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, occurrence, result or state of facts, has or would reasonably be expected to ( a ) have a materialadverse effect on the business, financial condition, assets, liabilities or results of operations of the Neuromed Entities, taken asa whole, except that none of the following shall be taken into account in determining whether there has been a NeuromedMaterial Adverse Effect : ( i ) changes in general economic or political conditions or the securities market in general ( whether asa result of acts of terrorism, war ( whether or not declared ), armed conflicts or otherwise ) to the extent they do notdisproportionately affect the Neuromed Entities, taken as a whole ; ( ii ) changes in or affecting the industries in which theNeuromed Entities operate to the extent they do not disproportionately affect the Neuromed Entities, 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 [COMPANY] or Merger Sub or expressly required by this Agreement ; ( v ) anychanges in or affecting research and development, clinical trials or other drug development activities conducted by or onbehalf of any of the Neuromed Entities in respect of Neuromed Products or any other product candidates ; and ( vi ) continuedlosses from operations or decreases in cash balances of any Neuromed Entity or on a consolidated basis among all NeuromedEntities ; or ( b ) prevent or materially delay the ability of Neuromed and Neuromed Canada to consummate the transactionscontemplated by this Agreement, in each case when viewed on a long - term or short - term basis