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ES, I only know that the pure drug needs to be formulated as tablet, gel, solution, etc in a GMP-approved facility. Big companies have their own facilities, small companies need to contract the manufacturing out, as Avacta has been doing.

Distribution I know less about, having only seen the loaded lorries leave our site. Warehousing and logistics would need to be contracted out by Avacta, for sure.

I also don't know what requirements the FDA has for manufacture and distribution beyond keeping the finished product in good condition, typically below the temperature defined during stability testing and within the expiry date.

Re: https://x.com/neutronicLSE/status/1900525129219613175/photo/1

Specifically: "The strong tumour response to FAP-DOX has resulted in Avacta [being] successful in getting health authorities to agree to increasing the maximum allowable cumulative dose of FAP-Dox to the equivalent of 550mg/m² of conventional doxorubicin; an increase on the 450mg/m² that is the standard of care. A higher maximum cumulative dose enables patients to be treated with FAP-Dox for longer, potentially out to eight months, doubling the treatment time compared to standard doxorubicin."

Applying simple, rounded maths to this, the standard of care with doxorubicin is six 3-weekly doses of 75mg/m² (450mg/m² over 18 weeks). If the time period is doubled to 36 weeks, being twelve 3-weekly doses, to reach the maximum of 550mg/m², then the amount of doxorubicin in the plasma per AVA6000 dose would be 45.8333mg/m² (550/12) and the amount of AVA6000 containing that would be 67.9mg/m² (45.8333*80/54).

67.9mg/m² represents 27% of the 3-weekly 250mg/m² dose, 22% of the 310mg/m² dose and 17.5% of the 385mg/m² dose. We don't know which of these dose levels they were using, do we?

Whichever dose level Avacta is using, the authorities have agreed to the higher 550mg/m² maximum cumulative dose.

The broker note continues: "Management believes that the maximum cumulative dose of FAP-Dox could be increased further based on the PK data. Discussions are ongoing with regulatory agencies to liberalise the dosing of FAP-Dox (AVA6000) further." Meaning that the trial has shown that the amount of doxorubicin in the plasma is less than 45.8333mg/m² per dose for twelve dosings.

...and of course I appreciate you making it widely available.

Thanks Thompi. I thought it might be a paid service.

My concern was whether it is ethical to provide such potentially market-sensitive information on a subscription service rather than to the whole market.

No, it's just 'doing coffee'

How can one access PL's broker note?

Just remember: you can't educate a troll.

It's all a white water ride with Avacta.

I just pull you out of the bin to have a laugh.

Good point. I forgot about that in my comments about that PL interview. Tbh, I didn't understand wtf she was on about.

Receieved and actioned.

Memo to self: put Pharma3 back in the bin.

Correctly formatted Google links:

Fibroblast activation protein in disease: https://www.google.com/search?q=%27fibroblast+activation+protein%27+in+disease

Pathway inhibitors in...

- Cancer: https://www.google.com/search?q=%27pathway+inhibitors%27+in+cancer

- Fibrosis: https://www.google.com/search?q=%27pathway+inhibitors%27+in+fibrosis

- Wound healing: https://www.google.com/search?q=%27pathway+inhibitors%27+in+wound+healing

- Inflammation: https://www.google.com/search?q=%27pathway+inhibitors%27+in+inflammation

- Arthritis: https://www.google.com/search?q=%27pathway+inhibitors%27+in+arthritis

- Atherosclerosis: https://www.google.com/search?q=%27pathway+inhibitors%27+in+atherosclerosis

Pathway inhibitor...

- Side-effects: https://www.google.com/search?q=%27pathway+inhibitor%27+side-effects

- Toxicity: https://www.google.com/search?q=%27pathway+inhibitor%27+toxicity

Something in the Panmure Liberum interview that has so far gone unnoticed was a little mention CC slipped in @ 15:10, transcript below:

Interviewer: The pre|CISION technology has clearly got very broad application. Can you expand on the other potential uses it has?

CC: So, one of the next medicines that we're looking to make is a targeted therapy, so it's not just chemotherapy. I know the first two have been sort of traditional chemotherapies but pathway inhibitors for example have been very effective in a number of diseases but they also can carry some very high toxicities and so therapeutic index with pathway inhibitors is also a problem. We hope to see one of those coming soon to the clinic. [CC then uses mouse and mobile to start talking about AVA7100]

https://fast.wistia.net/embed/iframe/jhkzsr4536

'Pathway inhibitors' is a ubiquitous term meaning inhibitors of biochemical/cellular pathways. Doxorubicin (topoisomerase II inhibitor) and exatecan (topoisomerase I inhibitor) are both pathway inhibitors, as is bortezomib (proteasome inhibitor). Bachovchin's team couldn't link bortezomib itself to the pre|CISION dipeptide because the chemistry didn't work, so they developed an analog, a chemically similar version, that they could link, which Avacta called AVA3996. With their new chemistry techniques Avacta can now probably make a bortezomib prodrug using pre|CISION should they so wish. The bortezomib patents in the US expired in 2022 and the drug is tumour agnostic so has very wide application.

It would be very ambitious for Avacta at this stage in their development to add another therapeutic area with all the inhouse expertise and scientific advisors that that would entail. Their strategy has been to take off-patent cytotoxins and target them to tumours so a pre|CISIONed bortezomib could be a definite possibility for a future oncology pipeline candidate.

However other companies could use pre|CISION with pathway inhibitors to treat indications in other therapeutic areas. Here are some links to Google searches about this that lead to a lot of information about what could be possible:

Fibroblast activation protein in disease: https://www.google.com/search?q=%27fibroblast+activation+protein%27+in+disease

Pathway inhibitors in...

- Cancer: https://www.google.com/search?q='pathway+inhibitors'+in+cancer

- Fibrosis: https://www.google.com/search?q='pathway+inhibitors'+in+fibrosis

- Wound healing: https://www.google.com/search?q='pathway+inhibitors'+in+wound+healing

- Inflammation: https://www.google.com/search?q='pathway+inhibitors'+in+inflammation

- Arthritis: https://www.google.com/search?q='pathway+inhibitors'+in+arthritis

- Atherosclerosis: https://www.google.com/search?q='pathway+inhibitors'+in+atherosclerosis

Pathway inhibitor...

- Side-effects: https://www.google.com/search?q='pathway+inhibitor'+side-effects

- Toxicity: https://www.google.com/search?q='pathway+inhibitor'+toxicity

All will be revealed...

Very good. Thank you thevid.

The troll asks "Why is significantly boosting the half life so exciting?"

It's clear the troll didn't watch yesterday's and the other recent presentations. Or if it did, it didn't understand.

Avacta only has the financial capacity to take AVA6000 to market for one indication at a time. That is now clearly SGC and the core reason is the lack of a SoC for SGC, so FDA support and AA are likely if Phase 1b are as expected.

As regards STS, I'd say partnership or licensing out is likely but, failing either of those, Avacta would develop AVA6000 for that indication once there was revenue available. However, I think a buyout would happen long before we got to that.

Probably because it would get to market around the time the patent life expired.

Just call them out as trolls so newbies get the message. That gives them nothing to argue against, they can only whine.