Member Info for sadoldgit

https://www.globenewswire.com/news-release/2021/06/29/2254675/0/en/Acrivon-Therapeutics-Launches-to-Advance-Clinical-Oncology-Pipeline-Leveraging-its-Groundbreaking-Precision-Proteomics-Platform.html

'Lilly chose prexasertib as its test case for such a process because it’s challenging to make. It is a chain of three aromatic rings, and one challenge comes because its central ring is formed using hydrazine. Hydrazine is used as a component in rocket fuel, and is also highly toxic. A second challenge comes from prexasertib itself, which, as a potent kinase inhibitor, is toxic to healthy cells, as well as cancerous ones, even at low doses. Lilly therefore wants to minimise its workers’ exposure.'

Hydrazine basically removes oxygen.

Now the decent bit
https://www.biospace.com/article/recently-launched-acrivon-nets-100-million-in-financing-and-licenses-cast-off-eli-lilly-oncology-drug/

The point I hope to have made here is that prexasertib by Eli lilly was shelved in 2019
Who has been working on CHK1 inhibitors and a former member of CRT with respects to resistance pathways and combination therapies?

Subsequently we have that Eli lilly on licensing to Acrivon in 2021.

Gus 79 not heard that one for a while but how so true. You can be the best bloke ever until you make an f up. That is what people remember you for.

Happy to post relevant information that people can use and make their own judgement and research further. I am not an avid fan of the P & D brigade.

People can invest on what they believe on little knowledge and some effer will come in and be excessively negative due to their own agenda and destroy their confidence. It can also go the other way with excessive ramping based on no substantiated info.

There are those that will say that. whatever you say on on a BB will not affect the SP. Whilst true for mega companies it is the opposite for small AIM.

I have seen this share drop 20 % over a week by gradual small sells. One small sell of a few hundreds pounds and the share drops 4%.
I have been here approaching 11 years.

Check a posters history.
How long have they been here?
Are they genuinely interested?
What factual information do they offer and separate that from opinion?
We have lost some good posters and gained recently some good ones. Schecks pretty good as are one or two others comparatively recent

Dont be concerned about asking them questions.
At the same time have a little consideration for those that have been here a while and get a little peeved when they ask questions that even the most novice of investor should know.
SP will go up and down. Up on the expectation of good news or good news and a retrace over a period of time if no news.
People here generally Ok.
All of us have an agenda. Mine is to make a decent sum. Have always said invest in what you can afford to lose, in this sense I dont mean all gone an lost forever but more so the price will rise it will fall and will eventually reach new highs.

Fell free to ask my opinion which I will answer as best I can. I cannot control the SP.
I do have a decent understanding of the science and pharmaceutical products in general.

Biggest fears is a new ground breaking blockbuster. They are either years away or we are sitting on it.

Regards

CHK1 has been around for some time, it has been well researched and later stage variants have proved significant gains.

Then it all stopped and PARP was the new way to go. CHK1 and resistance to has been mostly recognised with much hypothesis on a way forward.

Parp from 2021
Translational Relevance
Resistance to PARP inhibition has emerged as a therapeutic barrier in the treatment of high-grade serous ovarian cancer (HGSOC). Mechanisms of resistance, including restoration of ****logous recombination (HR) repair or stabilization of replication forks, can be overcome by checkpoint kinase 1 (CHK1) inhibition, which disrupts restored HR and destabilizes replication forks. Here, we report the safety and recommended phase 2 dose of the CHK1 inhibitor prexasertib combined with olaparib. Analysis of paired biopsies after combination treatment provided pharmacodynamic proof-of-mechanism, demonstrating CHK1-mediated modulation of HR repair via reduction in RAD51 focus formation and induction of replicative stress with increased pRPA staining. These effects were associated with increased DNA damage, assessed by ?-H2AX and pKAP1 expression. The prexasertib/olaparib combination demonstrated preliminary antitumor activity in patients with platinum- and PARP inhibitor–resistant HGSOC. This experience will inform further development of combination strategies directed at reversing PARP inhibitor resistance to enhance antitumor activity of these classes of agents.

Now bare in mind that development of prexasertib was ceased mainly due to toxicity issues
by Eli Lilly 2019

Compared to other drugs of the same class, prexasertib showed a better tolerability profile, causing moderate hematological toxicity. Further studies are needed to confirm efficacy and safety profiles of prexasertib in combined regimens. New early clinical trials may investigate prexasertib administered with programmed cell death ligand 1 (PD-L1) and PI3 K inhibitors due to the preclinical evidence of a synergic action.

We now have and bare in mind prexasertib iv administered
from 2021
Acrivon signs exclusive worldwide license agreement with Eli Lilly and Company to develop and commercialize prexasertib, a clinically advanced, selective inhibitor targeting DNA Damage Response (DDR) kinases CHK1 and CHK2, which has shown durable activity, including complete responses in a proportion of patients across multiple cancers in Phase 2 studies
full link below
https://www.globenewswire.com/news-release/2021/06/29/2254675/0/en/Acrivon-Therapeutics-Launches-to-Advance-Clinical-Oncology-Pipeline-Leveraging-its-Groundbreaking-Precision-Proteomics-Platform.html

Says it all. M Garrett been working on CHK1 inhibitors for past 12 years at least.

Certainly a much renewed interest. Understand the science.

When the price went south many blaming Tim and co, the price goes up and no one says well done Tim and co.
Market sentiment. Try defining it.

Woodlands why would you call it £8.10 a share for 737? On what do you make such an absurd assumption?
That would make a financial worth of approx 400 million for Sareums financial interest at 27.5%
Around 1.5 billion you are placing on 737 on licence or buyout value.
SDC1801 you only place a value of circa 400 million on clinical data? What actual clinical data are we looking at here, dose escalation and or results from psoriasis?

Your reasoning behind this would help immensely to the less experienced investor here.

Later stage down the line I am not opposed to the idea of a 1 billion pound plus market cap for what we have.

You explain your reasonings and I will explain mine.

Regards

Interesting week, shown buys way more than sells. A couple of attempts to put the SP red even the slight drop around midday probably pushing the traders out to take profits at end of week.
Subsequent 9% rise.
Anticipation of good news either 737 or CTA approval.

MHRA/GLPMA I would have thought wont give much away.

Discussions between interested parties with CPF looking very favourable. As we know there is more than one interested party then things should be hotting up over the remainder of this month. How watertight are the CPF?

Sareum tight with info as we know. How watertight are the CPF? Include those parties that have approached.
May I suggest a deal may take place pretty soon and merely waiting for full data review by a decent sized pharma.
Still early stages as only nearly a month since return of 737 end of 90 day notice period. 12th Jan.

Bare in mind we sit at 2.4p old money which for what we have is peanuts.

We also need to look at the reduced milestone payment from circa 7 million to 2 million. this was cleverly manipulated when the clause was first clinical patient treated in the USA.

No patient was ever treated in the USA and then they negotiate a reduced milestone payment to 2 million.

From memory the 2nd milestone payment was around 12 million for stage 2 trial ( not sure if this included as USA only)

In all it equates to around 19 million milestone payments that would have been due had SO progressed.

737 now sits ready for stage 2 trials with the added benefit of top line results in preclinical in combo ( yes that will include PD-1 WEE1 and LDG). Also further combo work with Michelle Garrett which has been reported and widely available in journals.

So i dont think it out of the question for a license deal with a minimum of circa 30 million up front with milestone payments totalling 600 to 700 million looking at it pessimistically.

It will take a month or so from now to finalise in my estimation. It may very well be in deep negotiations at this moment in time.
Someone will know and these developments are not as water tight as we may think

See how it runs next week but myself not really expecting news for another couple of weeks at least.

Confidence at the AGM meeting!

Beer time for me as just in from work.

Regards

Firstly a great spot by Potters.
If anyone shorting this stock must have nigh shat themselves on earlier post with link. But those here a while think this just dont add up Similarities with shares is issue of circa 68 million. But good we have posters like Potnak.

8 week period suggested by LeeMajor?
Not far out at all me thinks, give or take a couple of weeks either way.

A deal will take a time circa 3 months with regards 737.
CPF will require all info back.
At this stage CPF can place a value on 737.
This not easy by any means.
737 has proven to give positive results in combo, not outstanding but good.
Preclinical with Wee1 and PD-1 ( plus LDG) especially good, go as far to say knocks the scheissen out of what is available at the moment.
In addition we have AKT and P13k inhibitor.
Now before we all think marvellous we have to take into account toxicities introduced when in combo.
For example we can take SRA737 at 1000mg max before DLT comes in and then drops to around 800mg when used in combo with LDG.
LDG has toxicities at high dosages but can be drastically reduced when used in combo with 737.
All CHK1 inhibitors are not the same. Early inhibitors proved too tocic to be effective and many taken by iv route.
However as a minimum there is no reason why a company should not have an extreme interest for combo SRA737 and LDG as it works.
The potential here is combo with other therapies and indeed a chemo. CHK1 works by correcting or preventing cell growth at mitosis on recognition of DNA damage.

Understand that a CHK1 inhibitor will control cell production and at the same time cancer can and will find new ways to evolve by using different pathways.

These pathways have been recognised with very promising alternative treatments ( some of which are still in development)

Over 50% of cancer tumours are affected by P53 cell cycle checkpoint. Unfortunately mutant P53 develops resulting in loss of programmed cell death and consequent allowing of metastasis.

In combo therapy has the advantage of seriously altering the resistance and complications encountered by the formation of mutant P53 cell cycle arrest in combination with a CHK1.
inhibitor.

If we take HGSOC at late stage, 98% of cancerous cells are P53 related. Response to treatment is now limited. P53 checkpoint control has become inadequate due to mutational P53 burdens .
There is so much scope here for combination therapy, not only to provide effective treatment for these difficult to treat cancers ( and indeed the patients themselves) but also an opportunity to develop CHK1 to be a highly lucrative form of income to a suitable interested pharma choosing to explore all avenues in combination therapy to reach its full potential.

Regards to all

SCHeckler, Dilley worked in high position of Smithkline Beecham.

Nick Glover was a bit of a DDR pathway fanatic.
They ousted him.
No money for Sareum but they bought a Bet inhibitor supposedly for Momo. Momo coming up for NDA approval before the BET inhibitor came into play.

Regards

Surfie, Who has suggested it will go through £20.00 soon?

Will Take a while to look through it all.

The SO shareholders were not happy in the least at the take over price by GSK.

Sierra Oncology did state that 737 may prove to be more commercially viable than Momo. Give SO their due they turned a sows ear into a purse with momo.

No funding to continue 737 of course. Delayed development for over 2 years. I dont think we will see that happen again. initial on licence 320 million in milestone fees and now it is developed into phase 2.

Either combo with PD-1 or Wee1 with LDG should yield excellent results in clinical trials.

Until handed back and analysed by CPF it is just a waiting game.

As many will know here it was taken down from the shop window so as to speak around April 20. Clearly not for sale.

Regards

Trader Matt and as Ahfam said to Warthog. 'it was not a rejection.
With regards to 1801 the review by GLPMA had not even been started at time of AGM.

Still a bit early l feel for news on 737. But, TM stated a couple of weeks to get data back and between a day and a month to sort through it.

The two options that were put forward by TM was rapid on license or develop more and then on license.

My own view is a pharma buy the bl00dy compound outright for around 750 million.

It would give Sareum a couple of hundred million.

We are in a sweet spot with 737 at the moment but not duly reflected in SP.

Regards

Lately l think l wonder if anyone that will review or are reviewing the GLP compliance inform very close friends. Strictly not l think, too many upstanding, law abiding and honest citizens in the world.

AZ did not flop miserably they said. However they like to phrase it, it was still a failure.

Jemperli is owned bt GSK and doubtful whether they would be interested. They have their own combination inhibitors.

Notice the areas that the big pharma are pushing into. China and even pushing the drug in all Indications to the poorer areas. They don't give a toss whether the drug works or not as long as they can commercialise. No phase trials apply as such here.

Plenty if data on CHK 1 about and pre clinical combinations look outstanding compared to current standards of treatment.

However , take time and money to commercialise.

Regards

An excerpt from Michelle Garret. ( not in the link shown below)
The current study used the drug SRA737, a CHK1 inhibitor identified on a research project initiated by Professor Michelle Garrett, formerly of The Institute of Cancer Research (ICR) and now Professor of Cancer Therapeutics at the University of Kent’s School of Biosciences. The cancer cell killing activity of SRA737 was enhanced by blocking the function of the B-family of DNA polymerases that are important for DNA replication. This was achieved in both lung and bowel cancer cells using an experimental inhibitor of B-family DNA polymerases combined with SRA737.

The study also reports that cancer cells with low amounts of B-family polymerases may also be more susceptible to treatment with CHK1 inhibitors alone. This potentially provides a way to identify those cancer patients who may respond to a CHK1 inhibitor such as SRA737.

'Of the discovery, Professor Garrett said: ‘This work shows the potential benefit of blocking B-family DNA polymerases to boost the activity of drugs like SRA737 that target CHK1. It’s important too we have shown that detection of low levels of B-family DNA polymerases in tumours could be used to identify patients most likely to respond to a CHK1 inhibitor. Both discoveries offer a new approach to cancer treatment.’

If you look at figure 4 in the link you will see diagram indicating cell cycle. The mutated P53 gene inhibits tumour response to interferon beta. Then it would appear we have targeting interferon therapy. Maybe a means to overcome?
Notice also programmed death ligand 1 and its programmed death receptor. A reason maybe for very positive result and application for patent protection by SO for sra737 and PD-1 inhibitor.

regards

Just a refresher

Loss of p53 flips a microRNA switch to re-program neurons Damage to the p53 gene is a major characteristic of head and neck cancers. A tumor-suppressing master transcriptional gene that governs the expression of many other genes, p53 is also mutated in a variety of cancers.

Control of the P53 gene still looks crucial.
A long read and will take a while to digest.

It does indicate scope for a variety of approaches.

https://cancerci.biomedcentral.com/articles/10.1186/s12935-021-02396-8

The only involvement by CRT is by the two co leaders of the 737 project Paul Workman and Michelle Garret. Michelle Garrett was an advisor to SO and also carried out further research work with CHK1 inhibitors that included 737 and prexasertib.
Prexasertib was discontinued for clinical development due to toxicity issues and only available for research purposes.

The main objective of the CPF is to seek partners or on licensees to further develop a treatment through clinical trials.

regards

This is good for a laugh.

The FDA’s 2015 approval of Addyi was based on findings from three Phase III, randomised, double-blind, placebo-controlled studies of premenopausal women diagnosed with hypoactive sexual desire disorder.

According to Sprout Pharmaceuticals, the drug consistently showed a highly statistically significant difference over placebo on three key endpoints, including increase in sexual desire, decrease in distress from the loss of sexual desire and increase in the frequency of satisfying sex.

Those who derive benefit from treatment with Addyi reported experiencing an average of one more sexually satisfying event per month.

https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/sprout-pharmaceuticals-inc-610569-08312020

https://addyi.com/

https://swarthmorephoenix.com/2019/09/26/a-case-study-in-pharmaceutical-manipulation/

Regards

Dose escalation studies will be crucial in evaluating the value of not only 1801 but also 1802.

No idea how long before the GLP complete their review of preclinical data.

Returned SRA737 data will take a little while to process. An RNS indicating that 737 is available for on license from the CPF should push up the SP.

Have a feeling that both developments will come out within a short time of the other.

A waiting game nothing more. Not a case of if but a case of when.

regards

As an example of treatment.

Hyperventilation. Fast breathing resulting in an excess of oxygen into the body.
First aid measures are

Have the hyperventilating person breathe slowly into a paper bag that's held closely around his or her mouth and nose.
The person should breathe like this for five to seven minutes.

Talk to the individual the entire time. ..
.
If symptoms fail to improve or the person loses consciousness, take him or her to the emergency room.

The point of this example is that we do not treat the individual by allowing them to breathe in ordinary air. Ordinary air can be regarded as regulated air ie an Oxygen content of approximately 21% and around 0.4% CO2

We exhale approximately 4% Co2.

By breathing into the bag we reduce oxygen level and increase CO2 intake to compensate and reverse the effects of hyperventilation.

In many illnesses we need treatments that are well outside normal human parameters. Antibiotics and steroids produce a far greater amount of invasive cell control than that which is regulated by our own bodies. On a temporary basis it is needed to prevent poor health and in some cases death.

Regards