Firstly, how good is it to be an RAC shareholder!
From an investor standpoint, how could you ask for more from a company? Just this year so far, we have received preclinical trial results supporting the use of Bisantrene in breast and ovarian cancer, have initiated three preclinical programs, have received information pertaining to the initiation of three in-human clinical trials this year as well as two starting next year for all pillars, have had another prestigious research organisation support the role of Bisantrene as an FTO inhibitor, and have now signed a world leading professor, JianJun Chen, in a world leading research organisation specialising in the RNA space.
Shareholders can expect a massive amount of information to come before July 2021. Most importantly, we can expect the outcomes of low-cost collaborative preclinical heart safety profile discussion outcomes and signage of the Israel PI/II AML trial investigating Bisantrene in combination with Clofarabine and Fludarabine in the very short term. I expect that the preclinical Bisantrene-clofarabine-fludarabine data that supported the Israel trial to be published quite soon also. Note: the preclinical breast and ovarian cancer results are speculative based on previous data discussed
here.
In the medium-term, shareholders can expect a large amount of data -
far more than ever anticipated before. By comparison, at this time last year, RAC had a phase II AML trial and a single preclinical trial underway. Currently, arguably 5 preclinical trials (3 confirmed, 2 speculated) are underway (with the potential of an additional heart safety preclinical trial), three PII trials will be underway by this year, and potentially one PI dose escacalation study underway this year. Importantly, all clinical trials have the potential to provide information to RAC management about the effectiveness of Bisantrene as an FTO inhibitor in humans. This information is extremely valuable to the company, its shareholders, as well as cancer suferers around the world.
Preclinical and clinical programs addressing the clinical significance of Bisantrene as an FTO inhibitor are extremely important. Currently, FTO has been linked as a prognostic marker for up to 21 different cancer types (you could say every) and importantly, information is starting to come out supporting the contention that FTO is overexpressed in cancer stem cells (CSCs), which are thought to be the root of cancer progression and resistance. Additionally, due to the heirarchal nature of RNA epitranscriptomics, targeting FTO has a downstream effect on multiple cancer functions like energy production and drug resistance. Recently, JianJun Chen's group identified that Bisantrene could reduce cancer cell metabolism, essentially starving it of energy. Targeting FTO has the potential to synergise with other effective cancer therapies, by crippling the cancers defence system. Currently, there is independent research supporting eight different anti-cancer therapies, with the most significant being the anti-PD1 therapies. By demonstrating Bisantrene is an effective FTO inhibitor in humans, there becomes strong evidence to support the years of independent research that has been done investigating the role of FTO in cancer therapy. The implications of positive in-human clinically significant FTO efficacy data are very broad and profound.
What really sets RAC and Bisantrene appart is the competitors in this space. Bisantrene was recently identified as the most potent and selective FTO inhibitor among 260,000 compounds. While this find is tremendous, Bisantrene also has the advantage of a large amount of historic data that supports its safe and efficacious use in humans, particularly AML, but also in breast and ovarian cancer. The data collected around the 1990s led to Bisantrene being approved for AML in France before it was lost. Because of this, Bisantrene is not a basic preclinical drug with all the associated risks that come with taking a drug through the stages of drug development. Quoting JianJun Chen's groups most recent 2021 paper directly; "Several FTO inhibitors havebeen discovered previously but are unlikely clinically applicabledue to relatively low selectivity and/or low therapeutic efficacy". The important point when comparing other drugs to Bisantrene is the IC50 value, which is a measure of the drugs inhibitory concentration. Ideally, you want a very low concentration. Bisantrene was able to inhibit FTO with an IC50 value of between 22-175 nM, which is multiple folds lower than recent competitors. The only other molecule with that concentration is Brequinar, but that drug failed as an anti-cancer agent and transplant organ rejection drug, is immunosuppresive, and is impractical in the clinic.
Finally, as discussed previously, the RAC SP since March 2020 has followed a similar pattern. From the chart below you can see that since Bisantrene was identified as a potent and selective inhibitor of FTO, following an all time high, the shareprice retraces 61.8% before climbing to a new all time high, which has typically been 261% of the previous high. What we can also take away from the chart is that the MACD movements are closer together now than the were last year, with days between a negative cross and positive cross getting shorter (blue boxes with 105d, 84d, 43d, and an estimated 43d). Using the same principles, we can get an idea of the future trends for the RAC SP. Currently, the RAC SP has bounced off the 61.8% retracement line at around $3.03 and is maintaining its position in the grey area. The MACD is closing together and RSI is increasing towards the upper bounds of the channel. Interestingly, in the last 18 months, when the MACD has crossed positive by 2 or more points, it has resulted in significant positive price movements. Future price movements and times are based on historic movements and may not reflect actual changes in RAC SP. Although, based on what I know and how undervalued I believe RAC are, I think that we will maintain this positive pattern of movement going forward.
I just want to thank the RAC management team for all of their hard work. I also extend those thanks to the RAC shareholders who so frequently contribute to this forum and the advancement of knowledge in this area. It's been a pleasure riding this with you and look forward to the future.