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No Thompi, the pub bore is just wilfully ignorant.

Sorry to hear you're down at heel D-G.😉 Those buses can be very drafty so wrap up warm.

It's not me that's thick... "Mkt Cap is just a multiplier of SP." Well that multiplier is the number of shares in issue. If the number of shares go up 20% and the SP has gone down 10% then the pub bore says the company is worth less because the SP has gone down, but what has happened to the MCap? That's right, it has gone up, making the company more valuable and so more expensive for another company to acquire.

Your own holding, if you have one, may have gone down in value as your number of shares stays the same, but that's not what I'm talking about.

Wars are fought over resources and Ukraine ranks among the global leaders in reserves of coal, iron ore, natural gas, manganese, salt, oil, graphite, sulfur, kaolin, titanium, nickel, magnesium, timber, and mercury. They can either go to Russia or America, or to Russia or Europe if America steps back. I'm sure Trump's backers want those resources. Ukraine has a very strong bargaining chip afa America is concerned, plus a reserve-rich but bust Russia would be open to exploitation by US companies. I can see Trump turning the economic screw on Russia even more than he has already.

@D-G, do TLSA have FDA ODD, Fast Track, etc for their submitted drug? Well I doubt they could have Fast Track, etc if there's a delay in approval as with those designations there is increased interaction with the FDA including advice from the FDA, who want to see effective drugs have the best chance of success. If it's a run-of-the-mill drug and they've not had the benefit of much FDA interaction then they could just have messed up their application, thus reducing their chance of success.

My worry about being on Nasdaq would be the danger of litigation for claims of misleading management information. In that, Alan and Tony 'Abacus' Gardiner would have been a walking traffic accident waiting to happen for those ambulance chasers. At least the current management have Nasdaq and US mentality experience and hopefully enough nous to avoid such a catastrophe.

The pub bore is obsessing about the SP again when it is the MCap that is the measure of the value of a company. Very amateurish FUDing. And of course conflating the SP back in 2021 when the company was valued on early AVA6000 and a AffiDX® SARS-CoV-2 Antigen LFT near to comercialisation and now with AVA6000 at least a year away from commerialisation.

There may be money to be made on the start of peace talks but my personal opinion, as someone who's been following the war since February 2022, is that we are both a long way and very close to a peace settlement.

Russia has a long history of imperial expansion and of not keeping its word when it comes to peace settlements - Russia can't be trusted - and Ukraine has an awful lot of that history with Russia. The hatred goes very deep and their nationalism is very strong. I think they would rather continue fighting than cede variable portions of their land.

On the other hand, Russia is suffering severe economic pain - that's why Putin is desperate for 'peace talks' (really just a break in the decade-long way on Ukraine so that his but-hurt forces can rebuild) - and is edging closer to economic collapse, which could come any months now and would mean a complete end to the war (and possibly also Russia's occupation of Moldova and Georgia).

Eggy is a very tired old basher whose core fud has always been "it doesn't work" and who has never posted anything of value.

That link somehow got mangled and then chopped. This should work a lot better.

https://tinyurl.com/4xyttche

I run a profile like this one at 7am and throughout the day. You can modify it if you're interested in other industry sectors. You can also make profiles for individual companies, but I prefer to see what the whole sector, including AZ and GSK, is doing.

https://www.londonstockexchange.com/news?tab=news-explorer§ors=201020,201030

I don't know whether it could be made into an active alert service (as opposed to this passive search service) as I haven't really felt the need so haven't explored the possibility.

@yuyus, yeah, so did Hitler.

At the end of the day, people can argue till the cows come home about how many valuations can fit on a pinhead but at the end of the day the company and its assets are worth exactly what another company is prepared to pay, no more, no less. What does AI say to that?

Is that rag wet from your sweat or your tears?

Nah, what is hilarious ChatBOY is that a person can use AI and all of a sudden think he's an expert in all matters pharma valuations. This is the democratisation of the Dunning-Kruger effect: now anyone can think he's an expert. I'm not surprised; expertise has been increasingly despised and reviled these past few years. Enjoy your self-satisfaction.

Oh, I almost forgot.... 😁💯👍🙄

"If they can't summarise the news accurately, then why do we think the heavy use of these tools on here, to present theories and valuations, are of any use?"

It's the age of the Idiocracy. Get with the program...

@LLP, I'll wager Novartis are testing pre|CISION/canSEEK with their own and Lilly's radioligands in animal models. If they find good efficacy (and better efficacy with Lilly's disclosed radioligands than with their own) then buying the tech and terminating Lilly's agreement with Avacta is (almost) a no-brainer. Almost, because it would depend on the price, and what prices other farmers would be prepared to counter-offer with.

Probably more than you'll ever want to know about ADCs!...

Recent Advances in ADCs ( https://njbio.com/antibody-drug-conjugates/ )

Abstract:

"ADCs (Antibody-drug conjugates) represent an innovative class of chemotherapeutics, which combine the precision of monoclonal antibodies (mAbs) with potent cytotoxic agents. Each generation of ADC has steadily progressed closer to the goal of targeted cancer therapy, with enhanced efficacy and reduced off-target toxicity. Notably, there have been 11 FDA approvals, till date, and over 1,000 ADCs are currently in various stages of development. The momentum of the ADC field is underscored by several billion-dollar industry deals, and the global ADC sales exceeding $9 billion in the last year.

"This review navigates the complex ADC landscape by focusing on critical aspects of ADCs, including their key features, mechanisms of action, bioconjugation techniques, and the selection of linkers, cytotoxins, and linker-payload combinations. The review provides an in-depth overview of approved and clinical candidates, while examining significant business activities, including mergers and acquisitions, offering a comprehensive resource on both the scientific and commercial landscapes of ADCs. It also addresses ADC toxicity mechanisms and reasons behind discontinuation of various clinical drugs, further explaining strategies to overcome these challenges and providing insights into the future direction of research and development of next-generation ADCs."

Hmm... I think it's just that the number of postings was distorted by the concentrated news flow in September-October. Take those out and the posting is pretty flat.

I remember reading that the toxicity profile of ADCs is down to the warhead, not the full ADC entity, and that that is due to linker instability - warheads are cleaved off before the ADC reaches the tumour, so the side effects are the same as would be expected from the administering the warhead neat. So...

Q to Google: List of discontinued ADC warheads ( https://www.google.com/search?q=List+of+discontinued+ADC+warheads ):

A notable discontinued ADC warhead is "calicheamicin," which was used in the drug Gemtuzumab ozogamicin (Mylotarg), initially approved but later withdrawn due to significant toxicity concerns; other ADC warheads that have been discontinued or had development halted due to safety issues include:

Dolastatin 10 derivatives:

Some early ADC designs utilizing dolastatin 10 analogs were discontinued due to toxicity issues.

Maytansine analogs with poor linker stability:

Certain versions of maytansine, a common ADC payload, were abandoned due to concerns about premature release of the cytotoxic agent.

Highly potent DNA-damaging agents:

Some highly toxic DNA-damaging agents, like certain anthracyclines, have been explored as ADC warheads but often faced limitations due to severe side effects.

Key points to remember about discontinued ADC warheads:

Toxicity issues:

The primary reason for discontinuation is often excessive toxicity, leading to unacceptable side effects in patients.

Linker instability:

Problems with the linker connecting the antibody to the cytotoxic payload can lead to premature release of the drug, causing off-target toxicity.

Lack of efficacy:

In some cases, even with a potent warhead, the ADC may not demonstrate sufficient efficacy in clinical trials, leading to discontinuation.

Q to Google: How many ADCs have been discontinued? ( https://www.google.com/search?q=How+many+ADCs+have+been+discontinued%3F ):

Over 150 antibody-drug conjugates (ADCs) have been discontinued in clinical trials, and many more are currently inactive.

Reasons for discontinuation

• Insufficient efficacy: ADCs may not have been safe or effective enough to be dosed at the required levels.

• Toxicities: ADCs can have toxicities similar to chemotherapy, and these toxicities are often dose-limiting.

• Financial and strategic reasons: These may also contribute to discontinuation.

Other ADC development challenges

• The right mix of antibody, linker, and payload may not have been used.

• The challenge of matching the linker-payload and mAb specifically to the target.

• The challenge of obtaining the optimal concentration in formulation to enhance local bioavailability and tissue penetration.

Learning from discontinued ADCs

It's important to learn from the failures of discontinued ADCs so that future ADC research and development doesn't repeat the same mistakes.

Bella wrote: "So who do we know who dropped their ADC's or who hasn't entered that marketplace...???"

The below was noted some time ago, but worth repeating as Novartis obtaining pre|CISION would not only give access to PDCs (and potentially AffDCs) as a step ahead of ADCs but also to pre|CISION-enabled competition to whatever Lilly might produce out of the Avacta-POINT agreement (and I guess they could terminate that agreement):

JPM24: As cancer players jump head-first into ADC field, Novartis CEO explains how he's resisted the temptation ( https://www.fiercepharma.com/pharma/jpm24-cancer-players-jump-head-first-adc-field-novartis-ceo-explains-how-hes-resisted ), 8 Jan 2024

"San Francisco—Nearly all top cancer drugmakers have struck deals in the sizzling antibody-drug conjugate field—but not Novartis. On Monday, the Swiss pharma’s CEO Vas Narasimhan explained how he's resisted the temptation.

"The answer is radioligand therapies, Narasimhan said Monday during the 2024 J.P. Morgan Healthcare Conference in response to a question from Fierce Pharma.

"“We have a long history within research of ADCs, but we have not been successful,” Narasimhan said. “To be clear, part of our focus strategy is looking at places where we think we can create long-term sustainable leadership. And we are investing in radioligand therapies.”

"ADCs and radioligand therapies are similar in that both technologies act as guided missiles. For ADCs, the guiding force is an antibody, and the cancer-killing payload is a chemotherapy. A radioligand therapy uses a ligand to target cancer cells and kills them with a therapeutic radioisotope.

"Radiotherapies may have a safety edge compared with some ADCs, Narasimhan argued.

"“We believe that the therapeutic index on radioligand therapies, when you find the right target, gives you a pretty wide window to get a therapeutic effect without some of the safety issues,” the Novartis CEO said. [continues]"