On July 30, 2025 Espervita Therapeutics, a biotechnology company developing targeted metabolic reprogramming therapies, reported the publication in Nature featuring groundbreaking preclinical 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) (Press release, Espervita Therapeutics, JUL 30, 2025, View Source [SID1234654654]). Over 80% of people with advanced HCC do not respond to immunotherapies due to a "cold" immune deficient tumor microenvironment. EVT0185 reverses this effect, making tumors "hot" and harnessing the body’s immune system to attack and kill tumors more effectively than current standards of care.
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Unmet Need
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 < 5% and the five-year recurrence rate for earlier-stage HCC following surgical resection or ablation is > 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.
Preclinical Efficacy in HCC
Espervita Therapeutics evaluated the therapeutic potential of acetyl-CoA metabolic enzyme inhibition in MASH-HCC using EVT0185 across three preclinical models.
Key findings from the studies:
EVT0185 significantly reduced tumor 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.
EVT0185 enhanced immune recognition of tumors by reprogramming the tumor microenvironment, increasing CXCL13 expression and B cell infiltration, and triggering strong anti-tumor responses.
Through tissue-selective activation, EVT0185 minimized off-target effects and avoided immune cell suppression.
"These findings illustrate how targeted metabolic reprogramming can counter the immunosuppressive tumor microenvironment and significantly reduce tumor burden in MASH-HCC," said Spencer Heaton M.D., CEO at Espervita Therapeutics. "They also highlight the potential of EVT0185 to redefine how we approach oncology immunotherapies."