Gilead, Merus Strike Deal to Develop Novel Trispecific T-Cell Antibodies for Cancer Treatment

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This morning, Gilead and Merus announced an agreement focused on developing novel dual tumor-associated antigens (TAA) targeting trispecific antibodies. As a part of this collaboration, the companies will utilize Merus’ Triclonics platform along with Gilead’s oncology capabilities during research and development. Under terms of the deal, Merus will receive an upfront payment of $56 million and a $25 million equity investment from Gilead, with potential future earnings up to $1.5 billion based on development, commercial milestones, and sales royalties. Additionally, Merus will have the option to pick a 50/50 profit and loss sharing model on one program over milestone and royalty payments.¹

"We have seen the successful application of bispecific antibodies as an immune-modulating modality used to treat cancer. We are now looking ahead to the development of additional multispecific antibodies capable of driving robust anti-tumor immune responses with an improved efficacy and safety profile," said Flavius Martin, MD, EVP, research, Gilead Sciences, in a press release. "We are excited to explore the potential of Merus’ differentiated Triclonics platform to discover and advance transformative new cancer therapies as we deepen our portfolio across oncology indications."

According to a study published in Signal Transduction and Targeted Therapy, multispecific antibodies have quickly earned a great deal of attention over the past 30 years, being used as beneficial means to support unmet clinical needs.

“The recent spike of interest in antibody-mediated immune cell engagement for cancer treatment has driven many multifunctional antibodies into clinical studies. Approximately 30% of T cell-engaging [bispecific antibodies] are in clinical trials for treating hematological malignancies, and the specific targets are mainly well-known [tumor-associated antigens], such as CD19, CD20, CD33, CD38, CD123, and BCMA,” the study authors wrote.

They explained that a variety of designs have been mapped out for multispecific antibodies to support different tools throughout cancer immunotherapy.²

“Multispecific antibodies are engineered to target distinct antigen epitopes simultaneously and thus may exhibit synergistic therapeutic efficacy,” explained the authors of the study. “The modes of action of multispecific antibodies include but are not limited to redirecting the human immune system to fight cancer, regulating a receptor signaling pathway, combinational targeting of different tumor antigens to increase tumor selectivity or mitigate antigen loss-related relapse. With suitable target combinations and optimal format design, multispecific antibodies may achieve the desired therapeutic outcome and are feasible for large-scale production. In the near future, an extensive pipeline of multispecific antibodies may provide valuable candidates to meet the needs for clinical cancer treatment.”

Merus’ two multispecific antibodies, Biclonics and Triclonics, are created through light chain technology. According to the press release, Triclonics offers the ability to design antibodies capable of simultaneously binding to three targets at once.¹

"We are looking forward to working with Gilead to develop novel T-cell engager antibodies using our Triclonics technology," said Hui Liu, PhD, EVP, chief business officer, head of Merus US, in the press release. "We are grateful for our collaborations which represent opportunities for Merus to leverage our research capabilities to pursue innovative biology and to address significant unmet medical needs. Importantly, this collaboration represents the first for our proprietary Triclonics platform."

References

1. Gilead and Merus Announce Collaboration to Discover Novel Antibody-Based Trispecific T-Cell Engagers. Gilead. March 6, 2024. Accessed March 6, 2024. https://www.gilead.com/news-and-press/press-room/press-releases/2024/3/gilead-and-merus-announce-collaboration-to-discover-novel-antibody-based-trispecific-t-cell-engagers

2. Emerging new therapeutic antibody derivatives for cancer treatment. Signal Transduction and Targeted Therapy. February 7, 2022. Accessed March 6, 2024. https://www.nature.com/articles/s41392-021-00868-x#:~:text=A%20broad%20variety%20of%20multispecific,to%20block%20or%20activate%20synergistic