Alloksys Initiates Phase III

Alloksys Life Sciences has initiated a phase III clinical trial (APPIRED II) in patients undergoing cardiac valve surgery. The study will be carried out at CZE (Catharina Hospital Eindhoven, The Netherlands). This phase III study is a follow-up to APPIRED-I in which Alkaline Phosphatase (AP) was found to reduce post-surgical systemic inflammatory responses (SIRS). AP is positioned as gate-keeper to SIRS preventing cytokine storms, specific TNFa, IL6 and IL8 responses.These cytokines trigger inflammation and , when not counteracted upon, may result in adverse clinical complications and outcome. The acronym APPIRED reflects the predominant mechanism of action of the anti-inflammatory acitivity of AP: Alkaline Phosphatase mediated Prevention of Ischemia REperfusion Damage (ischemic injury).

April2010

Alloksys Life Sciences initiates phase III clinical studies in cardiac valve surgery, see news Alloksys Life Sciences announces positive results with alkaline phosphatase in a phase IIa Clinical Tri

Bunnik, The Netherlands, 23 April 2008 - Dutch biotechnology company Alloksys Life Sciences announces the successful completion of a phase IIa clinical trial (APPIRED) in patients undergoing bypass surgery with cardiopulmonary bypass with a low-medium EuroSCORE risk profile. The study was performed at the Catharine Hospital, Eindhoven, The Netherlands with dr JPAM Schonberger as principle investigator and Aix Scientifics, Aachen, Germany as CRO. The objective of the APPIRED study was to show that alkaline phosphatase enabled to attenuate the ischemia reperfusion induced inflammatory damage by acting on pro-inflammatory moieties like endotoxin translocating from the gastro-intestinal tract and nucleotides leaking from damaged tissue during surgery and thereafter. Assessed were a total of 31 patients received alkaline phosphatase, whilst 30 patients received placebo treatment. Alkaline phosphatase was shown to be safe. Efficacy was demonstrated indirectly: in the placebo-treated group post-surgical inflammatory responses were observed in 5 out of 30 patients, whereas no such inflammatory responses were observed in the patients treated with alkaline phosphatase (p<0.01). Alkaline phosphatase was administered as a bolus pre-operatively followed by a 36 hours intravenous infusion. A further outcome of the study is that a more comfortable dosing regime, consisting of solely bolus administrations, will very likely be applicable. This above APPIRED study confirms pre-clinical data and the demonstrated safety sets the stage for several follow-up studies in patients that will undergo invasive surgery. Thus a study is foreseen in complicated cardiovascular surgery and organ transplant surgery as well as in patients that suffer from variceal bleeding. The current APPIRED data suggest that those patients vulnerable to post surgical inflammatory responses (e.g.SIRS) benefit of alkaline phosphatase treatment.

April 23, 2008

Drug development program started based on CAP Human Cell Line. New platform may provide solutions for many RA-patients around the world.

Alloksys Life Sciences BV (Bunnik, The Netherlands), CEVEC Pharmaceuticals GmbH (Cologne, Germany) and PharmaCell BV (Maastricht, The Netherlands) announce the start of Theraptech, a 2.4 million Euro therapeutic protein development program subsidized under the European Trans Bio Program. The major objective of the Theraptech project is to develop a recombinant human alkaline phosphatase (rhuAP) using the novel versatile human CAP cell line, which has been shown to efficiently express glycosylated proteins. The rhuAP produced in CAP cells is expected to feature improved pharmacokinetic and safety profile allowing for repeated dosing of alkaline phosphatase in chronic diseases. Based on a the anti-inflammatory mechanism of action of alkaline phosphatase towards e.g. TNFa, IL-6 and IL-8, as shown in both pre-clinical and clinical studies in acute conditions, we propose it to be developed as a therapeutic protein in major chronic diseases such as Rheumatoid Arthritis. The combined expertise of the members participating in the consortium covers the entire spectrum of activities needed to drive the project from molecular biology to GMP-production and recombinant product testing in preclinical and clinical trials, pushing towards a clinical phase II compliant product within the 3-year-time frame of the project. Commenting on this unique co-operation, PharmaCells CEO, Maurice Horsten, commented: Combining the strengths of our companies provides us with an excellent opportunity to build on PharmaCells motto Humanizing Medicine and to push this important project forward to the benefit of many patients around the world. Cevec CEO Dr Rainer Lichtenberger added: CEVEC is excited about the strong scientific and commercial prospects of the Theraptech project. rhuAP will turn out to perfectly demonstrate the unique strengths of CEVECs proprietary CAP cell expression technology, in combination with the proven capabilities of our partners. On the scientific importance Alloksys COO, Dr Ruud Brands commented: rhuALP, based on the proposed mechanism of action in innate immune modulation, may enable the application in a wide array of disabilitating chronic inflammatory conditions, thereby eliminating the potentially adverse effects of currently marketed blockbuster products. About Alloksys Life Sciences BV Alloksys, established in 2005 and located in Bunnik, The Netherlands Alloksys Life Sciences BV is a biopharmaceutical company dedicated to the R&D of therapeutic proteins for the treatment of both acute and chronic inflammatory diseases. The lead phase II compound bIAP, an innate-immune system-modulating compound is developed for the indication: prevention of ischemia-reperfusion damage in invasive surgery. Chronic applications atherosclerosis, rheumatoid arthritis, Alzheimer and asthma are targeted. Alloksys established an integral research network comprising of several academic and biotech collaborations, both nationally and international. Partnerships with pharmaceutical companies for co-development of these indications are welcomed. About CEVEC Pharmaceuticals GmbH CEVEC Pharmaceuticals GmbH, operational since 2004 and located in Cologne, Germany, is a biopharmaceutical company that specializes in developing and producing therapeutic proteins and monoclonal antibodies with human glycosylation patterns. CEVECs novel proprietary and patent-protected human CAP and CAP-T expression systems are ideal for manufacturing complex biopharmaceutical molecules. CEVEC is licensing out its human cell-based expression platform as well as the biological product candidates in internal development through partnerships with renowned pharmaceutical and biotech companies. About PharmaCell PharmaCell provides contract services in the area of human cell & tissue banking & culturing as well as human cell line development and manufacturing of (bio) pharmaceuticals. Next to a GMP license, PharmaCell is the only commercial company in The Netherlands to hold an official license as Registered Tissue Establishment. PharmaCell is also actively engaged in Research & Development work, both on behalf of some of its customers as well as in research consortia together with Universities, Academic Hospitals and other (bio)tech companies.

February 25, 2009

IBET (Instituto de Biologia Experimental e Tecnologica) joins ETB program Theraptech

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November 2010

Initiation of Phase IIIa study

Alloksys announces to start phase IIIa clinical trials in patients undergoing combined aortic valve replacement and coronary artery bypass grafting. Alkaline phosphatase, an enzyme that prevents ischemic injury and counteracts pro-inflammatory triggers is used to attenuate inflammation-mediated post-surgical trauma. The APPIRED II study follows the positive results from the APPIRED-I study in patients undergoing bypass surgery

1 Dec 2009