Beer goes flat for Kirin, splashes cash on 'ultimate cancer warrior' instead

For Y300bn (€1.85bn), Kirin will get a 50.1 per cent stake in Kyowa Hakko and intends to integrate it into its existing biotech franchise, Kirin Pharma. Both firms already focus on antibody drugs and so by merging, they can expect to make a number of cost and efficiency savings. The beer market in Japan has gone flat of late, and so it is perhaps not surprising that Kirin is looking for other growth areas to exploit. Therapeutic antibodies would certainly fall into that category and Kyowa's 'Potelligent' antibodies had already drawn interest from big pharma firms such as Genentech, Biogen Idec, Medarex, MedImmune and Takeda, leading many industry insiders to tip them as an acquisition target. Just last week, the world's second largest pharma firm GlaxoSmithKline (GSK) added their name to the list of licensees through a non-exclusive deal with BioWa, a wholly owned subsidiary of Kyowa Hakko. The financial details were undisclosed. Potelligent antibodies are designed to increase the Antigen Dependent Cellular Cytotoxicity (ADCC) activity of an antibody - where an antibody first binds to an antigen on tumour cells and then to Fc receptors on monocytes, macrophages, and natural killer cells, for example. These cells then engulf the tumour cell and destroy it. This is the mechanism at work with Genentech and Biogen Idec's Rituxan (rituximab), which targets the CD20 antigen on tumour cells. However, the scientists at Kyowa Hakko realised that removing fucose from sugar chains on an antibody increases the binding affinity of the antibody to Fc?RIIIa (CD16), the major Fc receptor for ADCC in humans. This, in turn, enhances ADCC. The technology also reduces the negative effect of genetic polymorphisms on an antibody's effectiveness. The fucose-free antibodies are manufactured using CHO cells where the FUT8 gene has been suppressed since it is this gene that is responsible for adding fucose to sugar chains in antibodies. More recently, Kyowa announced it was launching a second antibody technology​, called 'Complegent'. For this latest advance over traditional antibodies, scientists have taken parts of Immunoglobulin G3 (IgG3) antibody molecules and inserted them into IgG1 molecules, which is the standard isotope used in therapeutic monoclonal antibodies (mAbs). This is in an attempt to increase their complement-dependent cytotoxicity. The technology could lead to a new type of antibody that is effective at lower doses and could therefore be used as a monotherapy. BioWa also said at the time it licensed the technology that the new class of drug could have fewer side effects compared to antibodies carrying radioisotopes or toxic payloads. Since IgG3 molecules have an increased ability to bind to receptors and initiate the complement system compared to IgG1 antibodies, the resultant IgG3/IgG1 chimer is more effective at destroying tumour cells than either type of immunoglobulin alone. The complement system causes the target cell membrane to be punctured, which, in turn, causes cell lysis and death. The new type of antibodies also retain the desirable features of standard IgG1 molecules, such as ADCC, good pharmacokinetic profile and Protein A binding, according to BioWa. The two technology platforms combined form the recently launched AccretaMab platform, which BioWa claims has "the potential to be the ultimate antibody warriors to annihilate tumour cells."​ According to the terms of the deal, Kirin will initially buy a 27.95 per cent stake in Kyowa Hakko - worth Y1.67bn - before acquiring the rest of the shares in an exchange agreement. The resultant entity will be called Kyowa Hakko Kirin. The respective company's non-pharmaceutical businesses also look set to be integrated although not as part of this deal and nothing has been finalised.