Found some good information on Chemokine inhibitors, how they work and challenges
Molecular determinants of antagonist interactions with chemokine receptors CCR2 and CCR5
I won't provide too much from the link but my understanding is that Chemokines are like pathways for the immune system to move to places of infection. Some key statements:
The human immune system is a remarkably intricate and precise network of specialized cells, meticulously coordinated to protect the body against injury and infection, yet its damage and dysregulation results in devastating disease states such as inflammatory and autoimmune disorders. On a wide variety of immune cells are transmembrane chemokine receptors which, in normal physiology, play pivotal roles in orchestrating immune cell chemotaxis and migration to sites of injury and inflammation via interactions with their endogenous chemokines
AND
Among factors contributing to clinical failures are suboptimal properties of drug candidates [29]. At least in inflammatory contexts, therapeutic efficacy of chemokine receptor inhibitors has been linked to high in vivo receptor occupancy over extended periods of time [47,48]. This is a challenging task, given that CCR2 antagonists have to competitively inhibit what effectively is a high-affinity (sub-nanomolar) protein-protein interaction (receptor-chemokine) with abundant levels of the competitor (chemokine). To further complicate the situation, all known inhibitors of the CCR2-CCL2 system result in an apparent “CCL2 induction” where plasma chemokine increases far above pre-treatment levels. Although this phenomenon has been known for a long time [37–39,43], only recently we started to understand and appreciate its convoluted biological mechanisms which involve constitutive production of CCL2 by tissues, constitutive uptake and intracellular degradation (“scavenging”) of the chemokine by CCR2, and the inhibition of such scavenging by drugs [49,50]
Already there have been a few failures in using Chemokine blockers for treatment of Kindey disease. Some notable ones include the following:
Bristol Meyers Squibb
BMS-813160 | CCR2/CCR5 Antagonist
Diabetic Kidney Disease Terminated Phase 2 Trials for BMS-813160
Vifor in partnership with ChemoCentryx (Vifor now part of Aussie favourite CSL)
VFMCRP Press Release Phase-ii Lumina-1 Trial of Ccx140
ChemoCentryx now acquired by Amgen
Need to do more research whether Dimerix has really cracked the holy grail of chemokine blockers in kidney disease where others have failed.
Didn't want to make other holders nervous as it is now tempting to sell given the above and also that Corticosteroids were not mentioned by Dimerix as the main pathway for treatment (they could have been referring to the above trials in their slides).
In my view, I've gained a lot of understanding on this topic given I know someone who is diagnosed with kidney disease.
So been a good experience holding DMX overall.
[held]