ANNUAL FINANCIAL REPORT 2010 2010 - TiGenix

Allogeneic approachAn allogeneic treatment is advantageous over an autologousfor several reasons such as:(a) Producing cells for many patients is more efficient:• Scale-up can go much further• Quality control can be applied to larger lots• Existing attachment cell technology for production scaleis useful• Material of high consistency• Allows high patient throughput(b) Cells are always available:• Can address emergency indications• Represents a good commercial opportunity(c) No patient biopsy/tissue procurement needed:• Less clinical time and resources• Avoids needing biopsy consent from severely ill patients• Enables patients who may not possess sufficient tissue orwho for any other medical reason cannot undergo tissueprocurement(d) Commercial product orientated. Lower product cost ofgoodstheir immunomodulatory effects are based on this activationcascade. This immune-modulation is described shortly asfollows:During the inflammatory process, IFN-γ is secreted by thepatient’s lymphocytes. When eASCs are injected into theinflamed site, they are activated by the IFN-γ, resulting in theexpression of the enzyme IDO. The enzymatic activity of IDOsuppresses the proliferation of activated lymphocytes, shuttingdown chronic inflammation and thereby allowing a naturalhealing of the inflamed tissue. In parallel, physical interactionof lymphocytes with the eASCs generates antigen specificTreg (T-suppressor) cells, which allows a systemic suppressionof an activated immune system, an important aspect inregulating autoimmunity. Importantly, the immunomodulationcapacity is not altered within ex vivo expansion of ASCs but thedifferentiation capacity is indeed limited with expansion.Product development strategy and pipelineCellerix aims to exploit the immuno-modulatory capacityof eASCs pursuing the delivery of the cells via the mostappropriate route of administration according to the indicationtargeted. Accordingly, clinical stage programs are currently inplace using both local and systemic administration. Furtherprograms are in pre-clinical development using additionalroutes of administration within these two categories. Theplatform development strategy is pictured in figure 6.9.Mechanism of actionIt has been scientifically documented 65 that certain stemcell populations are capable of acting as immunoregulatoryagents by interacting with cells of the immune system.Scientists at Cellerix in agreement with published data fromacademic groups have confirmed an activation of eASCs by thecytokine interferon-gamma (“IFN-γ”) 66 , and the subsequentexpression of the tryptophan metabolizing enzymeIndoleamine 2,3 dioxygenase (“IDO”) 67 as pivotal processes.The underlying mechanism of action (MoA) of eASCs and65 Isr Med Assoc J. 2010 Feb;12(2):110-5. “Cellular therapy in 2010: focus onautoimmune and cardiac diseases.”Perl L, Weissler A, Mekori YA, Mor A.66 Best Pract Res Clin Haematol. 2011 Mar;24(1):49-57. Epub 2011 Feb 23.“Mesenchymal stem cells and autoimmune diseases.”67 Stem Cells Dev. 2008 Aug;17(4):681-93.”Soluble factors-mediatedimmunomodulatory effects of canine adipose tissue-derived mesenchymalstem cells.” Kang JW, Kang KS, Koo HC, Park JR, Choi EW, Park YH.139 •