In recent years angiogenesis has generated overwhelming interest for the development of anti-cancer therapeutics exemplified by successes of Avastin (bevacizumab) of Genentech/Roche. A product of over $7 billion in 2015 global sales, Avastin is a humanized antibody and an inhibitor of the angiogenic factor vascular endothelial growth factor (VEGF), one of the key signaling molecules for angiogenesis. A second antibody product, Cyramza (ramucirumab), which is a fully human antibody against VEGF receptor, VEGFR2, has been introduced in the US market in 2014 by Eli Lilly and Co. for the treatment of stomach and NSCLC.
Angiogenesis is a complex process that supports solid tumor growth
Although Avastin is used worldwide in the treatment of colorectal, brain, lung and kidney cancer, the drug is somewhat controversial since it causes various side effects and provides only a moderate increment in overall patient survival. Some of the side effcts include
hypertension, thromboembolism, and gastro-intestinal perforations and potentially life-threatening
events such as wound dehiscence in certain patients. Cyramza has also not been recommended for approval in UK by its drug regulatory authority NICE. Recently, the US FDA revoked the earlier approval of Avastin for use in breast cancer and it also rejected approval for use in ovarian cancer, although a new set of recent data from the U.S. National Institutes of Health showed that Avastin increased lifespan in patients with advanced cervical cancer. Various shortcomings of the current anti-angiogenic antibody drugs represent significant unmet medical needs and major opportunities for generating more efficacious and safer anti-angiogenic drugs.
Anti-Vasculogenic Antibody Therapeutics:
We have been developing polyfunctional antibody drugs that not only hinders the development of tumor angiogenesis but in addition inhibits other functionalities of the vasculogenic pathways responsible for growth and progression of cancer. Our most advanced candidates in our pipeline are tumor-targeted antibody fusion proteins generated from our A-TAP (Antibody-Targeted Anti-vasculogenic Payload) platform. A-TAP involves linking of an antibody with a newly identified variant of endostatin, endostatin-P125A, as an anti-vasculogenic biological effector molecule. Additionally, we also have a first-in-class bitargeted fully human antibody candidate, Anti-Ang-1/2 MAb, which concomitantly targets both Angiopoietin-1 (Ang-1) and Angiopoietin-2 (Ang-2).
Immuno-oncology Antibody Fusion:
We are also developing a second class of fusion proteins aimed at delivering immune effector molecules to the site of human tumors. Such fusion proteins are generated by utilizing co-stimulatory ligands for NK and T-cell receptors and are aimed at targeting specific tumor cell surface antigen. Some of the fusion proteins have been tested in animal models which are capable of augmenting antitumor immunity in a manner which invokes both the innate as well as the adaptive immune response.
"We have to ask ourselves whether medicine is to remain a humanitarian and respected profession or a new but depersonalized science in the service of prolonging life rather than diminishing human suffering".