Pipeline overview

Since its foundation, Axelar has continuously been active in discovering and developing new small-molecule IGF-1 receptor inhibitors. As a result, Axelar’s pipeline currently includes a number of promising back-up compounds to its lead program AXL1717. To secure a solid IP position for its compounds, Axelar has established a close collaboration with external advisors within the area.

	–		A targeted small-molecule IGF-1 receptor inhibitor with no effect on the highly homologous insulin receptor.
	–		Extraordinary anti-tumor efficacy, including tumor extermination, demonstrated in animal models for a wide range of human malignancies such as breast and prostate cancers, malignant melanoma, multiple myeloma, glioblastoma and sarcoma.
	–		Encouraging tolerability profile demonstrated in preclinical toxicological studies (with GLP standards).
	–		Other AXL1717-characteristics include being a small & chemically stable molecule that is easy to synthesize. The drug is given orally and has high potency, high bioavailability, and high tumor cell accessibility.
	–		Phase I/II clinical trial on cancer patients was initiated 1st half of 2008.
	–		Although Axelar’s primary area of interest is treatment of different forms of cancer, AXL1717 has also shown promising preclinical data for other diseases, e.g. restenosis after angioplasty and macula degeneration.

AXL1717 and its inhibition of the IGF-1 receptor

AXL1717 inhibits the activity and downregulates the cellular expression of the IGF-1 receptor without interfering with the insulin receptor, the epidermal growth factor receptor, the platelet-derived growth factor receptor, Kit, or fibroblast growth factor receptor.

AXL1717 and its anti-tumor effects

AXL1717 demonstrates strong anti-tumor efficacy, including tumor extermination, in animals xenografted with human malignant cells, including breast cancer, prostate cancer, glioblastoma (intracerebral implants), malignant melanoma, sarcoma and multiple myeloma.

The figures below show the effects of AXL1717 on prostate cancer and breast cancer xenografts. As shown in the control groups of mice, not receiving any treatment with AXL1717, the tumors continued to grow until the mice were sacrificed. In contrast, in mice receiving AXL1717 daily (start of treatment indicated by arrows) the tumors decreased in size and eventually became undetectable.