside the United States and Canada) and Moderna Therapeutics, as they have announced the expansion of their 2016 collaboration—their fourth collaboration in three years. The original agreement, focused on the development and commercialization of novel personalized messenger RNA (mRNA) cancer vaccines, now includes the development of shared antigen mRNA cancer vaccines, including mRNA-5671, an mRNA KRAS cancer vaccine being developed by Moderna.
Under this expansion, Moderna and Merck will jointly advance mRNA-5671 in human studies, with the expectation of conducting combination studies with immuno-oncology therapeutics. Moderna will be responsible for clinical supply of mRNA-5671 and associated costs, while Merck will assume responsibility for clinical development and associated costs. Once human proof-of-concept studies are complete, Merck will have the option to opt-in on further development and commercialization of mRNA-5671, pending the payment of an undisclosed fee to Moderna. Should Merck elect to opt-in, the two companies will split costs and global net profits associated with the compound equally. The expanded agreement also covers collaboration on other shared antigen mRNA cancer vaccines programs, and dictates that Merck will invest $125 million in Moderna in a newly priced series H preferred equity.
“We are excited to build upon our productive relationship with Merck and to rapidly advance our novel mRNA-based KRAS cancer vaccine into the clinic,” said Stephane Bancel, Moderna’s CEO. “While KRAS has long been a challenging target, we believe our mRNA platform offers a novel approach designed to generate and specifically present KRAS mutations to the immune system, potentially allowing the patient’s own immune system to attack and eradicate cancers that harbor these mutations.”
Merck's Keytruda, an anti-PD-1 therapy, is a humanized monoclonal antibody that blocks the interaction between PD-1 and the ligands PD-L1 and PD-L2, which activates T lymphocytes that can impact tumor cells and healthy cells.
As Moderna notes on its website, “We are 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.” When epitopes containing KRAS mutations are presented to the immune system, it can trigger an anti-tumor response. mRNA-5671 is encoded for the four most common KRAS mutations, and has been developed to target the majority of the KRAS mutations that appear in non-small cell lung cancer, colorectal cancer and pancreatic cancer. In pursuit of more personalized cancer treatment, Moderna's KRAS mRNA program sequences tumors to identify patients with specific mutations who would most likely benefit from mRNA-5671 therapy.
“Augmentation of immune responses offers great promise in cancer therapy, as our work with the PD-1-specific antibody KEYTRUDA has shown,” commented Dr. Roger M. Perlmutter, president of Merck Research Laboratories. “We now look forward to expanding our exploration of mRNA cancer vaccines, working in concert with our colleagues at Moderna.”
This isn't the only partnering news related to Keytruda for Merck in recent months. In March, the company announced a strategic collaboration for the worldwide co-development and co-commercialization of Lenvima, Eisai's orally available tyrosine kinase inhibitor. Per the agreement, the companies will jointly develop and commercialize the drug, as a monotherapy and in combination with Keytruda. Eisai will book Lenvima's sales globally, both as a monotherapy and a combination therapy, and both companies will share gross profits equally.
The agreement also stipulates that Merck and Eisai will jointly launch new clinical studies for the combination of Lenvima and Keytruda to support 11 possible indications in six types of cancer—non-small cell lung cancer, hepatocellular carcinoma, endometrial cancer, head and neck cancer, bladder cancer and melanoma—in addition to a basket trial focused on multiple cancer types. At present, a Phase 3 study sponsored by Eisai is slated to assess combinations of Lenvima/Keytruda or Lenvima/everolimus vs. chemotherapy alone in patients with renal cell carcinoma. The Lenvima/Keytruda combination received Breakthrough Therapy Designation from the FDA in January for advanced and/or metastatic renal cell carcinoma.