BerGenBio ASA: Primary Insider notification
Bone Marrow-Derived AXL Tyrosine Kinase Promotes Mitogenic Crosstalk and Cardiac Allograft Vasculopathy
Posted: February 05, 2021
https://www.biorxiv.org/content/10.1101/2021.02.04.429773v1 (DOI)
Cardiac Allograft Vasculopathy (CAV) is a leading contributor to late transplant rejection. Although implicated, the mechanisms by which bone marrow-derived cells promote CAV remain unclear. Emerging evidence implicates the cell surface receptor tyrosine kinase AXL to be elevated in rejecting human allografts. […] Utilizing experimental chimeras deficient in the bone marrow-derived Axl gene , we report that Axl antagonizes cardiac allograft survival and promotes CAV. Flow cytometric and histologic analyses of Axl-deficient transplant recipients revealed reductions in both allograft immune cell accumulation and vascular intimal thickness. […] Inhibition of AXL-protein, in combination with current standards of care, is a candidate strategy to prolong cardiac allograft survival.
Herein we investigated the causal role of recipient and bone marrow-sourced Axl during cardiac transplantation. To accomplish this, we performed allogeneic heterotopic heart transplants in Axl bone marrow-deficient recipients and monitored key cellular and molecular indices of graft rejection. Our findings newly reveal a detrimental role of Axl sourced from the bone marrow, and in cardiac allografts, and offer new insight into how AXL-inhibition may be targeted to reduce myocardial CAV.
For selective inhibition of AXL, R428 (Apex Bio) was reconstituted in hypromellose solution (0.5% hypromellose, 0.1% Tween 80) versus solvent-only control and delivered to mice every other day via oral gavage at 25 mg/kg.
(Bemcentinib, also known as BGB324 or R428)
Så vi snakker om daglig Bem. som en av de faste medisiner livslang som skal hindre graftrejection hos TX pasienter (hjerte og sannsynlig andre transplantadjonsfoemer)! Det blir en stor dag for slik pasientgruppe 
(og BB investorer)
BERGENBIO ASA: Board approval of 2020 annual financial statement
BERGENBIO ASA: ANNUAL REPORT 2020
BERGENBIO ASA: NOTICE OF ANNUAL GENERAL MEETING
Noen som har lest hele enda?
Fra side 17: Near Term Goals - H1 2021:
- COVID-19: Trial and Key Secondary End Point data
- AML: Proof of Concept data
- MDS: Proof of Concept data
Fra side 29: “Bemcentinib has presented a unique dual mechanism of action to combat COVID-19 infection”
Fra side 23: “Comparing oncology drugs developed with a biomarker vs those without showed an almost seven-fold improvement (10.7% vs 1.6%)”
Fra side 34: “Probability of success for a drug development programme is greatly improved in the presence of a biomarker”
Fra side 24: “BerGenBio is also developing predictive biomarkers and companion diagnostics to identify patients most likely to respond to treatment…”
Fra side 46: “In a time where many businesses have struggled, BerGenBio has been fully operational all year, without the need for government grants, and expanding as it prepares for late-stage asset development.”
Hver måned kårer jeg det jeg kaller Teksperter™ for noen av de mest populære investeringene våre 
Det er de 3 medlemmene som har fått flest likes på innleggene sine de siste 90 dagene. Teksperter™ får også en unikt merke på profilen sin og et trofé-ikon ved siden av navnet sitt. Du kan bli Tekspert™ i flere aksjer/investeringer, og troféet vil bare vises i tråder der du er Tekspert™.
Her er denne månedens Teksperter™ og det mest likte innlegget deres fra de siste 90 dagene:
- @Londonmannen (189 likes)
- @anon28800809 (148 likes)
- @Mykle (148 likes)
Resten av topp 10:
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@HeldigFyr (133 likes)
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@drdr (123 likes)
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@Ekornet (116 likes)
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@Hfyh (106 likes)
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@Savepig (101 likes)
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@eiken (99 likes)
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@Fornybar (96 likes)
Gratulerer!
BerGenBio ASA: Increase of share capital, exercise of share options
BERGENBIO CLOSES RECRUITMENT INTO TRIAL ASSESSING BEMCENTINIB IN COVID-19 PATIENTS
Bra! Få ut datasettet og finn ut om covidsagaen skal fortsette. Data tilgjengelig fra alle pasientene om max 17 dager.
God speed.
"A total of 114 out of the target 120 hospitalised COVID-19 patients have been
recruited across five sites in South Africa and seven sites in India. 56
patients received bemcentinib (as monotherapy or in combination with standard of
care medication) and 58 patients in a control group (receiving standard of care
treatment only) "
BerGenBio ASA: Share capital increase
Macrophage AXL receptor tyrosine kinase inflames the heart after reperfused myocardial infarction
Published: February 2, 2021
JCI - Macrophage AXL receptor tyrosine kinase inflames the heart after reperfused myocardial infarction (DOI)
Tyro3, AXL, and MerTK (TAM) receptors are activated in macrophages in response to tissue injury and as such have been proposed as therapeutic targets to promote inflammation resolution during sterile wound healing, including myocardial infarction. While the role of MerTK in cardioprotection is well-characterized, the unique role of the other structurally similar TAMs, and particularly AXL, in clinically-relevant models of myocardial ischemia-reperfused infarction (IRI) is comparatively unknown. Utilizing complementary approaches, validated by flow cytometric analysis of human and murine macrophage subsets and conditional genetic loss and gain of function, we uncover a unique maladaptive role for myeloid AXL during IRI in the heart.
Administration of a selective small molecule AXL inhibitor alone improved cardiac healing, which was further enhanced in combination with blockade of MerTK cleavage. These data support further exploration of macrophage TAM receptors as therapeutic targets for myocardial infarction.
The specific and highly selective AXL inhibitor (BGB324) used in our studies is orally bioavailable and has demonstrated favorable safety profiles and activity over prolonged periods of administration in clinical trials for the treatment of cancer in humans.
Given the potential dominance of AXL over MerTK and the relative ease in therapeutic targeting of AXL compared to MerTK cleavage, strategies that inhibit AXL may yield more immediate clinical benefits in cardiovascular disease.
Administration of a selective small molecule AXL inhibitor alone improved cardiac healing, which was further enhanced in combination with blockade of MerTK cleavage.
In conclusion, our findings reveal that AXL aggravates cardiac repair by directing proinflammatory metabolic reprogramming of macrophages and that the mechanism is distinct from MerTK, the latter of which is necessary for macrophage efferocytosis of apoptotic cardiomyocytes to initiate inflammation resolution. These findings support exploration of leveraging macrophage TAM receptors in humans to promote inflammation resolution and limit adverse ventricular remodeling that leads to heart failure.
(Bemcentinib, also known as BGB324 or R428)
Dette er stort, og viser nok en gang potensialet til AXL-inhibitorer i antiinflammatorisk sammenheng.
Jeg tror at det å eie Bgbio-aksjer er som å fiske gjedde i et stille vann. Ingenting skjer og man er nær ved å gi opp før monstergjedda gaper kompromissløst over hele sluken…
BERGENBIO ANNOUNCES START OF PHASE 1B TRIAL OF ANTI-AXL ANTIBODY TILVESTAMAB (BGB149)
BERGENBIO PRESENTS PRECLINICAL COVID-19 DATA AT ANNUAL CONFERENCE ON RETROVIRUSES AND OPPORTUNISTIC INFECTIONS (CROI 2021)
Thank you Wendy Maury:clap:
In conclusion, the effect of bemcentinib demonstrated potent antiviral effects
in preclinical SARS-CoV-2 and other coronavirus models. Further, the findings
support BerGenBio’s ongoing Phase II trial evaluating bemcentinib for the
treatment of hospitalised COVID-19 patients in South Africa and India.
