Resetting the Immune System
Xenikos is a biotechnology company that is developing an innovative new medicine to help patients suffering serious immune diseases or rejection after transplantation.
T-Guard® is a potential new treatment for Graft versus Host Disease (GVHD), a frequent and potentially life-threatening complication of bone marrow and blood stem cell transplantation. There are currently no registered therapies for GVHD patients, who have failed standard first line corticosteroid therapy, and the prognosis for these patients is poor. Following promising trial results, Xenikos hopes to develop T-Guard® as an effective, commercially-available medicine for treatment of GVHD and other life-threatening immune conditions.
A Medicine with Potential to Save Lives
Transplantation of allogeneic (donor-derived) blood stem cells is a widely accepted medical procedure to restore normal blood cell production (hematopoiesis) in patients treated for blood- or lymphatic cancers, or otherwise suffering from defective blood formation, or immunity. In the last twenty years, there has been a steady annual growth in the number of allogeneic blood stem cell transplants performed in the European Union (EU) and the United States (US) and this increase is set to continue. However, a significant proportion of patients develop a life-threatening immune reaction – Graft versus Host Disease (GVHD)- when donor-derived T cells (immune cells) attack the normal tissues of the patient. T cells can be beneficial in fighting any residual cancer cells, but in GVHD, they recognize their new host as ‘foreign’ and an immune chain reaction is triggered that results in host tissue damage. Severe acute GVHD causes blistering of the skin, liver failure and severe diarrhea. Approximately 30% of patients develop severe acute GVHD that does not respond adequately to standard first-line corticosteroid therapy. Only 5-25% of these patients with steroid-refractory GVHD survive the condition after five years depending on the severity.
There are no currently registered treatments available. As the number of patients receiving high risk transplants from
unrelated donors is expected to double in the next five years, it is important to find new, effective treatment options for GVHD.
T-Guard consists of a combination of two toxin-loaded anti-T-cell antibodies, and shows promise as a therapeutic tool for safely and swiftly resetting the body’s immune system in T cell mediated diseases. Once injected into the body, T-Guard specifically identifies and eliminates adult T cells, with a strong preference for the activated ones. The particular combination of immunotoxins used to construct T-Guard provides a unique blend of synergistic efficacy, narrow specificity and multiple, gentle mechanisms of action. Its action is unparalleled by any immunosuppressive product currently available commercially. T-Guard is not only very effective in killing activated T cells, but also acts through mechanisms associated with minimal side effects (via apoptosis). Its targeted action leaves patients less vulnerable to opportunistic infections as compared to currently available treatment options.
Dedicated to Development
Developing a new medicine is a tremendous, long term scientific and business undertaking, with every step in the process subject to a myriad of complex and specific rules and regulations. Development of T-Guard demonstrates Xenikos’ commitment to finding innovative solutions for patients from all over the world by developing high quality immunotherapy medicines that meet unmet medical needs. Xenikos was established in 2009 by pioneering scientist and researcher, Ypke van Oosterhout. Biopharmaceutical development expert and former Managing Director of Sanquin Pharmaceuctial Services, Peter Van Mourik, joined Xenikos as COO and co-statutory director in 2012. Today, Xenikos comprises of a team of experts with cross functional capabilities including hematology, biopharmaceutical and corporate development.
The safety and efficacy of T-Guard was first explored in a clinical pilot study at the Radboudumc, Nijmegen, in the Netherlands in 2001. The encouraging results, showing T-Guard’s clear therapeutic window in the treatment of severe acute GVHD, and other details of the study were published in a leading scientific journal. This generated further interest in the product and contributed towards securing additional support for further research. T-Guard was granted EU Orphan Drug Designation in 2005 and US Orphan Drug Designation in September 2013. T-Guard’s Phase 1b/2a trial, involving a larger cohort of patients with severe acute GVHD, who have failed standard corticosteroid therapy, is taking place across the Netherlands and Germany at two leading European academic medical centers with specialist hematology capabilities (Radboudumc, in Nijmegen, the Netherlands and the University Hospital Münster, in Münster, Germany). Interim results are anticipated in 2014. Preparations have also been made for a Phase 2b/3 study in the European Union (EU) and the United States (US), which will ideally enable Xenikos to acquire marketing authorization for T-Guard in both continents during the first half of 2018.
While current registration procedures are initially targeted at T-Guard’s use in the treatment of acute GVHD, there is no reason why its use should be restricted to this. The medicine could have great promise in treating several other diseases involving hyperactive, misdirected, or malignant T cells, such as:
Solid organ rejection – another widespread medical procedure for replacing malfunctioning organs of an increasing range. Lifelong treatment with immunosuppressive drugs is usually required to help the patient’s body accept the transplanted tissue, but despite this precaution, acute rejection can still occur. T-Guard may provide an attractive alternative to other experimental drugs used in this incidence, based on its better tolerability and faster action.
Autoimmune diseases – Current medications for the wide range of auto-immune diseases that exist are typically directed at limiting symptoms and managing pain, rather than curing the condition. Long-term use of many of them can cause significant side-effects. Auto-reactive T cells play a crucial role. A relatively new treatment strategy is to reset the body’s immune system through self- or donor-derived blood stem cell transplant. This is a complex process associated with many side effects. T-Guard might provide a milder, more specific alternative, applicable to a wider patient group.
T Cell Derived Blood Cancers – Pre-clinical research with well–known hemo-oncology centers has already been scheduled to investigate the potential of the medicine in killing malignant T cells.
Partners in Progress
Xenikos is a global company, headquartered in the Netherlands. It is continually looking to enlarge its clinical footprint by expanding its research and development program. As well as expanding the extent of clinical trials in size and geographical coverage, it is also planning to further explore the potential of its products in treating other clinical indications, in which, T-cells play a crucial role. Forming partnerships that can help support and advance portions of the clinical research program is a high priority. In addition, joining forces with organizations and associations and fostering close links with research, industry, healthcare professionals and the medical authorities that shape the healthcare landscape is important to ensure that Xenikos contributes as much as possible to medicine. Xenikos is interested in discussing new strategic collaborations on internal programs or apply its technologies against novel targets with serious potential partners.