Nature has published Espervita Therapeutics’ clinical data for the treatment of hepatocellular carcinoma (HCC) with its lead drug candidate, EVT0185, a first-in-class liver and kidney targeted inhibitor of acetyl-CoA metabolic enzymes (ACLY, ACSS2, ACC).
More than 80% of people with advanced HCC do not respond to immunotherapies due to a ‘cold’ immune deficient tumour microenvironment. EVT0185 reverses this effect, making tumours ‘hot’ and harnessing the body’s immune system to attack and kill tumours more effectively than current standards of care.
Liver cancer is the third leading cause of cancer death globally. HCC, the most common form of liver cancer, is increasingly caused by the global rise in metabolic dysfunction-associated steatohepatitis (MASH). With current treatment options, five-year survival for advanced HCC is less than 5% and the five-year recurrence rate for earlier-stage HCC following surgical resection or ablation is more than 75%, with HCC being the only common cancer in the world with no approved adjuvant therapy. HCC is thus one of the highest priority unmet needs in oncology.
Espervita Therapeutics evaluated the therapeutic potential of acetyl-CoA metabolic enzyme inhibition in MASH-HCC using EVT0185 across three preclinical models.
The study showed EVT0185 significantly reduced tumour burden in multiple preclinical models of MASH-HCC prevention and treatment, both as a monotherapy and in enhancing the effects of existing treatments, including tyrosine kinase inhibitors and immunotherapies.
It also enhanced immune recognition of tumours by reprogramming the tumour microenvironment, increasing CXCL13 expression and B cell infiltration, and triggering strong anti-tumour responses.
Through tissue-selective activation, EVT0185 minimised off-target effects and avoided immune cell suppression.
“These findings illustrate how targeted metabolic reprogramming can counter the immunosuppressive tumour microenvironment and significantly reduce tumour burden in MASH-HCC,” said Spencer Heaton, CEO at Espervita Therapeutics.
“They also highlight the potential of EVT0185 to redefine how we approach oncology immunotherapies.”
Jim Cornall is editor of Deeptech Digest and publisher at Ayr Coastal Media. He is an award-winning writer, editor, photographer, broadcaster, designer and author. Contact Jim here.
