Member Info for RorkesDrift

Since SD have been looking at tumour concentrations of dox for different mechanisms. Still some way to go for max killing effect. Alongside that the increased tolerability means they know dose size can be increased but so can frequency. If confident for completion of P1 by summer to inform P1b then I'm guessing they will do both. Not sure whats in data that suggests one more fairly small adjustments gets us anywhere near MTD - indeed proper SD experts suggested as much

T

Given the volumes why do you think it is not an II selling ?

Relax - several potential good news RNS possible due to multiple projects. Licensing deal will change everything.

Likewise PAH.

Problem with making extreme all encompassing claims especially before data is presented is it undermines confidence not builds it.

AE are a major drawback for chemo. Making treatment more tolerable will be a huge step forward especially when AE stop treatment and therefore efficacy. We know dox is appearing in blood stream and it also appears that this is correlated to initial dose of Ava6000. Company have confidence to suggest that the significant reduction holds promise of many more doses. How many will be a balance between dox in tumour and dox in blood - whilst we haven't had that data yet company seem to be suggesting 18 cycles and my assumption is tumour dox levels will be as high as conventional. Dangerous assumption but if so tumour will be hit by 3x as much dox as conventional. I suspect their modelling is they are 1 or 2 DE away from either this or saturating the FAP enzyme. Accept this is guess work. Strategy becomes hit tumour multiple times rather than huge doses - company have said as much previously. If huge doses were to be the aim I cannot see them completing this by summer

Several people guessing next DE may be achieved by existing dose but more frequently- every week rather than every three - can pull trt if AE - washout dox will be quick due to low circulating levels hence weekly or something similar

I'm going with the converted shares being sold. Once that's over we will get back to some stability. No evidence, just gut feel.

We know Avacta are hoping to licence at least one precision product. This will presumably be for a significant initial payment followed by others.

This payment will be cash increasing liquid asset value. Weirdly it will also increase the other asset values - IP of the tech. As soon as pK published think this deal will be inked. Mid summer is my guess but September holds a special place. Inflection point for SP that won't be visible in Elliot wave but has high chance of occurring- enough data for BP to take a punt.

Until then rampers ramp, derampers deramp but LTH relax.

McN valuation is different to Stiffel. Who to believe?

Both are probably wrong.

Personally love it when price goes up, hate it when goes down. Have held from 20p to £2.80ish and back up and down.

This investment is years in the making and could be years before it comes off - if it does.

SD was positive for me. However, lots of stuff not there. Timeliness and cash do not match - see costs of pharma R&D - ignore CoGs they have little influence on it. Quoting £800 for a cycle of dox !!!!!

My expectation is a licensing deal and staged mikestones payments. Might be me crossing fingers for less dilution. Sooner it happens the better.

Next key data is the pK of te leaving group. Suspect presentation already submitted. Could give us a marker for AuC of dox in tumour.

SP has fallen - that is a fact

Volume looks to have exceeded average by 4million shares. So somewhere between one large holder and hundreds of smaller ones have decided to swap Avacta shares for cash. Presumably they see a better return elsewhere.

Plenty of LTH on here (Inc Wyn) disagree with their analysis or have a different perspective to risk reward. Neither group are right but to ignore differences in opinion is probably verging on religious zealots.

To continually state the market is wrong based on an individuals understanding of numerous details they dont really understand is starting to tire.

The IIs literally pay £100ks to individuals who do understand terms such as proven, hypothesis and how to correctly value risk. Quoting your own calculation of risk discount cf. the market is as much FUD as is possible. The companies publishing their own valuations (£1.85) have done more analysis than any of the twitter attitudes and have more expertise than them.

I believe Avacta have the potential to be a huge company one day but equally there is a risk this falls over. P1 was about safety - the drug is not free of side effects but at current doses is an improvement. Ramping chemo without side effects is a lie.

P1 was about pK as well and limited mention of this at SD. I am hoping this is being saved for a different audience later this year.

SD was for investors - great idea but slides on financials and options were missing. Like trying to build a house without foundations.

I believe Avacta could come good in a spectacular way. Like most here I accept that there is a long way to go and hurdles to jump. Delude yourself but try and refrain from doing the same to others

Half life in mice has been published. Lower than dox from memory).

Half life can be linear depending on

1. Are you plotting on log paper
2. What are the saturation dynamics
3. Possibly what compartmental model are you using - memory being stretched.

4. Mainly are you using log paper in a single compartmental model

Drugs with longer half life's are may not need to be dosed as regularly but therapeutic window comes into play - note sometimes you want rapid on, rapid off for different reasons.

Science day - call it explanation day.

1. The science behind precision.
2. The clinical need
3. How precision meets that need
4. Potential financial
5. Roadmap for next 12 months inuding nod and a wink at options (licensing vs nasdaq)

Nothing new

Then rabbit out of hat with progress on other programs

I'm expecting a bit of a non event but plenty of room for error.

Hold for another six months then boom or bust

Great stuff. Learnt some things to although not completely sure of some of it. On a related note many antibody conjugates struggle to penetrate due to their size. One of the proposes advantages of affimers is they are considerably smaller. From there build FAP activates affiner linked molecules

Oh hang on...... (SCIENCE DAY)

Given chemotherapy is often combined with immunotherapy then penetration could be synergistic.

Mouse Pk is becoming more interesting as we try and fill gaps but let's not forget the picture of the tumour melting - that only happens with dox conversion.

Not sure if the debate sheds light. The simplest model needs to take into account

1. Half life of ava6000 - published for mice
2. Conversion rate to dox at tumour site- this varies with concentration of ava6000 in blood but will reach a maximum. Adjustments to posology can be made to optimise.
3. Rate of loss of dox from tumour - varies also. Note volume of tumour x high concentration will in theory only put up systemic dox slightly. Again look at mouse model

We don't have the numbers to know what's going on and that's what the trial is for. What we do know is that at a point in time ava6000 delivers a therapeutic dose to tumour. Clever people could time biopsy for a laG between Cmax of ava6000 and conversion to dox. This is a start and the fact that the safety committee have said continue is a good sign that the higher doses are likely to provide clinical benefit over and above that already achieved. What would be interesting is the pk of the leaving group especially AuC to give us idea of dox at tumour. Let's see but suspect this will be kept under wraps until trial finished.

I am expecting breadth rather than depth. We have several irons in the fire but they are all early stage and therefore carry a high degree of risk and potential return.

Precision is one of these so expect the same slides plus one on current data overview - nowt more than currently expresses. However, there will be additional slides on market size and potential.

The next wave of precision drugs and their financial.

Then an update and new timeline on affimer based drugs. Expect these to start emerging into spot light soon - more preclinical data.

Then more detail and dummies guide to the various partnership programs including progress.

I could go on but each of these projects enable a spread of risk.

Avacta need money to bring them to market so I expect the licencing issue to be tackled. A good upfront payment on first two Precision drugs with subsequent milestones sees this into the SP being discussed - more so than very early phase1 data.

Lol - the tw atterati are posting to mislead and either the congregation are in on it or lack the ability to think critically. Just look at the responses - no-one can be as genuinely as sycophantic as some of the replies to what is nonsense.

By the way most of the comments are multiple accounts including threepence the dog and spreadsheets the donkey.

In the meantime your analysis seems as valid as most and probably fits with most LTH here. No benefit misleading ourselves or others - indeed the discussion helps me think a bit harder - even wyn (on occasions)

Wow. Thanks for posting bolsters my faith. Especially "We have designed, characterized and optimized a number of prodrugs activated by FAP and will review how well these are working and how they might be improved still further"

Given the disease area and the number of trials I'm not sure if it is appropriate to recruit to a waiting list of the duration suggested. I believe that once next cohort Green lighted you get on with it. Given last RNS then perhaps dose already decided and the information provided satisfies requirements. Think Fiona Mc has brought better discipline to forecasted dates so summer 23 will be next pivotal date unless licensing announced before then. Likely news on other programs also incoming for science day

Over on BMN he told them he'd been a miner in South Africa. Quite funny if it wasn't for the fact that some people believe it but I think he trades on the spike.

Seems quite a lot of pharma people on here who pull him up on some of it - hence move to channels where it is possible to block when its pointed out he is not the ex-spurt he makes out.

Be careful though - might end up on one of his fatwas

Philosophical question. What if he was to exit stage left in his normal widow tw anky inpression from the Telegram group. Would we have to auction it off like one of those storage units. Pay up only to find a timeline of indeterminent accuracy, some McD serviets with September scrawled all over them like a manic has been let loose with a crayon and a 1976 medical textbook that hasn't been returned to the polytechnics library.

I'm thinking spreadsheets and threepence has had another trip to the reliable source serving big mac and fries. Happy days although bit late for panto season.

Love the combination of pumping made up stuff on a board that knows better whilst at the same time putting own scientific knowledge on a self made pedestal.

The investment case for Avacta is sound and I'm still holding. Not risk free but the plan to increase dose above that required to achieve threshold therapeutic concentrations at the tumour with improved tolerability is very exciting. No need to make up anything whilst that is in the bag. Lots of questions and unknowns but thats pharma and biotech. Certain amount of faith and acceptance of risk required.

Thinking the old Bmn crowd up to past tricks. Ignore.

I'm guessing it says tumour concentration is 20x normal dox at only twice the administered dose. Not sure how that is calculated and on current data impossible to prove or disprove.

What this bb knows is based on AS stating excellent tolerability and dox at least therapeutic levels in tumour. Additionally safety committee has said raise the dose - presumably they believe additional benefits to be had. Difficult to see how that matches tumour concentration at 20x normal dox or the 6x ava6000 admin = 18x normal dox at tumour in mouses.

:-)

Yep - think they are having a long think about posology to find optimum approach. The next dose increase is going to be interesting.

I'm happy with low AEs and therapeutic tumour levels at what is a "low" dose compared to potential. The window for dox may just have been rewritten.

Sorry JT posts crossed. I'm fairly sure the aim will be to avoid cardiotoxicity rather than small marginal gain (if any) in efficacy. The dose effect curve for these two factors will mean a low increase in efficacy for a "high" increase in toxicity - gain not worth it. Particularly true when consider combination therapy.