in myelofibrosis , bms is conducting a phase 2 clinical trial in patients with myelofibrosis-associated anemia , and initial results from this trial were presented in december 2019 at the 61st american society of hematology annual meeting and exposition showing that luspatercept-aamt improved anemia in patients receiving and not receiving rbc transfusions , with more profound effects in patients treated with ruxolitinib , a small molecule jak inhibitor . based on these data , we and bms announced plans to initiate by the end of 2020 the phase 3 independence study in patients with myelofibrosis-associated anemia who are being treated with jak inhibitor therapy and require rbc transfusions . if approved in the united states and europe , we believe that there is an annual peak sales opportunity for reblozyl in excess of $ 2 billion in lower-risk mds and beta-thalassemia , and upon successful development and approval in the united states and europe , an additional $ 1 billion in myelofibrosis and other future development opportunities . we and bms are evaluating luspatercept-aamt for the treatment of anemia in potential new indications that could provide additional sales opportunities . bms is responsible for paying 100 % of the development costs for all clinical trials for luspatercept-aamt . we may receive a maximum of $ 125.0 million for remaining potential regulatory and commercial milestone payments . we have a co-promotion 54 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 . pulmonary we are actively developing our lead pulmonary program , sotatercept , for the treatment of patients with pulmonary arterial hypertension , or pah . sotatercept is generally partnered with bms , but we retain the exclusive rights to fund , develop , and lead the global commercialization of sotatercept in pulmonary hypertension , which we refer to as the ph field , and that includes pah . pah is a rare and chronic , rapidly progressing disorder characterized by the constriction of small pulmonary arteries , resulting in abnormally high blood pressure in the pulmonary arteries . in january 2020 , we announced that the pulsar phase 2 clinical trial of sotatercept for the treatment of patients with pah met its primary and key secondary endpoints , as well as other secondary endpoints . the 18-month extension period of the pulsar trial is ongoing . we are also currently enrolling an exploratory study called spectra to provide us with greater understanding of sotatercept 's potential impact on pah , with preliminary results expected in 2020. if sotatercept is commercialized to treat pah and we recognize such revenue , then we will owe bms a royalty in the low 20 % range on global net sales . in certain circumstances , bms may recognize revenue related to the commercialization of sotatercept in pah , and in this scenario we will be eligible to receive a royalty from bms such that the economic position of the parties is equivalent to the scenario in which we recognize such revenue . neuromuscular we are independently developing our wholly-owned neuromuscular candidate , ace-083 . ace-083 is designed for the treatment of focal muscle disorders . we are currently conducting a phase 2 clinical trial with ace-083 in patients with charcot-marie-tooth disease , or cmt , and an extension study for eligible cmt patients who have completed treatment in the phase 2 clinical trial with ace-083 . we previously announced results from part 1 of this phase 2 clinical trial showing increases in mean total and contractile muscle volume , and reductions in fat fraction . the results also showed that ace-083 was generally well tolerated . enrollment is complete in part 2 of this trial and we expect to announce topline results from part 2 in the first quarter of 2020. in september 2019 , we announced that ace-083 did not achieve functional secondary endpoints in part 2 of a phase 2 clinical trial in patients with facioscapulohumeral muscular dystrophy , or fshd , and we are discontinuing development of ace-083 in fshd . funding and expense as of december 31 , 2019 , our operations have been funded primarily by $ 105.1 million in equity investments from venture investors , $ 773.8 million from public investors , $ 154.1 million in equity investments from our collaboration partners and $ 356.7 million in upfront payments , milestones , and net research and development payments from our collaboration partners . we estimate that we have spent approximately $ 154.0 million , $ 103.9 million , and $ 89.7 million , on research and development for the years ended december 31 , 2019 , 2018 , and 2017 , respectively . we expect to continue to incur significant expenses and increasing operating losses over at least the next several years . we expect our expenses will increase substantially in connection with our ongoing activities , as we : conduct clinical trials for sotatercept in the ph field , ace-083 or any future therapeutic candidates ; 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 . story_separator_special_tag 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 59 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 . due to the lack of a public market for our common stock prior to the completion of our initial public offering in september 2013 , and resulting lack of company-specific historical and implied volatility data , we have based our estimate of expected volatility on the historical volatility of a group of similar publicly traded companies . for these analyses , we have selected companies with characteristics that we believe are comparable to ours , including enterprise value , risk profiles , position within the industry , and with historical share price information sufficient to meet the expected life of the stock-based awards . we compute the historical volatility data using the daily closing prices for the selected companies ' shares during the equivalent period as the calculated expected term of our stock-based awards . 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 $ 23.0 million , $ 24.6 million and $ 28.2 million for the years ended december 31 , 2019 , 2018 and 2017 , 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 , 2019 and 2018 replace_table_token_5_th revenue . we recognized revenue of $ 74.0 million in the year ended december 31 , 2019 , compared to $ 14.0 million in the year ended december 31 , 2018 . all of the revenue in both periods was derived from the bms agreements . this increase in revenue of $ 60.0 million was primarily due to the recognition of milestones from bms ( then celgene ) for the acceptance of the bla and validation of the maa for reblozyl , as well as the approval of the bla for reblozyl . 60 research and development expenses . research and development expenses were $ 154.0 million in the year ended december 31 , 2019 , compared to $ 103.9 million in the year ended december 31 , 2018 . this $ 50.1 million increase is 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 $ 6.0 million related to increased headcount to support our growth ; an increase in external clinical trial expense of $ 8.7 million related to our ongoing clinical trials ; an increase in toxicology expense of $ 6.7 million related to the advancement of our clinical and preclinical programs ; an increase in contract manufacturing and drug supply expense of $ 11.1 million related to our ongoing clinical and preclinical programs ; an increase in in-licensing expense related to payments that were made in connection with achievements of milestones in 2019 totaling $ 3.6 million ; an increase of $ 10.0 million in relation to the execution of the license and collaboration agreement with fulcrum therapeutics , as discussed further in note 10 to the financial statements in this annual report on form 10-k ; and an increase in miscellaneous research expense and professional fees of $ 4.0 million . selling , general and administrative expenses . selling , general and administrative expenses were $ 56.5 million in the year ended december 31 , 2019 , compared to $ 34.5 million in the year ended december 31 , 2018 . this $ 22.0 million increase was primarily due to the following factors : an increase in selling expense of $ 5.1 million in preparation for the launch of reblozyl , our first commercial product approved by the fda on november 8 , 2019 ; an increase in personnel and facilities-related expense

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_7_th operating activities . net cash used in operating activities was $ 93.8 million for the year ended december 31 , 2019 , compared to $ 94.7 million and $ 76.5 million for the years ended december 31 , 2018 and 2017 , respectively . net cash used in operating activities has decreased over this three-year period as a result of $ 60.0 million of milestone payments received in 2019 , offset by increased operating expenses over the same period . the increase in operating expenses consists of increased expenses related to headcount and facilities , increased external expenses for clinical and preclinical activities , contract manufacturing , consulting , and other external expenses to support our wholly-owned therapeutic programs , as well as expenses for commercial activities in advance of and in conjunction with the commercial launch of reblozyl . the change in 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 , 2019 , a net loss of $ 124.9 million adjusted for non-cash items including : stock-based compensation expense of $ 23.0 million and depreciation and amortization expense of $ 3.9 million , and a net increase of $ 4.0 million due to changes in operating assets and liabilities . the significant items in the change in operating assets and liabilities include an increase in accrued expenses of $ 6.3 million and an increase in collaboration receivable of $ 1.5 million . for the year ended december 31 , 2018 , a net loss of $ 118.9 million adjusted for non-cash items including : stock-based compensation expense of $ 24.6 million , depreciation and amortization expense of $ 3.7 million , and a net decrease of $ 4.6 million due to changes in operating assets and liabilities .


 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_7_th operating activities . net cash used in operating activities was $ 93.8 million for the year ended december 31 , 2019 , compared to $ 94.7 million and $ 76.5 million for the years ended december 31 , 2018 and 2017 , respectively . net cash used in operating activities has decreased over this three-year period as a result of $ 60.0 million of milestone payments received in 2019 , offset by increased operating expenses over the same period . the increase in operating expenses consists of increased expenses related to headcount and facilities , increased external expenses for clinical and preclinical activities , contract manufacturing , consulting , and other external expenses to support our wholly-owned therapeutic programs , as well as expenses for commercial activities in advance of and in conjunction with the commercial launch of reblozyl . the change in 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 , 2019 , a net loss of $ 124.9 million adjusted for non-cash items including : stock-based compensation expense of $ 23.0 million and depreciation and amortization expense of $ 3.9 million , and a net increase of $ 4.0 million due to changes in operating assets and liabilities . the significant items in the change in operating assets and liabilities include an increase in accrued expenses of $ 6.3 million and an increase in collaboration receivable of $ 1.5 million . for the year ended december 31 , 2018 , a net loss of $ 118.9 million adjusted for non-cash items including : stock-based compensation expense of $ 24.6 million , depreciation and amortization expense of $ 3.7 million , and a net decrease of $ 4.6 million due to changes in operating assets and liabilities .
```    
 Suspicious Activity Report : in myelofibrosis , bms is conducting a phase 2 clinical trial in patients with myelofibrosis-associated anemia , and initial results from this trial were presented in december 2019 at the 61st american society of hematology annual meeting and exposition showing that luspatercept-aamt improved anemia in patients receiving and not receiving rbc transfusions , with more profound effects in patients treated with ruxolitinib , a small molecule jak inhibitor . based on these data , we and bms announced plans to initiate by the end of 2020 the phase 3 independence study in patients with myelofibrosis-associated anemia who are being treated with jak inhibitor therapy and require rbc transfusions . if approved in the united states and europe , we believe that there is an annual peak sales opportunity for reblozyl in excess of $ 2 billion in lower-risk mds and beta-thalassemia , and upon successful development and approval in the united states and europe , an additional $ 1 billion in myelofibrosis and other future development opportunities . we and bms are evaluating luspatercept-aamt for the treatment of anemia in potential new indications that could provide additional sales opportunities . bms is responsible for paying 100 % of the development costs for all clinical trials for luspatercept-aamt . we may receive a maximum of $ 125.0 million for remaining potential regulatory and commercial milestone payments . we have a co-promotion 54 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 . pulmonary we are actively developing our lead pulmonary program , sotatercept , for the treatment of patients with pulmonary arterial hypertension , or pah . sotatercept is generally partnered with bms , but we retain the exclusive rights to fund , develop , and lead the global commercialization of sotatercept in pulmonary hypertension , which we refer to as the ph field , and that includes pah . pah is a rare and chronic , rapidly progressing disorder characterized by the constriction of small pulmonary arteries , resulting in abnormally high blood pressure in the pulmonary arteries . in january 2020 , we announced that the pulsar phase 2 clinical trial of sotatercept for the treatment of patients with pah met its primary and key secondary endpoints , as well as other secondary endpoints . the 18-month extension period of the pulsar trial is ongoing . we are also currently enrolling an exploratory study called spectra to provide us with greater understanding of sotatercept 's potential impact on pah , with preliminary results expected in 2020. if sotatercept is commercialized to treat pah and we recognize such revenue , then we will owe bms a royalty in the low 20 % range on global net sales . in certain circumstances , bms may recognize revenue related to the commercialization of sotatercept in pah , and in this scenario we will be eligible to receive a royalty from bms such that the economic position of the parties is equivalent to the scenario in which we recognize such revenue . neuromuscular we are independently developing our wholly-owned neuromuscular candidate , ace-083 . ace-083 is designed for the treatment of focal muscle disorders . we are currently conducting a phase 2 clinical trial with ace-083 in patients with charcot-marie-tooth disease , or cmt , and an extension study for eligible cmt patients who have completed treatment in the phase 2 clinical trial with ace-083 . we previously announced results from part 1 of this phase 2 clinical trial showing increases in mean total and contractile muscle volume , and reductions in fat fraction . the results also showed that ace-083 was generally well tolerated . enrollment is complete in part 2 of this trial and we expect to announce topline results from part 2 in the first quarter of 2020. in september 2019 , we announced that ace-083 did not achieve functional secondary endpoints in part 2 of a phase 2 clinical trial in patients with facioscapulohumeral muscular dystrophy , or fshd , and we are discontinuing development of ace-083 in fshd . funding and expense as of december 31 , 2019 , our operations have been funded primarily by $ 105.1 million in equity investments from venture investors , $ 773.8 million from public investors , $ 154.1 million in equity investments from our collaboration partners and $ 356.7 million in upfront payments , milestones , and net research and development payments from our collaboration partners . we estimate that we have spent approximately $ 154.0 million , $ 103.9 million , and $ 89.7 million , on research and development for the years ended december 31 , 2019 , 2018 , and 2017 , respectively . we expect to continue to incur significant expenses and increasing operating losses over at least the next several years . we expect our expenses will increase substantially in connection with our ongoing activities , as we : conduct clinical trials for sotatercept in the ph field , ace-083 or any future therapeutic candidates ; 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 . story_separator_special_tag 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 59 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 . due to the lack of a public market for our common stock prior to the completion of our initial public offering in september 2013 , and resulting lack of company-specific historical and implied volatility data , we have based our estimate of expected volatility on the historical volatility of a group of similar publicly traded companies . for these analyses , we have selected companies with characteristics that we believe are comparable to ours , including enterprise value , risk profiles , position within the industry , and with historical share price information sufficient to meet the expected life of the stock-based awards . we compute the historical volatility data using the daily closing prices for the selected companies ' shares during the equivalent period as the calculated expected term of our stock-based awards . 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 $ 23.0 million , $ 24.6 million and $ 28.2 million for the years ended december 31 , 2019 , 2018 and 2017 , 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 , 2019 and 2018 replace_table_token_5_th revenue . we recognized revenue of $ 74.0 million in the year ended december 31 , 2019 , compared to $ 14.0 million in the year ended december 31 , 2018 . all of the revenue in both periods was derived from the bms agreements . this increase in revenue of $ 60.0 million was primarily due to the recognition of milestones from bms ( then celgene ) for the acceptance of the bla and validation of the maa for reblozyl , as well as the approval of the bla for reblozyl . 60 research and development expenses . research and development expenses were $ 154.0 million in the year ended december 31 , 2019 , compared to $ 103.9 million in the year ended december 31 , 2018 . this $ 50.1 million increase is 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 $ 6.0 million related to increased headcount to support our growth ; an increase in external clinical trial expense of $ 8.7 million related to our ongoing clinical trials ; an increase in toxicology expense of $ 6.7 million related to the advancement of our clinical and preclinical programs ; an increase in contract manufacturing and drug supply expense of $ 11.1 million related to our ongoing clinical and preclinical programs ; an increase in in-licensing expense related to payments that were made in connection with achievements of milestones in 2019 totaling $ 3.6 million ; an increase of $ 10.0 million in relation to the execution of the license and collaboration agreement with fulcrum therapeutics , as discussed further in note 10 to the financial statements in this annual report on form 10-k ; and an increase in miscellaneous research expense and professional fees of $ 4.0 million . selling , general and administrative expenses . selling , general and administrative expenses were $ 56.5 million in the year ended december 31 , 2019 , compared to $ 34.5 million in the year ended december 31 , 2018 . this $ 22.0 million increase was primarily due to the following factors : an increase in selling expense of $ 5.1 million in preparation for the launch of reblozyl , our first commercial product approved by the fda on november 8 , 2019 ; an increase in personnel and facilities-related expense

