Europa are delighted to link with I3E and look forward to early September Serenity appraisal spud. Watch the full video here.
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Cancer profiling is critical. Both Cellsearch & Parsortix (liquid biopsy) should be researched thoroughly by anyone invested in cancer drugs and therapies. As should traditional tissue biopsy to which Parsortix has been given exact parallel status by FDA in MBC. In short, both traditional biopsy and Parsortix give DNA, RNA and specific protein data that cannot be achieved by other means. They stand alone.
That said, there are some bloody clever people in these drug development companies who have such a deep and substantive understanding of the immune system and cancer that they can can find alternative routes. I think such people are amazing.
Your Friday 9.05
Unfortunately cancer evolves and changes. Once cancer spreads to a secondary site the mean survival rate is 10%. The point of chemo is to destroy cancer before it spreads. I would imagine this is what Avacta are trying to achieve
I asked earlier in this thread why Oncologists are often "flying blind" and getting it wrong when matching a type of chemo to a generic tumor IE Dox and other forms of chemo work better on some tumors than others even though the cancer might be the same type. I received the following comprehensive reply from BuzzLightyear:
I think the term ‘flying blind’ is more in reference to the current diagnostic procedure where a tissue biopsy (usually when a tumour is removed) is taken prior to treatment and used as a guide to treatment.
So in that respect, they know what to do after all these years, but often this refers only in the initial stages.
There are two considerations to add to which can affect patient outcomes.
First, cancers mutate and what worked (treatment wise) at first, may no longer work as the treatment cycle progresses, hence the need for further biopsy during treatment (Longitudinal testing)
As we know, that can’t usually be done using additional tissue biopsy as there is nothing to remove or test or the patient is too ill to undergo more surgery.
Hence the term ‘Flying Blind’.
The second consideration which is particularly pertinent to cancers such as Prostate and Ovarian cancer :
Sometimes it is preferential to reduce the size of a tumour before surgery, and since tissue biopsy is surgery, the only way to define the best treatment before surgery is to do a liquid biopsy to guide the best personalised treatment for that patient.
The second reason - many abnormalities discovered that could be aggressive tumours, may in actual fact be slow growing tumours that are best monitored rather than have surgical interrogation - often it’s best not to intervene at all but to just continue monitoring testing every few months to look for change.
Indeed, I have read in the past that the actual physical act of surgery on a tumour at the wrong time can have a severely detrimental effect on metastatic process thus making spread worse.
Many people die with Prostate cancer than because of prostate cancer. Often they don’t even know they had cancer as it didn’t affect them and was contained.
In addition, surgery can have lasting quality of life issues for a high percentage when they didn’t actually needs any surgery as the lump is either slow growing or benign.
The way cancers are treated these days are often more calculated than just going in and removing what they find as they used to in the past… and it’s the liquid biopsy that can improve guidance on the best intervention (or not).
Might be of interest "FAP-Targeting Imaging Tracker Prepares for Phase 1 Brain Cancer Trial"
@D-Geeman unfortunately FAP(a) is upregulated in some types of pulmonary fibrosis. See attached paper:
(and yes I am sceptical that the AVA6000 molecule can pass the blood brain barrier)
Quite possibly D-Geeman. I think it would depend on the level of FAP in areas of fibrosis.
FAPI PET image analysis is going to be of great benefit to Avacta, the clinician and the patient both as a diagnostic to identify (maybe even unknown) areas of raised FAP level and as an aid to treatment by dtermining whether the differential between FAP in the tumour and raised FAP elsewhere is favourable or not for treatment with AVA6000.
You can also see that metastasised cancer cells express FAP from the body images in the paper from which the relative amounts of FAP in various cancers and their metastases are calculated:
68Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer
However, because FAP is present in those cases doesn't necessarily mean that FAP is present in all metastases of cancers in which FAP is overexpressed. It would take an oncology expert and a revue of the literature to make such a call.
I recall a post by Ophidian to someone on the board with a brain tumour (I have a feeling I recall the name of the person but won't mention it in case I am wrong, but I have not forgotten) where Ophidian said that AVA6K would never reach the brain due to the size of the molecule(?) and the fact it couldn't penetrate the tiny 'access' through a membrane. Something like that.
So there's another question if breast cancer, for example, has metastasized to the brain then perhaps it wouldn't work https://breastcancernow.org/information-support/facing-breast-cancer/secondary-metastatic-breast-cancer/secondary-breast-cancer-in-brain#what%20is%20secondary%20breast%20cancer%20brain 'Breast cancer that has spread to the brain
This is known as secondary breast cancer in the brain. It can also be called brain metastases or brain mets.
It’s not the same as having cancer that starts in the brain. The cancer cells that have spread to the brain are breast cancer cells.
For most people with secondary breast cancer in the brain, breast cancer has already spread to another part of the body such as the bones, liver or lungs.
For some people, the brain may be the only area of secondary breast cancer. '
My dad died as a result of fibrosis of the lungs. I read in a post here that FAP can be produced in areas of fibrosis so would that mean that AVA6000 could damage lung tissue as a side effect, in such people as my dad?
If precision does work in that way then that really would be the most fantastic news as so many cancers are "caught" too late.
"Assuming precision works, would it also "work" on metastasied cancers in the body?"
Decent question. It seems very probably 'yes' but it depends on how much the same 'similar' is:
"When tumor cells metastasize, the new tumor is called a secondary or metastatic tumor, and its cells are similar to those in the original or primary tumor. This means that if breast cancer metastasizes to the lungs, the secondary tumor is made up of abnormal breast cells, not of abnormal lung cells. The tumor in the lung is then called metastatic breast cancer, not lung cancer."
CO back to your earlier point, and something that may influence your thinking on your last post, the error bars are likely to be min mean max as opposed to 1std dev. With those sample sizes no statistician would use SD it's just too small to be representative of the sub-population. That narrows the range significantly if true. I'd also suggest that there is enough to test the hypothesis that all tumors are the same in terms of FAPa and there is a statistical difference even with those small sample sizes as the differences are large from top to bottom of the chart. Confidence intervals about the size of the difference would be large though.
don't know if this is covered or not so forgive if its a dumb question:
Assuming precision works, would it also "work" on metastasied cancers in the body?
Could it target the main tumour but also allow Dox to be released on smaller tumours as well at the same time when injected as a dose?
Very good critical thinking CO!
So many typos, sorry.
*part of the body
Having actually read that full paper now, one key thing to stress is that the chart showing FAP levels per cancer gives the beguiling and misleading suggestion of a confident ranking of cancers by FAP expression.
It’s a great start but in truth based on only 80 patients with 54 primary tumours and 229 metastases (where cancer has spread to another pet of the body). The patient selection bis is that these were patients whose cancers were obviously progressed and complex enough that their clinicians decided they wanted to run this Nobel scan for increased precision in tumour delineation.
The error bars show there is a big range on each cancer type, and relatively low sample size. Primary and metastatic tumours are lumped together, although data suggest slightly different FAP activity for each (albeit not statistically significant).
So my key take-homes are:
- It gives a pointer towards cancer types that might on average have more FAP.
- We can’t definitively say “X cancer type is always low/mod/high FAP because it shows it on this chart.”
- This is probably why we need patient-specific PET scans in Phase Ib, to more directly relate therapeutic benefit to actual FAP activity in the tumour(s).
Some centres concentrate on specific Cancer types. In this way the practically "guarantee" a progression of patients into the trial and make comparison and monitoring more straight forward.
My simple point was, Sorcerer, why did could we only narrow it down to ovarian cancer and soft tissue sarcoma at this stage when surely, but apparently not, the wider oncology community should know after all these years that Dox is most successful on those fronts? I guess AVCT might have wanted to test the waters where other areas are concerned with AV60K?
CO/Sorcerer, I am going to put a shameless plug plug in here for AGL's Parsortix Circulating Tumor Cell (CTC) retrieval 'liquid biopsy' system which has just been FDA approved (contrary to what the subsequent SP movement has suggested!) and is the first of its type to have been so. Now, before others jump on me for doing cross ramping, I mention it with the following in mind, based upon my having invested over there and gained an understanding of the term "Longitudinal monitoring" IE The liquid biopsy enables Physicians to monitor the progression of a tumor through the chemo process where ordinary invasive biopsies cannot be undertaken to monitor that repeatedly for obvious reasons. The CEO of AGL pointed out that not all types of chemo work for the different types of cancer (as you have said) and so these Physicians are often "flying blind" where tumor progression is concerned. And so my question is this: Surely after all this time we should know by now which type of chemo is suited to what type of cancer tumor?
Our posts crossed again CO. Good point about unmet medical need. That is also important and cuts across my three categories as 'potential uses' for AVA6000.
MrA, our posts crossed. I could clearly be more concise!
Jimmy, good point on the cancer types. I noted they split the cancers into low, moderate and high FAP groups with dividers at SUVs 6 and 12. Ovarian is right in the middle of the moderate group.
I’m sure there was also some logic around market size, unmet need, and/or conditions for which Dox is already used as standard of care.
There are three factors that needed to be juggled when deciding which cancers to progress AVA6000 with. The factors are unrelated, as far as I can see, but fortunately work together. They are:
1. Cancers that respond well to doxorubicin - these are the easiest indications for which to introduce a pro-doxorubicin.
2. Cancers that are high in FAPa - these show AVA6000 at its most efficacious.
3. Cancers that offer the biggest market opportunities - obviously.
All this comes together in "The estimated market size (peak sales) of a safer/more efficacious form of doxorubicin in just three indications (ASTS, breast and ovarian cancer), in the US/EU alone, is $1.5bn* pa."
* Commercial Evaluation: AVA6000, Globe Life Sciences, March 2020
Slide 10 of February 2022 Investor Presentation "Shaping the future of medicine with novel cancer therapies"
and several other recent slideshows.
Jimmy, they would also consider market size, actual current and projected or potential as data from Phase I can go into Phase II cases for studying particular cancer types and STS and ovarian (and breast) cancer have been used to describe the projected market size in the US and Europe in presentations.
Ace thread btw, thanks for sharing the info MrA/CO/
68Ga-FAPI PET/CT: Tracer Uptake in 28 Different Kinds of Cancer is the article cited on slide 2 of the poster presentation talk by AS.
The figure is from this paper:
The figure on slide 2 shows average FAP SUVmax (max standard uptake value, a proxy for concentration) for each cancer type, with an error bar, presumably 1 standard deviation. n=8 means that there were 8 measurements from that cancer type.
The paper’s a relatively short read and great for more insight on what they might get from PET scans.
The number of each cancer type measured may involve some selection bias and may or may not relate to the size of the market.