Cancer

Cancer is one of the leading causes of death worldwide. According to the World Health Organization, cancer accounted for 7.6 million deaths in 2008 and deaths from cancer are projected to continue to rise to over 11 million in 2030.

In general, cancer therapies are toxic because they don't discriminate between diseased and normal cells, resulting in dose-limiting side effects that curtail the effectiveness of treatment. The Company is addressing this limitation by developing antibodies that only bind to and kill tumor cells without affecting normal cells.

Amorfix's proprietary drug discovery technology, ProMIS™, is a computer based algorithm that predicts Disease Specific Epitopes (DSEs), those regions of proteins most likely to misfold in diseases.

The Company uses this technology to identify DSEs which are only expressed on tumor cells and not on normal cells as a way of developing antibodies that only bind to and kill tumor cells without affecting normal cells. Using this technology, Amorfix has the potential to create antibody therapeutics that are more efficacious and have a much better safety profile, with fewer side effects than current cancer therapeutics.

The Company has three active cancer development programs:

Anti-PrP (Ovarian Cancer)

Ovarian cancer is the fifth most common cancer among women, and it causes more deaths than any other type of female reproductive cancer. Ovarian cancer is often not diagnosed until late-stage disease when the cancer has spread to other organs in the body, which contributes to the short survival time following diagnosis. Ovarian cancer is typically treated with surgery and chemotherapy. Chemotherapy is not very effective as a treatment and is associated with a number of potential dose-limiting side effects due to its non-specific killing of both tumour and normal cells.

Amorfix has completed a series of studies with its lead anti-misfolded PrP antibody, AMF-1c-120. In pre-clinical studies, the antibody shows excellent binding to ovarian tumours in animal models (Figure 1). Cytotoxicity of AMF-1c-120 is enhanced when coupled to a toxic payload (ie. urease) (Figure 2). In in vivo experiments, AMF-1c-120/urease reduced tumor growth similar to taxotere (standard chemotherapeutic agent) in both the aggressive ES-2 model and in the slower growing SKOV-3 ovarian cancer model (Figure 3).

The proof of concept animal studies were conducted with very low doses of antibody-toxin conjugate. The next step is to increase the dosage by changing the antibody/toxin ration. The dosage can be increased 50-fold from the proof of concept studies. In addition, Amorfix will be investigating the effectiveness of other toxins conjugated to AMF-1c-120

Development Partners:

  • Epitomics, Inc has used its RabMAbs® platform to generate high affinity antibodies against the DSE targets
  • Helix Biopharma has used its proprietary technology to conjugate urease to anti-PrP antibody
  • BC Cancer Agency/University of British Columbia is conducting the animal studies

Figure 1. Binding of AMF-1c-120 to ES-2 tumours - The brown staining demonstrates excellent binding to AMF-1c-120

Figure 2. Cytotoxicity of the AMF-1c-120 antibody to ovarian cells

Figure 3. In vivo result of animals treated with 0.138mg/kg (iv) drug

Anti-Fas receptor (Melanoma)

The biology of the Fas receptor is well characterized and it has been shown that antibody binding to Fas receptors cause cell death. Initial attempts by others to develop antibodies against Fas receptors as a novel treatment for cancer were halted because the receptor is expressed on both normal cells and tumour cells (Figure 4 - Native Fas expression) and treatment resulted in toxic side effects; particularly liver toxicity.

The Amorfix lead anti-Fas receptor antibody was shown to bind to melanoma cell lines (Figure 4 – AMF-3d-19) while having only minimal binding to normal cells, including liver cells.

The Company is now preparing to test the lead antibody in animal models of melanoma. Amorfix's anti-Fas receptor antibody is expected to be safe and effective because it exhibits little to no binding to normal liver cells yet shows a high degree of selective binding to melanoma cells.

Development Partners:

  • Epitomics, Inc has used its RabMAbs® platform to generate high affinity antibodies against the DSE targets

Figure 4. Binding of Amorfix lead anti-Fas receptor antibody to melanoma and normal cells

Anti-CD38 (Myeloma/Leukemia)

CD38 is a well characterized target on the surface of a variety of lymphoid tumours including multiple myeloma, AIDS-related lymphomas and and several types of leukemia and is part of a complex network producing growth and survival signals to tumour cells. As such, CD38 represents an attractive target for therapeutic intervention with a specific antibody and can also be used as a prognostic marker, which fits well into the Company's strategy of developing companion diagnostics along with novel therapeutic antibodies.

Amorfix has identified 5 DSEs with the ProMIS™ algorithm. The Company has completed the initial stages of antibody generation.

Development Partners:

  • Epitomics, Inc has used its RabMAbs® platform to generate high affinity antibodies against the DSE targets