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Https://x.com/mbdaytrading/status/2046561662086324661?s=46

That’s been discussed on X and the consensus (which I now agree with) is they’ll present the updated trial design with new indications. If memory serves in 3 weekly scans were every 8 weeks so it’ll be interesting if that’s the same and for both arms.

Yep fair point but given they'll have biomarker data from a few patients as at the time of the RNS I bet all is working as planned which is why they're adding indications to the expansion trial.

Https://x.com/tom_the_bomb__/status/2046472139058888913?s=46

Love this. They’re saying it’s behaving as they hoped in clinic. Boom.

Ald, that’s the beauty. Keep tumour at bay and get treated with very few side effects so quality of life and whoever is providing fari-dox doing very well

The didn’t find the MTD but could’ve continued dosing and no doubt would have. Not because of specificity but because of the half-life it’s cleaved very quickly and the TME can’t hold all that dox so it leaks out.

Smith said wouldn’t it be great if we didn’t find one, we didn’t as we moved on without needing to. There were too many AEs at 385 so no need to go higher given how much dox is getting into tumour below.

6103 could be unbelievable, clearing plasma in a handful of hours and then sustained release in TME over 5 days. Wow. With BOIN surely from dose 2 will see some efficacy and changing lives in a safety trial. Here’s hoping.

I think there was leakage in the very highest dose 385 (?) as too much was cleaved (very quickly) so leakage whereas lower doses the drug was able to remain in the TME. They’ve taken away the cumulative max I assume on the understanding it won’t be given at 385 which wasn’t taken forward in expansion.

I wouldn’t be surprised to have one end of the year once we’ve dosed multiple patients, lots of data, a decent number of biopsies and many scans. 6103 worked superbly on refractory tumours in animal models, if we get similar results (more likely after the first dosing level) I suspect there will be a bidding war.

The CEO was a sales guy who no doubt was given more money and little expected given MIRI's history so a win-win. No reputational damage done. My understanding is the sales guy hadn't been a director before so good for him. People were saying why would these big brands work with MIRI if it was about to fail but brands give minnows money all the time and sometimes they fail, so what. We'll know soon if this has finally died a death but I expect one more pump so large holders can try and offload some.

Https://x.com/blueberrymgmnt/status/2043611925490065568?s=46

these questions are bizarre. one could say mirriad’s pumping on linkedin and elsewhere gave an impression all was well so mush bought. when they don’t pump people also moan. that’s **** all to pump ffs. they were pumping massively all the way from 60p to 3p and even at 1p. industry know them so you jokers asking for promotion is odd as i doubt you’d see any meaningful trade stuff they’d do and spending money on ir a waste as they need instis to fund and that will require solid, material (rnss) news which ain’t happening as there’s no proper business or rather one worth investing in.

No you tool, RNSs cost money and updating every couple of weeks pointless and immaterial.

Worth remembering unlike dox many tumours will be sensitive to exatecan and in the 6103 preclinical mouse models they used tumours that were refractory. Even if the tumour to plasma ratio doesn't improve like 6000 did in clinic after dose 1 (likely very low) we will surely see early signs of efficacy and once the dosing increases who knows so if all goes well there may not be an Avacta come 2027. That's my hope, decision taken out our hands as we get an early, chunky TO.

Https://x.com/emily1katie/status/2042174449097556219?s=46

With #AVCT on the cusp this morning, I recall this from the CEO, kindly transcribed by Sandy:

"As we know, the learnings from AVA6000 have informed a number of key decisions with AVA6103, particularly around tumour-plasma exposure. That doesn't totally eliminate FIP risk, but it does reduce translational risk relative to where 6000 started and helps de-risk the programme going forward.

With AVA6000, tumour:plasma ratios in animals were only ~4-15x, yet in patients this translated to a median of ~100x - materially better than preclinical data suggested. What's notable is that AVA6103 is already showing ~99x tumour:plasma in animals. If the same direction of translation holds, we are starting from a considerably stronger position than we were going into the AVA6000 FIP."

Yes Adverse events can take time but they’ll know if the sustained release in tme works and if cleared within 4 hours if plasma (which will give a good idea re AEs). The recent RNSs suggest early data as hoped

Again with no RNS saying otherwise and now with the below surely 6103 working as designed and who knows we may know this for more than 1 patient -

The sustained release mechanism allows the modulation of the kinetics of payload release, and also opens up the platform to many therapeutic modalities over the Gen One approach.

Https://x.com/asininitybeyond/status/2041871398897856587?s=46

If the IP was any good it'd have been acquired and the fact they said they will simply drop signage into scenes post production which anyone can do and they do this manually told me it's going under.

Ha, MMs doing retail a favour, wonders never cease!

The 66% spread says it all.