Member Info for RorkesDrift

How I long for a leek....

Add my tuppence worth. I like the thought ava6000 is a pro drug. P1a is about the pk not efficacy. Phase III is efficacy but as Rory has suggested we already know the efficacy of dox.

There must a regulatory route that negotiates the spectrum between generic, modified generic, prodrugs and NCEs.

Big P are probably more adept at this than Avacta.

My thoughts are we progress to P2 rather than P1b (not even sure what that is) and build a case for approval on basis of efficacy of dox is known. I'm an optimist

BP sees this opportunity and offers £200 ex-China shortly after full P1a data published

To be honest I haven't seen any posts that claim once cleaved from ava6000 dox is anything but dox. There are lots of posts decrying FUD of this nature but no actual posts. Apologies if I've missed them.

Where do you sign up for the next trial. Just asking. For a friend..

I take a slightly different view in that there is two types of analysts working in IIs. There are those that run the financial numbers and then there are the specific area specialists. There will be more than one oncology expert working in financial houses, jet setting to lots of lovely places and advisory boards are fairly easy things to put together. These people probably have a different and possibly better informed view of all the opportunities than most PIs. The caveats they place when telling the numbers guys is that the data is not yet availsble - equates to risk in a high risk area. No one loses their job by advising wait until data there even if it means entry is higher.

The good news is that this could mean large sums sitting on the side line waiting for definitive news.

I continue to hold with top up on stand by

The forecast of 4 cycles to find MDT must have been based on animal data.

MDT is correlated with systemic dox

The need to extend the number of cycles may be because systemic dox is lower. Several mechanisms for that - some good, some bad.

I wonder what the dox levels were in animal models in tumours. We have release of dox from ava6000 and increased doses should increase tme levels (otherwise stop now).

My take. Ava6000 behaves differently in humans than mice. Trial continues until max dox in tumour vs systemic exposure is identified. Not there after 4 cycles but 7 will be enough given that f/c based on human data

Let's say ava6000 is going to be used to ensure pfs to match the use of normal dox.

We can be conservative and say every month rather 3 weeks so 12 cycles per year. This doubles pfs.

At $10,000 per cycle (a AS discount). That's $120k per patient per year.

US 13,000 patients

That's $1.5B. For one indication, in one country.

Needs a QALY approach to pricing rather than £/mg compared to dox

Olaratumab is supplied as a sterile, preservative-free, clear to slightly opalescent, and colorless to slightly yellow solution.9 It is available in 19-mL and 50-mL vials containing 10 mg/1 mL with average wholesale prices of $1,098 and $2,889, respectively.

The FDA-approved dosing for STS patients is 15 mg/kg of IV olaratumab on days 1 and 8 every three weeks,

A70kg person would need 70x15= 1050mg

So 2large x $2889 (+ a bit) twice per cycle. So minimum about $12000 per cycle.

Now compare ava6000 with Ola - even the promise before withdrawal.

If ava6000 can deliver what ola promised then its $12,000 per cycle. Why would you price it any lower except in China

Not sure the pricing will be modelled on like for like per mg of normal dox. Pharma companies don't work like that and neither do regulators. This will not be sold as an improved generic - it might replace dox but that is true of other non dox based drugs.

In effect the price will be based how much is an extra year of quality life worth. The benchmark is all the other drugs out there especially oncology.

Then there is the treatable population expansion argument which multiplies this. So yes, ava6000 sales value once commercialised will be many times that of generic dox. It will replace dox overnight apparently meaning product cycle is longer than normal - however need to get a move on

We might get answers to the questions submitted at the agm. I submitted a couple including cod or haddock

I've heard RAH and Tom are organising a supporters bus complete with songbook and pom poms.

The rumble with Touch light has been cancelled, honestly 😏

HCG?

Given the stated position that affirmers are quicker to develop than MABs then then this approach could match the problem of antigenic drift. Added to this the ability to link different affirmers gives an opportunity to attack different epitopes (ala polyclonal)

MABs have been discussed for a long time and covid saw lots of people jump on the band wagon. Synergis has been sold for RSV prophylaxis. Sort of thing BP might jump in given potential market size.

However, immediate opportunity is diagnostics. Wonder if this was what was pulled from agm.

Wow. Great find. I'm thinking this might be a hidden gem....

Furthermore, an Affimer-Enzyme-Inhibitor Switch Sensor has been developed (47) that would allow multiplexed detection of respiratory viruses when IAV specific

Affimers are combined with Affimers against other respiratory viruses (e.g. SARSCoV-2, human respiratory syncytial virus or influenza virus B).

Sounds like new diagnostic.

Oh hang on.....

The magic calculator in full effect. I'm not sure why he does it - I suspect there are not enough real facts to enable the usual suspects to post 20 odd times a day so have to make it up. I'm at a loss as to what it achieves but the self help circle might explain it. Other groups demonstrate similar activity

https://www.scientificamerican.com/article/bonobo-sex-and-society-2006-06/

Why would cells hit by dox released by ava6000 be more or less likely to develop resistance?

In the meantime I'm thinking that a) the SP doesn't respond to the volumes bought or sold because of comments on a bulletin board or Tw4tter. Big moves will be in response to real data.

C2 if you invest in other pharma let ud know. Liquid biopsy seems to be choice place for money to be made or lost - competitive and fragmented and ive avoided due to lack of my own knowledge and blatant ramping by the BMV crowd. Suspect McPumpy will find one soon.

We can systemic levels of dox with ava6000 are very low. Reasonable assumption is this correlates with low adverse events.

The data on biopsy values shows dox getting into tumour. The ratio between tumour and systemic suggests its the mechanisms is working.

AS is claiming it hits therapeutic levels but at same time says no-one knows what therapeutic levels in tumours are cause no-one has ever measured it. The therapeutic level I think is based on in vitro data where dynamics would be different.

That said

1. Biopsy were at 1 day. Levels should be higher up to that point

2. Avacta has continued to increase doses which suggests they believe more dox into tumours is likely. More dox, more efficacy - PLs point below.

3. The units between the paper and avacta numbers are different

4. Systemic dox is not necessarily available - significant protein binding

I have no idea what these numbers mean - avacta have put some of the data out there but not the important stuff. I'm hoping for right reasons but wouldn't bet the house on it. Continue to hold with top up cash waiting

We need more alcohol and thank you for your work - my other half works there too

I think this board needs more C2H5OH.

Perfect 😁

I cannot work out if normal dox is higher or lower than levels in tumour for ava6000.

Still room to increase dose but if 100% conversion wouldn't levels be massively different at C4 (and C1)

Assumption. For normal dox the concentration in the blood is the same as in the tumour at 24 hours.

This paper has normal dox pk in STS patients dosed at 75mg/m2.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6997100/

After one day Cmax was 2570ng/ml

This compares to 1317ng/g at similar time point in patient with highest biopsy level. concentration.