Member Info for Rambo23

Lets refresh DLT's

In each cohort 3 patients are needed to have 2 cycles at a single dose level plus observation periods before the next cohort can start. If one of these patients has a DLT another 3 new patients are enrolled automatically. If 2 patients have DLT's at that same dose then a maximum tolerated dose is confirmed. This never happened over 7 cohorts and no MTD was declared. This in itself shows how hugely improved the safety profile is. Also remember C7 was dosing approx 3.5 times the standard dox dose given today that would likely kill you if given in one go.

We were told last year a patient from an early cohort had heart failure. This was also confirmed unrelated to AVA6000 as they had heart issues previously. However technically that patient had a DLT whilst on trial so you can't not record that hence the reference. They also stated several times last year as the cohorts progress that the usual symptoms of cardiotoxicity had not been observed a massive positive.

The abstract wording 'Two DLTs were observed of grade 2 cardiac failure (120 mg/m2; LVEF decrease 61 to 39%) and grade 4 neutropenia/ thrombocytopenia (200 mg/m2).' This could be related to the same patient but describing two different DLT symptoms but we don't yet know. However we do know no MTD was found over 7 cohorts at massive doses.

Ignore the FUD experts as based on what we already know if you had a choice between Dox and AVA6000 you would never choose Dox unless you can't grasp the facts they have already presented. Then consider the RP2D chosen may not be from the higher dose cohorts anyway where you would expect to see the worse side effects. Looking forward to first line patient data which will provide a better view on all this in time.

Strangy83 you have been moaning about questions for several days now. Why don't you consider this

1. Anyone can email management if they choose

2. If you don't ask you don't get

3. What is wrong with any group of shareholders on on here, on TG or anywhere else for that matter debating questions to ask management today, tomorrow or whenever?

4. The TG group was formed to get away from the petty bickering and childish behaviour offered by some on LSE to have a more informed discussion. There are some great posters on here with a lot of knowledge but it gets ruined by the nonsense.

5. The Turner Pope platform clearly invites you to submit questions when you register so take advantage of that.

Do you actually have any sensible questions to ask next week? I haven't seen one from you yet.

Oldtrader I think it is a buy its above the VWAP and someone else saying this printed above the live bid/offer price at the time. Big ticket!

Bella you are adding to the confusion here although not intentional. We are going round the houses on this now.

We ned to differentiate patient and cohorts.

The sequential 'patient' element from Q3W is no longer a requirement for Q2W so they can dose patients in a single cohort in parallel/ all on the same day if recruitment allows therefore this saves a lot of overall duration time vs Q3W approach.

However from a cohort perspective they won't start the next one until the SDMC reviews 3 patients who have had 2 doses and deemed it safe. I have not seen anything to suggest otherwise on this point.

The outcome here is the Q2W cohorts are sequential in nature as it is a dose escalation study. The nuance here is eventually we have multiple Q2W cohorts running at the same time due to patients having more than the minimum 2 cycles therefore that becomes cohorts in parallel.

The fact we are debating this means the comms have not been explicit on these key points. We cannot afford ambiguity going forward and a short video update post an RNS will help.

BV - That is likely now but dependent on recruitment which on the positive side of things should be aided by more sites.

Once they have the 3rd patient for each cohort dosed once it only takes a month to complete the mandatory aspects to tick the cohort box. A little slippage fair enough. I would much rather the prep work for the expansions are expedited where possible in the meantime now we know that is the plan. Obviously RP2D is an outcome of Q2W that is needed. It's also possible they see DLTs at C3 or C4 dose over two weekly. We can't rule that out entirely given its a 50% increase in cumulative dose over a 12 week period.

At least Q2W C1 is rolling now. April the 17th is the week after AACR and the 3rd patient will have completed their 2 week observation period on the second dose. Not far away.

BV he refers to patients in parallel not cohorts in his reply to you. That’s my concern. Just ask him to clarify.

BV - where have you got the suggestion Q2W cohorts could be started at the same time? (your text below) A minimum requirement is 3 patients having 2 doses then a 2week observation period and SDMC review before another cohort can start. They can dose all 3 patients in a single cohort on the same dose on one day one if recruitment allows but they can't start multiple cohorts at the same time in Q2W. I don't believe they have committed to that either.

'All the cohorts could be started at the same time or staggered - staggering by 2 weeks for example (IF there was a fixed stagger period) would allow assessment of the first cycle of the lower dose after two weeks before starting the first cycle of the higher dose and the timescale for Q2W for that (fixed 2 week stagger) would be 10 weeks plus time for the SDMC to review the 4th cohort.'

BV thanks for sharing.

Having patients for a single cohort dose across the UK and US is fine . However nothing in the reply or the RNS suggests he can start a higher dose cohort until the previous one has finished and SDMC has reviewed.

So they can dose patients in the same dose cohort in parallel (a change from Q3W) but they can't dose higher until 3 patients have had 2 doses in a cohort and SDMC have reviewed. They get 50% more 6k than the Q3W over a 12 week period and this is still a dose escalation study. If patients then go on to have more cycles as we expect does it mean you have multiple cohorts running at the same time. That is my take.

Great start to the morning....'TheValueCurve' troll consigned to the bin 22 negative posts!

ATBD I disagree they knew where the placing was going to be some while ago. They could and should have done an open offer at £1 to start with and you might have got half the funds no problem. You fail to mention the short attacks, the leaks the broker smashing the bid that all played a role in the end price. The Price moved lower 24hrs to go to get more money from an II and therefore the 50p wasn't premeditated by the company more a consequence of what had happened before and an II saying £X at 50p if you want it. If it were me I wouldn't have signed off 50p to anyone unless it was Musk or Bezos coming onboard. I'm not sure many funds have a lure bigger than those two guys. Anyway it is done now, not happy but we move on and hopefully in the fullness of time we understand the rationale. We can all be arm chair experts from the outside right.

Hurst how so? What events need to occur in your opinion?

General Oz, JW Bellamy - filtered

Icecool what is your rationale to say Q2W is a waste of time out of interest?

I see this differently and that Q2W was the compromise with the FDA to avoid a lengthy P1B. We have saved a lot of cash by not having to do that which is a bonus. On top of that Q2W lets the FDA see first line patient data across multiple indications. It's possible the heavily pre-treated patients in P1A some might have been resistant to Dox as a result of previous treatments. Therefore if you strip out some of those patients Q2W lets them get more reliable efficacy data but also on a first line setting. That then makes the decision much easier how to proceed. The fact the Dox control arm was removed is a huge positive but again something that's been glossed over. The FDA must have sanctioned it. Lastly other trials have dosed Dox fortnightly I believe so perhaps that standard is another reason why they are doing this Q2W. J?ust my thoughts.

AS said he would update us mid year on the FDA engagement. I thought that was odd to make that commitment but there must be a reason. Already 6k is much better than Dox on S&T alone. The risk is now low imo.

Icecool if people are excited to learn more about C7 data they should also pay attention to the lower half of slide 11 from the Dec presentation and look closely.

During the fortnightly dosing patients will receive 50% more cumulative dose of AVA6000 in Q2W vs Q3W. Even at the lowest 160mg/m2 dose that equates to more than double the life time allowance ( I haven't deducted the substate element here so I'm approximating to make the general point) of Dox. If they dose 4 cohorts the top end is a whopping 1860 cumulative dose! Next level stuff.

Energy with circa £18m in the bank they are not running out of money! Everyone needs to ignore the trolls. They arrive as fast as they disappear but should not determine your investment decisions. Imagine taking the lead from a complete stranger hiding behind a false name on a BB. Madness isn't it. Shorts close and this goes back up quickly. Why? there isn't anything wrong with the business.

Timster you have posted here over 180 times in the last 30 days but most of the posts add zero value. Please can you only post relevant content here. This board loses credibility every time people post nonsense. Thanks

@BV I think for the clinical leads in these hospitals AVA6000 is an easy sell due to the lack of side effects alone vs Dox. When you also consider that as there is no placebo, straight Dox arm or randomised trial aspects they can talk openly about AVA6000 at such an early stage. This shouldn't be over looked imo as it is massively positive and patients although might get a choice the steer from your Dr goes a long way as you need confidence in them they know what they are doing.

When we consider the scope of fortnightly the patient population should increase not decrease. They can now choose patients from more indications in the first line setting not less. High levels of FAP are a requirement for this trial and P2 as it is expected to yield better results so best to screen low FAP patients out.

Obviously there is competition for trials but I hope to see we open up new sites in the coming months to support P2. At a minimum we need 9-12 patients for fortnightly only.

Lastly what does give me confidence that the patient recruitment isn't going as badly as people make out is this. They plan to backfill cohorts where possible to capture more data. So although they only need 3 patients per cohort to have 2 doses they will add more patients as and when recruitment allows. You don't do this if you struggle to get patients in the first place and going back to my first point do you want the standard version with horrendous side effects or the Prodrug version with little to no side effects.

I think the comms have missed a trick in recent months to spell out the significance of backfilling cohorts , allowing first line patients in C7 and now in fortnightly, along with multiple indications and the ability to dose multiple patients one day 1 . This should have been explained further in Dec perhaps this was deliberate. Time will tell. Key is in the detail.

AS said he doesn't intend to come back to the city to do a placing with PIs (because the last ones were leaked) and as I took part in previous ones I'm pleased to report the broker hasn't called. They have plenty of cash in the bank. More likely we see a commercial deal in the near term. Ignore the noise.

JWBELLAMY - with your over 300 posts on HE1 in the last 30 days I hope you don't inflict that sort of misery on here.

People overlook the fact that most of the previous interviews are done by people who actually know little about AVCT and what they are doing. This is obvious when you listen to the interviews. This limits the questions asked, the accuracy of the points made and the missed opportunity to ask more targeted questions. I suggest we wait for the output to make a more informed view but I think Myles will cover many points that have often been overlooked or even avoided.

Consillium might have been an option to host but frankly shareholders wouldn't know they even exist if there hadn't been an RNS saying they had been signed many months ago as it's unclear what they have been doing. Therefore why risk a party that potentially lacks the scientific or financial knowledge to host an interview and just cover the basic convenient questions which don't take us any further forward. I wasn't impressed with Gervais W a fund manger comments on Vox recently as he muddled the topics multiple times and got things wrong. Rather have an SME whoever that is put the questions to AS and use the time wisely. Judge the output not dismiss the opportunity is my suggestion.