definiens: means any state of facts, circumstance, change, development, event, effect, condition, occurrence, action or omission that, individually or in the aggregate : ( a ) has prevented, materially delayedor materially impaired, or would reasonably be expected to prevent, materially delay or materially impair, the ability of theCompany or its Subsidiaries to consummate any of the Transactions or otherwise has prevented or would reasonably expectedto prevent the performance by the Company or its Subsidiaries of any of its respective material obligations under thisAgreement and the Ancillary Agreements ; ( b ) materially and adversely has affected or would reasonably be expected to affectthe financial condition, properties, Assets, Liabilities, business or results of operations of the Company and its Subsidiaries, taken as a whole and/or ( c ) has resulted in or would reasonably be expected to result in, a material and adverse effect on thesupplies of OncoVEXGM - CSF, including viral seed stock for OncoVEXGM - CSF, or the failure of OncoVEXGM - CSF to receiveregulatory approval for the Commercial Sale of OncoVEXGM - CSF in the United States and/or the European Union basedprimarily on the OPTiM Pivotal Trial in Melanoma ; provided, however, that Company Material Adverse Effect shall notinclude any effects to the extent arising out of, resulting from or relating to : ( i ) changes in the national or world economy ornational or foreign financial credit or securities markets as a whole ; ( ii ) changes in the biopharmaceutical industry generally;(iii ) any hostilities, acts of war, sabotage, terrorism or military actions, or any escalation or worsening of any such hostilities, acts of war, sabotage, terrorism or military actions, in each case, directly involving the United States or the United Kingdom;(iv ) any change in the generally accepted accounting principles or interpretation or application thereof ; ( v ) any adversechange or effect directly arising out of the announcement or consummation of the Transactions contemplated by thisAgreement ; ( vi ) any development with respect to any product or product candidate of any third party ; ( vii ) the continuedincurrence of expenses by the Company in the ordinary course of business consistent with past practices ; and ( viii ) changes inlaw, rule or regulations or the interpretation thereof ; provided, further, with respect to clauses ( i ) through ( iv ) and ( viii ), suchchange, effect, circumstance or development does not disproportionately adversely affect the Company and its Subsidiaries, taken as a whole, relative to other participants in the biopharmaceutical industry