XBiotech Announces Publication of Breakthrough Findings for Potential Role of Interleukin-1 alpha in Risk for Heart Attacks
Findings Demonstrate Ability of MABp1 (Bermekimab) to Block In Vitro Neutrophil Mediated Vascular Endothelial Activation and Thrombosis
AUSTIN, Texas, Aug. 27, 2018 (GLOBE NEWSWIRE) -- XBiotech Inc. (NASDAQ: XBIT) announced today the publication of findings that point toward a white blood cell-derived interleukin-1 alpha (IL-1⍺) as a cause of blood clots that could lead to heart attacks or strokes. The research was headed by a world-leading cardiovascular researcher, Dr. Peter Libby, Mallinckrodt Professor of Medicine at Harvard Medical School and clinical cardiologist at Brigham and Women’s Hospital. Dr. Libby’s team discovered that white blood cells, known as neutrophils, can release IL-1⍺ that could possibly lead to life threatening strokes in patients with heart disease, which offers the potential for new treatment approaches involving XBiotech’s anti-IL-1⍺ antibody, bermekimab.
The findings describe for the first time an intriguing mechanism whereby so called neutrophil extracellular traps (NETs), released from neutrophils, are laden with IL-1⍺ that is capable of activating cells of the artery wall in a way that in turn activates blood clotting mechanisms and recruits further white blood cells. The publication reports work done by Dr. Libby’s colleagues Drs. Folco and Mawson that describes how in certain kinds of heart disease where the blood vessels become partially blocked by atherosclerotic plaques, activation of the blood vessels by IL-1⍺ on NETs could be an important contributing factor of heart attacks. These findings are among the first to provide a clear mechanism by which neutrophils could cause heart attacks, and at the same time offer hope for a treatment by blocking IL-1⍺. These findings also suggest treatment opportunities for other inflammatory diseases in which neutrophils, and more specifically NETs, play a role in disease pathology, such as in cancer, pulmonary, autoimmune, and gastrointestinal diseases.
Dr. Libby stated, “Our data suggest that activation of vascular endothelial cells by NET-associated IL-1⍺ can not only amplify, sustain, and propagate local vascular inflammation; this process may also be involved in promoting thrombosis. We believe these findings may have very important clinical implications.”
John Simard, XBiotech’s President & CEO, commented, “Dr. Libby’s discovery provides a new mechanism by which to understand where and why we might target IL-1⍺ to treat inflammatory diseases. It is a fundamental advance in biology and an exciting day for us.”
Dr. Libby’s findings are published online in a journal of the American Heart Association (AHA). The article titled, Neutrophil Extracellular Traps Induce Endothelial Cell Activation and Tissue Factor Production Through Interleukin-1α and Cathepsin G, is featured in the August print issue of Arteriosclerosis, Thrombosis, and Vascular Biology .
Coronary artery thrombosis can be caused by either plaque rupture or plaque erosion1. Superficial plaque erosion causes up to one-third of all acute coronary syndromes2 ,3. Erosion-prone atheromatous plaques, rather than lesions with stable or rupture-prone characteristics, associate with neutrophil extracellular traps (NETs)4. The study performed at Dr. Libby’s laboratory probed the influence of NETs on the endothelial cell (EC) functions related to erosion-associated thrombosis. These data show that exposure of human saphenous veins ECs (HSVECs) to NETs increase expression of adhesion molecules on the surface of endothelial cells such as VCAM-1 and ICAM-1, which may participate in atherogenesis. In addition, pre-treatment of NETs with bermekimab, an anti-IL-1⍺-neutralizing antibody, or IL-1R antagonist, but not with an anti-IL-1β-neutralizing antibody, blocked the initiation of VCAM-1, ICAM-1, and TF expression, each of which link to coronary thrombosis5 ,6. In conclusion, NETs increase thrombogenicity in vitro through a response mediated by IL-1⍺. These data point to a potentially important role for bermekimab therapy in treating certain kinds of heart disease and other neutrophil mediated diseases.
About True Human™ Therapeutic Antibodies
XBiotech’s True Human™ antibodies are derived without modification from individuals who possess natural immunity to certain diseases. With discovery and clinical programs across multiple disease areas, XBiotech’s True Human antibodies have the potential to harness the body’s natural immunity to fight disease with increased safety, efficacy and tolerability.
XBiotech is a fully integrated global biosciences company dedicated to pioneering the discovery, development and commercialization of therapeutic antibodies based on its True Human™ proprietary technology. XBiotech currently is advancing a robust pipeline of antibody therapies to redefine the standards of care in oncology, inflammatory conditions and infectious diseases. Headquartered in Austin, Texas, XBiotech also is leading the development of innovative biotech manufacturing technologies designed to more rapidly, cost-effectively and flexibly produce new therapies urgently needed by patients worldwide. For more information, visit www.xbiotech.com.
Cautionary Note on Forward-Looking Statements
This press release contains forward-looking statements, including declarations regarding management's beliefs and expectations that involve substantial risks and uncertainties. In some cases, you can identify forward-looking statements by terminology such as "may," "will," "should," "would," "could," "expects," "plans," "contemplate," "anticipates," "believes," "estimates," "predicts," "projects," "intend" or "continue" or the negative of such terms or other comparable terminology, although not all forward-looking statements contain these identifying words. Forward-looking statements are subject to inherent risks and uncertainties in predicting future results and conditions that could cause the actual results to differ materially from those projected in these forward-looking statements. These risks and uncertainties are subject to the disclosures set forth in the "Risk Factors" section of certain of our SEC filings. Forward-looking statements are not guarantees of future performance, and our actual results of operations, financial condition and liquidity, and the development of the industry in which we operate, may differ materially from the forward-looking statements contained in this press release. Any forward-looking statements that we make in this press release speak only as of the date of this press release. We assume no obligation to update our forward-looking statements whether as a result of new information, future events or otherwise, after the date of this press release.
1 Crea F, Libby P. Acute Coronary Syndromes: The Way Forward From Mechanisms to Precision Treatment. Circulation 2017;136:1155–1166.
2 Franck G, et al. Flow Perturbation Mediates Neutrophil Recruitment and Potentiates Endothelial Injury via TLR2 in Mice – Implications for Superficial Erosion. Circ Res 2017;121:31-42.
3 Libby P. Superficial erosion and the precision management of acute coronary syndromes: not one-size-fits-all. Eur Heart J. 2017;38(11):801-803. doi: 10.1093/eurheartj/ehw599.
4 Quillard T et al. TLR2 and neutrophils potentiate endothelial stress, apoptosis and detachment: implications for superficial erosion. Eur Heart J. 2015 Jun 7;36(22):1394-404. doi: 10.1093/eurheartj/ehv044. Epub 2015 Mar 8.
5 Tousoulis D , et al. Inflammatory and thrombotic mechanisms in coronary atherosclerosis. Heart. 2003;89(9):993-7.
6 Folco EJ, Mawson TL, Vromman A et al. Neutrophil Extracellular Traps Induce Endothelial Cell Activation and Tissue Factor Production through Interleukin-1α and Cathepsin G. Arteriosclerosis, Thrombosis, and Vascular Biology 2018; 2018;38:1901-1912.
One Liberty Plaza - 165 Broadway
NY 10006 New York
GlobeNewswire is one of the world's largest newswire distribution networks, specializing in the delivery of corporate press releases financial disclosures and multimedia content to the media, investment community, individual investors and the general public.
Subscribe to releases from GlobeNewswire
Subscribe to all the latest releases from GlobeNewswire by registering your e-mail address below. You can unsubscribe at any time.
Latest releases from GlobeNewswire
Maha Energy AB (publ) Announce June Production Volumes3.7.2020 17:13:36 CEST | Press release
Maha Energy AB (publ) Strandvägen 5A SE-114 51 Stockholm www.mahaenergy.ca Press release Stockholm July 3, 2020 Maha Energy AB (publ) Announce June Production Volumes Production Volumes The Company's aggregate sales production for the month of June totaled 112,1511 barrels of oil and 57.090 million scf of gas for a combined average production of approximately 4,056 BOE/day2, before royalties and taxes. Other than some minor unplanned shutdowns, production continues to be affected by the impact of the Covid-19 pandemic. 1 Subject to minor standard industry adjustments at the time of custody transfer. 2 Barrels of oil equivalent ("BOE") conversion ratio of 6,000 scf: 1 bbl is used. For more information, please contact: Jonas Lindvall (CEO) Tel: +46 8 611 05 11 Email: email@example.com or Victoria Berg (Investor Relations) Tel: +46 8 611 05 11 Email: firstname.lastname@example.org Maha in Brief Maha Energy AB is a Swedish public limited liability company. FNCA Sweden AB has been engaged as C
Norsk Hydro: Production resumed at Paragominas and Alunorte3.7.2020 17:00:00 CEST | Press release
The power supply to Hydro’s Paragominas bauxite mine, in the state of Pará in northern Brazil, has been restored, allowing production to restart. As a result, production is being ramped up at Hydro’s Alunorte alumina refinery. On June 20, three power transmission towers overturned, cutting the power supply to the mine and temporarily halting production. The transmission towers have been repaired, and the power has been restored. There were no personnel injuries, damage to other production assets or impact on the nearby environment related to the power outage. The company is cooperating with local authorities to determine the cause of the incident. Preliminary findings indicate that parts were stolen from the towers causing them to overturn. Investor contact: Line Haugetraa +47 41406376 Line.Haugetraa@hydro.com Media contact: Anders Vindegg +47 93864271 Anders.Vindegg@hydro.com
Norsk Hydro: Produksjon gjennopptatt ved Paragominas og Alunorte3.7.2020 17:00:00 CEST | Pressemelding
Strømtilførselen til Hydros bauksittgruve Paragominas i Parà nord i Brasil har blitt gjenopprettet og produksjonen har startet opp igjen. Produksjonen ved Hydros aluminaraffineri Alunorte vil som følge av dette også bli normalisert. Tre høyspentmaster veltet 20. juni og førte til strømbrudd for Paragominas. Strømbruddet stanset midlertidig produksjonen ved gruven. Høyspentmastene har nå blitt reparert og strømtilførelsen er gjenopprettet. Det var ingen personskader, miljøskader eller skader på produksjonsutstyr relatert til strømbruddet. Hydro samarbeider med lokale myndigheter for å finne årsaken til hendelsen. Foreløpige undersøkelser tyder på at deler fra mastene har blitt stjålet og at dette forårsaket at mastene veltet. Investorkontakt: Line Haugetraa +47 41406376 Line.Haugetraa@hydro.com Pressekontakt: Anders Vindegg +47 93864271 Anders.Vindegg@hydro.com
CONDITIONS FOR RIKSBANK BID PROCEDURE KOMMUNINVEST BONDS3.7.2020 16:20:00 CEST | Press release
Sveriges Riksbank Bid procedure details Kommuninvest Bonds, 2020-07-07 Maturity dateLoanISIN codeCouponVolume, SEK million2021-09-15 2109 SE00069950641.00 %500+/- 2502024-10-022410 SE0010469205 1.00 %500+/- 250 Settlement date 2020-07-09 Bids have to be entered by 11.00 on JUL 07, 2020 Highest permitted bid volume: A maximum of SEK 500 million per bid in issue 2109 and 2410. Lowest permitted bid volume: 50 SEK million per bid Bids only through counterparties approved by the Riksbank RESULT OF AUCTION WILL BE PUBLISHED NO LATER THAN 11.15 (CEST) ON JUL 07, 2020 For more information, please contact: Trading desk at the Riksbank + 46 8 696 6970 General and special terms and conditions can be retrieved at http://www.riksbank.se
CONDITIONS FOR RIKSBANK BID PROCEDURES SEK COVERED BONDS3.7.2020 16:20:00 CEST | Press release
Sveriges Riksbank Bid procedure details Covered Bonds, 2020-07-09 Maturity dateLoanISIN codeCouponVolume, SEK million2025-09-17 5535 SE0013358413 1.00 %1,000 +/- 5002024-12-18 579 SE00121936211.00 %1,000 +/- 500 2024-12-031589SE00116433861.50 %1,000 +/- 5002025-06-18195SE00135460661.00 %1,000 +/- 5002024-12-182412SE00126218521.00 %400 +/- 2502025-09-17518SE0011309244 1.25 %400 +/- 2502025-06-11 146 SE0013381571 0.50 %400 +/- 250 Settlement date 2020-07-13 Bids have to be entered by 10.00 on JUL 09 2020 Highest permitted bid volume: 1,000 SEK million in issue 5535 1,000 SEK million in issue 579 1,000 SEK million in issue 1589 1,000 SEK million in issue 195 400 SEK million in issue 2412 400 SEK million in issue 518 400 SEK million in issue 146 Maximum volume: 5 billion SEK in total Lowest permitted bid volume: 50 SEK million Bids only through counterparties approved by the Riksbank RESULT OF AUCTION WILL BE PUBLISHED NO LATER THAN 10.15 (CEST) ON JUL 09, 2020. For more information, pleas
CONDITIONS FOR RIKSBANK BID PROCEDURES SEK GOVERNMENT BONDS3.7.2020 16:20:00 CEST | Press release
Sveriges Riksbank Bid procedure details Government Bonds, 2020-07-10 Maturity dateLoanISIN codeCouponVolume, SEK million2025-05-121058SE00056766082.50%500 +/- 2502028-05-121060SE00094963670.75%500 +/- 250 Settlement date 2020-07-14 Bids have to be entered by 10.00 on July 10, 2020 Highest permitted bid volume: 500 SEK million in issue SGB 1058 and 500 SEK million in issue SGB 1060 Lowest permitted bid volume: 50 SEK million Bids only through counterparties approved by the Riksbank RESULT OF AUCTION WILL BE PUBLISHED NO LATER THAN 10.10 (CEST)ON JULY 10, 2020. For more information, please contact: Trading desk at the Riksbank + 46 8 696 6970 General and special terms and conditions can be retrieved at http://www.riksbank.se