BACKGROUND
Immune-checkpoint blockades targeting CTLA-4, PD1, PDL-1 are major breakthroughs in cancer therapy, increasing overall survival. The launch of these premium-priced metastatic immunotherapies will extend treatment duration and replace cheaper, generic, chemotherapy regimens.
But still, too few patients respond to these therapies: 10% to 57% depending on the cancer type and the treatment combinations.
HOW IT WORKS
A team of chemists and biologist physicians demonstrated that the inhibition of the non-canonical NF-kappa-B pathway by DMPB5, a new multi-kinase inhibitor:
KEY BENEFITS vs. STATE OF THE ART
DEVELOPMENT STATUS
In vitro: high potencyon melanoma cells, metastatic melanoma primary cells from patient, non-small cell lung cancer and colorectal cancer cells
In vivo activity at 10mg/kg, i.p., on colorectal cancer cells injected subcutaneously into syngeneic mice; greater activity for combination DMBP5/PD-1 (Figure)
Ongoing hit-to-lead and lead optimization, target validation and non-regulatory preclinical validation on melanoma tumors and metastases mouse models
APPLICATIONS
Melanoma and metastatic melanoma (B-Raf mutated and wild type)
Solid tumors including colorectal, prostate, pancreatic and lung (NSCLC) cancers