Seagen and clinical-stage immuno-oncology company LAVA Therapeutics, headquartered in Utrecht, the Netherlands, have confirmed that the companies will be working together in developing, manufacturing and commercializing LAVA-1223, an advanced preclinical, proprietary, Gammabody™ technology designed to target epidermal growth factor receptor (EGFR)-expressing solid tumors.
Under the terms of the agreement, Seagen will receive an exclusive global license for LAVA-1223 and pay LAVA Therapeutics US $50 million upfront; up to approximately US $650 million in potential development, regulatory and commercial milestones; and royalties ranging from the single digits to the mid-teens on future sales.
The agreement also provides Seagen with the opportunity to exclusively negotiate rights to apply LAVA’s proprietary Gammabody™ platform on up to two additional tumor targets.
“Seagen is committed to driving innovation to improve the lives of people with cancer, and this agreement represents the company’s entry into a novel class of therapeutics that are designed to overcome the challenges of standard T cell engagers by leveraging the activity of a distinct T cell subset,” said Roger Dansey, M.D., interim CEO and Chief Medical Officer, Seagen.
“This exclusive license from LAVA provides Seagen with the opportunity to harness its expertise in developing first-in-class targeted cancer therapies, along with the company’s global development and commercialization capabilities.”
‘Unconventional’ Vγ9Vδ2 (Vgamma9 Vdelta2) T cells are the largest γδ (gamma delta) T cell subpopulation in healthy adults. They are naturally occurring cells in the human immune system that are endowed with a tumor recognition mechanism, allowing them to specifically recognize and kill cells under stress, such as cancerous cells, while leaving healthy cells unharmed.
These unconventional are amongst the best understood unconventional T cells, since they are easily accessible in peripheral blood, can readily be expanded and manipulated in vitro, respond to microbial infections in vivo and can be exploited for novel tumor immunotherapies.  They play an important role in bridging innate and adaptive immunity by promoting the activation and differentiation of various types of antigen-presenting cells (APCs) and even turning into APCs themselves, and thereby pave the way for antigen-specific effector responses and long-term immunological memory.
LAVA Therapeutics’ novel Gammabody™ platform triggers the potent and precise antitumor properties of Vγ9Vδ2 T cells, targeting both novel and well-characterized targets in liquid and solid tumors. It is the first off-the-shelf bispecific γδ T cell engager platform.
LAVA-1223 is a potential first-in-class therapy designed specifically to target and activate Vγ9Vδ2 T cells in the presence of epidermal growth factor receptor (EGFR)-expressing tumor cells.
EGFR is a well-validated target that is over-expressed in multiple solid tumor types including colorectal cancer, lung cancer and head and neck cancer.
The investigational agent employs a targeted approach that is designed to amplify natural tumor recognition by directing gamma delta T cells to the EGFR+ tumor to kill target cells and trigger immune activation while minimizing impact to normal antigen-expressing tissue. Activating the adaptive immune system with this approach has the potential to provide durable immune responses with the possibility of enhancing patient survival.
“LAVA Therapeutics is pioneering the development of gamma delta bispecific antibodies to treat cancer, and we are pleased to work with Seagen in this pursuit. The combination of LAVA’s proprietary Gammabody platform and deep bispecific expertise, with Seagen’s leadership in developing targeted therapies for cancer and commercialization infrastructure, makes this an ideal partnership to advance novel therapies for patients,” noted Stephen Hurly, President and Chief Executive Officer of LAVA Therapeutics.
“This agreement enables LAVA to further validate its platform in a second solid tumor product candidate, bringing us closer toward our goal of generating effective Gammabody medicines for cancer patients. We look forward to working with Seagen to develop potential next generation cancer treatments.”
 Tyler CJ, Doherty DG, Moser B, Eberl M. Human Vγ9/Vδ2 T cells: Innate adaptors of the immune system. Cell Immunol. 2015 Jul;296(1):10-21. doi: 10.1016/j.cellimm.2015.01.008. Epub 2015 Jan 28. PMID: 25659480.