Brain cancer drug ANG1005 shows promise in resistant tumors: Angiochem

ANG1005, an experimental drug from Angiochem Inc, to treat glioblastoma or brain cancer, has been found effective in studies.

ANG1005 appears to cross a protective barrier in the brain that screens out most chemicals, offering potentially better ways for difficult to treat brain tumors or glioblastomas.

ANG1005 was safe and showed evidence it could shrink tumors in two separate early phase studies including more than 100 people with a brain cancer called glioblastoma.

ANG1005 is a novel, next-generation taxane derivative, targeting the LRP pathway to cross the blood-brain barrier and reach therapeutic concentrations in the brain. The drug was created with Angiochem’s Engineered Peptide Compound (EPiC) platform technology.

Studies have shown that ANG1005 gains entry into the brain compartment by targeting the low-density lipoprotein receptor-related protein (LRP) which is one of the most highly expressed receptors on the surface of the BBB.

Once inside the brain, ANG1005 enters tumor cells using the same receptor-mediated pathway through LRP, which is upregulated in various cancer cells including gliomas and metastatic brain cancers.

In the recently completed Phase 1/2 brain metastases clinical trial, greater than 70% of patients receiving therapeutic doses experienced disease control with more than half of them showing clear reduction in tumor size.

Furthermore, 78% of patients with taxane resistant tumors showed responses, indicating ANG1005 has the potential to be effective against resistant tumors.

Therapeutic doses of ANG1005 were present in patient brain tumor samples, indicating that the drug successfully crosses the blood-brain barrier (BBB) and concentrates in the tumor, without showing central nervous system (CNS) toxicity or immunogenicity.

Similar trends in patient responses have been observed to-date in the on-going Phase 1/2 recurrent glioblastoma clinical trial with approximately 65% of patients experiencing disease control.

ANG1005  has also been shown effective for people whose cancers had spread or metastasized to the brain, the researchers reported at the annual meeting of the Society for Neuroscience in Chicago.

ANG1005 caused shrining of tumors in patients who got a higher dose of the drug in both studies.

ANG1005 has also seen effective n patients whose cancers resisted the chemotherapy drug taxane.

“It is highly encouraging to see that ANG1005 has shown the potential to be effective in metastatic brain cancers and against drug-resistant tumors,” Dr. Jan Drappatz of Dana-Farber Cancer Institute and Brigham and Women’s Hospital in Boston, who is studying the drug, said in a statement.

ANG1005 led to shrinkage of tumors shrank significantly in some patients and some neurological problems were reversed in several, Dr Drappatz said

Studies of brain tumor samples showed concentrations of ANG1005 in the tumors, proving it successfully crossed the blood-brain barrier and accumulated.

The blood-brain barrier (BBB), which is made up of a network of blood vessels, prevents 95 percent of all chemicals from leaving the bloodstream and entering the brain safeguarding the vital organ form harmful chemical and pathogens.

The blood-brain barrier (BBB) also presents major challenges for treating disease in the brain, such as Alzheimer’s or cancers — which must typically be treated by surgery and radiation.

Angiochem’s ANG1005 uses a separate mechanism to cross this barrier through hijacking a protein called low-density lipoprotein receptor-related protein that is commonly found on the surface of the blood-brain barrier.

Angiochem is a clinical-stage biotechnology company discovering and developing new drugs that are  capable of crossing the blood-brain barrier (BBB) to treat brain diseases. Angiochem’s lead product candidate, ANG1005 is in two separate Phase 1/2 clinical studies in patients with brain cancers and cancer metastases. Angiochem is also developing small and large molecules, for the potential treatment of a wide range of CNS diseases, including neurodegenerative and metabolic diseases, brain cancer, psychiatric disorders and many others.