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Well, permeabilty/penetration could be increased by smaller doses at more frequent intervals for instance - not that the two are correlated, just intervals that allow time for the dead tumour cells to disperse before hitting the tumour again.

Anyway, lots of possibilities now that the mode of action has been proven and who knows what Avacta and the SDMC have in mind, except that it will be better than any of us could come up with.

What sort of person wants to promulgate the wish that this drug won't prevent a lot of suffering and might actually cure people of cancer? Very, very sad characters indeed. We should pity them; to be so obsessed with trying to make money that they've lost all vestiges of humanity.

Ceri, ask your son whether fibroblasts are integral to tumour growth.

I must add a rider to that post.

One of the requirements for a patent to be granted is that the invention is "non-obvious". Whilst we all here can see that replacing doxorubicin by another cytotoxic is obvious, a company could still try to patent and thus tie Avacta up in litigation battles. I wouldn't give much for their chances but they would have more cash to spend in court and patent law can be very wobbly.

Matml74's excellent post, part-quoted below, got me thinking. Excluding TMAC, there are three distinct groups of commercial opportunities to make prodrugs using the pre|CISION platform.

"Doxorubicin is considered one of the strongest chemotherapy drugs ever invented. It can kill cancer cells at every point in their life cycle."

"Once [the optimum dose] is established you have the most powerful chemotherapy ever invented…… but without the issue of cardiotoxicity, the main limiting factor of the treatment, as well as a significant reduction in all other side effects."

(#83 reply in the Price thread- thanks Expect for getting this train of ideas flowing)

The groups are:

1) Prodrugs associated with off-patent chemo drugs, of which there are two sorts: prodrugs of chemo drugs, such as AVA6000, which now that the platform has been proven should sail through clinical trials and onto the market; and prodrugs of analogues of chemo drugs, such as AVA3996, which will require extensive studying in clinical trials since, as analogues, they are new chemical entities and hence unknowns.

2) Prodrugs associated with on-patent chemo drugs, of which the same two sorts apply. These would be of enormous interest to the pharma companies that hold the IP on the drugs and any pharma company worth its salt will have picked up the pre|CISION technology through the patent literature and be busy even now working on these. One would assume that the IP Avacta has licensed in from Prof Bachovchin & Tufts has been put together in such a way as to include phrases like "and other chemo drugs, both existent and future" in the same way as the IP for the on-patent chemo drugs would include "and all prodrugs thereof" - if that latter is not included then what's to stop Avacta, or any company licensing the platform, from making prodrugs of the best selling on-patent marketed drugs?

3) The third group is what Matml74's quotes above sparked off. The cupboards of pharma companies will be crammed with samples of compounds that never made it. Never patented, never made it past animal studies because whilst they had shown good in vitro activity they were too toxic in whole animals. If not doing it already, pharma companies will be going through their internal records looking for cytotoxics with a spare -NH2 that can be linked to 5140 and even better cytotoxicity than doxorubicin or the exemplified prodrugs in any of the other classes of cytotoxics in the Avacta pipeline. Again, Avacta's IP coverage needs to be comprehensive and watertight.

Big opportunities ahead!

Valuation. Shouldn't that be Vauasian?

Lovely view riding opinion

Enough?

With all due respect I have to disagree MrR.
Their understanding of puer illogical arguments , when consider... Oops , what a giveaway ! Damn ! Done it again . And again . ...OK , start again .
The pure dialectical existentialism of their reasoning leads me to one and only one final and unavoidable conclusion . I need a crap . Must that fruitcake I scoffed at earlier .

I know a couple of Ians who may be interested. Shall I give them the nod?

Sea lions congregate in gregarious groups called herds or rafts that can reach upwards of 1,500 individuals.

Oh God, I hope not 1,500 of them.

Will be in receivership by this time next week. FACT.

I thought the question might be more along the lines "What happens to FAP when the tumour cells die?"

I don't know how the cells that are killed by doxorubicin die or what happens to FAP when the TME breaks up but here's a decent paper about FAP! Hopefully someone with the requisite level of knowledge will be able to help.

Fibroblast activation protein-a: a key modulator of the microenvironment in multiple pathologies
https://pubmed.ncbi.nlm.nih.gov/22608558/

Abstract
Fibroblast activation protein-a (FAP) is a serine protease that can provide target specificity to therapeutic agents because in adults its expression is restricted to pathologic sites, including cancer, fibrosis, arthritis, wounding, or inflammation. It is not expressed in most normal tissues. The majority of FAP is expressed by activated fibroblasts responding to the pathologic situations. FAP is typically found as a type II transmembrane protein physically attached to cells and with the bulk of the protein, including the catalytic domain, exposed to the extracellular space and accessible to small molecules. In this chapter, we review the structure, substrate specificities, signaling functions, and current design of FAP inhibitors. Evidence indicating the presence of FAP in multiple cancers, arthritis, fibrosis, keloids, and other pathologies is described and indicates possible roles for FAP in facilitating cell invasion and growth. Separate sections are devoted to the role of FAP in coordinating the stromal response to cancer, including a role in angiogenesis and a potential role in modulation of the antitumor immune response. Finally studies attempting to demonstrate the clinical potential of FAP are discussed, as well as some novel applications employing FAP in therapy or diagnosis. Throughout this review, effort is made to highlight areas where information is lacking and to highlight important questions that require further investigation.

Strange you should say that WeAreGroot. I had a very vivid dream several years ago that was very much along that line and has always stayed with me since. It was actually me repeatedly going back from starting my journey to try and stop the dog yapping. A life-changing dream.

The points have been made already, but worth summarising in light of the current protocol:

"Experimental: AVA6000 Phase 1a
Patients in Phase Ia will receive escalating doses of AVA6000 following a 3+3 design, commencing with a starting dose of 80mg/m2, once every 3 weeks (Q3W) starting on Cycle 1, Day 1 (C1D1), until disease progression, unacceptable toxicities, withdrawal from treatment for other reasons, reaching maximum lifetime cumulative exposure to doxorubicin (or other anthracyclines), or death, whichever occurs first.

"Experimental: AVA6000 Phase 1b
Patients in Phase Ib will receive the RP2D dose of AVA6000, once every 3 weeks (Q3W) starting on Cycle 1, Day 1 (C1D1), until disease progression, unacceptable toxicities, withdrawal from treatment for other reasons, reaching maximum lifetime cumulative exposure to doxorubicin (or other anthracyclines), or death, whichever occurs first. One to three tumour types will be selected based on the assessment of Phase 1a data."

If safety and tolerability have been proven to the SDMC's satisfaction by the data so far, then surely Avacta and clinicians would all want to revisit both the maximum lifetime cumulative exposure and the 3 week cycle. They may also want to vary the concentration and rate of infusion and, although these are not in the publicly available protocol, they may be specified elsewhere for the trial. Or they may want to keep them the same for consistency across cohorts. Or, with a lot of changes to the protocol, they may be wanting to do what would effectively be a second Phase 1a trial starting at a higher dose level.

In any case, changes to the protocol would have to authorised by the ethics commitee and you can guarantee that they will be crawling all over the data before allowing changes to maximum lifetime cumulative exposure and cycle frequency for what is effectively massive amounts of a highly toxic killer ...being administered in a straitjacket.

Do you have any issue with the substance of what I wrote? If so, I'd like to hear it

"Worst case? It replaces straight dox (same efficacy) with fewer side effects. That takes the entire marker ($1Bn plus as a chunky CAGR)."

It is wrong to equate the doxorubicin market with the future AVA6000 market as doxorubicin is given for cancers where FAP is not upregulated. There are other differences (both positive and negative wrt AVA6000) between the two markets but that one is fundamental.

And hopefully more wonderful weeks to come with further announcements in the lead-up to Science Day.

You know that our 'precision' tech has a trademarked name? pre|CISION, or pre|CISION™ to be exact.

Good point. Nice find.

Also, note the size of the women-specific ovarian and breast cancer markets.

To quote from that document:

Intravenous Chemotherapy Regimens Suitable for Scalp Cooling
Scalp cooling can be used with all solid tumour cancers treated with intravenous SACT
agents such as taxanes, alkylating agents and anthracyclines / DNA intercalating agents. The
most suitable agents include:
• Cyclophosphamide
• Daunorubicin
• Docetaxel
• Doxorubicin
• Epirubicin
• Paclitaxel

Three of these, the -rubicins, are anthracyclines.
QUESTION: Would AVA6000 replace other anthracyclines? Do the others have a big advantage in certain treatment regimens?