Percheron Therapeutics (ASX:PER) and researchers at QIMR Berghofer unveiled new preclinical findings at the American Society for Clinical Oncology annual meeting that suggest the immune checkpoint VISTA as a potential driver of treatment resistance in triple-negative breast cancer.
The team used spatial multiomics to map VISTA expression across tumour tissue, lymph nodes and circulating tumour cells and compared profiles from patients before and after chemoimmunotherapy, including data from 83 patients treated with atezolizumab.
The QIMR group observed that VISTA is upregulated after chemotherapy and PD-1/PD-L1 inhibition, a pattern the authors say implies that VISTA may be part of an adaptive resistance mechanism to current therapies. The data show increased VISTA and co-expression with other inhibitory receptors, such as TIM3, LAG3, CTLA4, and TIGIT, in exhausted T cell niches and in metastasis-associated cells.
Percheron CEO Dr James Garner described the collaboration with Professor Sudha Rao as productive and comprehensive.
"It has been a pleasure to work with Professor Rao and her team on this very comprehensive research project," Dr Garner said. "Despite huge progress in the treatment of breast cancer over recent decades, there continues to be significant unmet medical need in the disease, and TNBC remains especially challenging. This work indicates that VISTA, the molecular target of Percheron’s HMBD-002, may play an important role in treatment resistance. We have previously seen indications of this in other cancer types, but the current project is the first attempt to elucidate its role in TNBC so exhaustively. We look forward to discussing these findings further, and to considering their implications for future clinical trial directions."
HMBD-002 is a nondepleting recombinant IgG4 antibody targeting VISTA, and phase 1 data showed the agent to be generally safe and well tolerated. The researchers plan a manuscript for peer-reviewed publication, and Percheron expects to start a new clinical trial of HMBD-002 in the second half of calendar year 2026.