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Terry why don’t you go back to retail banking ,oil , and energy. Pharma is clearly not something you have patience for… and you are wearing thin here whilst most here actually have a grasp of the actual science.

The material information has already been supplied to the Market… it is has just chosen to not believe it at face value.

Good thing we had MATERIAL new information over a month ago ! Lollollolololol

SD may or may not be an inflection point but there are a lot of good signs that the detailed data we have yet to be informed is very positive. All eggs in one basket argument… depends on stage in life and portfolio size and attitude to risk. I have about 30% capital in here… more at current valuation but it is a sizeable chunk of shares and I feel pretty confident that the next 12-24 months will be great for my portfolio and amazing for providing hope to cancer patients. This board has moments of excellent threads but it is so drowned out by the prolific back an forths covering the same old ramping and deramping spats. Just discuss the science … it is the only thing that is actually relevant.

The thing that you can’t ignore is that there is dox in the tumours - 6/6 biopsies. We don’t know exactly the quantity but it is working… and it could be working very well indeed.

The chance of success is much higher than where we are SP wise… doesn’t mean there isn’t risk as there is with all phase 1 trials but this is a delivery system and we have had the statement that there has been some dox posted through the letterbox and the postman was AVA6000

Tumours can have molecular changes that make them resistant to the kind of chemotherapy being administered - not just specifically doxorubicin. Oncologists will try a new treatment in situations like this.

I guess that is why having a platform of the major chemotherapies that can leave healthy cells alone could give oncologists a much bigger ****nal to attack molecular mutations in tumours.

Thanks Matml - another 3 patients if DLT. With regards to DLTs I know from my own experience that the actual cause of problems after an infusion is not clear cut. You are often given filgastrim (white blood cell booster) and this can cause some unpleasant side effects and from my conversation with a private oncologist it can be hard to distinguish whether the chemotherapy is causing a fever or whether the filgastrim is the issue - when there is no infection found in blood/urine/swabs/sputum etc. They always treat as it were sepsis as the risk is too high.

Neutrophil counts can be difficult to control and given the exclusion criteria if someone was below the minimum level they would delay the cycle or perhaps the patient would have removed themselves as well… I imagine there could be a number of situations that could occur but ethically they would always do what is in the best interests of the patient.

If you have a full read through of the inclusions and exclusions for eligibility for the trial you will see that patients must have minimum 3 months life expectancy - which is not very much but also just an estimate. The trial is a 3x3 design. So if someone has disease progression (palliative care) or sadly dies then another patient is added to the cohort. They will also add another patient if there is a dose limiting toxicity but I assume this hasn’t been the case otherwise the statement about no cardio toxicity would be worded differently.

So I expect some patients have been moved to palliative care and this is why we have 19 patients rather than 12 (4 cohorts). I would add that this is to be expected given the very advanced stages these patients are at and take a moment to consider what they are doing for the progression of science - very brave people who have battled cancer for a number of years maybe in some cases a decade or more. It is quite selfless to give more of your time at this point in your treatment to be poked and prodded more. Yes it gives some hope - but they are sadly very unwell already.

So despite disease progression (which should be expected with those with just a few months of life expectancy) they have not found cardio toxicity biopsies all (6 out of 6) have therapeutic levels of doxorubicin. This is what stands out for me.

Happy to be corrected on my understanding of the 3x3 trial design by someone with more knowledge of trials.

Here is a link
http://onbiostatistics.blogspot.com/2015/01/phase-i-dose-escalation-study-design-3.html?m=1

AVA6000 Trial inclusions and exclusions

https://clinicaltrials.gov/ct2/show/NCT04969835

Riesgo - did you actually look into what happened? The test was developed by 3rd party Mologic. They used off the shelf design with antibodies on the the control line and this was the problem. Affimers could have been used throughout but I guess Mologic took the view it would take too long to redesign what they already had. I think focusing on this a comparison to a clinical trial is what I find really odd. One is product development and the other has the product already designed and even produced (albeit not in commercial quantities - which is a completely different discussion) and trials are collecting data.

Riesgo
Legal would have had to approve the RNS. I’m not concerned about the lack of exact data when the wording ‘therapeutic levels’ was used with no ambiguous adverbs or adjectives mixed in.

LFT - the mutation and the government were the main issues there. This board including myself completely underestimated how excellent science could be ignored in such a massive global pandemic. Not to mention the manufacturing of a product from scratch… the Chinese had the edge there (I wonder why, don’t you?).

Why is this different ? This has been in development years… this has the backing and support of established regulatory and clinical trial research teams. There is no Bojo types getting kick backs or government contracts. This is just the science and now actual human data is available but not published (yet). This is what makes the wording different to that of the LFT. And don’t forget that the specificity and sensitivity data of the LFT was excellent before the mutation. Also - important to state the obvious… cancer is NOT a virus but most are gonna get it…. And it means that chemotherapy drugs like the very old doxorubicin are still highly effective but highly toxic. If we can reduce the latter… winner winner

Riesgo - exactly… what causes dose reductions or early cessation of therapy? All these crappy life threatening side effects… neutropenia sepsis heart toxicity… markedly reducing these even at same therapeutic levels will lead to better outcomes and success rates with a whole lot less pain for patients and less costs in treating these horrible side effects (some of which can be permanent).

Seems to be a few suggesting the term ‘therapeutic levels’ is ambiguous. In trials this is not ambiguous. They have to work out maximum tolerated doses and therapeutic levels to work out dosing safety and efficacy. Doxorubicin is a well established drug and these therapeutic levels WILL be established (they can’t dose people safely without them). I don’t see the statement from AS as ambiguous in the slightest.

Everyone reacts to chemotherapy differently and different bodies metabolises it differently. If someone has a serious reaction like neutropenia sepsis or even signs of heart/lung/kidney damage (patients get thoroughly checked out before each cycle) then a dose reduction is tried. These dose reductions would have been part of the original trials for these chemotherapies. They have to be still considered therapeutic - otherwise they are poisoning people for no benefit. I kid you not - these are horrible poisons. I’ve not had a fun experience… a stream of side effects - a gift that keeps giving…. Almost like clockwork. I may even have some permanent gifts. I’ve had a dose reduction and I’ve had this exact conversation with a private oncologist. He explained the dosing levels and how it would have been established in initial trials. The lower level may well have reduced efficacy but quantifying it for the individual is difficult- they can only look at trials which need 10 years of data outcomes to analyse it for populations. There are no guarantees it will work for me, but I can at least hope that I end up the other side of this roughly no worse than I came in and still breathing… all due to trials looking at therapeutic levels and MTD.

Why are they looking for a MTD if already therapeutic? Well the beauty of the delivery system is the there are markedly reduced side effects and no cardio toxicity. Therapeutic levels could be markedly increased … It is a very important question for patients, regulatory approvals, buyers and other interested parties. Knowing the range they can give patients is so crucial. If you can’t see that, think perhaps about when you get cancer (50%-+ chance) - wouldn’t you want them to have established the most effective dosing regimen to give you the best outcome? That is the point here.

What is so different here is the cleaved drug is well established so there is much to compare to so poking doubt in ‘how good it works’ seems to ignore this fact and entirely. For a brand new drug - the phase ‘therapeutic levels’ would be a red flag. Not the case here at all.

I love that you added ‘majestic’ to it Timmy

Majestic Unicorn more likely …

He wasn't an uber ramper, but he felt Avacta was going to 'take off'. He had a basic understanding of AVA6K and though he didn't sing and dance about £5B he clearly outlined the facts. AND the facts as we know them are extremely positive.

Personally I don't mind this kind of publicity, but I feel like poop right because of chemotherapy so maybe I have brain fog.

Apologies - did have a brief scan but I guess it got lost amongst the 80% bickering. Oh well! On the bright side the chap seemed genuinely positive about Avacta and it does feel like more of this is what is needed for more powerful media to get interested.

From about 22:10

Apologies Uk investor magazine podcast

I posted before I could get a decent title.

https://ukinvestormagazine.co.uk/shell-amazon-and-avacta-with-alan-green/

Squirrel - I'm sorry to hear about your husband experience with chemotherapy. I hope his treatment plan is adjusted. All chemotherapies have horrendous side effects so this technology, if successful, which be life changing for existing patients and future patients.

Apologies - the thread title is IHT, but I wasn't advocating that it be increased. It is double taxaction and isn't even in the top 10 sources of taxation for the treasury. What I was advocating is just spending it now - it will do more good than hiding it way from IHT.

Agree government are the biggest problem in spending it wisely and agree they are one's finding the way to not pay tax. I personally think they should be jailed and barred from public office. Yes I understand the balance between higher taxation and lower total revenue but I do think the brain drain has already happened and people are generally miserable everywhere I look. We absolutely need a new government, massive slashes in the right places, but with inflation as it is, if we don't increase tax to a degree we are going to see the brain drain regardless.