LAVA Therapeutics N.V. announced it will present preclinical data on its Gammabody™ platform and data on its lead solid tumor Gammabody™ LAVA-1207. The presentation will also include new non-human primate data with a fully cross-reactive gamma delta bsTCE utilizing a surrogate Fc-containing Gammabody™ format to assess the safety of its most advanced solid tumor programs, LAVA-1207 and LAVA-1223. Paul W.H.I. Parren, Ph.D., executive vice president, head of research and development, will present these data at the 21st Annual PepTalk Conference Jan.

18, 2022 from 5:00 – 5:30 p.m. PST in the Sapphire Session Room in San Diego. The presentation will be available on the conference website for viewing during and after the meeting. In preclinical experiments, LAVA-1207 has shown the ability to activate V?9Vd2 (Vgamma9 Vdelta2) T cells to exert cytotoxicity toward PSMA (prostate specific membrane antigen)-expressing tumor cells at picomolar concentrations.

Using prostate cancer patient samples, LAVA-1207 activated autologous V?9Vd2 T cells and triggered lysis of tumor cells, while sparing normal prostate tissue. The mechanism of preferential tumor cell killing may be due to a demonstrated overexpression of a range of V?9Vd2 T cell ligands on tumor cells. A first-in-human Phase 1/2a open-label trial to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and antitumor activity of LAVA-1207 in patients with therapy refractory metastatic castration-resistant prostate cancer (mCRPC) is currently recruiting.

In addition, data from the non-human primate study showed an EGFR (epidermal growth factor receptor)-targeted surrogate Gammabody™ to be safe and well-tolerated in non-human primates. The EGFR Gammabody™ was administered at doses up to 23 mg/kg leading to high sustained plasma levels and dose-dependent accumulation in relevant tissues with no safety-related effects and no signs of cytokine release syndrome (CRS). LAVA's clinical stage PSMA Gammabody™, LAVA-1207, is an Fc-containing Gammabody™ for which pre-clinical data from in vitro, ex vivo and in vivo models will also be presented.

In the non-human primate study, animals were administered weekly intravenous doses of 1, 5 or 23 mg/kg of an EGFR gamma delta bsTCE that is fully cross-reactive with EGFR and V?9 T cells in non-human primates. At all doses, the EGFR gamma delta bsTCE only induced minimal levels of cytokines such as IL-2, IL-6 and IFN-gamma and there were no signs of CRS. No changes in general health parameters, clinical chemistry, hematology or histopathology were observed.

The compound was pharmacologically active in the animals, with V?9-positive T cells expressing markers indicating activation (CD25 and CD69). Presence of the injected compound in EGFR-expressing tissues, such as skin, muscle and colon, was demonstrated using immune-histochemistry. The elimination half-life was similar to the half-life of regular human IgG and ranged between 84.7 and 127.4 hours.