Lava bags cash from Gilde and Versant and hires Genmab veteran to advance bispecific T-cell engagers

Gilde Healthcare and Versant Ventures have driven Lava Therapeutics to a €16 million ($18.8 million) financing. The round equips Lava to advance bispecific engagers of gamma-delta (γδ) T cells, a small subgroup of lymphocytes involved in natural and induced immunity to cancer.

Like other bispecific T-cell engagers, Lava’s drugs are designed to activate the lymphocytes while also acting on tumor cells. The drugs could, for example, block the EGFR-signaling pathway and activate T cells, triggering the production of pro-inflammatory cytokines and killing of tumor cells that express EGFR.

Lava’s platform is differentiated by its focus on Vγ9Vδ2 T cells. Researchers have plugged away on γδ T cells over the past 15 years without garnering the sort of results seen by peers focused on alpha-beta lymphocytes, such as CD4+ helper and CD8+ cytotoxic T cells. But interest has grown as studies have shown intratumoral γδ T-cell signatures correlate to positive prognoses and linked the cells to a range of antitumor activities.  

"The cells exhibit potent cytotoxicity and interferon-γ secretion and HLA-unrestricted tumor cell killing and have antigen-presenting capabilities for αβ-T cells promoting the development of adaptive immune responses," a spokesperson for Lava said. 

Gilde and Versant have bought into the idea, as has Paul Parren, Ph.D. Parren, the former head of preclinical R&D at Genmab, has joined Lava as head of R&D. With MRL Ventures Fund also stepping up and joining with founding backers Lupus Ventures and Biox Biosciences to support Lava financially, the Dutch biotech is set up to move programs toward clinical trials.

In keeping with other preclinical biotechs, Lava is yet to say much about targets, indications or other specifics but the activities of the academic group that originated the platform provide some clues. Hans van der Vliet, M.D., Ph.D., Lava’s CSO and CMO, and his team at VU University Medical Center have published a series of papers on Vγ9Vδ2 T cells in recent years.

The papers analyzed the activity of the T cells and described the use of llama-generated single domain antibodies—the modality in which Ablynx is specialized—to activate them. The series culminated in a paper linking an anti-EGFR bispecific to decreased tumor burden and increased overall survival in mice. 

That mice study administered the T-cell engagers in combination with Vγ9Vδ2 T cells. However, Lava thinks its candidates will work without an accompanying infusion of T cells. 

"These cells are very potent and we believe that sufficient cells are available in tumors and in circulation to obtain an effective therapy," the spokesperson said. "The administration of therapeutic bispecific antibodies is a much more widely applicable and cost-effective treatment as it avoids cumbersome and costly ex vivo expansion of these cells."

Lava is now progressing several T-cell engagers toward human testing but is yet to commit publicly to a timeline for getting into the clinic. To support the activity, the biotech is looking to add five to seven new hires to its existing nine-person team. Lava is outsourcing the bulk of its operational activities. 

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