definiens: means any change, circumstance, condition, development, effect, event, occurrence, result or state of facts that, individually or when taken together with any other such change, circumstance, condition, development, effect, event, 101occurrence, result or state of facts, has or would reasonably be expected to ( a ) have a material adverse effect on the business, financial condition, assets, liabilities or results of operations of [COMPANY] and its Subsidiaries, taken as a whole, exceptthat none of the following shall be taken into account in determining whether there has been a [COMPANY] MaterialAdverse Effect : ( i ) changes in general economic or political conditions or the securities market in general ( whether as a resultof acts of terrorism, war ( whether or not declared ), armed conflicts or otherwise ) to the extent they do not disproportionatelyaffect [COMPANY] and its Subsidiaries, taken as a whole ; ( ii ) changes in or affecting the industries in which CombinatoRxoperates to the extent they do not disproportionately affect [COMPANY] and its Subsidiaries, taken as a whole, in anymaterial respect ; ( iii ) changes, effects or circumstances resulting from the announcement or pendency of this Agreement or theconsummation of the transactions contemplated by this Agreement or compliance with the terms of this Agreement ; ( iv ) anyspecific action taken at the written request of Neuromed or expressly required by this Agreement ; ( v ) any changes in oraffecting research and development, clinical trials or other drug development activities conducted by or on behalf ofCombinatoRx or its Subsidiaries in respect of [COMPANY] Products or any other product candidates ; and ( vi ) continuedlosses from operations or decreases in cash balances of [COMPANY] or any of its Subsidiaries or on a consolidated basisamong [COMPANY] and its Subsidiaries ; or ( b ) prevent or materially delay the ability of [COMPANY] and Merger Sub toconsummate the transactions contemplated by this Agreement, in each case when viewed on a long - term or short - term basis