ASX Shares 10 bagger

And how many approved medcines have been withdrawn?
Each country has it's own medical system with many medicines allowed in some and not in others.

In a professional setting that quote would be seen as not true or not yet true.
Anyone trying to sell bisantrene with such a statement would be prosocuted.
RAC would be making that statement if they could, but thy can't do anything of the sort.
And you may want to reread the studies as toxicity was found.

If you read RAC statements the word "safe" is always qualified by other factors.

 

RACE aren’t likely to be the ones pursuing FDA/EMA approval.

What we have is multiple runways of preclinical and clinical ( trial ) activities to position Bisantrene for regulatory approval. Theory is that at some point on the runway Big Pharma will make an offer based on:

• Preclinical activities
  • Breast and ovarian - this data will be written up and published in a journal during this year. I also expect results to be presented at conferences.
  • New preclinical study initiated for EM AML ( we should get initial results within 6 months )
  • FTO - New preclinical study initiated for Melanoma ( we should get initial results within 6 months )
  • FTO - New preclinical study initiated for renal cancer ( we should get initial results within 6 months )
• Trials
  • Israel AML trial should start recruitment soon ( we will get dosing updates and are likely to get first readouts this year )
  • Breast cancer trial should start recruitment soon ( we will get dosing updates and are likely to get first readouts this year )
• ASH conference in December has been a trigger event for big pharma awareness for other buyouts. This is focused on haematology indications so I expect RACE will also aim for a presentation at a conference more focused on solid tumours.

I think the above activities in combination will be the trigger for a buyout or partnership offer.

Race may also kick off a dose escalation study for FTO.

Big Pharma often strike during Phase 1 and Phase 2.

 

This thread should be renamed to the RAC thread!

I am now in. Not as early to the party as many others, nor with as much, but from my initial readings and due diligence it sounds like a good opportunity so moved some funds from another stock which hasn't really been doing anything (literally) and will now follow RACE.

 

Treatment of cancer with drugs is trading off clinical benefit against safety. In general to achieve approval the clinical benefits need to demonstrably outweigh the clinical risk ( namely safety ). Drugs don’t usually come without downsides.

If the clinical trials can show patient outcomes through treatment with a new therapy are better versus current approved standard of care, then a treatment will be approved ( even with some level of safety risk ).

RAC is a risk-reward play where the historic data from 80s / 90s and more recent preclinical/clinical data help provide a perspective on risk. RAC to their credit have spent the last 6-9 months reviewing their clinical strategy and plans ( with support of a second regulatory advisor ) to try to ensure as best as possible their approach is sound before they start trials.

 

How many shares of RAC do you own?
- I will not tell you a number, but I will say that my proportion of shares increased substantially as my research into this area increased. I will also say that I am looking to buy again on market when funds become available.

What is your relationship (previous and or current) with the company, and do you receive any payments from RAC?
- Independent shareholder.
- No payments ever.

Do you have ay medical or research qualifications in this field?
- I have a Bachelor of Science in Nutrition and a Masters of Dietetics. Dietetics has a large research component. I have one published research paper where I was evaluating the relationship between saturated fat intake and cognitive decline in eldery people. It's available here: Dietary saturated fats and apolipoprotein B48 levels are similarly associated with cognitive decline in healthy older aged Australians - PubMed
- I am not an expert in this field and I have and may make more mistakes.

The CEO says it's not yet arrived at that point.
"we just have to demonstrate that it can be used in humans to inhibit FTO as we believe is the case." Phillip Lynch 23/03/2021
That study was with on mice according to the COH website.
"The upcoming preclinical study will use a rat-based model" Phillip Lynch 30/03/2021
So the obvious question is which of all these studies and trials mentioned are on mice and which on people?

Bisantrene absolutely is a highly potent and selective inhibitor of FTO. From the City of Hope paper:



There is no denying that based on in vitro and in vivo studies that in comparison to all other FTO inhibitors on the market at the moment Bisantrene represents arguably the most potent and selective inhibitor of FTO. There are graphs and figures within the City of Hope document that demonstrate the efficacy of genetic knockdown of FTO and demonstrate the efficacy of pharmacological inhibition of FTO - comparing the results are quite impressive. In comparison to FB23-2 (another very low concentration FTO inhibitor recently developed), Bisantrene is 10- to 30- fold more potent at inhibiting FTO. I could go into the comparison between Bisantrene and Brequinar if you would like to. Some of the results are very impressive. Again, from the City of Hope (note: Huang et al., 2019 is referring to FB23-2):



I agree with you that it is very important that RAC management demonstrate that Bisantrene is effective in humans. Fortunately for holders there is data that we can look at that may provide some indication that Bisantrene was functioning as a highly effective anti-cancer agent. The figure below summarises past phase II trials in AML that used Bisantrene with a similar dosing schedule and an average complete response rate of 52%. The average was a 7 day dosing schedule (allbeit at a dose much higher than expected to inhibit FTO) with the potential of 3 extra days. That means that if Bisantrene is an effective FTO inhibitor, then it would have been 100% inhibiting FTO for up to 15 or so days (allowing time for the large dose half lives to cross the dose required to inhibit FTO 100%). Now, the effects of FTO inhibition of cancer are complex, although some of the key ones I will focus on are cell cycle arrest and apoptosis. Based on current knowledge of Bisantrene being used in cells and animal models, we can theorise that AML cells had entered the G0 phase of cell cycle (causing them to become stationary; niether growing or proliferating) and initiated apoptosis (programmed cell death). The only issue that we have with this research is that we do not have a measure of FTO inhibition, but it is valuable data none the less. Nothing has changed about the qualities of Bisantrene over the years and there is other data that I can bring into this argument to support Bisantrene as an effective FTO inhibitor over a chemotherapeutic if you would like.



So is it mice or humans?
Previous independent research was done in mice, although the mice were transfected with human AML cells. There is other research evaluating gene knockdown in mice with other transfected human cancer cells supporting FTO inhibition. There is a lot of research being done at RAC at the moment. The dedicated pillar one studies involve cells and mice. However, the RAC management have genioiusly piggy backed pillar one FTO data onto phase II breast and AML trials. RAC management have stated that they will measure FTO and m6A content in all clinical trials. So, by making these phase II trials open label, RAC management will quickly see whether FTO is being inhibited by Bisantrene and if this is having an effect on m6A content. From my understanding, there is no delay from dosing to inhibition of FTO, so there could be efficacy data quite soon.

Also the company is burning cash at 250k per mth, so it has about 7mth of cash atm.
What happens after that?
How will it make to 2022?
And if there are delays?

This is better answered by Wombat - he's the money marsupial. From what I do know, this company is very efficient at handling their cash. To give you an idea of the mentality at RAC, they provided themselves options at the last AGM at a ~45% increase to the VWAP. If we compare to another well known biotech company, then you can start to see just how efficient they are:

 

In vitro is no different to in theory.

Toxicity was also reported in France.

This isn't simple research.
Bluntly, they are administering these drugs to people as a last resort. They are on their death bed or close. And in conjunction to a stack of others.
It's very difficult to ascertain exact efficacy and what effects or side effects are due to whichever drug has been administered.

After all the baffle, basically it comes to:
It worked on mice, we are experimenting on rats based on promising past results (some with people) and new technology may expand the drug's usage.

You can put all the fancy words, pics, cut'n'paste press releases around it as you like, but that's pretty much where rac is atm.

Acompany like csl could a check for rac tomorrow and buy it. But clearly those inthe industry are not yet convinced.
And of course there is much $$ to be made in the R&D process which they would pay a premium for.

That's my point.
Given that you guys are only looking at the blue skies, I'm interested in looking at the risk side.

 

Not only looking at the blue skies. There are two other pillars to the strategy ( AML & Breast Cancer ). It’s these areas where there is strong historic evidence supported by recent preclinical and clinical trial activity.

FTO is the blue sky territory.

 

In vitro is no different to in theory.

That may be the case. However, from my understanding that is for a company bringing something from development through each clinical stage. There is significant risk doing this as at any stage there could be safety, tolerability, or dosing issues that creep up as you transition from preclinical to clinical. Having data in humans is essential to being confident about the chemical compound. The preclinical studies RAC are doing are to confirm independent research that has shown genetic knockdown (similar to pharmacological inhibition) of FTO showed favorable outcomes for melanoma and ccRCC cancers.

Bisantrene has preclinical data in vitro and in vivo as well as a host of in-human clinical data that supported its approval for AML in the EU. RAC have a lot of historical data that supports its use in humans, so if we are taking a risk perspective that is a major tick on the board. I think you have ignored the points that I have made about Bisantrene being a potent and selective FTO inhibitor in historic trials as well as todays preclinical trials - nothing has changed about the drug, only the knowledge that underpins its specific mechanism of action. With that in mind, we need to consider if the dosing regimen could have been enough to elicit a response. The estimated dose required to inhibit FTO in humans is around 7.5 mg/m2, which is estimated from the rodent models in the City of Hope paper. 100% inhibition of FTO may require a smaller dose. There is a large difference (~33 times) between the historic dosing regimen (~250 mg/m2) to the estimated dose required to inhibit FTO (7.5 mg/m2), which tells me that if Bisantrene was a potent and selective inhibitor (which it is as stated by the highly credentialed scientists at City of Hope), it would have been at a dose appropriate enough to elicit a response.

Thus, the question truly is whether the patients included in the study overexpressed FTO or not. Now, I will agree that it is impossible to know whether the historic patients overexpressed FTO or not. However, FTO was not known of back then, so we will have to look at other data that is available. In 2017, the City of Hope researchers published a paper demonstrating the FTO is overexpressed in multiple AML subtypes (below) and summarise their work by stating "In addition, given the functional importance of FTO in leukemogenesis and drug response, targeting FTO signaling by selective inhibitors may represent a promising therapeutic strategy to treat leukemia, especially in combination with ATRA treatment. As FTO has also been implicated in other types of cancers, our discoveries may have a broad impact in cancer biology and cancer therapy."
FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N6-Methyladenosine RNA Demethylase - ScienceDirect



Thus, Bisantrene works in humans with AML. It worked well enough to be approved in the EU. Since Bisantrene's rediscovery, FTO overexpression has been linked to multiple subtypes of AML and Bisantrene has been identified as a highly potent and selective FTO inhibitor. The dosing regimen used in historical trials is roughly 33 times greater than what is theorized to work in humans. Based on this data, I believe it is highly probably that Bisantrene was functioning as an FTO inhibitor in these instances. If Bisantrene was not functioning as an FTO inhibitor, then how do you explain the results seen below - an average 52% complete response rate.



Questions to you:
Are you aware of the side effects of anthracyclines like doxorubicin?
Are you aware of the commonness of anthracyclines in cancer therapy?

 

Classic Bears Vs Bulls, looks like Bears will win today........price down again

 

Personally, I am loving the discussion haha

Today's SP doesn't matter - this time next year will be a different story though..

 

It is the case.
In vitro alcohol kills almost anything including covid.
And while some be happy with the idea of intravenous alcohol infusion, it doesn't really work in practice.

I agree with that.
There is also a chance that long term negative side effects of previous drugs may be attributed to bisantrene as they have been mainly tested after others did not work.

That's why it's gotten this far. Still not a done deal.

I think you ignore any possible negative and present your side as if this is a miracle drug that does what still not been proven.

Hey I think it's exciting research, but i don't come to an investment forum for molecular research.

Unfortunately that is not much value for the cause .Here a list of a few drugs withdrawn
List of withdrawn drugs - Wikipedia
Drug recalls in the US

This is good for the cause as toxicity was encountered in it's usage.

Actualy the words are "response rate".
What you are implying is that a few days of bisantrene and cancer is cured. Disappeared. Complete response.
And they just thought "Nah, lets just sell some vitamins instead".
Really? I say there's a bit more to that story.

And here a pic from when RAC listed on the ASX in July 2016


Yeah, I know this stuff looks promising but it takes a long time and process is complex.
The sizzle has been a winner wish I'd bought some a while ago too, just still no sausage.

As an investor, could'nt care less. I'm only interested in the result.
Will the price go up, down or stay the same.
Today, next week, next year, next 5 or whatever my time frame is.

Just as I would'nt care what type of tubing and lubricant Amazon use for the rollers in their warehouses. Just how quick products are shipped after ordered.

 

I'm curious - after your own research, where do you see the SP going over the next 12 months?
Do you have a holding in RAC?

 

So, instead, investors should avoid any historical data supporting the use of Bisantrene in humans and classify RAC as a preclinical stage company with all the associated risks. Haha.

Absolutely. There could be long-term side effects that we don't know about. Doxorubicin (an anthracycline approved for many cancer therapies) has a very strong and well-known relationship with increased cardiac risk. It should be noted that multiple studies have demonstrated Bisantrene demonstrates very little cardiac risk, even in patients with substantial pretreatment with doxorubicin - which may actually be related to the FTO mechanism.
Alteration of m6A RNA Methylation in Heart Failure With Preserved Ejection Fraction

Never said it was a done deal. I have provided very clear data that I can provide referrences for showcasing the potential of a highly potent FTO inhibitor.

I think I am presenting my side quite well and have listened to all your questions and answered them with credible data.

Withdrawals are not my concern. Bisantrene was lost due to a series of mergers. The leading PD1 inhibitor Keytruda was also almost lost once. Wombat has touched on its sales/potential sales.

Yep. Toxicity is pretty common accross cancer therapies.

Sorry. In that table CR = complete response, which the average is 52%. The only respone rates recorded was 89% from one trial. I am stating based on research that it is highly probable that an FTO inhibitor was used in AML patients (a cancer type known to overexpress FTO) and the effect seen was a complete response rate of 52%. I think that is pretty clear.

The discovery of Bisantrene as a highly potent and selective inhibitor of FTO in 2020 fundamentally changed the direction of RAC and so pulling up company data prior to that date is pointless in my opinion. There is an update to strategy released March 31st which covers everything quite well.

 

I guess someone's gotta ask the question with ''RAC'' as by reading this post a lot would have bought in below 20 cent's as it's not that long ago it was in that price range..
Have you sold some off your holdings --or do you intend to hold ..

 

I’m waiting for a buyout but may reduce holding up to 5% down the track. May also add to holdings before I decide. Depends what occurs with other plans beyond my share portfolio.

Intend to add in SMSF.

 

No idea. Looks very interesting and promising.

Nope.
Status = interested.

 

wombat, that's good to hear ,selling with the way
from what I read the numbers you control would work out very well as they would have been help for over 12 months..
Either way, it's going to pay off big time or ..thanks again..

 

Hi, is today the start of the next reversal?

 

If anyone here could answer that, they already would have made $billions

 

I'm always hopeful! Life would be dismal otherwise.
And we did catch the last reversal, didn't we? Even with the sharp retraction, we're still in the green zone. Let's see what the next few days bring.
KY