Moderna Therapeutics, a company discover and develop of messenger RNA (mRNA) therapeutics and vaccines, and Merck, known as MSD outside the United States and Canada, announced an expansion of their 2016 collaboration to develop and commercialize novel personalized messenger RNA (mRNA) cancer vaccines to now include shared antigen mRNA cancer vaccines including mRNA-5671, Moderna’s mRNA KRAS cancer vaccine.

Moderna developed mRNA-5671 starting in 2017.  The two companies will now advance jointly mRNA-5671 in human studies, and plan to conduct combination studies with additional immuno-oncology therapies.

“Augmentation of immune responses offers great promise in cancer therapy, as our work with the PD-1-specific antibody Keytruda has shown,” said Dr. Roger M. Perlmutter, president, Merck Research Laboratories.  “We now look forward to expanding our exploration of mRNA cancer vaccines, working in concert with our colleagues at Moderna.”

Under the expanded agreement, Merck will be responsible for clinical development of mRNA-5671 and associated costs while Moderna will be responsible for clinical supply and associated costs. Following the completion of human proof-of-concept (hPOC) studies, Merck may opt-in on further development and commercialization of mRNA-5671 upon payment of an undisclosed fee to Moderna.  Following opt-in, the parties will share equally the global net profits and costs associated with mRNA-5671.  As part of this agreement, the parties may also initiate and collaborate on other shared antigen mRNA cancer vaccines programs. In addition, Merck will make a $125 million investment in Moderna in newly priced series H preferred equity. Moderna closed a series G round earlier this year.

“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 chief executive officer. “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.”       

KRAS is one of the most frequently mutated oncogenes in human cancer, occurring in approximately 90 percent of pancreatic cancers and 30 percent of non-small cell lung cancer (NSCLC), where they are associated with worse outcomes.  Presentation of epitopes containing KRAS mutations to the immune system may elicit an anti-tumor response.  mRNA-5671 encodes for the four most commonly found KRAS mutations, and is designed to target most of the KRAS mutations that occur in NSCLC, colorectal cancer and pancreatic cancer.

The Moderna KRAS mRNA program utilizes tumor sequencing to identify suitable patients with specific mutations in KRAS in order to personalize their therapy, and complements the other personalized mRNA cancer vaccines in the collaboration.

This is the fourth collaboration between Merck and Moderna in the past three years. The oncology alliance builds upon an initial June 2016 agreement to jointly develop personalized mRNA cancer vaccines, combining Merck’s established leadership in immuno-oncology with Moderna’s pioneering mRNA vaccine platform and GMP manufacturing capabilities. Under the 2016 personal cancer vaccine (PCV) agreement, Merck made an upfront cash payment to Moderna of $200 million to discover and develop individually tailored cancer vaccines for patients across a spectrum of cancers through proof of concept.

In November, 2017 the companies announced a key milestone with the first-in-human dosing of mRNA-4157, an mRNA PCV.  The phase 1 open-label, dose escalation, multicenter study in the United States (KEYNOTE-603) will assess the safety, tolerability and immunogenicity of mRNA-4157 alone in subjects with resected solid tumors and in combination with Keytruda (pembrolizumab) an anti-PD-1 therapy, in subjects with unresectable solid tumors.

Keytruda is an anti-PD-1 therapy that works by increasing the ability of the body’s immune system to help detect and fight tumor cells.  Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry’s largest immuno-oncology clinical research program, which currently involves more than 750 trials studying Keytruda across a wide variety of cancers and treatment settings.  The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers.

Moderna pioneers the discovery and development of messenger RNA (mRNA) therapeutics and vaccines, an entirely new class of medicines that directs the body’s cells to produce intracellular or secreted proteins that can have a therapeutic or preventive benefit for both patients and healthy individuals.