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]

Although I have little medical background, I do know that Rituximab is one of the go-to drugs for Kidney disease, particularly FSGS which is the main focus for Dimerix's candiate DMX-200

What is Rituximab?

Rituximab is a cancer drug called a monoclonal antibody. Monoclonal antibodies target proteins on the surface of cancer cells. Rituximab targets a protein called CD20. (Cancer research UK)

The CD20 protein is also found on white blood B cells and is part of our immune system which is also where this gets interesting. When someone has kidney disease, the immune system come and fight the infection, but also may get too active and end up harming the kidney - similar to autoimmune disease. Rituximab is administered to reduce the number of B-cells and protect the kidney from further harm by the immune system.

So now Rituximab is not just used for cancer, but also treatment of Kidney disease due to the above characteristics.

Problems with Rituximab

By weakening the immune system, Rituximab can cause problems with other conditions and side-effects such as being more exposed to infections and viruses. Most critical one is the weakening of the Liver which is troublesome for people who had hepatitis B in the past. Weakening the immune system may activate hepatitis B lying dormant in the Liver. The obvious workaround is taking an antiviral such as Entecavir before taking Rituximab.

I've also been told that the Rituximab is not always successful in fighting kidney disease from one of the renal doctors. Usually there is 70-80% chance of treatment being effective

Opportunities/shortcomings for DMX-200

I haven't found much on how DMX-200 works. From the Dimerix website we know that DMX-200 is a chemokine receptor (CCR2) blocker taken in conjunction with Avapro/Irbesartan. But there could be lots of positives if DMX-200 can overcome the shortcomings of Rituximab.

We probably won't know too much until the Phase III trials are finished some time at the beginning of 2026 which is a long wait which I found when going to the clinical trials website.

Therefore much of the success in Dimerix hinges on license deals as well as any indication of the product being safer to use against the current treatments such as Rituximab

Anyway I thought I would share what is weighing on my mind while holding Dimerix.

[held]

After posting some great news on the Phase III trials, Dimerix does a $20m placement for 30c .

Seems lots of people kicking up a fuss for this raise as it favoured the "big end of town" over long term holders that held before the share price pop. Who then probably went on to sell their shares for short term profit this morning.

Not sure what to think of this placement. It was oversubscribed but seemed this was done at the expense of longer term holders that held before the update.

[held]