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One of the primary challenges in effectively treating brain cancers is the ability to get therapeutic agents into the brain; the blood-brain barrier (BBB) acts as a natural defense system to keep most drugs out. Angiochem addresses this challenge by engineering its drugs with the dual-targeting ability of crossing the BBB via the lipoprotein receptor-related protein (LRP-1) as well as to access cancer cells expressing LRP-1 throughout the body and in the brain.

In the area of oncology, Angiochem has multiple pharmacologic agents designed to cross the blood-brain barrier under evaluation that are designed to cross the BBB.


ANG1005 is a novel targeted taxane derivative that is the first oncology product to leverage Angiochem’s technology platform to cross the blood-brain barrier (BBB) and enter cancer cells.  ANG1005 is an Angiopep-2 paclitaxel conjugate that gains entry into the brain by targeting the LRP-1, 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-1, which is upregulated in various cancer cells including malignant glioma and metastatic cancers in the brain.  For more information on ANG1005 mechanism of action, please view this video.

To date, ANG1005 has been studied in over 200 patients with primary or secondary brain tumors.  Two Phase I, multi-center, sequential cohort, dose escalation studies (NCT00539344 and NCT00539383) have been conducted with ANG1005 in order to identify the maximum tolerated dose (MTD) and obtain data on safety, tolerability, and preliminary evidence of efficacy.  The first study was in patients with malignant glioma (Drappatz et al. 2013) and the second study was in patients with advanced solid tumors with brain metastases (Kurzrock et al. 2011). 

A Phase II, multi-center, open label study has been conducted with ANG1005 in patients with brain metastases from breast cancer (NCT01480583).  The anticancer activity of ANG1005 was extremely encouraging and 2 additional Phase II trials have been conducted to further confirm its clinical activity in patients with recurrent high grade glioma (NCT01967810) and breast cancer patients with recurrent brain metastases (NCT02048059). These two studies are no longer recruiting patients.

For more information on ANG1005, please download the Angiochem Corporate Presentation and browse the Publications.

Peptide Antibody Conjugates

There are currently over 1,000 monoclonal antibodies (mAbs) in development by pharmaceutical and biotech companies.  These mAbs are designed to bind specifically to target cells or proteins.

The global monoclonal antibody market was $48 billion in 2010 with the top 10 mAb therapies commandeering the majority of sales. These include products like Remicade®, Avastin®, Rituxan®, Humira® and Herceptin®.

As a class, monoclonal antibodies hold enormous promise as therapeutics for the treatment of many neurological diseases due to their inherent qualities.  Unfortunately, the BBB prevents mAbs from reaching therapeutically necessary concentrations in brain and thus greatly restricts their treatment potential.  The receptor-mediated transcytosis approach has moved to the forefront of BBB research as it is proving to be a tractable method for achieving relevant concentrations of mAbs to brain parenchyma.

Angiochem is using its proprietary technology to discover and develop new brain penetrant “Peptide-Antibody Conjugates” that reach therapeutic concentrations inside the brain. This technology will allow leaders in the field of biologic drug development to harness the potential of mAbs in the central nervous system (CNS).

These new Peptide-Antibody Conjugates have been engineered to:

  • Cross the blood-brain barrier via receptor-mediated transcytosis using the Angiopep moiety

  • Retain their affinity to the target receptor and in vivo functionality. 

As a proof-of concept, Angiochem has created a brain penetrant peptide-antibody conjugate of anti-Her2 (ANG4043) that get into the brain in therapeutic concentrations.


Approximately 25% of breast cancers overexpress the gene encoding the HER2 receptor, which is associated with a very poor prognosis and a high tendency to form metastases.  The development of Herceptin® (trastuzumab) by Genentech, a monoclonal antibody (mAb) that targets the HER2 receptor, has significantly improved the survival of HER2+ patients.  However, since trastuzumab has limited ability to penetrate the blood-brain barrier (BBB), the central nervous system (CNS) may actually serve as a sanctuary for breast cancer metastases in HER2+ patients.   

ANG4043 was created by conjugating the Angiopep-2 to a mAb that is similar to trastuzumab to bring an effective anticancer therapy to treat HER2+ breast cancer metastases in the brain.  In a series of in vivo experiments, ANG4043 has demonstrated that it reaches the brain, targets HER2+ tumors, induces intracranial tumor shrinkage, and increases survival in mice that have been intracranially implanted with HER2+ tumor cells. 

Overall study results of ANG4043 further validate the potential of the applicability of Angiochem technology to create brain-penetrant mAbs. 

For more information on ANG4043, please download the Angiochem Corporate Presentation.

Antibody-Drug Conjugates (ADCs)

Antibody-drug conjugates (ADCs) are a new class of biopharmaceuticals composed of an antibody (either a whole monoclonal antibody, mAb, or a fragment of a mAb), linked to a biological active cytotoxic drug.  Monoclonal antibodies seek out the target proteins expressed on the cell surface of cancer cells.  Once attached, a signal is triggered in the tumor cell and the mAb is internalized along with the conjugated cytotoxic drug.  Once in the tumor cell, the cytotoxic drug is released and kills the cancer.  By combining the targeting specificity of monoclonal antibodies with the anti-cancer capabilities of cytotoxic drugs, ADCs can discriminate between a healthy tissue from a disease tissue, and thereby lowering the side effects.

A crucial aspect of an ADC is designing a stable link between the antibody and the cytotoxic agent.  Angiochem is leveraging its proprietary technology and its expertise in designing linkers to discover new brain penetrant ADCs.  These new ADCs have been engineered to:

  • Cross the blood-brain barrier via receptor-mediated transcytosis using the Angiopep moiety

  • Target tumor markers to trigger internalization of the ADC

  • Deliver the cytotoxic agent to the tumor cells

At Angiochem, two anticancer drugs (docetaxel and maytansine) have been successfully conjugated to peptide-antibody conjugate of anti-HER2.  These two, proof-of-concept ADCs have demonstrated increased anti-proliferative activity and blood-brain barrier uptake when compared to unconjugated peptide-antibody conjugate of anti-HER2, as well as improved survival in preclinical studies.

For more information on brain penetrant ADCs, please download the Angiochem Corporate Presentation.