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Tissera Reports Year 2005 R&D Achievements and Year 2006 R&D Forecast January 3, 2006
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The year 2005 has been marked by significant achievements and considerable progress made in the research and development work performed by Tissera-sponsored research team at the Weizmann Institute of Science, led by the immunologist Prof. Yair Reisner. Throughout the year, the scientific team has been working and advancing on both company main applications: the pancreatic application, for the treatment of insulin-dependent (type I) diabetes mellitus, and the liver application, for the treatment of liver related genetic deficiencies and of terminal liver failure. Those applications consist of studies of pig embryonic precursor tissues xenotransplantation, based on the company's technology, at the core of which is the identification and definition of patent pending organ-specific optimal gestational time windows for harvesting the tissues to be transplanted.
Following are highlights of year 2005 R&D achievements in both afore-mentioned applications:
The pancreatic application
Year 2005 Achievements
Extensive experiments on mouse models have further supported and solidified previous research results demonstrating the advantage of the company's approach to xenotransplantation of pig embryonic pancreatic precursor tissue harvested within a specifically defined gestational time window.
Those experiments showed prolonged impressive growth of the transplanted tissues within the mouse recipients.
The functionality of the grafts was underscored by the presence of insulin within the islet cells and by the demonstration of progressively increasing levels of pig insulin within the recipients' blood, along with increased pig insulin secretion in response to glucose challenge
What is further, in contrast to transplantation of adult pancreas, a relatively high number of graft islet cells were shown to be proliferating, suggesting the sustained growth ability of the graft.
A major potential advantage of embryonic tissue implantation is associated with its reduced immunogenicity, meaning that less immune suppression would be needed to prevent graft rejection. In this aspect also, the experiments showed pig embryonic tissue harvested within the optimal gestational time window identified by the company to be clearly advantageous over later gestational time pancreatic tissue. This is of major importance to the company's future prospect of using its technology in human diabetics.
The pancreas normally consists of endocrine elements, called islet cells, responsible for insulin and other hormones production, and of exocrine elements, responsible for the production of proteolytic enzymes associated with food digestion. A major concern associated with pancreatic tissue implantation is how to avoid destruction of the growing organ by the possible local release of such proteolytic enzymes by the exocrine elements. The company' studies showed that the relative expression of the exocrine and endocrine structures within the growing grafts was entirely different than what would have been seen in the adult pig pancreas, which is largely composed of exocrine tissue. A marked preference for the development of the endocrine elements was noted, with a progressive disappearance of the exocrine elements. When measured in very long-term grafts, at 8 and even 10 months after transplantation, no evidence for exocrine cells was seen, and the graft was completely occupied by endocrine islet structures – it must be recalled that 10 months constitute a very long period in a mouse life, usually lasting an average of about 2 years.
The curative value of the company's approach was further strengthened by the successful results of studies in two different diabetic mice models, in which the potential of transplanted pig embryonic pancreatic precursor tissue to restore and maintain normal blood sugar levels was clearly exhibited.
Taken together, those results showed that pig embryonic pancreatic precursor tissue harvested within the optimal gestational time window identified by the company might afford an excellent new source for transplantation in diabetic patients.
On the basis of these successful achievements, large animal model studies were initiated. In these experiments, embryonic pig pancreatic precursor tissues were transplanted into non human primates, and followed for various periods and under various immunosuppressive regimens for survival, structural and functional growth and proliferation within the recipient primates.
A follow-up of seven weeks after transplantation showed marked engraftment and tissue growth, with considerable proliferation activity of the transplanted cells. The pig embryonic pancreatic grafts were shown to get their blood supply predominantly from the host primate blood vessels, a fact likely to provide a significant benefit for the successful acceptance and thriving of the graft and for the company's future goal of using minimal immune suppression in transplanted patients.
The ability to produce insulin was also demonstrated by specific staining for intra-cellular insulin presence.
The presence, in primates and among them in humans, of specific antibodies to certain pig antigens is known to be a determinant factor in the development of hyperacute and acute rejection reactions, responsible for early graft rejection. This problem was shown to be surmountable by the company's technological approach and by the immunosuppressive protocol adopted for the implementation of this approach.
Year 2006 Tasks
The tasks for 2006 in the company's large animal studies of pancreatic transplantation will include the following:
Future successful accomplishment of those 2006 tasks will mark a most significant milestone in the company's efforts to get approval for and initiate human clinical studies on diabetic patients.
The liver application
Year 2005 Achievements
Whereas previous studies, performed by other groups, showed that proliferation of transplanted isolated hepatocytes (liver cells) can be achieved only in conjunction with destructive manipulations of host liver, the company' studies showed extensive proliferation of hepatic cells after pig fetal liver fragments transplantation, without any preparative manipulations of the host liver.
Transplantation of isolated hepatocytes has been advocated as an alternative for whole organ transplantation in the treatment of liver failure and liver-based metabolic diseases and has been extensively studied during the past decade. However, transplantation of isolated hepatocytes in the clinical setting has been associated with limited efficacy, which may be explained in part by negligible proliferation of the transplanted cells in the quiescent host liver (by "quiescent" is meant that host liver has not been subjected to any prior destructive manipulations). Those disappointing results emphasize the need for alternative approaches that can enable proliferation of transplanted hepatic cells in the quiescent host liver.
Transplantation of pig fetal liver fragments, harvested within an optimal gestational time window previously defined by the company's research team, led to mature liver function (albumin production) as early as three days after transplantation and exhibited a dramatically increased proliferative capacity, in comparison with isolated fetal hepatocytes harvested at the same gestational age.
Subsequent to multiple trials of various sites, the preferred sites for pig embryonic liver tissue transplantation were defined. In those sites, the best acceptance, survival and function (in terms of albumin production) of the liver grafts were observed.
An appropriate immunosuppressive regimen to prevent rejection of the transplanted tissue was determined by the company. Due to a much reduced immunogenicity entailed by the utilization of embryonic liver fragments, this immunosuppressive regimen could be of mild nature. The important implication of adopting such a mild regimen is that the milder the immunosuppressive treatment is, the lesser are its side effects and the better it is tolerated by the graft recipient.
The company conducted experiments of syngeneic transplantation on a mouse model of toxic milk syndrome, a severe genetic disorder of copper metabolism ("syngeneic transplantation" means transplantation of tissue from genetically identical mice, except for the mutated gene bringing about the disorder). Preliminary data of those experiments suggest that embryonic liver tissue might potentially cure the toxic milk syndrome, thus demonstrating the therapeutic potential of the company's approach to liver transplantation.
Taken together, the afore-mentioned results of the studies implementing the company's approach to liver tissue transplantation suggest that transplantation of fetal liver fragments can potentially resolve the obstacles associated with isolated hepatocytes and thus might offer a novel efficacious therapeutic approach in the treatment of patients with advanced chronic liver failure or metabolic diseases.
Year 2006 Tasks
The tasks for 2006 in the company' studies of liver transplantation will aim at demonstrating and validating the curative value of properly timed pig embryonic liver tissue xenotransplantation in the following mice models:
Prospective success in those experiments will be pivotal in the company's aspiration to advance toward the conduction of human clinical studies of liver tissue xenotransplantation for correction of fatal genetic deficiencies and for treatment of advanced chronic liver failure patients.
Tissera Inc. was established to develop, test and commercialize tissue transplant therapies based on an approach employing porcine embryonic organ-specific precursor tissues, developed throughout years of research by Prof. Yair Reisner and his team at the Weizmann Institute of Science.
The Company's R&D efforts, conducted under an exclusive license agreement with the Weizmann Institute of Science, are directed towards fulfilling its mission of providing a universally available and reliable source of donor organs to many patients who could benefit from organ or tissue transplantation, were it not for the severe shortage of donor organs.
The achievements of R&D Year 2005, together with a prospective successful accomplishment of Year 2006 tasks, will constitute a big leap forward toward clinical application and commercialization of the company's transplantation technology.
Safe Harbor Statement "Statements in this document that are not purely historical are forward-looking statements. Forward-looking statements in this release include statements regarding our developing technology into a useful product, our moving forward with our plans for trials, and our plans to expand the Company's infrastructure. Actual outcomes and our actual results could differ materially from those in such forward-looking statements. Such statements, including statements regarding freedom to operate, patentability, infringement, clinical trials, involve significant risks and uncertainties and actual results could differ materially from those expressed or implied herein. Factors that could cause such differences include, but are not limited to, risks associated with new product development (including clinical trials outcome and regulatory requirements/actions), competitive risks to marketed products and availability of financing that could cause actual results to differ materially include risks and uncertainties such as the inability to further finance our plans and unforeseen technical difficulties in developing our technology, which could among other things, delay or prevent product development and our planned results. For further risk factors see the Company's 10-KSB filed with the SEC for our latest fiscal year."
CONTACT: Tissera Inc. Dr. Uri Elmaleh Tel: +972-9-9561151 Fax: +972-9-9561152 |
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