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It doesn't "see" that because it is a very sad sealion individual. What a wasted life! Think of all the positive things it could be doing with its life rather than just hanging around here all the time like a rotten mackerel smell hoping it can get people arguing with it in order to create some traffic for LSE.

You miss the points I was making.

Firstly, for the trial data, the cohorts cannot exceed the administered LCD if that is set at 550mg/m² so the question of administered bound doxorubicin or systemic free doxorubicin doesn't arise. See C3 for an 'ideal' 64 day 2 cycle cohort.

Secondly, for those patients that continue on AVA6000 post-cohort, the clinicians will need to keep a tab on how much doxorubicin has been in their circulatory system as to not do so would be remiss.

It is 'elimination half-life': the time it takes for half of the existing amount (concentration) of a drug in the bloodstream to be eliminated from the body through the kidneys, tears, sweat, etc.

The trial protocol mentions only 2 cycles with Secondary Outcome Measures (maximum drug concentration, area under the curve, elimination half-life, and renal clearance) for 72 hours post-dose. The maximum dose allowed by the MHRA is 400mg/m², which would contain 270mg/m² of bound doxorubicin, so 2 cycles of that would mean the administration of 540mg/m² of bound doxorubicin.

Those PK and PD Secondary Outcome Measures will tell how much free systemic doxorubicin each patient has circulating following those 2 cycles, and it will not be more than 540mg/m² administered. If a patient continues on treatment post-cohort, then I guess the clinicians will need to keep on with those Secondary Outcome Measures, which will be useful data to have anyway in this 'data rich' study.

@Rorydinho, yes, the wording in the RNS of 21 June makes it clear that patients in at least 2 of the UK-based cohorts have responded during treatment ("several patients in cohort 5 and earlier cohorts remain on treatment as their disease has not progressed").

Oncology Phase 1, certainly Phase 1a, studies are always done on terminally ill patients for ethical reasons because non-terminal patients still have 'proven' lines of treatment available to them and the purpose is to test a previously unstudied drug for safety and tolerability and to characterise the PK and PD of the drug, not to trial the efficacy of this unstudied drug as a treatment.

Whilst AVA6000 seems to have shown clear efficacy, there are problems with reporting this: 1) the small sample sizes are not statistically meaningful; 2) the patients have (most likely) been pretreated with other lines of treatment for their various, different cancers; and possibly 3) the variable susceptibility of different cancers to doxorubicin.

Avacta will be free to publish any data they like (that can't be tied to individual named patients) but at this stage, Phase 1a, it will, for the reasons given above, be annecdotal as regards responses to treatment. Nevertheless, Avacta can certainly cite the number of patients who have benefitted from the trial and how they have benefitted and no doubt point to these as indicators that AVA6000 is on course to provide good data in these Secondary Outcome Measures of the trial when stsatistically significant data have been collected in Phase 1b/2:

Objective response rate (ORR) [ Time Frame: Up to one year ]

ORR is defined as the proportion of patients achieving a best overall response of confirmed partial responses (PR) or complete response (CR), per Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

Duration of Response (DoR) [ Time Frame: Up to one year ]

DoR is defined as the duration of time from date of first response to date of disease progression, as per RECIST v1.1

Progression-free-survival (PFS) [ Time Frame: Up to one year ]

PFS is defined as the time from the date of the first dose to the date of the first documentation of confirmed disease progression or death, whichever occurs first, as per RECIST v1.1

Overall survival (OS) [ Time Frame: Up to one year ]

Overall survival (OS), defined as the date of first dose) to the occurrence of death from any cause

Anyone who has a genuine interest in investing in Avacta because of Dx (as well as the more lucrative Tx side) should be pleased with the Dx division's well thought out and measured strategy. Of course anyone who is obsessed with the failed Avacta LFT venture either doesn't understand the current situation or has malicious intent.

New LFTs containing Affimers may take some time to appear. For now, I'm just looking forward to seeing the Dx division's revenue figures.

It is actually 2.79 times the standard dose of doxorubicin, as confirmed to me by AS (the 9 got dropped during draft revisions), with the 'standard dose' now being the higher 75mg/m² rather than the 60 dose previously used by Avacta for comparison. This change of comparison is now being used, I believe, because the intention is to use the 75 dose as comparator in the Phase 1b/2 part of the trial. So, in short, one fk of a lot of bound doxorubicin is being administered to the patients.

Touk wrote: "And like it or not what happened with the LFT is one of the reasons that the big investors we need aren’t on board yet."

Now, this IS interesting. It is a classic example of stupidty: because a person has a limited knowledge of a subject he thinks he knows a lot about it - it is only those who know a lot about the subject who realise that the subject is actually very complex and nuanced. However the ignorant, arrogant one sails along on his merry way regarding anyone who disagrees with his 'knowledgeable' view as WRONG.

https://www.youtube.com/watch?v=I9XTox7zlSw

The sun has indeed disappeared. Tears are falling from the sky.

😭

🌧️

...or, 'Nothing works better than Orenetide'

This company should, by all reasoning, crash and burn today: https://www.londonstockexchange.com/news-article/OVB/summary-results-of-phase-ii-study-for-orenetide/16104149

Some quotes:

"We are surprised and disappointed that the Study did not have a positive conclusion regarding the superiority of Orenetide versus placebo. The Company now intends to analyse the results from the Study in further detail, including investigating the reasons for potential differences between the Study results and results from previously conducted clinical trials of Orenetide."

"The Company is currently developing Orenetide (BP-101), a novel synthetic peptide administered through a nasal spray as a novel treatment for women with hypoactive sexual desire disorder (HSDD), a condition characterized by a distressing lack or loss of sexual desire affecting an estimated ~4 million premenopausal women in the US alone."

The company, which acquired Ivix, the developer of BP101, only has that one candidate and seems to have been taken in by any possible placebo effect on efficacy in the Phase 1 study and by Russian 'vranyo' in Phase 2 and 3 studies.

I had no interest in this company or product (and certainly have none now!) and so this is not a cross ramp! I just posted this news because, contrary to what some FUDsters might have - or more accurately did in the past want us to - believe, Avacta with AVA6000 in Phase 1a is in a very different situation from this binary outcome company:

- AVA6000 was never Avacta's only 'jewel'.

- Doxorubicin is an approved and very effective anticancer drug and AVA6000 has been shown to target tumours in therapeutically significant concentrations.

- True efficacy has been demonstrated in Phase 1a of AVA6000's 'safety & tolerability' study by some patients continuing to be dosed post-cohort and some patients' cancers not progressing.

- Sexual dysfunction, with its psychological component, is likely very susceptible to the placebo effect and of course anything done in Russia is, almost by definition, bound to be lied about. Cancer trials in the UK are a totally different kettle of fish. Arf! Arf!

The sun will rise at 06:12, yawn, wash and have breakfast and, if there's no Avacta megaRNS, start crying and head off back to bed.

You've been gone a while. Has the medication stopped working.

Btw Agent! Had you heard that deranged crooked evil Satanist Bill Gates has bought a controlling interest in cancer? We'd all better watch out from now on, starting tonight. There's a Super Blue Moon (yes, it really WILL be blue!) tonight and Gates has arranged for cosmic metathoughts to be radiated in the moonbeams. You'd better have your best tinfoil and RefleXo™ gear on tonight.

I don't know who runs withpower.com but it's certainly not Avacta. From memory, the withpower.com pages just contain cr@p scraped from the ClinicalTrials site.

WeAre Groot wrote: "AVA6k only needs to show a modest improvement over dox to become the standard of care overnight. Everything is pointing to extended survival and dramatically reduced side effects. Couple this with opening up treatment to patient types previously excluded and increased dosing (both frequency and duration ) and the potential to treat other tumours, means this isn’t a $2bn p annum drug, it’s a $5bn+ drug. And it’s only the first one in the pipeline."

I don't know about the addressable market. I leave all that fantasy stuff to the keen ones on TwaZZer. For sure, if the reduced side-effects profile is proven in Phase 1b, then single treatment with AVA6000 will save $millions in treating side-effects from doxorubicin. Now, if AVA6000 can be used as first line treatment in several cancers rather than in combination with another that causes side-effects, then that would be a whole new market - e.g. (relatively very) cheap AVA6000 as first line treatment for breast cancer, followed if necessary by second line treatment using other drugs with or without AVA6000.

This is going to be an interesting story to follow.

Thank you LL, thank was my understanding as well,but only from what has been written on here: that there is a 3 week wait (a full cycle), rather than the 2 weeks observation period, until subsequent patients receive their first dose.

Any thoughts on the minimum number of cycles per patient until cohort completion. C3 lasted only, or under, 64 days (RNSes on 29th June and 1st September about completion of C2 and C3 respectively) which very much suggests 3 cycles for the first patient and 2 cycles for the subsequent patients, with a 2 week observation period for all of them at the end. That's just about as short a time as possible for a cohort.

We don't know when the first patient was dosed but if, for the sake of argument, it was on 1 July (a Saturday) then we are coming to the end of week 8.

There's complete uncertainty about what has been happening, ranging from the cohort about to complete with no DLTs or withdrawals to the cohort needing to continue for a while yet due to withrawals and/or a DLT or two.

A couple of questions for anyone who knows how Phase 1a trials are carried out:

- How soon after patient 1 receives the first dose do the other patients get their first dose?

- What is the minimum number of cycles for each patient? (I remember seeing two cycles being mentioned in those sites publicising the trial to potential recruits)

No gje, there IS a shadier reason. All the clinicians are in on the conspiracy and very, very, very keen to spend their time on this useless trial that will ruin their reputations. And why are they doing this for Avacta and no other drug trial? Well, because, er... um, because they, well, I suppose the 🦭 can come up with a reason or three.

It's one of the bashers' favourite ploys; whinging about missed deadlines, delays and that 'nothing is happening, boo hoo, boo hoo' as if the CEO is a useless omnipotent, omniscient god who has failed to control the universe and all that's in it enough to be able to achieve some stated objective. Very tedious. And I've got to say the 🦭 is a very odd character, the amount of time it spends hanging around here begging for mackerel. Do not feed it.

Do you think Avacta might one day be sponsoring QPR or Wetherby Athletic?

Oxfordshire Bioscience Network

Although I would've liked it to have been Ocean Bottom Nightmare