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Not true B2H.

"validated dual payload release mechanism" means they proved/validated/confirmed through "biologic and biochemical analyses" that they achieved "simultaneous release of two independent payloads from a single FAP cleavage event".

The use of the term 'linker' by the CSO is not the best use of the word.

AVA6000 has a cleavable link:

dipeptide ----|---- warhead

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AVA6103 has a cleavable link covalently bonded to a self-immolative linker:

dipeptide ----|---- linker ------- warhead

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There is therfore some muddled logic in the X post. The cleavage off to the right of the dipeptide (as represented by --|--) is proven - it is a hydrolysable peptide bond specific for FAPα, but there is much more to making a drug than just that. The chemists spent a lot of time studying structure-activity relataionships (SAR) for the many compounds they made. The importance of being able to characterise the 'docking' space of FAP can be seen by analogy to a lock and key where FAP is the lock with its fixed conformation and the drug is the key which must fit in the hole and the dipeptide is the business end of the key that actually turns the lock. If the rest of the key - the barrel - is too short, too thick or not straight, then the key won't fit the lock and so won't work. It is this 'barrel' that has to be designed for EVERY candidate drug and that is where the learnings from the SAR data comes in. It's more complicated than just the fit to FAP though because they also considered the pharmacokinetics - half-life, slow release, etc - and, as mentioned in one of the Spotlights, a change to one part of the molecule effects other parts of the molecule (electron distribution, polarity and 3D structure) so it's a sort of iterative process, even whilst knowing a lot about the SAR.

It should be remembered that AVA6103 was not originally a single drug candidate but rather a series of similar chemical compounds from which they selected the one with the best efficacy, PK, etc.

Without a licence that allows them to sell faridox for financial gain, of course I'm saying they have no right! The whole point of a patent is to have EXCLUSIVE rights for a limited time in exchange for publicly disclosing the invention. A patent gives the owner the legal right to prevent others from making, using, selling, or importing the invention without permission, without a licence.

There is also the little matter of quality - the purity of the chemical. Does faridox have a BP or USP standard yet?

My guess would be that, if not manufactured separately under licence, what's on offer here is faridox that is excess to what's needed for Avacta's trials programme. Only a tiny amount is used in the trials and a GMP facility is set up for bulk production. The cost of making 'excess' would be minimal and would bring the unit cost down.

I don't understand this, but then I'm not getting a good view of this website on my mobile. Bachovchin and Avacta own the commercial rights to faridox. No one can sell it or use it in a commercial product without a licence. So what's on offer here?

"Gradually, and then suddenly"

~ Ernest Hemingway (from 'The Sun Also Rises')

As an engineer and insurance banker, you will surely now what a development S-curve is ...a graphical representation of progress over time, named for its "S" shape, which reflects a slow start, followed by a period of rapid growth, and then a leveling off as a project or process matures. It is used to track cumulative progress, costs, or performance in fields like construction, technology, and individual learning.

Also, history may instruct but doesn't determine the future.

For anyone who isn't/wasn't aware... @Moneysponge

Aldebaran pumping desperately. Will he disappear again come 13 December? Maybe he'll buy a better dictionary for next time.

Next resistance level after 82/83 is 90, assuming no news.

83.2 was a UT.

You thinking of applying for a job at an investment bank Touk?

You have no integrity and no credibility. You just hang around this BB like a bad eggy smell.

But a targeted exatecan is revealed...

Re: rinatabart sesutecan (Rina-S), ProfoundBio’s star asset.

Sesutecan is a novel, hydrophilic, protease-cleavable linker that connects the antibody to its cancer-killing agent, exatecan. The linker is designed to be cleaved by enzymes in the body, releasing the cancer-killing drug directly at the tumor site.

https://ir.genmab.com/news-releases/news-release-details/genmab-announces-new-data-demonstrating-investigational

Thanks for the invite but I'll sit this one out.

@Bella, it was the 'average' in 2024.

There ws an average of 151 employees (including Directors) in 2024, however an 'average' is worked out. https://avacta.com/wp-content/uploads/2025/06/ARandA.pdf (page 90)

128 Commercial & Operation, and 23 Administrative

Missing link! https://patents.google.com/patent/US20230390409A1/

Note: All inventors are in Bachovchin's group and all patents mention self-immolative linker, including the latest one, US20250108031A1, filed 9 September 2024, so I'll be interested to see 'our ' patent that CC said was filed last September after giving the Avacta chemists so much credit. It could be that there will be anoher patent or two that specifically claim exatecan, etc. as the conjugated warhead and that give the Avacta chemists as inventors. A patent that specifically claims the drug of interest, together with supporting preclinical data showing activity, is important for full protection.

The original: https://patents.google.com/patent/US9737556B2 (Granted, Anticipated expiration 15 June 2035)

FAP-activated therapeutic agents, and uses related thereto: Disclosed are prodrugs of anthracyclines (such as doxorubicin) and derivatives thereof that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of “warhead” anthracycline or anthracycline derivative to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compositions comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, undesirable fibrosis, and undesirable inflammation.

- - - - -

Extension: https://patents.google.com/patent/US20210353652A1/ (Pending)

Tumor microenvironment-activated drug-binder conjugates, and uses related thereto: Disclosed are binder-drug conjugates that are activated extracellular, with both the binder and the free drug moiety have pharmacological activity.

Extension: c (Pending)

Fap-activated serum extended half-life therapeutic conjugates: Disclosed herein are therapeutic conjugates having an extended circulating serum half-life. The therapeutic conjugates comprise a therapeutic moiety linked to a half-life extension moiety via a fibroblast activation protein, alpha (FAPα)-cleavable linker. Methods of using the therapeutic conjugates are also provided.

Extension: https://patents.google.com/patent/US20240398842A1/ (Pending)

Fap-activated therapeutic agents, and uses related thereto: Disclosed are prodrugs of anthracyclines (such as doxorubicin) and derivatives thereof that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of “warhead” anthracycline or anthracycline derivative to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, undesirable fibrosis, and undesirable inflammation.

Extension: https://patents.google.com/patent/US20250108031A1/ (Pending)

Fap-activated therapeutic agents, and uses related thereto: Disclosed are prodrugs of cytotoxic anthracyclines (such as doxorubicin) and other therapeutic agents that are selectively cleaved and activated by fibroblast activating protein (FAP). The prodrugs are useful for targeted delivery of cytotoxic and other agents to FAP-expressing tissues, including cancer (e.g., solid tumors). Also provided are pharmaceutical compounds comprising the prodrugs, as well as methods of using the prodrugs to treat a disorder characterized by FAP upregulation, e.g., cancer, fibrosis, and inflammation.

Another description of the programme: "Prof Sarah Blagden is attempting to stop cancer before it even starts. Can she bring together several recent breakthroughs to create a vaccine for lung cancer?"

- - - - -

There are two main types of lung cancer: non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). NSCLC is the more common type and is further divided into subtypes such as adenocarcinoma, squamous cell carcinoma, and large-cell carcinoma. Small-cell lung cancer is less common and tends to spread faster.

Non-small-cell lung cancer (NSCLC)

• Adenocarcinoma: The most common type of NSCLC, it develops in the cells that produce mucus and is often found in the outer part of the lung.

• Squamous cell carcinoma: Starts in the flat cells that line the airways and is typically found in the center of the lungs.

• Large-cell carcinoma: A less common type that can be found in any part of the lung.

• NSCLC, not otherwise specified: A category used when doctors cannot definitively classify the subtype.

Small-cell lung cancer (SCLC)

• This type is less common and is almost always associated with smoking.

• It tends to grow and spread more quickly than NSCLC.

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The press pack Q&A's for the whole three-part series: https://www.channel4.com/press/press-pack/cancer-detectives-finding-cures-press-pack-qas

Interview with Prof Sarah Blagden for Episode 1: https://www.channel4.com/press/news/press-pack-interview-professor-sarah-blagden-episode-1

Yes I do. The share price went down because of the funding problem, not the science.