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Just a reminder for those who don't engage their brains...

DE5 (dose escalation 5) would be C6 (cohort 6)

We are currently on DE4, cohort 5

Similarly, DE7 would be cohort 8. That would be a further three dose escalations or cohorts to what might be 400mg/m² (270mg/m² straight doxorubicin)!

I think that patentwise and clinically, AVA6000 is a slam dunk. Just a matter of going through the necessary hoops to regulatory approval, first for STS and then, with appropriate trials, for other indications as sole therapy or in combination IF shown to be better in some way (efficacy, side-effects, cost) than the current standards of care.

But the thread title is about pre|CISION.

AVA3996 needs to be proven safe, tolerated and efficacious. Patentwise, coverage is fine but I don't know about remaining patent life for this new chemical entity which will spend a long time in clinical trials. Clinically, it is looking as promising as it can be from the early preclinical studies.

For the rest of the pre|CISION pipeline, I don't know the situation for patent coverage, patent life or clinical prospects. If there is long patent coverage for straight prodrugs (like AVA6000, not analogues like AVA3996 is) then the prospects there should be similar to AVA6000, dependent on what the leaving group is and how inert it is alone and in the prodrug substrate.

My only other concerns are, firstly, competitors able to find holes in the patent coverage that would enable a nimble company to patent, develop and market similars ahead of AVA3996 and other follow-on pre|CISION prodrugs. AVA6000, as a prodoxorubicin, I don't think can be caught at this stage.

And my other concern is Avacta's ability to conclude licence deals for AVA6000 (non-STS indications, bulk manufacturing of AVA6000, pharmaceutical production, marketing and sales & distribution) and the rest of the pre|CISION platform. I don't thnk Avacta's history has been good at licensing out (licensing in has been brilliant!) but with new people onboard in new licensng and contracting roles that will hopefully not be a problem going forward. Avacta does, I feel, need to be nimble here though as patent life does run out quickly! An academic can take time exploring new fields and getting everything just right but a commercial outfit needs to maximise its ability to get the revenue flowing in.

"Within a year or two, we will be banning lab-grown meat – and, just like Italy, dooming ourselves to a generation or more of relentless economic decline"

Who said that, who's "we" and citation please.

Needs a human interest angle: a person cured; a person with a better quality of life as in prolonged and without side effects. That sort of thing.

Everything pre-clinical can be made in a 'test tube' and formulated in the lab.

For clinical trials, the raw ingredient needs to be of a certain purity and formulated in a GMP facility.

For marketted products, the raw material needs to be produced in bulk to an authorised purity (BP or British Pharmacopoeia) in the UK and formulated in a GMP facility.

The bulk manufacturing will use a different process, designed by chemical engineers rather than lab chemists.

Planning, and contracts, for these need to be set in place well before they are needed.

The bulk process designed by chemical engineers is an opportunity to gain further patent protection.

I'm pretty sure from what AS said in the Paul Hill interview that Avacta will be licensing AVA6000 out to various pharma companies as exclusive licences for particular cancers and that those companies will foot the bill for the necessary clinical trials. This in addition to the licencing out of the pre|CISION pipeline, and possible licensing out of AVA6000 production, marketing and distribution for STS in the various geographic regions. All assuming no takeover in the meantime of course.

Re 3-week vs shorter cycle times, in the Paul Hill interview AS mentioned "different dosing levels, possibly different dosing cycles as well. Not determined yet" in design for Phase 1b and Phase 2.

https://www.voxmarkets.co.uk/articles/q-a-with-avacta-s-ceo-alastair-smith-e87d9e8/
@ 7:00

I'm not sure they'd be able to dose, say 100mg/m² every week (so 'equivalent' to 300 every 3 weeks), without testing at that dosing regime in Phase 1a. That would speed up Phase 1a by up to 2 weeks per cohort were they to use that strategy.

The updated Phase 1a protocol approved by MHRA has not been published yet. Neither has there been mention of any FDA approval if the US sites are to be involved in Phase 1a (with any high-FAP cancer - MSK is not limited to STS!).

Personally, I'm struggling to see how 2 cohorts (without delays) could be managed in the 86 days to 30 June using 3-week cycles except by only giving each patient one or two cycles. With weekly cycles it becomes clearer and maybe the strategy for the two AVA6000 dosing regimens might be as I previously suggested:

- 'low' dose of say 150mg/m² every 3 weeks
- 'high' dose of say 100mg/m² every week (i.e. total dose twice the 'low' dose given)

I think 'fine-tuning' the highest dose levels to the effect on the tumour with weekly cycles would be a more rational and safer method than hitting the patient's tumour every 3 weeks with massive doses of AVA6000 and the increased likelihood of side effects that that would cause. It should be remembered that there are two categories of side effects: transient such as nausea, fatigue, constipation, etc; and cummulative such as cardiotoxicity. It may not be pleasant to have nausea every week (or continually) for 18 weeks but... well probably better than any of the alternatives.

Long and unreviewed so I hope this ramble makes sense.

INT230-6 is an injected drug

https://intensitytherapeutics.com/technology/mechanism-of-action/

I wouldn't regard this as a threat to pre|CISION.

https://bit.ly/3ZmrUbd

Nice deal by Bicycle Therapeutics with Novartis for development of their small peptide scaffolds in oncology. This follows a multiyear partnership agreement with Astrazeneca.

Why can't Avacta sign any lucrative deals with pharma majors for the development of Affimers?

I agree that the route to approval is very clear and vastly derisked but it is not a formality yet because the dose level and cycle frequency still need to be determined for optimal cytotoxic effect on DIFFERENT cancer types - aggressive, slow growing, intermediate and plain incurable by doxorubicin alone.

It is clear to me that Phase 1b is planned to be low dose AVA6000 (say 150mg/m²), suitable for slow growing or persistent, incurable tumours, and high dose (MTD or BED, say 300mg/m²), suitable for aggressive tumours, versus standard 75mg/m² doxorubicin.

I would expect that data on the efficacy of these two AVA6000 3-week cycle regimens in comparison with the doxorubicin standard of care to become clear by 2 months (7-8 weeks of dosing) and if, as we hope and believe, AVA6000 is showing superior efficacy by then, then submission of a product licence under Accelerated Approval would start to be prepared.

Phase 2 I see as being weekly cyles of a ? doses, so 50mg/m² and 100mg/m², versus weekly 25mg/m² or 20mg/m² doxorubicin. Those, as product licence variations, would give much greater dosing flexibility and options in the clinic for pure doxorubicin (non-combination) chemo.

Thereafter the trials would apply what is known about dose acceptance to other cancers, with breast and ovarian being the first ones (maybe one trial for both indications). Plus trials of combination therapies but by that time the income from approved treatments would cover the costs of trials.

The big questions I have are: who will be the manufacturing, marketing and distribution partners; and which geographic markets will they have exclusive rights to.

The original plan was for 80 patients in Phase 1 in the UK and US. There have been 19 so far in Phase 1a (min 12 expected). Another two cohorts, minimum 6 patients. Possibly more expensive to use more centres and the total for Phase 1 will go over the originally planned 80 so more expensive than first budgetted fore, which was before last October's fund raise. FDA grants in support of the ODD for STS may still be forthcoming - part of the imminent newsflow and improved comms? - in which case funding should not be a problem.

You should get a job there Klunk. I'm sure you could knock something for a multimillion dollar market up in an afternoon. Your talent is wasted here.

From yesterday's RNS
"The US trial sites will initially contribute patients to the dose escalation phase, while being uniquely positioned to lead the enrolment of soft tissue sarcoma patients in the phase 1b dose expansion stage of the AVA6000 study when this begins. Patients will receive the same doses at each stage of the trial as in the UK."

We also saw that the MSK site is listing all the Phase 1a cancer types for enrollment.

It has been made clear that Phase 1a is purely about safety and tolerability and NOT about efficacy. Patients enrolled in Phase 1a are at the end of their lives and will have had all the standard of care levels appropriate for their cancer. They are also preferred to be anthracycline naïve, hence STS is NOT a cancer type of choice for Phase 1a as doxorubicin is standard of care for that cancer type.

Whilst I appreciate the OP's enthusiasm and intent, I find it rather depressing that the post has received so many recs when it is riddled with inaccuracies.

DYOR people. Don't take ANYTHING written on this board as gospel truth. Use original sources.

The fruit loop's back. Who did the Gates chant?

And yet again this board is ahead of the market thanks to our supersleuths. Well done ES!

Quack Quack Quack Mooo Quack Baaa Quack

Maybe still a bit of work required.

Bill Gates slipped the word out you numpty. Didn't you get the email?

Just put your tinfoil helmet on and go back to your cupboard under the stairs.

Governments are going to block AVA6000 because Bill Gates runs the WHO?

NURSE!!!!!!!!!!

No not you nursesteve, you can stand down. We need the nurses that have the white jacket with the long straps.

Cuckoo! Cuckoo!