A landmark FDA approval last week in breast cancer defined a new cancer target, expanding the number of patients that can be treated. Mersana Therapeutics is going after that same new target with a drug from the same class of therapies and the biotech is readying for a clinical trial that could show whether its twist on the approach works in other cancers. GSK wants a piece of that potential and it is paying the biotech $100 million to begin a partnership.

The sum announced after the market close Monday is an upfront payment that gives GSK an exclusive option to license and co-develop the Mersana drug, XMT-2056. Exercising that option would give the pharmaceutical giant the opportunity to add another drug to its portfolio from the class of therapies called antibody drug conjugates (ADCs), but one that works in a slightly different way.

ADCs are traditionally comprised of a tumor-target targeting antibody that’s linked to a tumor-killing drug payload. The goal is to provide a targeted effect that spares healthy tissue. More than a dozen such therapies have passed FDA muster, most recently last Friday’s expanded approval of AstraZeneca and Daiichi Sankyo drug Enhertu to include the treatment of breast cancers that express low levels of the protein HER2.

Cambridge, Massachusetts-based Mersana aims to take ADCs beyond the delivery of toxic drug payloads. XMT-2056 still offers targeted delivery to tumors, but its cargo instead activates stimulator of interferon genes (STING), a pathway of the innate immune system. Other biotechs are developing STING-activating drugs for cancer, some of them given as injections into the tumor. Mersana said in an investor presentation that its approach leverages the targeting ability of an ADC to elicit an immune response in both tumor cells as well as immune cells found inside the tumors. This “one-two punch” to both is intended to provide a more potent therapeutic effect while at the same time reducing toxic effects elsewhere in the body.

In preclinical research, Mersana has reported that its drug showed robust anti-tumor activity in animal models expressing high HER2 levels as well as those with low HER2. The company said the efficacy of the therapy was enhanced when the drug was used in combination with other cancer drugs, including Roche’ drugs transtuzumab and pertuzumab, checkpoint-blocking drugs that target the protein PD-1, and the AstraZeneca and Daiichi drug Enhertu. In a prepared statement, John Lepore, GSK’s senior vice president of research, said that XMT-2056’s “preclinical data demonstrate how it might work to harness the immune system by activating the STING pathway, and its differentiated mechanism of action offers the potential for additional clinical benefit in patients with HER2-expressing tumors.”

Though Enhertu and XMT-2056 both target HER2, Mersana’s drug is designed to target a novel part of that protein. A Phase 1 test of the drug is expected to begin “imminently,” Mersana said in the investor presentation. That study will span a range of HER2-expressing tumors. In addition to breast cancer, the study will include gastric cancer and non-small cell lung cancer.

GSK’s oncology portfolio already includes Blenrep, an ADC that won its FDA approval two years ago for treating multiple myeloma. According to a Mersana regulatory filing, the pharma giant may exercise its option on the Mersana-partnered ADC after it delivers dose-escalation data from the Phase 1 study that includes investigation into the subgroups of breast cancer patients most likely to benefit from the therapy. If GSK elects to exercise its option on the Mersana drug, it’s on the hook for a $90 million option exercise payment. Achieving clinical, regulatory, and commercial milestones could bring Mersana up to $1.27 billion more.

GSK is the second Mersana partner that the biotech has signed on this year. In February, the company unveiled a partnership with Johnson & Johnson’s Janssen Biotech subsidiary. According to terms of that deal, Mersana will work with antibodies provided by Janssen for three unspecified targets. Janssen paid Mersana $40 million up front. Mersana could receive up to $1 billion in milestone payments.

Photo by GSK