Finally!
Let's get these clinical trials underway.
For those that may not be aware, extramedullary (EMD) AML is essentially metastatic AML. A metastatic cancer is one that has advanced biologically to be more aggressive and difficult to treat, and explains in part the difficulties in treating people with EMD AML. This complexity is due to a range of different factors related to the cancer, and, more specifically, is controlled by the intracellular methylation/demethylation dynamic influencing the expression of genes and proteins regulating cellular function. FTO is a protein that demethylates m6A and has been routinely implicated in metastatic cancers as being overexpressed, which has a long-reaching, domino effect on the genes and proteins produced by the cell to influence metastatic characteristics.
Inhibiting this process by Zantrene in combination with Decitabine (DAC) has already shown phenomenal results in vivo, where mice tumor growth was almost completely halted by day 28 in comparison to control, DAC, and even Zantrene.
Of particular note: the four mice who are shown as dead in the far right column (DAC + ZAN) were euthanised as per requirements from animal rights authorities due to weight changes. The way that I interpret this is that all mice experienced
significant benefits in terms of limiting tumor growth, and Zantrene (technically an anti-obesity drug/pathway) induced weight loss in the mice. Highlighting the multi-system targeting of Zantrene. This trial is extremely exciting because of the 4 EMD AML patients included in the proof of concept AML trial completed in 2020 that all achieved a clinical response (1CR: 3PR) with a sub optimal, single-agent dosing regimen (1). For those that have followed my research (and may I reiterate undisputed) to date, you are most likely aware of my position of Zantrene as an extremely good FTO inhibitor and an extremely woeful anthracycline. This implicated Zantrene unequivocally as an FTO inhibitor in this trial, and now with the preclinical research, it solidifies my thinking.
So, we have a drug that had a 100% response rate in one of the most difficult to treat cancers in the world using a sub-optimal, single agent dosing regimen that now has a backlog of preclinical data demonstrating the true MoA entering into a clinical trial targeting specifically those patients likely to respond that would generate the first data of an entire new, untouched field of oncology likely relevant in ~30 different cancers. I feel pretty confident and excited in saying that the clock has well and truly started ticking for the first ever big pharma buyout of a drug targeting the m6A proteins. I am hopeful that this process is a total shit fight between big players.
Word has reached my ear that there are people in here who consider RAC a preclinical company with regards to FTO. I humbly return to suggest from my own opinion that these people are wrong. First of all, RAC are working on developing a process, where they identify patients, screen them for their sensivitiy to Zantrene, treat them, and then evaluate the response. This process has literally already happened well before anyone even knew about FTO. The screenshots below are taken from a phase 1 clinical trial that included patients whose tumors were sensitive to Zantrene at low uM concentrations. All of the patients showed improvement with 75% achieving a clinical response with sub-optimal, single agent dosing of Zantrene (1CR: 2PR) (2). More to the point. Just because the clinical trials investigating Zantrene of the past did not use an optimised dose and did not screen patients appropriately does not mean that the Zantrene today is not a clinical-stage product. I suspect that people are trying to make sense of why the market is doing what it is doing, which I understand. This is beyond our control. RAC has become further and further derisked over the last 12-months, and I do not see that changing over the next 12-months.
Also, whilst it is none of anyone's damn business, my shareholding in RAC is actually the largest it has ever been, I am looking to add to it, and I am routinely talking to people about RAC. Because I am not vocal on here as much is not a reflection of my holding or sentiment. Opportunities have arisen in other areas of my life which I am taking by the horns and running with; applying the same energy I did to my research into RAC. I will most likely be more vocal as the clinical work develops.
1.
https://pubmed.ncbi.nlm.nih.gov/33159365/
2.
https://pubmed.ncbi.nlm.nih.gov/7037174/
