in december 2020 , the european commission granted orphan drug designation to sotatercept for the treatment of patients with pah . if sotatercept is approved and commercialized to treat pah , then we will recognize revenue from global net sales and owe bms a royalty in the low 20 % range . in addition to sotatercept , we are currently advancing our second pulmonary therapeutic candidate , ace-1334 . ace-1334 is a wholly owned tgf-beta superfamily-based ligand trap designed to bind and inhibit tgf-beta 1 and 3 ligands but not tgf-beta 2. we recently completed an ascending-dose phase 1 clinical trial in healthy volunteers , and the fda has granted fast track designation to ace-1334 in patients with systemic sclerosis-associated interstitial lung disease , or ssc-ild , as well as orphan drug designation for the treatment of systemic sclerosis . ssc-ild is a rare , progressive , autoimmune connective tissue 54 disorder characterized by immune dysregulation . we intend to initiate a phase 1b/phase 2 clinical trial with ace-1334 in patients with ssc-ild in 2021. hematology our first commercial product , reblozyl® ( luspatercept-aamt ) , is a first-in-class erythroid maturation agent designed to promote red blood cell , or rbc , production through a novel mechanism , and is partnered with bms . reblozyl is currently approved to treat certain adult patients with beta-thalassemia or mds in the united states , european union and canada , as further described in `` business `` above . for additional patient populations , bms is currently conducting a phase 2 clinical trial with luspatercept-aamt in non-transfusion-dependent beta-thalassemia patients , referred to as the beyond trial , with results currently expected in the first half of 2021 , and a phase 3 clinical trial , the commands trial , in first-line , lower-risk mds patients , with topline results expected in or after 2022. in myelofibrosis , bms is conducting a phase 2 clinical trial with luspatercept-aamt in patients with myelofibrosis-associated anemia , and is in the process of initiating the phase 3 independence study in patients with myelofibrosis-associated anemia who are being treated with jak inhibitor therapy and require rbc transfusions . we believe that there is a global annual peak sales opportunity for reblozyl in excess of $ 4 billion for all currently approved indications and those in development , including future clinical development expansion . bms is responsible for paying 100 % of the development costs for all clinical trials for luspatercept-aamt . we may receive a maximum of $ 100.0 million for remaining potential regulatory and commercial milestone payments . we have a co-promotion right in north america and our commercialization costs provided in the commercialization plan and budget approved by the joint commercialization committee , or jcc , are entirely funded by bms . activities that we elect to conduct outside of the approved development or commercialization budgets to support reblozyl are at our own expense . we are eligible to receive tiered royalty payments from bms on net sales of reblozyl in the low-to-mid 20 % range . funding and expense as of december 31 , 2020 , our operations have been funded primarily by $ 105.1 million in equity investments from venture investors , $ 1.3 billion from public investors , $ 164.1 million in equity investments from our collaboration partners and $ 431.7 million in upfront payments , milestones , royalties , and net research and development payments from our collaboration partners . we have spent approximately $ 173.9 million , 154.0 million , and 103.9 million , on research and development for the years ended december 31 , 2020 , 2019 , and 2018 , respectively . we expect our expenses will increase substantially in connection with our ongoing activities , if and as we : conduct clinical trials for sotatercept in the ph field or any future therapeutic candidates ; prepare for the potential launch and commercialization of sotatercept in the ph field ; continue our preclinical studies and potential clinical development efforts of our existing preclinical therapeutic candidates ; continue research activities for the discovery of new therapeutic candidates ; manufacture therapeutic candidates for our preclinical studies and clinical trials , and potentially for commercialization ; establish and maintain a sales , marketing and distribution infrastructure to commercialize any products for which we have or may obtain regulatory approval ; acquire or in-license other therapeutic candidates and patents ; seek regulatory approval for our therapeutic candidates ; and attract and retain skilled personnel . if we obtain regulatory approval for sotatercept in the ph field , or any future therapeutic candidate , we expect to incur significant commercialization expenses related to product sales , marketing , manufacturing and distribution to the extent that such costs are not paid by future partners . we will seek to fund our operations through royalty revenue from the sale of our first and only commercial product , reblozyl , and potentially from the sale of equity , debt financings or other sources , including potential additional collaborations . however , we may not generate sufficient royalty revenue and may be unable to raise additional funds or enter into such other arrangements when needed on favorable terms , or at all . if we fail to generate 55 significant revenue or capital , or enter into such other arrangements as , and when , needed , we may have to significantly delay , scale back or discontinue the development or commercialization of one or more of our therapeutic candidates . to date , we have only generated limited revenue from royalties on the sale of our first and only commercial product , reblozyl , since receiving our first regulatory approval from the fda in november 2019. our ability to generate product revenue and become profitable depends upon our and our partners ' ability to successfully commercialize products . story_separator_special_tag the financial terms of these agreements are subject to negotiation , vary from contract to contract and may result in uneven payment flows . there may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the expense . additionally , invoicing from third-party service providers may not coincide with actual work performed and can result in a prepaid position at period end . we make significant judgments and estimates in determining the services incurred as of each balance sheet date , which may result in either an accrual or prepaid balance . as actual costs become known , we adjust our estimates . although we do not expect our estimates to be materially different from amounts actually incurred , our understanding of the status and timing of services performed , the number of subjects enrolled , and the rate of enrollment may vary from its estimates and could result in us reporting amounts that are too high or too low in a particular period . our accrued and prepaid expenses are dependent , in part , upon the receipt of timely and accurate reporting from cros and third-party service providers . to date , we have not experienced any material differences between estimated costs and actual costs incurred . stock-based compensation we account for our stock-based awards in accordance with asc topic 718 , compensation—stock compensation , or asc 718 , which requires all stock-based payments to employees , including grants of employee stock options , modifications to existing stock options , and restricted stock unit awards , to be recognized in the statements of operations and comprehensive income ( loss ) based on their fair values . we recognize the compensation cost of awards subject to service-based vesting conditions over the requisite service period , which is generally equal to the vesting term . for awards subject to both performance and service-based vesting conditions , we recognize compensation cost using an accelerated recognition method when it is probable that the performance condition will be achieved . if achievement of the performance condition is not probable , but the award will vest based on the service condition , we recognize the expense over the requisite service period . forfeitures are recognized as they occur . we estimate the fair value of our stock-based awards to employees and non-employees using the black-scholes option pricing model , which requires the input of highly subjective assumptions , including ( 1 ) the expected volatility of our stock , ( 2 ) the expected term of the award , ( 3 ) the risk-free interest rate and ( 4 ) expected dividends . we have estimated our volatility by using a blend of our stock price history , for the length of time we have market data for our stock and the historical volatility of similar public companies for the expected term of each grant . as of september 2019 , we had sufficient company-specific historical volatility data to begin estimating our stock 's expected volatility by using our own stock 's data rather than a blended rate for most awards . we have estimated the expected life of our employee stock options using the `` simplified `` method , whereby , the expected life equals the average of the vesting term and the original contractual term of the option . the risk-free interest rates for periods within the expected life of the option are based on the u.s. treasury yield curve in effect during the period the options were granted . stock-based compensation totaled approximately $ 30.2 million , $ 23.0 million and $ 24.6 million for the years ended december 31 , 2020 , 2019 and 2018 , respectively . we expect the impact of our stock-based compensation expense for stock-based awards granted to employees and non-employees to grow in future periods due to the potential increases in the value of our common stock and headcount . results of operations comparison of the years ended december 31 , 2020 and 2019 60 replace_table_token_3_th revenue . we recognized revenue of $ 92.5 million in the year ended december 31 , 2020 , compared to $ 74.0 million in the year ended december 31 , 2019. all of the revenue in both periods was derived from the bms agreements . this increase in revenue of $ 18.5 million is primarily due to the following factors : an increase in royalty revenue from reblozyl sales of $ 54.8 million ; offset by a decrease in milestone revenue of $ 35.0 million due to the recognition of multiple milestones in 2019 from bms ( then celgene ) for the acceptance of the bla and validation of the maa , as well as approval of the bla for reblozyl , compared to the recognition of one milestone in 2020 for the approval by the ema ; and a decrease in cost-sharing revenue of $ 1.3 million primarily due to a decrease in trial management fees and development costs , offset by an increase in reimbursable commercial fees as we continue to expand our commercial footprint . research and development expenses . research and development expenses were $ 173.9 million in the year ended december 31 , 2020 , compared to $ 154.0 million in the year ended december 31 , 2019. this $ 19.9 million increase was primarily related to growth in order to support our wholly-owned therapeutic candidates and preclinical programs and includes : an increase in personnel and facilities-related expense of $ 14.1 million related to increased headcount to support our growth ; an increase in contract manufacturing , drug supply , and development expenses of $ 20.3 million related to our ongoing clinical and preclinical programs ; and an increase in miscellaneous research expense of $ 4.1 million ; offset by a decrease in external clinical trial expense of $ 9.2 million due to the discontinuation of our ace-083 program ,

cash flows the following table sets forth the primary sources and uses of cash for each of the years set forth below : replace_table_token_5_th operating activities . net cash used in operating activities was $ 130.3 million for the year ended december 31 , 2020 , compared to $ 93.8 million and $ 94.7 million for the years ended december 31 , 2019 and 2018 , respectively . the increase in operating expenses relates to headcount and facilities , contract manufacturing , consulting , and other external expenses to support sotatercept and our wholly-owned therapeutic programs , as well as expenses for commercial activities for reblozyl . net cash used in operating activities primarily consists of our net losses adjusted for non-cash items and changes in components of operating assets and liabilities , as follows : for the year ended december 31 , 2020 , a net loss of $ 166.0 million inclusive of $ 54.8 million of royalty revenue ; non-cash adjustments of $ 35.5 million , primarily from $ 30.2 million of stock-based compensation expense ; change in operating assets and liabilities of $ 0.2 million , primarily from an increase in accounts payable and accrued expenses of $ 5.8 million and $ 19.5 million respectively , offset by an increase in prepaid expenses and other current assets of $ 7.2 million , and collaboration receivable of $ 17.6 million ; for the year ended december 31 , 2019 , a net loss of $ 124.9 million adjusted for non-cash items primarily made up of $ 23.0 million of


 Write a concise suspicious activity report of the following text delimited by triple backquotes. Return your response as a formal report which covers the key points highlighting the location,dates,entity names and account holder information in chronological order of the text.
     ```cash flows the following table sets forth the primary sources and uses of cash for each of the years set forth below : replace_table_token_5_th operating activities . net cash used in operating activities was $ 130.3 million for the year ended december 31 , 2020 , compared to $ 93.8 million and $ 94.7 million for the years ended december 31 , 2019 and 2018 , respectively . the increase in operating expenses relates to headcount and facilities , contract manufacturing , consulting , and other external expenses to support sotatercept and our wholly-owned therapeutic programs , as well as expenses for commercial activities for reblozyl . net cash used in operating activities primarily consists of our net losses adjusted for non-cash items and changes in components of operating assets and liabilities , as follows : for the year ended december 31 , 2020 , a net loss of $ 166.0 million inclusive of $ 54.8 million of royalty revenue ; non-cash adjustments of $ 35.5 million , primarily from $ 30.2 million of stock-based compensation expense ; change in operating assets and liabilities of $ 0.2 million , primarily from an increase in accounts payable and accrued expenses of $ 5.8 million and $ 19.5 million respectively , offset by an increase in prepaid expenses and other current assets of $ 7.2 million , and collaboration receivable of $ 17.6 million ; for the year ended december 31 , 2019 , a net loss of $ 124.9 million adjusted for non-cash items primarily made up of $ 23.0 million of
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 Suspicious Activity Report : in december 2020 , the european commission granted orphan drug designation to sotatercept for the treatment of patients with pah . if sotatercept is approved and commercialized to treat pah , then we will recognize revenue from global net sales and owe bms a royalty in the low 20 % range . in addition to sotatercept , we are currently advancing our second pulmonary therapeutic candidate , ace-1334 . ace-1334 is a wholly owned tgf-beta superfamily-based ligand trap designed to bind and inhibit tgf-beta 1 and 3 ligands but not tgf-beta 2. we recently completed an ascending-dose phase 1 clinical trial in healthy volunteers , and the fda has granted fast track designation to ace-1334 in patients with systemic sclerosis-associated interstitial lung disease , or ssc-ild , as well as orphan drug designation for the treatment of systemic sclerosis . ssc-ild is a rare , progressive , autoimmune connective tissue 54 disorder characterized by immune dysregulation . we intend to initiate a phase 1b/phase 2 clinical trial with ace-1334 in patients with ssc-ild in 2021. hematology our first commercial product , reblozyl® ( luspatercept-aamt ) , is a first-in-class erythroid maturation agent designed to promote red blood cell , or rbc , production through a novel mechanism , and is partnered with bms . reblozyl is currently approved to treat certain adult patients with beta-thalassemia or mds in the united states , european union and canada , as further described in `` business `` above . for additional patient populations , bms is currently conducting a phase 2 clinical trial with luspatercept-aamt in non-transfusion-dependent beta-thalassemia patients , referred to as the beyond trial , with results currently expected in the first half of 2021 , and a phase 3 clinical trial , the commands trial , in first-line , lower-risk mds patients , with topline results expected in or after 2022. in myelofibrosis , bms is conducting a phase 2 clinical trial with luspatercept-aamt in patients with myelofibrosis-associated anemia , and is in the process of initiating the phase 3 independence study in patients with myelofibrosis-associated anemia who are being treated with jak inhibitor therapy and require rbc transfusions . we believe that there is a global annual peak sales opportunity for reblozyl in excess of $ 4 billion for all currently approved indications and those in development , including future clinical development expansion . bms is responsible for paying 100 % of the development costs for all clinical trials for luspatercept-aamt . we may receive a maximum of $ 100.0 million for remaining potential regulatory and commercial milestone payments . we have a co-promotion right in north america and our commercialization costs provided in the commercialization plan and budget approved by the joint commercialization committee , or jcc , are entirely funded by bms . activities that we elect to conduct outside of the approved development or commercialization budgets to support reblozyl are at our own expense . we are eligible to receive tiered royalty payments from bms on net sales of reblozyl in the low-to-mid 20 % range . funding and expense as of december 31 , 2020 , our operations have been funded primarily by $ 105.1 million in equity investments from venture investors , $ 1.3 billion from public investors , $ 164.1 million in equity investments from our collaboration partners and $ 431.7 million in upfront payments , milestones , royalties , and net research and development payments from our collaboration partners . we have spent approximately $ 173.9 million , 154.0 million , and 103.9 million , on research and development for the years ended december 31 , 2020 , 2019 , and 2018 , respectively . we expect our expenses will increase substantially in connection with our ongoing activities , if and as we : conduct clinical trials for sotatercept in the ph field or any future therapeutic candidates ; prepare for the potential launch and commercialization of sotatercept in the ph field ; continue our preclinical studies and potential clinical development efforts of our existing preclinical therapeutic candidates ; continue research activities for the discovery of new therapeutic candidates ; manufacture therapeutic candidates for our preclinical studies and clinical trials , and potentially for commercialization ; establish and maintain a sales , marketing and distribution infrastructure to commercialize any products for which we have or may obtain regulatory approval ; acquire or in-license other therapeutic candidates and patents ; seek regulatory approval for our therapeutic candidates ; and attract and retain skilled personnel . if we obtain regulatory approval for sotatercept in the ph field , or any future therapeutic candidate , we expect to incur significant commercialization expenses related to product sales , marketing , manufacturing and distribution to the extent that such costs are not paid by future partners . we will seek to fund our operations through royalty revenue from the sale of our first and only commercial product , reblozyl , and potentially from the sale of equity , debt financings or other sources , including potential additional collaborations . however , we may not generate sufficient royalty revenue and may be unable to raise additional funds or enter into such other arrangements when needed on favorable terms , or at all . if we fail to generate 55 significant revenue or capital , or enter into such other arrangements as , and when , needed , we may have to significantly delay , scale back or discontinue the development or commercialization of one or more of our therapeutic candidates . to date , we have only generated limited revenue from royalties on the sale of our first and only commercial product , reblozyl , since receiving our first regulatory approval from the fda in november 2019. our ability to generate product revenue and become profitable depends upon our and our partners ' ability to successfully commercialize products . story_separator_special_tag the financial terms of these agreements are subject to negotiation , vary from contract to contract and may result in uneven payment flows . there may be instances in which payments made to our vendors will exceed the level of services provided and result in a prepayment of the expense . additionally , invoicing from third-party service providers may not coincide with actual work performed and can result in a prepaid position at period end . we make significant judgments and estimates in determining the services incurred as of each balance sheet date , which may result in either an accrual or prepaid balance . as actual costs become known , we adjust our estimates . although we do not expect our estimates to be materially different from amounts actually incurred , our understanding of the status and timing of services performed , the number of subjects enrolled , and the rate of enrollment may vary from its estimates and could result in us reporting amounts that are too high or too low in a particular period . our accrued and prepaid expenses are dependent , in part , upon the receipt of timely and accurate reporting from cros and third-party service providers . to date , we have not experienced any material differences between estimated costs and actual costs incurred . stock-based compensation we account for our stock-based awards in accordance with asc topic 718 , compensation—stock compensation , or asc 718 , which requires all stock-based payments to employees , including grants of employee stock options , modifications to existing stock options , and restricted stock unit awards , to be recognized in the statements of operations and comprehensive income ( loss ) based on their fair values . we recognize the compensation cost of awards subject to service-based vesting conditions over the requisite service period , which is generally equal to the vesting term . for awards subject to both performance and service-based vesting conditions , we recognize compensation cost using an accelerated recognition method when it is probable that the performance condition will be achieved . if achievement of the performance condition is not probable , but the award will vest based on the service condition , we recognize the expense over the requisite service period . forfeitures are recognized as they occur . we estimate the fair value of our stock-based awards to employees and non-employees using the black-scholes option pricing model , which requires the input of highly subjective assumptions , including ( 1 ) the expected volatility of our stock , ( 2 ) the expected term of the award , ( 3 ) the risk-free interest rate and ( 4 ) expected dividends . we have estimated our volatility by using a blend of our stock price history , for the length of time we have market data for our stock and the historical volatility of similar public companies for the expected term of each grant . as of september 2019 , we had sufficient company-specific historical volatility data to begin estimating our stock 's expected volatility by using our own stock 's data rather than a blended rate for most awards . we have estimated the expected life of our employee stock options using the `` simplified `` method , whereby , the expected life equals the average of the vesting term and the original contractual term of the option . the risk-free interest rates for periods within the expected life of the option are based on the u.s. treasury yield curve in effect during the period the options were granted . stock-based compensation totaled approximately $ 30.2 million , $ 23.0 million and $ 24.6 million for the years ended december 31 , 2020 , 2019 and 2018 , respectively . we expect the impact of our stock-based compensation expense for stock-based awards granted to employees and non-employees to grow in future periods due to the potential increases in the value of our common stock and headcount . results of operations comparison of the years ended december 31 , 2020 and 2019 60 replace_table_token_3_th revenue . we recognized revenue of $ 92.5 million in the year ended december 31 , 2020 , compared to $ 74.0 million in the year ended december 31 , 2019. all of the revenue in both periods was derived from the bms agreements . this increase in revenue of $ 18.5 million is primarily due to the following factors : an increase in royalty revenue from reblozyl sales of $ 54.8 million ; offset by a decrease in milestone revenue of $ 35.0 million due to the recognition of multiple milestones in 2019 from bms ( then celgene ) for the acceptance of the bla and validation of the maa , as well as approval of the bla for reblozyl , compared to the recognition of one milestone in 2020 for the approval by the ema ; and a decrease in cost-sharing revenue of $ 1.3 million primarily due to a decrease in trial management fees and development costs , offset by an increase in reimbursable commercial fees as we continue to expand our commercial footprint . research and development expenses . research and development expenses were $ 173.9 million in the year ended december 31 , 2020 , compared to $ 154.0 million in the year ended december 31 , 2019. this $ 19.9 million increase was primarily related to growth in order to support our wholly-owned therapeutic candidates and preclinical programs and includes : an increase in personnel and facilities-related expense of $ 14.1 million related to increased headcount to support our growth ; an increase in contract manufacturing , drug supply , and development expenses of $ 20.3 million related to our ongoing clinical and preclinical programs ; and an increase in miscellaneous research expense of $ 4.1 million ; offset by a decrease in external clinical trial expense of $ 9.2 million due to the discontinuation of our ace-083 program ,

