GlobeNewswire

XBiotech Announces Publication of Breakthrough Findings for Potential Role of Interleukin-1 alpha in Risk for Heart Attacks

Share

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.

About XBiotech
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.

Contact
Ashley Otero
aotero@xbiotech.com
512-386-2930

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. 

About GlobeNewswire

GlobeNewswire
GlobeNewswire
One Liberty Plaza - 165 Broadway
NY 10006 New York

https://globenewswire.com

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

Media Release | MCH Group | Art Basel in Basel6.6.2020 11:00:00 CESTPress release

MCH Group Cancels Upcoming Art Basel Show in September 2020 In view of the current global conditions, MCH Group has no option but to cancel the upcoming editions of Art Basel in Basel and Design Miami Basel, which had been postponed to mid-September 2020. The decision to cancel Art Basel was made after extensive consultation with many Art Basel gallerists, collectors, partners, as well as external experts. The primary considerations were the fundamental health and safety risks for everyone involved, the financial risks for exhibitors and partners, the ongoing impediments to international travel, and the fact that the regulatory environment around large-scale events in Switzerland has yet to be finalized. Marc Spiegler, Member of MCH Group's Executive Board and Global Director Art Basel, explains: "We are aware that our galleries are facing unprecedented challenges and economic difficulties, and we had really hoped to support the art market’s recovery with a successful show in September

Hexagon Mobile Pipeline® to virtually connect communities and industries to pipeline gas in the US6.6.2020 10:15:39 CESTPress release

Hexagon Mobile Pipeline®, a Hexagon Composites subsidiary, has received a substantial contract for TITAN® 53 transport modules from Xpress Natural Gas LLC (XNG) a leading full-service provider of compressed natural gas (CNG). The strategic agreement has a total value of USD 7.3 million (approx. NOK 70.2 million) and includes additional purchase and rental options through 2021. The TITAN® 53 large-capacity Mobile Pipeline® modules will serve virtual interconnect projects providing natural gas to communities and industries that do not have access to sufficient pipeline capacity in the US. "Since XNG started operations in early 2013, Hexagon's Titan products have proven to be high-quality products that deliver safety, reliability and performance," says John Nahill, CEO and co-founder of Xpress Natural Gas. "The higher volume of TITAN®53 means that we can serve our customers with fewer trailers and miles driven and that is key to our success. We appreciate the expertise and responsiveness

NEW ANALYSES OF PHASE 2 EQUATOR CLINICAL PROGRAM SUPPORT DURABLE EFFICACY OF FILGOTINIB IN PSORIATIC ARTHRITIS5.6.2020 22:01:00 CESTPress release

-- Data Were Presented at the European League Against Rheumatism, EULAR, European E-Congress of Rheumatology 2020 -- Foster City, Calif., & Mechelen, Belgium, 5 June 2020, 22.01 CET – Gilead Sciences, Inc. (Nasdaq: GILD) and Galapagos NV (Euronext & Nasdaq: GLPG) today announced new analyses from two clinical trials evaluating filgotinib, an investigational, oral, selective JAK1 inhibitor, in adults with psoriatic arthritis (PsA). The data from the double-blind, placebo-controlled, Phase 2 EQUATOR study and the EQUATOR-2 open-label extension study demonstrate filgotinib’s durable efficacy and consistent safety profile in people with active PsA, and showed rapid and sustained reductions in inflammatory biomarkers in patients with moderate to severe PsA. The new analyses were presented at the European League Against Rheumatism, EULAR, European E-Congress of Rheumatology 2020. “Despite existing treatments, people living with psoriatic arthritis can face challenging long-term symptoms incl

Agility receives order from new major global logistics customer for CNG trucks5.6.2020 20:19:33 CESTPress release

Agility Fuel Solutions, a business of Hexagon Composites, has signed a master services agreement with a global logistics customer to deliver compressed natural gas (CNG) fuel systems for medium and heavy-duty trucks. The initial order represents an estimated total value of USD 2.2 million (approx. NOK 20.5 million) with additional orders expected to follow. As a low carbon fuel, CNG can result in reductions of greenhouse gas (GHG) emissions compared to diesel of over 20% when using conventional natural gas, or 90% or more when using renewable natural gas (RNG) produced from landfills, dairy farms and other bio sources. “It makes environmental and economic sense to deploy CNG trucks right now, and the low cost and maturity of the technology make it possible to do so at scale,” says Seung Baik, President, Agility Fuel Solutions. Deliveries of the first order of CNG fuel systems are scheduled to start in the second quarter of 2020. For more information: David Bandele, CFO, Hexagon Composi

Hexagon Composites ASA: Mandatory Notification of Trade5.6.2020 17:11:41 CESTPress release

Dan Krick, SVP Organizational Development has sold 24,896 shares in Hexagon Composites ASA at a price of NOK 36,42 per share. The sale is primarily to finance tax obligations from his exercise of options earlier in the year. After the transaction Dan Krick holds zero shares in Hexagon Composites ASA. This information is subject to the disclosure requirements pursuant to section 5 -12 of the Norwegian Securities Trading Act. For more information: David Bandele, CFO, Hexagon Composites ASA Telephone: +47 920 91 483 | david.bandele@hexagongroup.com About Hexagon Composites Hexagon delivers safe and innovative solutions for a cleaner energy future. Our solutions enable storage, transportation and conversion to clean energy in a wide range of mobility, industrial and consumer applications.

CONDITIONS FOR RIKSBANK BID PROCEDURES SEK GOVERNMENT BONDS5.6.2020 15:05:00 CESTPress release

Sveriges Riksbank Bid procedure details Government Bonds, 2020-06-12 Maturity dateLoanISIN codeCouponVolume, SEK million2026-11-121059 SE00071259271.00 %1,000 +/- 2502031-05-12 1062 SE00139353190.125 %1,000 +/- 250 Settlement date 2020-06-16 Bids have to be entered by 10.00 on JUN 12, 2020 Highest permitted bid volume: 1 000 SEK million in issue SGB 1059 and 1 000 SEK million in issue SGB 1062 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 JUN 12, 2020. For more information, please contact: Trading desk at the Riksbank + 46 8 696 6970 General and special terms and conditions can be retrieved athttp://www.riksbank.se