Member Info for sadoldgit

Cineplex
On 6 July 2020 the Group confirmed that Cineplex had initiated proceedings against it in relation to its termination on 12 June 2020 of the Arrangement Agreement relating to its proposed acquisition of Cineplex (the “Acquisition”). The proceedings alleged that the Group breached its obligations under the Arrangement Agreement and/or duty of good faith and claimed damages of up to C$2.18 billion less the value of Cineplex shares retained by Cineplex share holders.
The Group defended these proceedings on the basis that it had terminated the Arrangement Agreement because Cineplex breached a number of its covenants and counter-claimed against Cineplex for damages and losses suffered as a result of these breaches and the Acquisition not proceeding, including the Group’s financing costs, advisory fees and other costs.

The Ontario Superior Court of Justice has now handed down its judgment. It granted Cineplex’s claim, dismissed the Group’s counter-claim and awarded Cineplex damages of C$1.23 billion for lost synergies to Cineplex and C$5.5 million for lost transaction costs. The Group disagrees with this judgment and has appealed the decision.

The Group does not expect damages to be payable whilst any appeal is ongoing, which is likely to take longer than the assessment out to 30 June 2023. No liability has been recognised in respect of the judgement on the basis that payment is not considered probable at this stage, and the directors have not factored any payment of damages within their assessment of whether it is appropriate to adopt the going concern basis for the Group as at 31 December 2021.

It is the view of the Directors that the appeal process is unlikely to conclude within the going concern assessment period

additionally
https://www.marketbeat.com/stocks/LON/CINE/price-target/

https://www.researchgate.net/publication/361382733_Evaluating_Upadacitinib_in_the_Treatment_of_Moderate-to-Severe_Active_Ulcerative_Colitis_Design_Development_and_Potential_Position_in_Therapy

Scroll down to mechanisms of action.

.. A large sum of clinical evidence has represented significant therapeutic advances of JAKi in the treatment of COVID-19 pneumonia, especially for severely ill patients. Whereas different JAKi inhibit JAK isoforms with different selectivity [52,150]. The variable selectivity of JAK inhibitors is cell-dependent, dose-dependent, time-dependent, and not absolute, which may result in variability regarding their immunosuppressive effects and toxicity profile [151]. ...
... Generally, inhibiting JAK1 would block the broadest cytokine profile compared with other JAKs. JAK2, JAK3, and TYK2 were linked to erythropoiesis and thrombopoiesis, immune homeostasis, and anti-viral responses, respectively [52]. Direct comparisons from head-to-head clinical trials of JAKi are still lacking.

full link below
https://www.researchgate.net/publication/333458396_Clinical_significance_of_Janus_Kinase_inhibitor_selectivity#:~:text=Selectivity%20to%20JAKs%20can%20be%20determined%20by%20the,stimulation%20of%20cells%2C%20with%20assessment%20of%20STAT%20phosphorylation.

a light read on Jaki's and covid July 2022.
https://www.researchgate.net/publication/361743452_JAK_Inhibition_as_a_New_Treatment_Strategy_for_Patients_with_COVID-19

Regards

Good evening SCHeckler.
Enjoy your glass of wine. Good to see you see the glass a quarter full than three quarters empty. All that means is that it will need recharging soon.
Sareum are a tad unpredictable. May not get an licence next week but maybe news on GSK owned 737. Maybe not.
Nothing moves fast in this game.

Regards

Good question regarding percentage value regarding selectivity. Probably not a good idea in a sense to put as a percentage.

Now
According to Euro patent for our SDC's our compound of the formulae 0, 1 or 2 we have selectivity for TYk 2 is at least 5 times greater over Jak1 and at least time times greater selectivity of Tyk 2 over Jak 2 and the same for Jak3. So scientifically speaking it would not be the correct means of establishing the amounts of differing kinase activity.

In essence this was done to just reinforce that we exibit slight Jak2 and Jak3.( Why were we more effective than others when investigating for covid? Baricitinib is Jak1 Jak2 and not the best of safety profiles.)

Maintaining our levels of selectivity of one kinase over another does not necessarily mean that would be the exact levels as a percentage taking effect, more along the lines of likely hood. Very difficult to explain.

two little bits here

'Most small-molecule kinase inhibitors are ATP competitive, which render them more likely to cross-inhibit other kinases in the same family or even kinases from other families. Assessing compound selectivity is therefore critical for drug development. Recent development of several cutting-edge technologies enabled rapid advances in kinase selectivity assessment and greatly facilitated the industrial drug discovery process. ( this is old at circa 2005)'

'Selectivity therefore is the capability of a method to distinguish a given analyte from other substances. This feature is mainly a function of the described measuring technique; however, it might vary with the type of compound or matrix. A method can be called specific when it shows the highest selectivity.

Selectivity is one of the main parameters that characterizes and describes an analytical procedure, particularly in the case of trace analysis.29

From a practical point of view, an analytical measurement is considered selective when obtained analytical signals can be selected (separated from other), and when a value attributable to the specific analyte's feature can be assigned to each signal; this definitely depends on the type of the received signal.

Selectivity is dealt with differently when analytical signals have an additional attribute, i.e., location. This takes place in chromatography, where retention time is the additional characteristic of the analytical signal assigned to a given analyte. In such case, it is necessary and obligatory to determine a minimum difference of location parameters for specific analytes, which allows discrimination of the signals.

Selectivity the full link below.

https://www.sciencedirect.com/topics/earth-and-planetary-sciences/selectivity#:~:text=Selectivity%20therefore%20is%20the%20capability%20of%20a%20method,called%20specific%20when%20it%20shows%20the%20highest%20selectivity.

I will delve further into this to give a better understanding. Will look to find the links in a while.

apologies here if cau

SCHeckler good evening,
Not so sure we will hear about a deal this week. My reckoning it will be jumped upon on at end of phase 1 trials testing in healthy patients. Psoriasis is a good earner and we can treat much more than this.

Regards

Correction. High dosages of Jak2 and Jak3 can and have shown cause for concern.

I will add but it is not always best to eliminate them completely.

There are very pertinent points to take into consideration with our molecules.
We are not pure TYK2 as most of us know.

From the slide. You can see down the bottom (approx 6.5 mins in)

Note carefully

' Inhibition of Tyk2 and jak1 has the potential to yield a superior efficacy compared to agents that only block one of the kinases'

interferon alpha tyk2 Jak1
IL-12 Jak2 Tyk2
IL-23 Jak2 Tyk2
IL-6 Jak1 Jak2 and Tyk2

In SDC1801 our Tyk2 has a minimum 5 fold selectivity over Jak 1 and minimum 10 fold selectivity over Jak3. We are approximately 70% Tyk2 14% Jak1 one and 7% for Jak 2 and 7% Jak3.

The balance of the Jak family ie Tyk2 Jak1 Jak2 and Jak3 is vitally important in maintaining a healthy immune system.

We have shown in models to be vastly superior to other treatments. Other kinase inhibitors have been investigated with very little positive effect. We do exhibit as previously mentioned small amounts of Jak2 and Jak3 which look to be beneficial and have more efficacy over those that do not inhibit these kinases.
Extremely high doses in preclinical modelling has shown the amount of Jak2 and Jak3 that we have with SDC1801 not to be a cause of concern.
It certainly does look like when in the early days primarily inhibitors Jak1 Jak 2 and Jak3 were considered to be the bees knees and then found out to have related adverse side effects that pharmas have tried to eliminate these targeted kinases completely. From one extreme to the other.

You can as I have research autoimmune diseases and the various IL's, interferons, GM-CSF and a myriad of other signalling pathways and receptors. Tyk 2 on its own falls short on many of the kinase inhibiting targets required for effective treatment. Good safety yes.

Bare in mind also that Jak2 and Jak3 have shown serious side effects albeit with good efficacy in some diseases. IBD being one. It is only in higher dosages that these effects can become apparent and hence then you reach a stage where the dose cannot be increased or continued in some cases due to the associated toxicity of Jak 2 and 3.

If we look at pure TYk2 it is very limited as to what indications it can treat effectively on its own. It has been shown to be OK and in psoriasis but flunked ie had no effect on IBD, Is this surprising we may well ask. Pure Tyk2 looks to be overly selective.
I would hazard and educated guess that at the present time we have the most effective autoimmune kinase inhibitor with SDC1801 currently in development.

Certainly food for thought.

Regards

Remember there has already been phase 1 and 1a with 737 and that 737 in combo with two other compounds have been patented.
Not so much high risk with 737 as its benefits partially investigated along with its potential.

Regards

Wise words SP. The media would not know fact from fiction if it stared them in the face. Their atttention is to make headlines so they can sell the 5hit they produce.
As you correctly state ( and the media have been abusing as opposed) to using terms potentially, expected, envisaged and the oh so famous 'an insider source, who refused to be named.' None of this ie ever to be taken as factual information.
All set to scare and control people. The media do not report fact just what they want you to hear based on their agenda.
Some good posters on this board and added this to my portfolio yesterday and today.

I do do deeply feel for those that are down considerably. At the same time i do detest those that mock or take relish in this. Lowest form of life, prawns, bottom feeders. Remember they have their agenda too!

Regards and a great weekend to the truly invested.

That is a very deep question and would require a lot more knowledge on this subject than I have.

What i will say however, is they are seeking compensatory payment for a contractual agreement that cineworld are claimed to have defaulted on.
I believe the original deal was around 2 billion dollars. Far from 100% sure on this.

What is the current value of the cineplex with regards to outright sale taking into consideration effects of covid 19?

The value would have diminished considerably. I suspect the compensatory payment they are looking for is the old agreed price versus current value. How on earth do you otherwise claim for such a payment.

I very much doubt that there would be any resuming of a such buyout.

A general rule of thumb is a company will put in a high figure for compensation. The respondent will put in a much lower offer. As a court date approaches there is in most cases an agreement reached on the amount via out of court settlement.

it is in the interest of both sides to settle amicably out of court and both sides i would add would be advised by their legal advisors on this in a roundabout manner.

Their legal representatives on both sides will point out what they consider a reasonable offer made and that by going to court they may well receive more but also run the risk of being awarded less or even losing the case altogether.

Regards

I doubt very much there will be an RNS Monday morning. Just what do you expect Cineworld to report?

I would hazard an educated guess that Cineworld and cineplex are in negotiations regarding an out of court settlement.

In this case it is imperative that cineworld make their financial situation look as dire as possible. Considering bankruptcy certainly makes things look dire. It is an option they have.

That means if we cannot agree on an out of court settlement we will very likely pursue bankruptcy.

No good for cineworld and no good for Cineplex.

For those that think that cineplex will definitely go into administration put yourselves in Cineplex position. What do you hope to gain?

You cannot release an announcement to say, we are or we are not, going into administration.

This information would be used by cineplex. Primarily to indicate whether Cineworld are bluffing. In may very well be that Cineworld have informally offered an out of court settlement that Cinemaplex are refusing. in response Cineworld are saying if you want more then we will be forced into bankruptcy and are now giving this option due consideration.

Very much like playing a game of poker, I think you are bluffing, Ok then try me.

So in this instance a confirmation by Cineworld will not be released at this moment in time with regards to administration.
All current payments have been made up to date. That indicates solvency. As for impending payments, until such a time that payments are not being met then insolvency becomes a major option or in some cases the onl option.. Restructuring is a possibility depending on assets, turnover and amount of immediate debt.

Regards

Just about spot on with that one with words of wisdom there Pokerchips.

I will ask what would happen if cineworld when bankrupt before the court case. Cineplex be well and truly stuffed. My own view is that bankruptcy neither side want. Hence out of court settlement, which you then have to take the liquidity and hence ability to pay a mutually agreed amount.

Regards

I dont think a case of shafting shareholders. They are protecting themselves. There is an impending court case looming in October. Most likely be an out of court settlement. With a very low market cap and very little liquidity the circa 900 million is likely to be substantially reduced.
Of course stating making plans or preparing for bankruptcy plays well into the hands of cineworld.

They have not defaulted on any of their payments.

Expect masses of volatility in the SP until end of October. You may well here of an out of court settlement payment. No side will really want to go to court. It is this impending court case that has led to the rapid decline in the SP.

Not long to wait I would hazard a guess around out of court settlement fee by end of September. The only guaranteed to make money are the brokers that are having a field day.

'These lower levels of admissions are due to a limited film slate that is anticipated to continue until November 2022 and are expected to negatively impact trading and the Group's liquidity position in the near term.'

Note the use of the phrase 'near term'

High risk? of course but at these levels so is the likely hood of very high gains.

PH recently and just prior to the RNS on the 17th dropped Cineworld target from 32p to 20p.

Weigh up the pros and cons and dont be swayed by those that have a different view than yours. Look for valid reasoning in points of view.

One final point I will make is that if and when an out of court settlement is made then Cineworld should then flourish. November onwards i would contemplate with a corresponding increase in the SP.

Regards and to all and that is irrespective of your point of view.

You can have a molecule that targets a specific domain, this molecule and the formulations thereof can be protected by
a patent. We are well protected in both invention of the compound and the manufacture thereof.
However, you cannot target a site with a patent.

That should read interferon gamma and not interferon question mark. Apologies.

https://www.differencebetween.com/difference-between-jak1-jak2-and-jak3/

light introduction to the Jak 1,2 &3

Worth a light read and it does now indicate as to why we showed good efficacy with Covid.

Deurcravaticinib has no inhibition of Jaks 1,2 and 3. Patients in trials with Deucravacitinib experienced no difference to people that had not had Deucravacitinib.
Deuravacitinib not of any use with regards to Covid.
Baricitinib (Jak 2 and Jak1 but no Tyk2) indicated efficacy in treatment.

I remember Tim discussing in presentation requirements for covid cytokine storm

gp 130
gm-csf
type 1 interferon alpha beta
type 2 interferon gamma.

First two are Jak2 inhibited and last two are Jak1 inhibited.

So although we are predominently a Tyk 2 inhibitor there are as we can see advantages in not being completely 100% selective over the other Jaks 1 2 and 3.
Jak3 type 1 receptors using common gamma chain and Interleukins 2,4, 7, 9,15and 21

As we can see from below Il-2 from Jak3 gives regulation of white blood cells. ( too much Il-2 inhibition ofJak3 and we risk severe infection)

Interleukin-2 (IL-2) is an interleukin, a type of cytokine signaling molecule in the immune system. It is a 15.5–16 kDa protein[5] that regulates the activities of white blood cells (leukocytes, often lymphocytes) that are responsible for immunity. IL-2 is part of the body's natural response to microbial infection, and in discriminating between foreign ("non-self") and "self". IL-2 mediates its effects by binding to IL-2 receptors, which are expressed by lymphocytes. The major sources of IL-2 are activated CD4+ T cells and activated CD8+ T cells.[6

Jak1 and Jak2 for inhibition of Il-10 consists of 4 sub units 2 of which Jak1 and 2 of which Tyk2

IL-10 is capable of inhibiting synthesis of pro-inflammatory cytokines such as IFN-?, IL-2, IL-3, TNFa and GM-CSF made by cells such as macrophages and Th1 T cells.
(Th1 cells are involved in the pathogenesis of organ-specific autoimmune disorders, Crohn's disease, Helicobacter pylori-induced peptic ulcer, acute kidney allograft rejection, and unexplained recurrent abortions. In contrast, allergen-specific Th2 responses are responsible for atopic disorders in genetically susceptible individuals.)

It does get very complex indeed. The balance of auto immune regulation is more an art that a science at times I think.

This will do this and this will do that along with the pros and cons. All about getting the balance right.

Regards to all

From our patent
We are not entirely Jak2 and Jak3 free. I had posted before on our compounds having small amount of other kinases apart from Tyk 2 and Jak1.

[0431] An advantage of compounds of the formulae (0), (1) and (2) as defined herein is that they exhibit selectivity for TYK2 kinase compared to other kinases of the JAK family.

[0432] For example, the majority of the compounds of formulae (0), (1) and (2) exemplified herein have at least a tenfold selectivity for TYK2 compared to JAK2 and JAK3 and at least a fivefold selectivity for TYK2 versus JAK1.

[0433] Whilst selectivity for TYK2 is considered advantageous, it is envisaged that, in some circumstances, activity against other JAK kinases as well as TYK2 may be beneficial. Thus, for example, compounds of the formula (0), (1) or (2) as defined herein may have IC.sub.50 values against TYK2 of less than 200 nanomolar (e.g. less than 50 nanomolar) and IC.sub.50 values against JAK1, JAK2 and JAK3 of less than 500 nanomolar (e.g. less than 200 nanomolar), but wherein the activity against TYK2 is greater than the activity against any of JAK1, JAK2 and JAK3.

Nothing to be overly concerned about I feel as we had experienced difficulties reaching an MTD. Pure Tyk 2 on its own does not always cut the mustard as we know. But now in the patent we now have an idea of just how much.

Pivotal will be phase 1 trial results.

https://www.iqvia.com/blogs/2021/02/interleukin-inhibitors-to-continue-driving-psoriasis-market-growth#:~:text=TYK2%20inhibitors%20hold%20the%20potential%20to%20provide%20an,its%20position%20as%20the%20leading%20dermatology%20market%20globally.

A very, very hot area is the immunotherapy and immuno oncology becoming.
Phase 1 for us will be pivotal.