Targeted treatment of therapy resistant malignacies using ROR1 inhibitors
| Reference number | |
| Coordinator | Kancera AB |
| Funding from Vinnova | SEK 1 500 000 |
| Project duration | June 2013 - November 2014 |
| Status | Completed |
Purpose and goal
The overall objective of the project was to develop a candidate drug that inhibits the survival factor ROR1. ROR1 selectively occurs in cancer cells in adult individuals. The candidate drug will enable a commercialization process where a partnership can be established with big pharmaceutical and biotech companies to bring the project into clinical trials.
Results and expected effects
The project goals have been met, in that we have been able to show anticancer effects at a tolerated dose for the ROR1 inhibitor KAN0439834 in an animal model of chronic lymphocytic leukemia. Thus, the candidate drug KAN0439834 has been selected. The company is preparing and launching a process to seek partnerships around the project with major pharmaceutical biotech companies.
Approach and implementation
Candidate drug KAN0439834: - Synthesis of novel compounds: > 350 unique end products have been synthesized - Potency, ADME and PK: IC50 against ROR1 in cells < 25 nM, orally bioavailable, acceptable metabolic stability - EC50 for apoptosis in human leukemic cells (hCLL): < 300 nM (14 µM in healthy cells) - Safetys profile against 44 mechanisms: Some ´off-targets´ has been observed - Tolerance studies incl. Histopat., Clin. Chem., Ames, hERG, CYPinh,, Met. ID, Conjug.: No observed side effects except for some effects in the liver at a dose that is significantly higher than effective dose.