LAVA Therapeutics Presents Preclinical Data on its Gammabody™ T Cell Engager Platform at the 21st Annual PepTalk Conference
The collective data indicate that LAVA’s approach to recruit gamma delta T cells with its bispecific antibody platform results in potent anti-tumor activity while avoiding off-tumor toxicity and cytokine release syndrome (CRS), potentially translating in a superior therapeutic index compared to CD3-based T cell engagers
New non-human primate data support the safety and tolerability profile of LAVA’s lead solid tumor Gammabody™ programs
Recruitment is underway for the phase 1/2a clinical trial of LAVA-1207 for metastatic castration-resistant prostate cancer (mCRPC)
UTRECHT, The Netherlands and PHILADELPHIA, Jan. 18, 2022 (GLOBE NEWSWIRE) -- LAVA Therapeutics N.V. (Nasdaq: LVTX), a clinical-stage biotechnology company focused on developing its proprietary Gammabody™ platform of bispecific gamma delta T cell engagers (gamma delta bsTCEs) to transform the treatment of cancer, today 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 today, Tuesday, 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.
“We are grateful for the opportunity to discuss both our Gammabody™ technology and our first clinical-stage solid tumor program, LAVA-1207, at the PepTalk Conference,” said Dr. Parren. “We beieve our preclinical dataset for LAVA-1207 is highly encouraging; showing potent and precise killing of PSMA-expressing tumor cells, most importantly including those obtained from patients.”
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.
“Solid tumors have proven an especially difficult challenge for CD3-based T cell engagers. First generation T cell engagers have shown a relatively high risk for CRS-related toxicities,” said Dr Parren. “Our Gammabody™ platform continues to show data supporting a larger therapeutic window with potent anti-tumor activity and a low risk of CRS and on-target/off-tumor toxicity – meaning a greater potential for achieving optimal dosing.”
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.
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