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New Results in Variant 501.v2 South Africa
Https://www.biorxiv.org/content/10.1101/2021.01.10.426143v1
K417(S)-D30(ACE2) and E484 (S)-K31(ACE2). These two mutations may thus be more than compensating the attractive effect induced by N501Y, overall resulting in an ACE2-binding affinity comparable to that of the wildtype RBD. Further analysis of the impact of these mutations on the interactions with mAbs targeting the spike indicate that the substitutions K417N and E484K may also abolish the salt bridges between the spike and selected mAbs, such as REGN10933, BD23, H11_H4, and C105, thus reducing the binding affinity and effectiveness of these mAbs.
but read on i have highlighted
One strategy to treat a virus infection is to develop antibodies that bind to a region of the virus that is highly conserved. However, this strategy cannot be used against the receptor binding domain, as mutations in the spike glycoprotein are frequent, making possible the evolution of mutants resistant to a single antibody. Over 7000 variants of the genome coding for the SARS-CoV-2 spike protein had been identified by April 2020. From the library the scientists had developed, they selected pairs of antibodies that could simultaneously bind to different parts of the receptor binding domain of the SARS-CoV-2 spike protein. In this way, they hoped to reduce the risk that viral mutants resistant to treatment would emerge. The antibodies were divided into four groups, according to the four epitopes in the spike protein to which they could bind. Two antibodies, ""REGN10933"" and REGN10987, were considered likely to be more effective than either alone, because they bound to two different epitopes
Https://www.cebm.net/covid-19/monoclonal-antibodies-directed-against-sars-cov-2-synthetic-neutralizing-antibodies-the-regn-cov2-antibody-****tail/
again this is the variant that so far in one Patient in Brazil has shown to re-infect
This falls back into what i said 10 months ago
For Scancell a virus its a step down in its ability and for its products
i made a difficult to treat list and because Cancer escapes the immune system Scancell had to develop vaccines that interacted beyond what a natural immune response could achieve far higher than what is required for a virus
as its turned out the Virus is a very easy target for vaccines, that has been proven by these High Efficacy rates for the current approved vaccines
The massive advantage scancell has is that we are Direct and Cross presented to Dendritic cell via effectively the adaptive system, basically Scancells Plasmid produces antibodies which is why you get these potent response its all about Signalling the high signalling rates, Keeps the T cell locked on to the APC cell for far longer giving it the High Avidity. The exciting bit is the new avidmab patent has turned the wick up again ......... from existing proved immune responses
every other vaccine out there is reliant on "Antigen take up by APC" you can improve that with Ajuvants to help improve the quality of the t cell engagement
in its pure form that is Moditope ......
AZN use a system that encodes the cell infected by the vaccine to produce the antigen ie the structure of the spike protein
moditope you inject only the protein but that is linked directly to the adjuvant
which is then taken up by the APC so the area around the injection site is not flooded with adjuvant but only the protein via this linker technology, you may consider if its so simple why has it taken so long to manufacture ...
soluble ... the most potent peptide for Moditiope is also hydrophobic
Hydrophobic literally means “the fear of water”. Hydrophobic molecules and surfaces repel water. Hydrophobic liquids, such as oil, will separate from water. Hydrophobic molecules are usually nonpolar, meaning the atoms that make the molecule do not produce a static electric field.
and then its linked ...... ISA pharma
once you have wrapped your head around that ........ which for me was a few years ago .. then you can appreciate why i keep buying regardless of market conditions
it only took one party to recognise what i understood ... and Booooom ... that was Diggle
Red Mile is the Icing on the cake .. effectively unlimited funding in the event of successful trials
so this is not about buy sell pick your timings ..... its about how many you own when this all kicks off .... oh its already started
Now at the moment Scancell appears to be making major discoveries which have not been priced in every two years
Homocitrulline Avidmab for instance .....
ATB
Gaz,
the point I was trying to make was IMO FWIW there has been a sea change in the Scancell situation. We are now funded (and the most immediate likely trial is/likely will be funded as a separate endeavour), the platforms have likely been bought towards trial readiness (they better had be since Lockdowns/Covid have provided a great deal of time for such development) and since the entire industry has been hamstrung to some degree by the Pandemic, played correctly Scancell has a great outlook on all fronts in the medium/long term on its core business, and that same optimistic outlook shorter term through Covidity.
As a result I think (again FWIW) that Scancell is in the best position it's ever been in in the Short,Medium and Long terms.
That makes me think that now we might be hopeful of a reversal from the eight/nine year downtrend to one of upward moves with smaller retraces. rather than the downward moves with the lesser recoveries.
We also have Interested and Financially astute Institutional backers who certainly don't invest (and I use the word advisedly) in companies without having assessed the likely future development and commercial possibilities for their products.
Scancell has a broad spread of IP and a globally saleable immediate vaccine that all need to be proved.
Anyone want to bet that Covidity isn't the first of the products to produce Data?
If it does become the first to produce trial Data (and to me that seems likely) then it seems to me that we are a Covid stock with (other) benefits.
that's why I think Scancell looks the most exciting stock in my portfolio on a medium term view.
AIMO
DYOR
ATB
TF, Just though it needed expanding a bit more, that's all.
Your Title implied that the BioNtech vaccine works against all known variants
unfortunately, that is not proven
If you had read and understood that link , why not Present it with the correct Title ?
I hope you don't take issue with this as you frequently repost from others on items you find interesting
ATB
Hasiba, I think you may have missunderstood what we are talking about
The reason why to vaccinate is because of "mutations" this is not about pandemic control , because at present you have no proof that the vaccines Sterilise , you may take away the ability of Covid to kill but not the mild infection that still comes from continued ongoing infections even after vaccination.
and it's that ongoing infection which will drive immune escape from the vaccine
Sacncells Covidity should take away that ability, because it targets a conserved area
Don't forget this is a Global problem, not just the UK, so that was my estimate that at least two years (so a best guess really). Just out of interest, my Son is just 40 and his Jab is confirmed here in the UK for February 2022!
ATB
Hasiba
It will take at least two years to vaccinate everybody ! are you saying the South African mutation is a "One off" , it has major changes to the Spike and it will probably mutate again .
look at the effects of the UK variant, might be ok for this vaccine but a serious change in transmission rates
the problem when you dont't plan for " unknown territory " is exactly why we are here now
Scancell vaccine if it works against the N also future proofs .
£1/2b valuation
which brings me to AZN/Oxford
they cannot keep using the same vector as the immune system will build resistance against it
so they cannot tweak the vaccine like biontech ...
taking them out of the race as they will have to start fresh trials with different vectors
so the yearly Modified jab may not be possible
BioNtech has temperature issues
Scancells DNA does not
ATB
Lets work this out
Variants could cause the industry to constantly update "Spike Vaccines"
the industry concentrates on Anti bodies not T cells
Scancell concentrate on Both antibody and T cells against multiple targets inc Spike and conserved area and is Known for its "Proven" cross presentation technology to stimulate potent t cells ... now with the addition of Avidmab technology
Ruck valuation £1/2 billion for Scancell entire IP if successful at phase 3 on all its range
yet ..............
the Covid Market has been valued
The future market for Covid-19 vaccines could be worth more than $10bn (£7.6bn) in annual revenues for pharmaceutical companies, according to industry experts, even though some drugmakers have pledged to provide their vaccines on a not-for-profit basis during this pandemic.
The calculations by analysts at Morgan Stanley and Credit Suisse assume people will need to be vaccinated every year, similar to the traditional flu jab, with an average price of $20 for a Covid-19 vaccine dose. Prices range from $3 a dose to $37.
Matthew Harrison, an analyst at Morgan Stanley, estimates that even if only those who receive an annual flu jab take a Covid-19 shot, this would generate $10bn a year in revenues for the pharmaceutical industry in the US, Europe and other developed countries. He put the cost of producing a vaccine at $5-$10 a dose. The size of the market depends on whether people need to take the vaccine every year, or less frequently, as well as vaccination rates, and could be worth up to $25bn a year globally, he said.
Https://www.theguardian.com/business/2020/nov/05/future-market-for-covid-vaccines-could-be-worth-more-than-10bn-a-year
Abstract
The N501Y and K417N mutations in spike protein of SARS-CoV-2 and their combination arise questions but the data about their mechanism of action at molecular level is limited. Here, we present Free energy perturbation (FEP) calculations for the interactions of the spike S1 receptor binding domain (RBD) with both the ACE2 receptor and an antibody derived from COVID-19 patients. Our results shown that the S1 RBD-ACE2 interactions were significantly increased whereas those with the STE90-C11 antibody dramatically decreased; about over 100 times. The K417N mutation had much more pronounced effect and in a combination with N501Y fully abolished the antibody effect. This may explain the observed in UK and South Africa more spread of the virus but also raise an important question about the possible human immune response and the success of already available vaccines.
Competing Interest Statement
The authors have declared no competing interest.
Https://www.biorxiv.org/content/10.1101/2021.01.07.425740v1
Https://www.biorxiv.org/content/10.1101/2020.12.23.424283v2
Part 2
TF your link and post because it carries no information from yourself or any in depth look and is not as Rosy as it appears
A healthcare worker prepares a Pfizer coronavirus disease (COVID-19) vaccination in Los Angeles, California, U.S., January 7, 2021. REUTERS/Lucy Nicholson
The not-yet peer reviewed study by Pfizer and scientists from the University of Texas Medical Branch indicated the vaccine was effective in neutralizing virus with the so-called N501Y mutation of the spike protein.
The mutation could be responsible for greater transmissibility and there had been concern it could also make the virus escape antibody neutralization elicited by the vaccine, said Phil Dormitzer, one of Pfizer’s top viral vaccine scientists.
The study was conducted on blood taken from people who had been given the vaccine. Its findings are limited, because it does not look at the full set of mutations found in either of the new variants of the rapidly spreading virus.
Dormitzer said it was encouraging that the vaccine appears effective against the mutation, as well as 15 other mutations the company has previously tested against.
“So we’ve now tested 16 different mutations, and none of them have really had any significant impact. That’s the good news,” he said. “That doesn’t mean that the 17th won’t.”
Dormitzer noted another mutation found in the South African variant, called the E484K mutation, is also concerning.
The researchers plan to run similar tests to see if the vaccine is effective against other mutations found in the UK and South African variants and hope to have more data within weeks.
Scientists have expressed concern that vaccines being rolled out may not be able to protect against the new variants, particularly the one that emerged in South Africa.
Simon Clarke, an associate professor in cellular microbiology at the University of Reading, said this week that while both variants had some new features in common, the one found in South Africa “has a number additional mutations” that included more extensive alterations to the spike protein.
The Pfizer/BioNTech vaccine and the one from Moderna Inc, which use synthetic messenger RNA technology, can be quickly tweaked to address new mutations of a virus if necessary. Scientists have suggested the changes could be made in as little as six weeks.
N501Y
Rapidly spreading variants of SARS-CoV-2 that have arisen in the United Kingdom and South Africa share the spike N501Y substitution, which is of particular concern because it is located in the viral receptor binding site for cell entry and increases binding to the receptor (angiotensin converting enzyme 2). We generated isogenic N501 and Y501 SARS-CoV-2. Sera of 20 participants in a previously reported trial of the mRNA-based COVID-19 vaccine BNT162b2 had equivalent neutralizing titers to the N501 and Y501 viruses.
N501y and K417N
Part 1
I suspect this is the path Scancell Covidity takes to activate Antibodies so the control is the Professional APC cross primed with Immunobody
Https://www.google.com/url?sa=i&url=https%3A%2F%2Fstep1.medbullets.com%2Fimmunology%2F105061%2Fhumoral-mediated-immunity&psig=AOvVaw2KRkRL7nOwNCX2VLqkvR9C&ust=1609953408799000&source=images&cd=vfe&ved=0CAIQjRxqFwoTCMC9iIymhe4CFQAAAAAdAAAAABAb
now you can see the Major difference in the way these antibodies are created
Oxford Route
The Oxford vaccine contains the genetic sequence of this surface spike protein. When the vaccine enters cells inside the body, it uses this genetic code to produce the surface spike protein of the coronavirus. This induces an immune response, priming the immune system to attack the coronavirus if it later infects the body.
completely reliant on the innate immune system to respond so has no control of that process
BioNtech is very similar
Once the mRNA vaccine is injected into a person, the lipid nanoparticles protect the mRNA from degradation and help it reach the cells where the information contained in the mRNA strand is read to produce the antigen protein that eventually triggers the desired immune response.
Scancell is straight to adaptive ... fully controls the process
Hope that explanation helps
You can now see the benefits of testing .......
BioNtech Tested 4 vaccine candidates
Oxford only developed one
Inovio 2hrs ... Dr Kim the star
scancell .......... 15 and spent 4 moths getting it right indeed it spun of a new patent as scancell integrated two technologies and a new delivery system
result
Gov Funding
New patent for Immunobody giving it a seriously valuable commercial life
a Chance to Test the Avidmab platform in the clinic at little cost bearing in mind we have 3 collaborations
Scancell's development pipeline includes mAbs against specific tumour-associated glycans (TaGs) with superior affinity and selectivity profiles, that have now been further engineered using the Company's AvidiMab™ technology; this confers the Scancell anti-TaG mAbs with the ability to directly kill tumour cells. The Company has entered into three non-exclusive research agreements with leading antibody technology companies to evaluate the Company's anti-TaG mAbs including those enhanced with the AvidiMab™ technology.
the commercial overlap ........................
its a very important RNS
ATB
Evening C7,
Best wishes to you
On the SCLP front, just like to say that whatever "we, the BB" may say or have oninions on regarding this company, it will not make any real difference really on the outcome. We are "in" or "out" on the shares so just remember that.
We can all chat on about SCLP, and all our other issues, but IMO this will not make any substantial changes to the final outcome.
We do need IP info though on all fronts, so please all keep researching and posting on all fronts.
Very much appreciated, thank you all.
Bunsie
C7,
Of course, my best wishes to you too.
What a year we have had to endure, maybe next year could be better.
Also, with all this time on my hands, I have got into a better lifestyle physically but maybe not mentally.
All the best to everyone on the BB.
Would be nice though to get a few techi/IP insights though at some point, where are our I/P guys these days? Could someone give Burble a nudge perhaps, we have nobody else now on that front.
Bunsie