Two peer-reviewed scientific journals, Chem and Cell Reports, published new data that sheds light on the mechanism of action of BeyondSpring’s (NASDAQ:BYSI) lead Phase 3 asset, Plinabulin, which is being developed in parallel for the treatment of cancer and prevention of chemotherapy-induced neutropenia.
In the Chem article, researchers utilizing x-ray crystallography and thermodynamics calculations demonstrated that Plinabulin, as a new chemical entity, is differentiated from other tubulin-binding agents in both its binding site and the kinetics of the binding.
The research also provides evidence that this binding may explain the beneficial efficacy and superior safety profile found with Plinabulin in the clinic, compared with other agents that bind to a nearby colchicine site in tubulin, such as combretastatin-A4 or colchicine.
The Cell Reports article demonstrates that Plinabulin destabilizes microtubule and releases immune defense protein, GEF-H1, a critical signaling protein for dendritic cell (DC) maturation, antigen cross-presentation and effective priming of CD8 T-cells.
Researchers noted that, in cancer patients, high expression of the GEF-H1 immune gene signature is associated with prolonged survival. Plinabulin has the potential to be among the most potent tubulin targeted agents for maturing DCs, which highlights its potential for combination immuno-oncology approaches seeking to overcome the limitations of checkpoint inhibitors in treating certain cancers.
“These papers validate our understanding of the mechanism of Plinabulin, which played a crucial role in selecting mechanism-targeted patients for our Phase 3 non-small cell lung cancer study and providing a rationale for all of our clinical studies,” Dr. Lan Huang, chairman and CEO, said in a statement.
“This data confirms our understanding of Plinabulin’s mechanism of action, and combined with our clinical approach, we believe it can potentially increase our chances of success,” she added.
The Cell Reports article can be accessed here.