Oncology-focused Merus has signed a research collaboration and licensing agreement with Eli Lilly’s Loxo Oncology. The partners will work together to research and develop up to three CD3-engaging T-cell bispecific antibody therapies for cancer.
To achieve this, Merus will contribute its proprietary antibody Biclonics platform, and particularly its new panel of antibodies that bind to the CD3 portion of the T cell, according to the company’s CEO Bill Lundberg. Lilly and Loxo Oncology will bring their oncology expertise to develop the oncology bispecific antibodies.
According to the terms of the agreement, Merus will receive an upfront cash payment from Lilly of $40m. The company will also be eligible to receive up to $1.6bn in development and commercialisation milestone payments across the three products. Lilly will also make an equity investment of $20m in Merus common shares.
This financing, as well as a public offering Merus is currently pricing, will support the company to fund its own clinical work to develop “novel bispecific and trispecific antibody drugs for patients with cancer”, explains Merus president and CEO Bill Lundberg.
The deal also supports Merus to “expand our CD3 T cell research, both in programmes that will be part of the Lilly collaboration and programmes that are outside of it”, adds Lundberg. “We want to continue to strengthen and deepen our capacity, capabilities and expertise in CD3 T cell engagers to make the best next generation of T cell engager.”
Merus’s Biclonics platform
Merus was founded on its technology platform, which allows for the production of bispecific anbibody therapies. The Biclonics platform allows Merus to generate many diverse panels of antibodies and carry out high-throughput production and screening of them to discover unique, innovative therapeutic candidates that bind to two targets.
These antibodies retain the qualities of human full-length IgG antibodies that do not require fusion proteins or linkers to pair the antibody’s heavy and light chains. This approach reduces the complexity characteristic of other approaches to developing bispecific antibodies. Lundberg explains other methods often create therapeutics that “behave weirdly, are hard to manufacturer and have short half-lives”, whereas Merus’s approach aims to create antibodies that are stable, with a long half-life and low immunogenicity.
CD3 T cell engagers for cancer
Building on this platform, Merus has focused on creating a new panel of antibodies that bind to the CD3 part of the T cell and allow for the development of T cell engager therapies. CD3 is so interesting as a target because it is a protein in the T cell receptor complex, explains Lundberg. When a T cell finds a target that represents a foreign antigen, it recognises that foreign antigen through the T cell receptor complex on the surface of the T cells. This can be used to latch it to a target, such as a tumour.
Lundberg notes the Merus CD3 platform has over 175 novel and diverse anti-CD3 common light chain antibodies with a range of characteristics, attributes and qualities. These provide Merus, he says, with “novel insights about how CD3 T cell engagers work, how they engage an activated T cell, [and] how you characterise T cells’ ability to expand and kill the target cell to release cytokines”.
He explains the strength of the platform was crucial to Lilly and Loxo Oncology’s interest in partnering with Merus to develop next-gen CD3 T cell engagers.
“CD3-engaging bispecific antibodies are rapidly becoming one of the most transformative immune-modulating modalities used to treat cancer,” commented Loxo Oncology at Lilly chief operating officer Jacob Van Naarden. “Merus has built a differentiated platform and one that we believe can enable us to create bispecific antibody therapies with wider therapeutic indexes than those available today. We look forward to working closely with Merus to develop new potential medicines for patients with cancer.”
Lundberg is similarly excited to be working with Lilly and Loxo Oncology on CD3 T cell engagers. He concludes that Lilly represents “both the strength of large pharma with the nimbleness of smaller biotech” and that Loxo Oncology, which has one FDA-approved cancer therapy in the form of RET kinase inhibitor Retevmo (selpercatinib) and several others in Phase I and II trials, has been “immensely successful in very specific and targeted oncology drug development”.