MetaboCure
- A breakthrough treatment for cancer cachexia, the body wasting in agressive cancer patients, based on mRNA/LNP technology
- Aimed at restoring Hepatocyte nuclear factor 4 alpha (HNF4a), a key regulator of liver metabolism, which is suppressed upon cachexia development
- First in human indication: pancreatic cancer cachexia – an unmet need with significant market
The Need:
Cancer cachexia represents a significant and multifaceted challenge in oncology, characterized by profound metabolic derangements and severe wasting syndrome in patients battling cancer. This complex condition is marked by involuntary weight loss, skeletal muscle atrophy, and systemic inflammation, often leading to compromised physical function and reduced quality of life. Despite advances in cancer treatment, the prevalence of cachexia remains high, affecting up to 80% of advanced cancer patients and contributing to increased morbidity and mortality.
The pathophysiology of cancer cachexia involves a cascade of inflammatory cytokines, metabolic dysregulation, and altered protein metabolism, driven primarily by the tumor microenvironment. Traditional strategies targeting inflammation and appetite stimulation have shown limited efficacy, highlighting a critical unmet need for novel therapeutic interventions that can effectively mitigate muscle wasting and improve overall patient outcomes.
Scientific background:
Liver metabolism is involved in extrahepatic tumor growth and progression. Following cancer-induced systemic inflammation, the innate immune cells (monocytes, neutrophils) are recruited to the liver by the chemokine CCL2. The resulting interactions lead to activation of the Erk kinase, secretion of IL-6 from immune cells, and initiation of the transcription factor STAT3 signaling in hepatocytes. Consequently, there is an almost complete loss of HNF4-α, the master regulator of liver metabolism.
Loss of HNF4-α perturbs the function of central liver metabolic pathways such as the urea cycle, albumin, and fatty acid synthesis, increasing plasma availability of nitrogen-rich metabolites such as ammonia, glutamate, and aspartate, promoting tumor growth. Notably, the high ammonia levels inhibit lymphocyte proliferation and activation, further empowering cancer cells’ survival. In addition, the dysregulation of albumin and fatty acid synthesis likely contributes to cancer progression and potentially to systemic CAC manifestations such as weight and fat tissue loss and muscle wasting.
Nuforal – MetaboCure’s novel cachexia drug
MetaboCure’s newly developed drug candidate Nuforal™ is designed to increase hepatic HNF4-a levels and to reverse weight and muscle mass loss leading to rehabilitation and enabling the body to more efficiently fight cancer
First Indication: Pancreatic cancer cachexia – an unmet need
Pancreatic cancer has the highest mortality rate of all major cancers, with 5-year relative survival rate of 13%.
- This poor prognosis is a consequence of number of factors:The disease usually progresses rapidly
- It has high rates of recurrence after surgery
- Is commonly resistant to chemotherapy
- Is especially associated with the development of cachexia
