BGBIO: FORSKNING OG MEDISINER RELATERT TIL BerGenBio


Her er en samling forskningsrelaterte artikler som samlet sett indikerer at de vaksinene som er under utvikling i fase III i dag, kanskje ikke kommer til å virke mer enn noen måneder, eller at de kanskje til og med kun kommer til å virke mot den opprinnelige virusvarianten D614 (Original Wuhan strain), mens det i dag finnes veldig mange andre varianter, der D614G er den som øker mest og er den mest vanlige.
Det finnes mange andre sars-cov-2 varianter, blant annet V483G* som har vist seg langt mer smittsom, uten å være mindre dødelig (så langt). Denne finnes nå i Brasil, Midt-Østen, UK og i USA.
(Her er en god artikkel som viser virusvarianter som nå er mest utbredt i ulike verdensdeler https://www.news-medical.net/news/20200925/D614G-mutation-now-the-dominant-variant-in-the-global-COVID-19-pandemic.aspx)

Årsaken til at vaksinene kanskje ikke kommer til å være effektive skyldes blant annet at antistoffer ser ut til å forsvinne relativt raskt, samt at vaksinene som nå er i fase III ble ferdigstilt rundt mars måned 2020, og har derfor ikke inkludert mutasjoner som har kommet til senere, eller som ikke var vanlige på det tidspunktet.


En kanadisk studie ledet av forskere ved Temerty Faculty of Medicine ved Universtitetet i Toronto viser at antistoffer kun er effektive i 3 måneder fra man får covid-19 symptomer. IgA og IgM antistoffer falt kraftig, og forsvant etter 3 måneder. IgG antistoffer var stabile opp til 105 dager etter virussykdommen inntraff. Studien vurderte til og med dag 115 (studien stoppet der). De siste dagene fra dag 105 til dag 115 ble det observert signifikant reduksjon i IgG, men siden studien ikke pågikk lengre er det vanskelig å dra konklusjoner ut av dette.
IgA antistoffer er antagelig de viktigste antistoffene mot covid-19, og kan være såkalte "neutralizing antibodies".
Flere studier har funnet at antistoffer mot sars-cov-2 i seg selv ikke beskytter mot covid-19. Det er "neutralizing antibodies" som beskytter best.
"Indeed, IgA is an important mediator of protection against gastrointestinal viruses (38), is essential in achieving immunity against avian viruses (39), has been shown to contribute to the neutralizing antibody (nAb) response to SARS-CoV-2 (28)".
https://www.thailandmedical.news/news/covid-19-antibodies-university-of-toronto-study-shows-that-sars-cov-2-coronavirus-antibodies-last-for-only-about-three-months-after-infection
https://immunology.sciencemag.org/content/5/52/eabe5511

En studie viste at barn kan ha IgG antistoffer mot SARS-COV-2, samtidig som de er smittet med SARS-COV-2.
https://www.thailandmedical.news/news/breaking-covid-19-pediatrics-study-shows-that-kids-can-have-the-sars-cov-2-coronavirus-and-the-antibodies-simultaneously
https://www.medrxiv.org/content/10.1101/2020.08.06.20162446v1

"SARS-CoV-2 reinfection in two patients who have recovered from COVID-19"
"During the second admission, both patients showed increases in their IgG anti-SARS-CoV-2 titers, and one patient also showed renewed reactivity for IgM anti-SARS-CoV-2. As both had recovered clinically and had negative throat swab viral RNA for 43–58 days before they became sick again with positive throat swab viral RNA together with an increase in IgG antibody (with one also showing IgM again), they were considered as having SARS-CoV-2 reinfection."
https://academic.oup.com/pcm/advance-article/doi/10.1093/pcmedi/pbaa031/5901533

ANTISTOFFER TILSVARENDE DET NIVÅ FORSØKSPERSONER FÅR ETTER BOOSTING DOSE (dose nr 2) MED COVID-19 VAKSINE HINDRET IKKE REINFEKSJON HOS PASIENT MED D614G strain.
https://www.thailandmedical.news/news/must-read-study-involving-case-of-reinfection-questions-efficacy-of-covid-19-vaccines-under-development-or-trials-against-em

"Covid-19 Immunity short-lived for those who are asymtpomatic or had mild symptoms. Doubts raised about ability of vaccines to really work".
https://www.thailandmedical.news/news/covid-19-immunity-short-lived-for-those-who-are-asymptomatic-or-had-mild-symptoms-doubts-raised-about-ability-of-vaccines-to-really-work
https://www.medrxiv.org/content/10.1101/2020.09.05.20187435v1.full.pdf

"Antibodies COVID-19: Another study shows that antibodies not effective in treating COVID-19 and warns of vaccines focusing only on spike proteins"
https://www.thailandmedical.news/news/antibodies-covid-19-another-study-shows-that-antibodies-not-effective-in-treating-covid-19-and-warns-of-vaccines-focusing-only-on-spike-proteins
https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1008796

En artikkel som beskriver hvordan sars-cov-2 smitten spres i land av asymptomatiske pasienter.
https://www.thailandmedical.news/news/the-frightening-tale-of-a-hypothetical-south-east-asian-country-where-4-percent-of-its-population-might-already-been-affected-by-milder-strains-of-sar

"COVID-19 Immunity: Study shows that protective immunity to current seasonal coronaviruses are short-lasting, SARS-COV-2 could be the same".
Studien går tilbake til data fra 1980-tallet til i dag, og ser på infeksjoner med coronavirus. Pasientene hadde 3-17 reinfeksjoner med coronavisu, og reinfeksjon skjedde fra 6-105 måneder. Reinfeksjoner ble hyppig observert etter 12 måneder.
https://www.thailandmedical.news/news/covid-19-immunity-study-shows-that-protective-immunity-to-current-seasonal-coronaviruses-are-short-lasting,-sars-cov-2-could-be-the-same
https://www.nature.com/articles/s41591-020-1083-1

"COVID-19 herd immunity is impractical and disastrous according to new study plus emerging studies indicate immunity is short lived".
https://www.thailandmedical.news/news/covid-19-herd-immunity-is-impractical-and-disastrous-according-to-new-study-plus-emerging-studies-indicate-immunity-is-short-lived
https://www.pnas.org/content/early/2020/09/21/2008087117

"Coronavirus latest: Experts concerned as reinfections occuring in shorter intervals, also new study shows antibodies in infected diminish in about 60 days".
https://www.thailandmedical.news/news/coronavirus-latest-experts-concerned-as-reinfections-occurring-in-shorter-intervals,-also-new-study-shows-antibodies-in-infected-diminish-in-about-60-
https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciaa1436/5908892

"MUST READ! Study involving case of reinfection questions efficacy of covid-19 vaccines under development or trials against emerging mutated strains".
https://www.thailandmedical.news/news/must-read-study-involving-case-of-reinfection-questions-efficacy-of-covid-19-vaccines-under-development-or-trials-against-emerging-mutated-strains

"BREAKING!! Covid-19 immunity: New study that is yet to be peer-reviewed says humans may never develop immunity against covid-19".
https://www.thailandmedical.news/news/breaking-covid-19-immunity-new-study-that-is-yet-to-be-peer-reviewed-says-humans-may-never-develop-immunity-against-covid-19
https://www.medrxiv.org/content/10.1101/2020.06.13.20130252v1.full.pdf+html


Missed the cut:
https://www.thailandmedical.news/news/covid-19-antibodies-new-york-university-scientist-discover-that-up-to-75-percent-of-recovered-covid-19-patients-have-low-neutralizing-antibody-titers
https://www.thailandmedical.news/news/breaking-covid-19-re-infections-more-cases-of-documented-covid-19-re-infected-cases-emerging-first-hong-kong,-now-belgium-and-netherlands
https://www.thailandmedical.news/news/covid-19-vaccine-researchers-identify-t-cell-epitopes-for-effective-vaccine-development
https://www.thailandmedical.news/news/thailand-covid-19-news-6-new-imported-cases-of-which-3-are-reinfections-opening-of-phuket-to-foreigners-delayed,-phangnga-imposes-strict-measures-
https://www.thailandmedical.news/news/rare-covid-19-antibody-development-in-cancer-patients-observed-in-german-study (Kun 6 av 77 smittede i en tysk studie hadde antistoffer).
https://www.thailandmedical.news/news/india-covid-19-coronavirus-news-documented-reinfections-emerging-in-india,-vaccines-and-antibodies-being-questioned,-record-94,000-cases-in-24-hours
https://www.thailandmedical.news/news/breaking-covid-19-research-mutated-sars-cov-2-spike-protein-variants-evade-neutralizing-antibodies-warning-of-emergence-of-antibody-resistant-variants
https://www.biorxiv.org/content/10.1101/2020.07.21.214759v1.full.pdf
https://www.thailandmedical.news/news/breaking-covid-19-reinfections-israeli-doctor-reinfected-with-sars-cov-2-just-12-weeks-after-recovering,-more-reinfections-appearing-globally
https://www.timesofisrael.com/israeli-doctor-diagnosed-with-virus-after-apparently-recovering-from-covid-19
https://www.publichealth.columbia.edu/public-health-now/news/risk-coronavirus-reinfection-remains-after-recovery
https://www.medrxiv.org/content/10.1101/2020.04.27.20082032v1

"Reinfections" i nyhetene:
https://www.sciencealert.com/35-year-study-of-coronavirus-reinfections-suggests-human-immunity-is-short-lived
https://news.harvard.edu/gazette/story/2020/10/covid-survivors-may-have-four-months-of-protection/
LES DENNE: https://www.scientificamerican.com/article/what-covid-19-reinfection-means-for-vaccines/
"The Kenya study on endemic human coronaviruses, however, offers evidence to the contrary that may turn out to be applicable to SARS-CoV-2. In some patients, it was found that high antibody levels actually potentiated infection rather than preventing or mitigating it"
https://bgr.com/2020/10/06/coronavirus-immunity-reinfection-cases-mount-second-wave/
https://www.theguardian.com/world/2020/oct/06/flurry-of-coronavirus-reinfections-leaves-scientists-puzzled
https://www.mlive.com/news/muskegon/2020/10/rise-of-coronavirus-in-nursing-homes-has-muskegon-county-probing-possible-reinfections.html


*V483G mutasjonen er motstandsdyktig mot antistoffer.
https://www.thailandmedical.news/news/v483g-mutation-warning-about-growing-prevalence-of-new-sars-cov-2-mutant-strain-v483g-that-is-antibody-resistant-and-even-more-infectious
Forøvrig spekuleres det i at dersom monoclonal antibodies fungerer (det Trump fikk), så kan prisen på hver behandling bli 6-8000 dollar.
Redigert 21.01.2021 kl 09:40 Du må logge inn for å svare
klaesp
02.12.2020 kl 08:24 5775

Flott, blir spennende å se hvor fort vaksineringen går og virning på vaksine ... Skal lagres i minus 80 grader og det skal gis 2.doser på hver pasient.
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare
BioBull
02.12.2020 kl 08:54 5721

Blir spennende å se når Bemcentinib blir “Booster” for Pfizer vaksinen


Storbritannia er første vestlige land som godkjenner Pfizer og BioNTechs coronavaksine. Vaksinen vil bli tilgjengelig allerede fra neste uke.
– Myndighetene har i dag akseptert anbefalingen fra enkeltstående Medicines and Healthcare products Regulatory Agency (MHRA), om å godkjenne Pfizers vaksine, sier myndighetene.
– Vaksinen vil bli tilgengelig over hele landet fra neste uke.
BioNTech, det tyske biotekselskapet som har utviklet vaksinen i samråd med Pfizer, sier i et notat at selskapet er klart til å levere vaksiner til Storbritannia umiddelbart.
– Dette markerer en historisk dag i kampen mot coronaviruset, sier Pfizer-sjef Albert Boura.
– Med tusener av nye smittetilfeller teller hver dag i dette løpet om å avslutte denne hardtslående pandemien
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare
Nanoq
02.12.2020 kl 14:22 5543

Håper ikke det kommer mange negative vaksinehistorier ut, den slags kan fort skape stor usikkerhet og stor vaksinemotstand i befolkningen...

her blir det bruk for meget troverdig kommunikasjon fra myndighetenes side - også på de sosiale media - med meget gode forklaringer fra troverdige fagfolk, ellers kan dette fort bli katastrofalt for alle parter.
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare
Nanoq
02.12.2020 kl 15:36 5456

Interessant Merck-nyhet i dag:

Bloomberg

Moderna Falls After Merck Sells Stake in the Vaccine Maker

John Lauerman

Wed, December 2, 2020, 3:00 PM GMT+1

(Bloomberg) -- Moderna Inc. shares fell after Merck & Co. said it sold its stake in the biotechnology company that’s in the midst of developing a Covid-19 vaccine.

Merck sold its direct equity investment in Moderna during the first half of the fourth quarter, according to a statement from the U.S. drugmaker on Wednesday. No terms of the sale of the holdings were given.
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

Denne er styggere! Han har jo solgt tidligere også.
"Moderna's CEO sold nearly $2 million of his stock ahead of the company's emergency use vaccine filing. He's now worth $3 billion."
https://www.businessinsider.com/moderna-ceo-sold-million-stock-company-emergency-use-vaccine-filing-2020-11

Les deg opp på bakgrunnen til Bancel, så er det lett å føle på litt ugler i mosen der... Les om arbeidsforholdene i selskapet, hva folk sier når de slutter osv. Det er ikke en vaksine jeg skal ta. Det selskapet stinker lurendreierier.
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare
Nanoq
02.12.2020 kl 22:01 5254

Kan se at Moderna-selskapet nå har en børsverdi på ca. 57 milliarder USD = ca. 500 milliarder NOK... 8 X mer enn for 1 år siden...

og de tjener fortsatt ingen penger, men går i minus med riktig mange millioner hvert kvartal...

Så ikke merkelig at noen av aksjonærene begynner å selge seg ned/ut nå. Dette ligner en aksjeprisboble som er klar til å implodere. Likesom Tesla...

Det er mange Covid-19 vaksiner på vei ut i markedet nå, både fra USA/Tyskland, UK, Kina og Russland. Og med andre land som Danmark også på vei med en vaksine...

Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare
BioBull
02.12.2020 kl 23:33 5052

Selv om BerGenBio ikke er Moderna - har BerGenBio en mer robust medisin som faktisk dreper COVID-19 og kreft med kroppens eget immunforsvar ( T- celler ) med en pille om dagen : BEMCENTINIB!

M-Cap på BerGenBio tilsvarende Moderna er ca 6000kr pr BGBIO aksje ... JUST SAYING ....
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare
Rule
03.12.2020 kl 00:29 4971

holy mother f.... - det er sygt. Jeg tænkte nyligt idag, da jeg læste danske covid19 tal at hvis jeg skulle blive smittet så vil jeg spørge min læge om jeg ikke kan få bemcentinib ! ! !
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

I fase III studien på Pfizer vaksinen med ... hva er det nå? ... nærmere 50-60.000 personer de testet den på? ... så ble det ikke rapportert om bivirkninger man kunne bekrefte skyldtes vaksinen.

Men så... blant de aller første som fikk Pfizer vaksinen i England utenfor studien, fikk 2 stykker alvorlige allergireaksjoner og måtte få behandling.

Her kommer det nok mer etter hvert. Stay tuned..

https://finansavisen.no/nyheter/helse/2020/12/09/7596722/storbritannia-med-allergiadvarsel-for-pfizer-vaksinen
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

Er det ikke dette de nå prøver å finne rett svar på nå BioBull? Det er vel ikke avklart ennå ellers hadde vel ikke verden kjørt disse forsøkene?. Du har svaret forstår jeg?
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare
klaesp
12.12.2020 kl 09:27 4316

Vaksinefiasko fra Glaxosmithkline og Sanofi

Britiske Glaxosmithkline og franske Sanofi har hatt skuffende resultater fra sine siste tester for en koronavaksine. Deres tester viser for store bivirkninger.

De to legemiddelgigantene må starte nye fase-3-tester i februar.

Tross forsinkelsene regner de to selskapene fortsatt med å være med på å spille en rolle i den globale vaksineringen i 2021

Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare
BioBull
12.12.2020 kl 10:07 4292

Det er avklart - ingen allergiske reaksjoner - bare gode resultater, kun noe papirarbeid gjenstår. STAY TUNED...
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare
klaesp
14.12.2020 kl 17:20 4042

Ny variant av covid viruset.
https://www.tv2.no/nyheter/11837582/
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

CNN nå:

Covid vaccines may not reach a quarter of the world's people until 2022, study finds

From CNN’s Maggie Fox

Dr. Victoria Adams, Infectious Diseases Clinical Pharmacist, holds one of the first Pfizer Covid-19 vaccine doses in the vaccination pod at Mt. Sinai Hospital in New York, on Tuesday, December 15. Victor J. Blue for CNN

Just over half of all planned doses of coronavirus vaccines have been bought up by high-income countries such as the US, Japan and Australia, which means as much as a quarter of the world’s population will be unable to get vaccinated until 2022, researchers reported Tuesday.

These rich countries have pre-ordered close to 7.5 billion doses of Covid-19 vaccines, enough to vaccinate 3.76 billion people, Anthony So of the Johns Hopkins Bloomberg School of Public Health and colleagues found.

“Just over half (51%) of these doses will go to high income countries, which represent 14% of the world’s population,” they wrote in their report, published in the BMJ.

At the time the report was written, the US accounted for one-fifth of all global Covid-19 cases but had reserved 800 million doses of vaccine. Japan, Australia, and accounted for fewer than 1% of cases but had options on 1 billion doses.

The researchers projected that the 13 major vaccine manufacturers working on coronavirus vaccines had the potential capacity for close to 6 billion courses of vaccine by the end of 2021. 

“High income countries have reserved just over half of these vaccine doses from 13 leading vaccine manufacturers. Low and middle income countries have the remainder, despite these countries comprising more than 85% of the world’s population,” they wrote.

“Even if all 13 of these vaccine manufacturers were to succeed in reaching their maximum production capacity, at least a fifth of the world’s population would not have access to vaccines until 2022.”

There’s one effort that is trying to get around this – COVAX, coordinated by the World Health Organization, global vaccines initiative Gavi and the Coalition for Epidemic Preparedness Innovations (CEPI). The group is trying to build manufacturing capacity for 2 billion doses of coronavirus vaccine. 

“The COVAX Facility could play a key role in ensuring access to Covid-19 vaccines. However, its target of two billion doses by the end of 2021 is still short on premarket vaccine commitments and financing to deliver on this goal,” So’s team noted.

.........
Med andre ord: Dersom BerGenBio lykkes med bemcentinib mot covid, så kommer det likevel til å bli stort behov. I tillegg kommer mulighet for å behandle personer post covid for fibrose etc

Husk at fibrose antageligvis er forstadiet til mange typer kreft.
I USA ligger det i skrivende stund 112.000 personer på ICU (intensiv). Det kommer i tillegg til alle som er innlagt med covid, men som ikke ligger på intensivavdeling. Studier så langt viser at en svært høy andel av disse får skader på lunger, blodårer, lever, nyrer og i hypothalamus (+ skader i reproduksjonsorgan som er mest relevant for de unge pasientene).
Hvor mange dette gjelder globalt gjennom hele pandemien når pandemien en gang er slutt... det er ikke godt å si. Men mulighetene er mange for bemcentinib.
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

Nearly one third of Black Americans remain hesitant to get Covid-19 vaccine, study finds

From CNN's Nicquel Terry Ellis

As the first Covid-19 vaccinations are being administered across the country this week, Black Americans remain among the groups that have the least confidence in the vaccine, according to a study from the Kaiser Family Foundation.

The findings come as the nation's top health leaders urge Black people to trust the vaccine, by hosting live events where Black health professionals are among the first to receive and administer it.

The Kaiser study found that 35% of Black Americans would probably or definitely not get the vaccine if it was determined to be safe by scientists and widely available for free.

Of the Black Americans who are hesitant to get the vaccine, the majority, or 71%, said they were concerned about possible side effects, half were worried they would get Covid-19 from taking the vaccine and 48% said they have a general distrust in vaccines.

Other studies have noted that Black and Latino people cite distrust in the federal government and the nation's history of racism in medical research as key reasons for their hesitancy.

Sandra Lindsay, a Black critical care nurse at Long Island Jewish Medical Center, was one of the first Americans to receive the vaccine on Monday. It was delivered by Dr. Michelle Chester, the corporate director of employee health services at Northwell Health, who is also Black.

Lindsay told CNN's Anderson Cooper that she felt fine after taking the vaccine. Lindsay said the shot felt no different than the influenza vaccine she gets annually.

"I have no fear. I trust my profession is deeply rooted in science ..." Lindsay said. "What I don't trust is getting Covid-19 because I don't know how it will affect me and the people around me that I could potentially transfer the virus to."

Nearly 40% of reported Covid-19 cases have been Black and Latino people, according to the Centers for Disease Control and Prevention.

Many people of color are concerned the vaccine developers haven't take into account the needs of their ethnic group, the Kaiser study shows.

It found that 48% of Black adults said they were not confident the needs of Black people were considered and 36% of Latino adults said the same about the needs of Latino people. 

However, people of color overwhelmingly, or 85%, said they would trust vaccine information from their personal doctor or health care provider at least a fair amount, according to the study.

Black doctors have been at the forefront of efforts to build trust around the vaccine with Black people.

Dr. Yves Duroseau, chair of emergency medicine at Lenox Hill Hospital, was also among the first to receive the vaccine this week. Duroseau told CNN's Poppy Harlow that he hoped to influence communities that have been disproportionately impacted by Covid-19.

"With the rollout of the vaccination there has been, quite frankly, message that we have to be ethical about this, we have to be fair, we have to protect the vulnerable," Duroseau said.

"And we have to reach out to not just minorities but rural areas, we have to make sure that everyone is included."

Ernest Grant, the president of the American Nurses Association, participated in a vaccine trial this fall to combat fears in the Black community with taking the vaccine.

"At some point there's always that potential that it (Covid-19) could happen to you and if I know there is a cure that could potentially save me from that, I think I would go for the cure," Grant told CNN last month.

Dr. Anthony Fauci recently acknowledged Dr. Kizzmekia Corbett, a Black woman and one of the lead scientists who helped develop the vaccine, with hopes that it would convince Black people to trust the process.

"So, the first thing you might want to say to my African American brothers and sisters is that the vaccine that you're going to be taking was developed by an African American woman," Fauci said at a National Urban League event earlier this month. "And that is just a fact."

Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare
xjack
16.12.2020 kl 08:17 3436

monitor1 skrev Innlegget er slettet
Var det en bedre ide, monitor1, å bruke natten til å få god, sammenhengende søvn?
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

Vi har snakket en del om Axl inhibition, og EMT reversal effekt for bemcentinib, og hvilke konsekvenser det har for den antivirale effekten for bemcentinib mot covid.

Denne studien viser konsekvensene av lav eller normal intracellular interferon mot Sars-CoV-2. Som kjent ser vi mer enn dobling av intracellular inteferon som konsekvens når bemcentinib gis til sars-cov-2 infiserte celler (se video av Wendy Maurys presentasjon på R&D dagen).


"Abstract

To understand the diversity of immune responses to SARS-CoV-2 and distinguish features that predispose individuals to severe COVID-19, we developed a mechanistic, within-host mathematical model and virtual patient cohort. Our results indicate that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses. In these in silico patients, the maximum concentration of IL-6 was also a major predictor of CD8+ T cell depletion. Our analyses predicted that individuals with severe COVID-19 also have accelerated monocyte-to-macrophage differentiation that was mediated by increased IL-6 and reduced type I IFN signalling. Together, these findings identify biomarkers driving the development of severe COVID-19 and support early interventions aimed at reducing inflammation.

Competing Interest Statement

The authors have declared no competing interest."
https://www.biorxiv.org/content/10.1101/2021.01.05.425420v1
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

"Our results indicate that virtual patients with low production rates of infected cell derived IFN subsequently experienced highly inflammatory disease phenotypes, compared to those with early and robust IFN responses."
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

Bemcentinib er så spot-on mot Sars-CoV-2, at det kunne knapt blitt bedre.
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

Her er ytterligere en studie som viser viktigheten at å oppregulere intracellular interferonproduksjon. Sars-cov-2 nedregulerer tetherin (th1) som gjør at den kan formere seg.
Bemcentinib oppregulerer interferon, som da hindrer nedreguleringen av tetherin.
https://www.biorxiv.org/content/10.1101/2021.01.06.425396v1
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

Fra hjemmesiden til National Cancer Institute:

Clinical Trials Using AXL Inhibitor BGB324 (red anm: BerGenBio sitt medikament bemcentinib)
Clinical trials are research studies that involve people. The clinical trials on this list are studying AXL Inhibitor BGB324. All trials on the list are supported by NCI.

NCI’s basic information about clinical trials explains the types and phases of trials and how they are carried out. Clinical trials look at new ways to prevent, detect, or treat disease. You may want to think about taking part in a clinical trial. Talk to your doctor for help in deciding if one is right for you.

Trials 1-5 of 5
Bemcentinib in Treating Patients with Recurrent Glioblastoma Undergoing Surgery
This phase I trial studies how well bemcentinib works in treating patients with glioblastoma that has come back (recurrent) who are undergoing surgery. Bemcentinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Location: 6 locations

A Phase Ib / II Multicenter Open-label Study of BGB324 in Patients With AML or MDS
A Phase Ib / II multicentre open label study of BGb324 as a single agent in patients with AML or MDS or in a combination with cytarabine and decitabine in AML patients. BGB324 is a potent selective small molecule inhibitor of Axl, a surface membrane protein kinase receptor which is overexpressed in up to half of AML cases.
Location: 2 locations

Bemcentinib with Nab-Paclitaxel, Gemcitabine, and Cisplatin in Treating Patients with Metastatic or Recurrent Pancreatic Cancer
This phase Ib / II trial studies how well bemcentinib in combination with nab-paclitaxel, gemcitabine, and cisplatin work in treating patients with pancreatic cancer that has spread to other places in the body or that has come back. Bemcentinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as nab-paclitaxel, gemcitabine, and cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bemcentinib with nab-paclitaxel, gemcitabine, and cisplatin may work better in treating patients with pancreatic cancer.
Location: 2 locations

Bemcentinib and Docetaxel in Treating Patients with Stage IV Non-small Cell Lung Cancer
This phase I trial studies the side effects and best dose of bemcentinib when given together with docetaxel in treating patients with stage IV non-small cell lung cancer. Bemcentinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving bemcentinib and docetaxel may work better in treating patients with non-small cell lung cancer.
Location: 2 locations

A Study of BGB324 in Combination With Erlotinib in Patients With Non-Small Cell Lung Cancer
A Phase I / 2 multi-center open-label study of BGB324 in combination with erlotinib in patients with Stage IIIb or Stage IV non-small cell lung cancer. BGB324 is a potent selective small molecule inhibitor of Axl, a surface membrane protein kinase receptor which is connected with poor prognosis and acquired resistance to therapy.
Location: See Clinical Trials.gov
https://www.cancer.gov/about-cancer/treatment/clinical-trials/intervention/axl-inhibitor-bgb324


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Tilbake i 2018 presenterte BerGenBio resultater av flere undersøkende studier. Disse studiene dannet grunnlaget for hvilke krefttyper selskapet skulle satse videre på.
Som dere vet har vi nå fått resultater fra AML (leukemi) og NSCLC (lungekreft) studiene, og begge viste solide data.


BerGenBio Provides Interim Update on Phase II Clinical Programme With Selective Oral AXL Inhibitor Bemcentinib
Published: Jun 03, 2018

CHICAGO, June 3, 2018 /PRNewswire/ -- BerGenBio ASA (OSE:BGBIO) announces that interim data from its Phase II clinical development programme with bemcentinib, a selective AXL inhibitor, was presented at a reception hosted yesterday by the company in Chicago, IL, USA. The reception, which coincides with the annual American Society of Clinical Oncology (ASCO) meeting, provided stakeholders, including clinicians, investors, analysts and media, with interim data from the ongoing clinical trials of bemcentinib alone and in combination with standard of care drugs in multiple cancer indications. Presentations were made by key opinion leaders, clinical trial principle investigators and members of the BerGenBio team.

All materials presented at the reception are available on the BerGenBio website in the Investors / Presentations section. A conference call to discuss the presentations and updates will be held on Monday 4thJune at 8:30 AM CEST (details below).

Key Findings

Note that all Phase II trials are ongoing and results presented are preliminary and subject to change as the trials progress to completion. Updated data will be presented throughout 2018.

Bemcentinib plus KEYTRUDA® (pembrolizumab) shows early promise in advanced lung cancer (NSCLC) patients who failed previous treatment (study BGBC008):
Tumour shrinkage was reported in 8 of 15 evaluable patients to date, including three Partial Responses (PR) and one mixed response,
Response assessment according to biomarker expression analysis available thus far:
6 of 7 PD-L1 negative patients reported clinical benefit, including 2 PRs and 2 patients with evidence of tumour shrinkage.
5 of 6 patients thus far tested for AXL expression with BerGenBio's proprietary immunohistochemistry assay, were AXL positive.
4 of 5 AXL positive patients reported clinical benefit including 1 PR and 2 patients with evidence of tumour shrinkage.
All 4 AXL positive patients reporting clinical benefit were found to be PD-L1 negative.
An acceptable safety profile of the combination was reported with only a minority of patients experiencing fully reversible adverse events.
Analysis of metastatic triple-negative breast cancer (TNBC) patients who had failed previous treatment and who were enrolled to receive bemcentinib plus KEYTRUDA (study BGBC007) showed low prevalence of AXL and PD-L1:
14 of 18 patients tested for AXL expression were AXL negative and reported no benefit.
12 of 15 patients tested for PD-L1 expression were PD-L1 negative; 6 were evaluable for efficacy with 1 reporting tumour shrinkage.
Superior response rates to bemcentinib monotherapy in relapsed/refractory (R/R) acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) could be predicted by soluble AXL (plasma sAXL) levels as determined by liquid biopsy (study BGBC003):
20 R/R AML and MDS patients who were evaluable for response were analysed for pre-treatment plasma sAXL
12 of 13 patients reporting sAXL levels below pre-defined thresholds at pre-treatment experienced clinical benefit, including 3 Complete Remissions, 3 Partial Remissions.
6 of 7 patients with sAXL above the threshold experienced a best response of progressive disease.
Bemcentinib in combination with established first-line therapies (KEYTRUDA or MEKINIST (dabrafenib) plus TAFINLAR (trametinib) in unresectable melanoma was well tolerated and showed encouraging tumour responses:
15 of 19 evaluable patients showed evidence of tumour shrinkage and to date there were 2 CRs, 8 PRs and a further 6 patients with a best overall response of stable disease.
Blood-based biomarker candidates were identified.
Bemcentinib in combination with targeted therapy TARCEVA® (erlotinib) or docetaxel chemotherapy (trials BGBC004 and BGBIL005, respectively) continue to show promising activity in heavily pre-treated patients:
Part C of the BGBC004 trial of bemcentinib in combination with EGFR targeted therapy introduces bemcentinib in a first-line setting in patients who have achieved their optimum benefit from TARCEVA monotherapy. 5 of 6 evaluable patients showed evidence of tumour shrinkage including 1 PR and 1 mixed response. In parts A and B, patients who achieved an objective response continue on treatment.
3 of 7 (43%) evaluable patients in a trial combining bemcentinib and docetaxel (BGBIL005) achieved durable PRs in a disease setting where the response rate to docetaxel monotherapy is expected to be 10-20%.

BerGenBio continues to develop a Bemcentinib companion diagnostic
A standardised AXL immunohistochemistry (IHC) assay, has reported strong correlation with tumour response to bemcentinib treatment.
Blood-based biomarkers continue to report correlation with tumour response to bemcentinib treatment with particularly encouraging results in R/R AML and MDS.

Richard Godfrey, BerGenBio CEO, commented: "We are excited to present these very encouraging interim results from our broad Phase II clinical development programme in a variety of tumour types with a significant unmet medical need. These results continue to support our view that bemcentinib could become a cornerstone of future cancer therapy. This data provides further evidence of bemcentinib's activity in patients whose cancer progression is mediated by AXL. In addition, we are making good progress with our studies to identify predictive biomarkers that we anticipate may be developed as companion diagnostics for personalized therapy. We look forward to advancing these studies to completion and defining the future development strategy of bemcentinib with the greatest value for patients."
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Her er en god oversikt over andre AXL hemmere, og hva de hemmer. Dere ser raskt hvor bemcentinib skiller seg ut.
Bemcentinib er det samme som BGB324 / R428

https://cancerres.aacrjournals.org/highwire/markup/344738/expansion?width=1000&height=500&iframe=true&postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed

Non-selective Axl hemmere vil normalt/sannsynligvis reagere med flere medikamenter og har flere bivirkninger. Ved at de er non-selective, så kan du oppnå noe positivt gjennom blokkering av AXL, mens du får negative bivirkninger fordi medikamentet også øker- eller hemmer andre markører.
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Takk for god info!
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BEMCENTINIB MOT COVID OG ANDRE VIRUS

"SARS-CoV-2 infection induces EMT-like molecular changes, including ZEB1-mediated repression of the viral receptor ACE2, in lung cancer models"

"Inhibition of AXL, a mesenchymal receptor tyrosine kinase, with bemcentinib downregulates ZEB1 and may serve as a therapy to shift SARS‐CoV‐2 infected cells away from a mesenchymal phenotype. Additionally, viral infection of epithelial
cells, which are glutamine‐dependent with high GLUL expression and presumably more metabolicallyprimed
for replication, promotes rapid replication due to the enhanced dependence on glutamine for
nucleotide synthesis.

Intriguingly, previous data demonstrated that over‐expression of miR‐200 family members (which inhibit
ZEB1 expression) or direct exogenous silencing of ZEB1 has a protective effect in a murine,
lipopolysaccharide‐induced model of ARDS31. In this context, our findings support a novel model for the
pathogenesis of SARS‐CoV‐2 in which the virus initially infects a small pool of highly epithelial cells of the
aerodigestive and respiratory tracts followed by those infected cells undergoing molecular alterations
typical of EMT (i.e., ZEB1 upregulation, GLUL loss). These EMT‐like alterations, in turn, result directly in
the down‐regulation of ACE2 expression and, in doing so, eradicate the proposed ARDS‐protective effect
of these ACE2‐positive cells."

"This suggests a novel model of SARS-CoV-2 pathogenesis in which infected cells shift toward an increasingly mesenchymal state and lose ACE2 expression, along with its acute respiratory distress syndrome-protective effect, in a ZEB1-dependent manner. AXL-inhibition and ZEB1-reduction, as with bemcentinib, offers a potential strategy to reverse this effect."
https://www.biorxiv.org/content/10.1101/2020.05.28.122291v1.full.pdf
https://pubmed.ncbi.nlm.nih.gov/32577652/

RE: studien over: Studien over har studert sammenhengen mellom ACE2, EMT og blant annet ZEB1. De har ikke studert Axl's rolle. Vi vet fra Wendy Maurys studier at Sars-Cov-2 viruset er avhengig av Axl for å kunne penetrere cellene via ACE2.
I tillegg vet vi at bemcentinib reverserer EMT, og vi vet at bemcentinib oppregulerer Interferon, som til sammen gjør at bemcentinib i hvert fall minst bekjemper SARS-COV-2 på 3 ulike måter. Antagelig flere, fordi det er mange følgekonsekvenser her.

Se følgende video fra 1:08:00 BerGenBio Virtual R&D Day
Videoen inneholder en gjennomgang der Wendy Maury forklarer hvordan bemcentinib virker mot covid.
I denne videoen sier hun ikke så mye om EMT, men i dag vet vi mer om EMTs rolle i covid.
(Hun visste nok mer ut fra allerede publiserte studier som indikerte EMTs rolle, men hadde ikke egen forskning på dette som hun kunne presentere).
https://vimeo.com/477021607
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"Axl Can Serve as Entry Factor for Lassa Virus Depending on the Functional Glycosylation of Dystroglycan."
https://jvi.asm.org/content/92/5/e01613-17 

"The Tyro3 Receptor Kinase Axl Enhances Macropinocytosis of Zaire Ebolavirus"
https://jvi.asm.org/content/85/1/334

"Axl Promotes Zika Virus Entry and Modulates the Antiviral State of Human Sertoli Cells"
Forskerne har brukt bemcentinib (R428). Last ned pdf for detaljer.
https://mbio.asm.org/content/10/4/e01372-19/article-info (2019)


Det er godt mulig at AXL hemming også reduserer risikoen for alvorlig covid for pasienter med diabetes.
Se for eksempel:
"AXL belongs to the TAM family of RTKS. Legend for RTK subfamilies: InsulinR, insulin receptor…"
https://cancerres.aacrjournals.org/content/77/14/3725.figures-only

https://www.researchgate.net/publication/273477358_Targeting_Inflammation_in_Type_2_Diabetes_by_Antibody-Mediated_TAM_Tyro-3_Axl_Mer_Receptor_Activation

"High glucose induces human endothelial dysfunction through an Axl-dependent mechanism"
https://cardiab.biomedcentral.com/articles/10.1186/1475-2840-13-53

Bemcentinib motvirker "endothelial dysfunction".

"COVID-19 and Rheumatoid Arthritis share myeloid pathogenic and resolving pathways"
https://www.biorxiv.org/content/10.1101/2020.07.26.221572v1

"Role of Vitamin K-Dependent Factors Protein S and GAS6 and TAM Receptors in SARS-CoV-2 Infection and COVID-19-Associated Immunothrombosis"
https://pubmed.ncbi.nlm.nih.gov/32998369/

 "ACE2-uttrykk i nyre og testis kan forårsake nyre- og testisskader etter 2019-nCoV-infeksjon"
https://www.medrxiv.org/content/10.1101/2020.02.12.20022418v1

"Red blood cell exchange for SARS-CoV-2: A Gemini of therapeutic opportunities"
https://pubmed.ncbi.nlm.nih.gov/33254534/

"Executive Summary
There is strong scientific rationale from US and UK research to support evaluating the selective AXL kinase inhibitor bemcentinib in the UK’s early-stage clinical study program, ACCORD, a new initiative to find potential COVID-19 therapies."
https://scrip.pharmaintelligence.informa.com/SC142133/Why-BerGenBios-Bemcentinib-Will-Kick-Off-UKs-COVID-19-ACCORD-Program
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

"Maury’s new studies suggest that the enveloped Coronavirus, SARS-CoV-2, which causes COVID-19, uses AXL to enter into some cells, and that bemcentinib profoundly inhibits virus entry into those cells. These preclinical findings suggest that bemcentinib is potentially useful for the treatment of early SARS-CoV-2 infection.

“Viruses must enter cells to replicate and my lab has previously shown that AXL is one of several cell surface receptors used by different enveloped viruses to enter cells,” explains Maury, professor of microbiology and immunology at the UI Carver College of Medicine. “Ebola virus and Zika virus use this type of receptor. We have now shown that SARS-CoV-2 uses AXL to enter multiple cell types; a finding that may explain some of the disease symptoms caused by SARS-CoV-2.”"
https://uihc.org/news/university-iowa-virology-research-helps-facilitate-new-clinical-trial-covid-19

"These data, in the context of ACE2’s role in preventing acute respiratory distress syndrome, suggest a shift from ACE2-expressing epithelial cells to a more mesenchymal phenotype characterized by low ACE2 and high AXL expression, upon infection of NSCLC cells with SARS-CoV-2. In addition to bemcentinib’s antiviral activity, it can also reverse EMT, further supporting AXL and EMT as novel therapeutic targets for COVID-19 treatment."
Legal entity responsible for the study
Lauren A. Byers."
NB!!! Husker dere det navnet fra i forgårs, der vi diskuterte artikkelen der de hadde brukt statiner og en Axl hemmer?
Da har Lauren A. Byers brukt bemcentinib…
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506415/


https://nordiclifescience.org/bergenbios-bemcentinib-potential-treatment-for-covid-19/

http://www.pmlive.com/pharma_news/uks_new_covid-19_trial_initiative_fast-tracks_bergenbios_bemcentinib_1339339

https://theprint.in/health/expert-panel-approves-clinical-trial-of-anti-cancer-drug-bemcentinib-for-covid-treatment/514724/

https://www.newswise.com/coronavirus/university-of-iowa-virology-research-helps-facilitate-new-clinical-trial-for-covid-19

https://www.firstpost.com/health/covid-19-treatment-bemcentinib-heparin-and-3-other-drugs-to-be-tested-by-uk-in-their-accord-programme-8439601.html

"Thereof, based on collective observations, R428, Teniposide, VS-5584, and Setileuton drugs were suggested to hold the potential to significantly occupy the active pocket of SARS-CoV-2 Mpro and can be used as its inhibitors."
R428 = bemcentinib
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7651494/

"Teniposide and etoposide (and its phosphate) are chemically related and exhibited good binding models ( Figure 1F). However, these chemotherapy drugs have a lot of strong side effects and need intravenous administration ( Table 4). The approved drug venetoclax ( Figure 1C) and investigational drugs MK-3207 and R428 scored well in both screens. Venetoclax is another chemotherapy drug that is burdened by side effects including upper respiratory tract infection ( Table 4). Not much has been disclosed about MK-3207 and R428."
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062204/
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klaesp
10.01.2021 kl 08:34 2417

Re
In addition to bemcentinib’s antiviral activity, it can also reverse EMT, further supporting AXL and EMT as novel therapeutic targets for COVID-19 treatment."
Legal entity responsible for the study
Det betyr at bemcentinib kan tas senere i sykdomsforløpet slik at pasienten og sykehuset slipper og bruke respirstor og forhindrer senskader/lungeskader. bemcentinib behandling kan startes under hele sykdomsforløpet ...Helt utrolig:)))))
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klaesp
10.01.2021 kl 09:00 2372

Og det er nettopp det Ceo prøver å formidle, sjekk oppsummering under seansen (covid)

presentasjon på DNB Nordic healthcare conference . https://dnb-play.screen9.tv/media/E0TATxo3cmugURN4iOD2vA/dnb-markets-session-i-bergenbio

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Yngling ØH
Tusen takk for ditt utrettelige arbeid med å grave frem dokumentasjon og knytte dine faglige kommentarer til innholdet. Det er til uvurderlig hjelp for oss som ikke er like bevandret innen den medisinske vitenskap. Må vedgå at jeg gleder meg til den dagen ledelsen i BGBIO skal presenentere data fra såvel covid-19 studier som diverse kreftforskning. Ikke umulig at 2021 blir året da BGBIO virkelig slår ut i full blomst.
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focuss
10.01.2021 kl 12:15 2072

Yngling ØH
"These preclinical findings suggest that bemcentinib is potentially useful for the treatment of early SARS-CoV-2 infection."

Jeg ser dette med treatment of early covid infection som sentralt. De som har vært positive til Hydrocloroquin og Remdesivir har ment at når det ikke gir ønskede resultater så er det nettopp fordi medikamentet gis for sent i sykdomsforløpet. Skal det samme skje med Bemcentinib, at det gis for sent til å gi effekt. Nesten så man kan bli konspiratorisk og tenke at det er noen som ønsker at disse medikamentene ikke skal virke.
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focuss
10.01.2021 kl 12:18 2103

Det er liksom noe med at dersom Bemcentinib skal hindre Covid å komme inn i cellene så må behandlingen nesten skje før covid har kommet inn i cellene.
Redigert 21.01.2021 kl 08:44 Du må logge inn for å svare

Prosessen med å reversere EMT er langsom. Hør hva Wendy Maury sier; bemcentinib bør gis tidlig i sykdomsforløpet. Det er også mer penger i det for BerGenBio om bemcentinib gis tidlig. Da vil jo medikamentet bli gitt til flere.
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Dersom bemcentinib reduserer andelen Sars smittede personer som får langvarige lungeskader, nyreskader, leverskader, hjerneskader, skader i hjerte-/karsystemet eller skader i huden (fibrose), så kommer det til å være samfunnsøkonomisk lønnsomt å gi bemcentinib i flere sykluser, selv om kostnaden for bemcentinib er høy.

For samfunnet er alternativet å sende disse personene på kanskje varige behandlinger som ikke virker, samt at langvarig økende fibrose vil lede til kreft, og dyr kreftbehandling. Nyrepasienter er for eksempel noen av de dyreste pasientene å behandle. Om samfunnet kan få noen færre med å dosere sars pasienter med bemcentinib, så vil det være lønnsomt.

Og så kommer plikten til å behandle det som kan behandles.

Det er bare å stålsette seg for en fantastisk reise.
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Ja, du behøver ikke ta Wendy Maurys ord for det. Det er etter hvert ganske mange studier som samlet sett tilsier at bemcentinib bør gis tildlig i covid sykdomsforløpet.
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Bemcentinib virker også etter at sars-cov-2 har penetrert cellene. Blant annet ved å hindre-, eller reversere EMT, og via oppregulering av intracellulært interferon. Det er altså fortsatt rasjonelt fornuftig å gi bemcentinib til alvorlig syke covid pasienter, men effekten mot den pågående akutte sykdommen vil måtte forventes å være mindre. Men fortsatt vil den ha effekt, og i tillegg så kan den sannsynligvis forhindre senskader som forårsakes av alvorlig covid.
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