I encourage you to go back and review my video from 12:45 to 14:00 where I explain exactly what you are talking about. Briefly, I state that looking at the P1 dose escalation trial in isolation
may potentially indicate that low dose Bisantrene is going to be safe in humans. However, if you put these smaller doses into the context of having 6 phase II R/R AML trials, where a dose of 250 mg/m2/d for 7 days (most with a 3 day consolidation) was used and relatively safe and tolerable effects were seen, it may provide a pharmaceutical company with more confidence that a low dose of Bisantrene is safe to use in humans.
This does not take into acount the >1000 other patients that have recorded safety and tolerability data at doses far exceeding that theorised for FTO inhibition in other regimens unlike that of an FTO inhibitor, which, of course, indicates further that a low dose of Bisantrene is likely to be safe. While I focused solely on safety and tolerability, there is also efficacy data that I did not discuss.
VIDEO @faul0038 you mentioned that there are 19 cancers linked to FTO. so my question is; why didn't bisantree display 'particular promise' in other types of cancer if the FTO factor was in play? Hey mate. I think some of the other investors here have answered your questions well, so I'll just reiterate with some extra details. Reviewing the data I have at hand, we indeed have strong efficacy data in AML, good efficacy in breast, and some efficacy in ovarian. What you may not be aware of is there is also some efficacy data in ccRCC at low dose (1) and advanced hormone resistant pancreatic cancer (2), and quite strong efficacy in follicular lymphoma (31% CR and 25% PR), which is mechanistically similar to EMD AML (3).
Like you, I would have liked to have seen stronger efficacy in more than the above cancer types. The main issue that I have with the historic data where there is and is not efficacy is that Bisantrene is being used as an 'anthracene' and not a precision oncology drug. This article is a great read if you would like to learn of the complexity of precision oncology applications compared to other methods (4). I do not know how many cancer types Bisantrene will be effective in, but I consider the following before making my judgement:
- The appropriate dose and dosing regimen for an FTO inhibitor
- The appropriate patient FTO expression and/or methylation/demethylation
- The appropriate combination therapy for the patient and cancer
Many of the historic trials have not considered the above, which leads me to keep the book open as to the potential cancers that an FTO inhibitor may be effective in. The ultimate truth is that there is much that we do not know yet, but based on the information available to me, I'm very keen to stay on for the ride.
1
https://pubmed.ncbi.nlm.nih.gov/7053862/ 2
https://pubmed.ncbi.nlm.nih.gov/2272771/ 3 https://pubmed.ncbi.nlm.nih.gov/3581102/
4
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7188913/ @SMN888 These are great questions!
@IndexInvestor and
@yannpiot have answered your questions well.
Does this mean that when we get told for instance "FTO is over expressed in ccRCC" what that means is actually "some but not all patients with ccRCC will have FTO over expression but we won't know which ones without some sort of test (biopsy?)" Yes, that is precisely correct. It is very similar to how you can have HER2, luminal, or TNBC breast cancer - just because there are breast cancers that do not express HER2 does not make a HER2 monoclonal therapy an ineffective or invaluable treatment. The evidence suggests that there is a subset of 19 cancers that overexpress FTO. The "test / biopsy" that you are talking about could more accurately be called a companion diagnostic. Companion diagnostic tests are medical devices that "provides information that is essential for the safe and effective use of a corresponding drug or biological product" (1). Essentially, it screens participants that may benefit from the treatment. In our case, it is likely to determine whether a patient is appropriate for the drug.
The way people here have been talking about potential drug synergies (e.g. Keytruda) makes it sound like bisantrene would just be prescribed along with whatever drug it's synergistic with as a default (standard of care?) for all patients. The majority of my work and line of thinking has been in FTO overexpressing cancers, where an FTO inhibitor would have the maximum effect as a single agent. This makes the most sense logically - an FTO inhibitor is effective in cancers that overexpress FTO. While this is true, we still do not know yet whether cancers that normally express FTO will synergise with other anti-cancer therapies. For example, does inhibiting a cancer cell with normal FTO alter the gene and protein profile of that cell to sensitize it to a given therapy. That
It would completely change my understanding of the FTO related applications for bisantrene if any and every patient that might potentially be prescribed bisantrene would first have to have some type of FTO test. Then the value of a drug like bisantrene relies so heavily on the testing it requires. What do we know about the types of tests that are available to figure out who might or might not benefit from an FTO inhibitor? Yes, that is the companion diagnostic test. It is active work within RAC at the moment and is of significant IP value.
@RaceOncology won't tell me yet and has instead said that I am "the kid in the back of the car asking if we are there yet". Something for your consideration is the patented advanced linkage technology used with Trodelvy that potentially influenced the eventual sale (2).
1
https://www.fda.gov/medical-devices/in-vitro-diagnostics/companion-diagnostics 2
https://www.annualreports.com/HostedData/AnnualReports/PDF/NASDAQ_IMMU_2019.pdf 
(20min delay)