Our Lead Asset
Numiera has secured FDA orphan designation to repurpose the first-in-class CPT1 inhibitor etomoxir for patients with malignant glioma - including the most aggressive form of this cancer, glioblastoma. Read more about the history of this drug, its impressive safety profile, and why we are repurposing it for cancer below.
Early work established CPT1 as a critical step in mitochondrial fatty acid oxidation. This molecule, Carnitine Palmitoyl Transferase I, transports fatty acids across the mitochondrial membrane. Once they are inside the mitochondria, the fatty acid chains can be broken down to make energy for the cell.
> McGarry et al. J Biol Chem 1978
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Researchers then developed a drug that would target CPT1, culminating in the synthesis of etomoxir.
> Crilley et al. Tetra Letters 1989
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Other researchers began to study how this new drug targeting metabolism might help people with diabetes.
> Spurway et al. Febs Letters 1997
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1978 - 1997
Identifying CPT1 as a critical transporter of fatty acids for mitochondrial beta-oxidation
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1998 -2007
Developing etomoxir as a new drug to treat Congestive Heart Failure
Showing mild effects in controlling blood glucose levels, etomoxir entered clinical trials instead for the treatment of congestive heart failure. The drug was well-tolerated in this Phase I study.
> Schmidt-Schweda et al. Clin Sci 2000
In 2001, etomoxir entered Phase II clinical trials, with a double-blind, randomized clinical study to evaluate the safety and efficacy of etomoxir in comparison with placebo - again, in patients with congestive heart failure. Notably, fewer patients died of cardiac events while taking the drug, compared with placebo. However, 4 of 226 patients taking the drug had high liver enzyme levels, and so the clinical trial was voluntarily ended by the sponsoring company. In 2007, the results were published, showing the high liver enzyme levels were reversible, no actual liver damage (e.g. high liver bilirubin levels) was observed, and no other side effects were reported, other than improved exercise tolerance in the cardiac patients.
The founder of Numiera Therapeutics started investigating cancer cell metabolism in 2008, and discovered that glioblastomas rely on fatty acid oxidation to make their energy. After many years of work on two continents, with a stellar team of students, staff scientists, and clinicians - and dozens of patient samples studied - the results were finally published.
Over the following eight years, five other labs around the world replicated this finding - that glioblastoma cells rely on fatty acid oxidation to make their energy, and that etomoxir slows the growth of these aggressive tumors.
> Kant et al. Cell Death Dis 2020
> Shim et al. Cancer Cell Int 2022
> Jiang et al. Nature Comms 2022
> Duman et al. Cell Death Dis 2023
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Meanwhile, researchers began to study fatty acid oxidation in other tumors, finding the same result - that many cancer cells rely on fatty acid oxidation to make their energy, and that etomoxir slows tumor growth in breast cancer, prostate cancer, bladder cancer, and more.
2008 - 2023
Demonstrating that etomoxir halts tumor growth in glioblastoma and other cancers
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2024 - onward
Evaluating the use of etomoxir in clinical trials for patients with glioblastoma and creating next-gen CPT1 inhibitors to treat other cancers
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We are at the next stage of this drug development program - repurposing etomoxir for the treatment of glioblastoma, a malignant brain tumor with no other good treatment options.
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With a strong safety profile - especially compared with the standard of care drugs temozolomide and bevacizumab used currently in neuro oncology - we believe etomoxir will be a better tolerated option for these patients.
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And with independently replicated preclinical efficacy data from multiple labs around the world, we believe the ability of etomoxir to slow tumor growth is a reliable result, and worth evaluating in a clinical setting for patients with glioblastoma.
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We know metabolic targets are important for overall health, and we are excited to bring this new target into the world of oncology therapeutics.