Research and Development
Axelar’s research program targets the treatment of insulin-like growth factor-1 (IGF-1) receptor-dependent diseases, primarily within oncology. The company focuses on the discovery and development of small molecules that inhibit the IGF-1 receptor signaling pathway.
Key features of Axelar’s lead drug candidate AXL1717:
- Targets the signaling pathway of the IGF-1 receptor without affecting the highly homologous insulin receptor.
- Also suppresses tumor cell division by arresting cells in mitosis through a non IGF-1 receptor-dependent mechanism.
- Extraordinary anti-tumor efficacy demonstrated in animal models for a wide range of human malignancies.
- Orally administered small molecule that is chemically stable and easy to synthesize.
Why Target the IGF-1 Receptor?
In recent years, large amounts of scientific data have demonstrated that the IGF-1 receptor has the potential to become an important target within cancer therapy. The IGF-1 receptor is overexpressed on cancer cells and its signaling pathway is crucial for the survival and growth of most types of cancer cells. It is also associated with increased resistance to therapy.
On the other hand, the IGF-1 receptor is not necessary for the growth of normal cells. This makes it an excellent target for cancer drug development. A wide range of major tumors could be addressed through the inhibition of this receptor signaling pathway.
To date, however, it has been a major obstacle to find molecules that selectively inhibit the IGF-1 receptor without affecting the almost identical insulin receptor. The insulin receptor is essential for glucose uptake and metabolism in normal cells, so a cross-reaction with this receptor is likely to result in severe side effects.
Axelar’s compound works indirectly to inhibit signaling from the IGF-1 receptor, and has been shown to have no effect on insulin receptor signaling.
The development of an efficacious treatment that successfully targets the IGF-1 receptor signaling pathway without interfering with the insulin receptor constitutes a potential breakthrough in cancer therapy.
Treatment with AXL1717 not only inhibits the IGF-1 receptor signaling pathway, but the compound also arrests cell division by a non IGF-1 receptor-dependent effect. This second activity may provide AXL1717 with enhanced efficacy against tumor cells compared with antibodies binding to the receptor and traditional small molecule drugs inhibiting the receptor kinase activity.
Results from AXL1717 Phase I/II clinical trial
PET images of three tumors on an NSCLC patient that was treated with AXL1717, at first dosing (upper panel) and at follow up at 12 weeks (lower panel). Partial response was confirmed according to RECIST criteria.