we intend to review our proposed confirmatory program with the fda , and to finalize its design in the first half of 2019. we hope to leverage the confirmatory program to expand tazemetostat into the second-line treatment setting for patients with fl , both with and without ezh2 activating mutations . in addition , we plan to evaluate tazemetostat treatment in combination with other therapies . in mid-2019 , we anticipate initiating a combination study that would compare tazemetostat plus rituximab and revlimid , a chemotherapeutic-free treatment regimen referred to as r 2 , versus r 2 with placebo in patients with relapsed or refractory fl , both with and without ezh2 activating mutations . in addition , we are finalizing plans for a trial of tazemetostat in combination with rituxan for the treatment of patients with relapsed and refractory fl . based on clinical activity observed with tazemetostat in combination with r-chop as a front-line treatment for 80 patients with diffuse large b-cell lymphoma , or dlbcl , we are evaluating the opportunity to investigate this combination as a front-line treatment for patients with fl . in collaboration with the lymphoma study association , or lysa , we are continuing to evaluate tazemetostat with r-chop as a front-line treatment for high-risk patients with dlbcl . in addition , genentech inc. , or genentech , is evaluating the combination of tazemetostat with its checkpoint inhibitor , tecentriq ( atezolizumab ) , for the treatment of patients with relapsed or refractory dlbcl , with preliminary data expected from that study in 2019. in our solid tumor program , we are evaluating tazemetostat 's treatment potential in adults and children with molecularly defined solid tumors , including ini1- and smarca4-negative tumors , which we collectively refer to as ini1-negative tumors . we are conducting a multi-cohort global phase 2 trial of tazemetostat in adults with ini1-negative tumors , including epithelioid sarcoma or chordoma . based on positive data that we have observed in patients with epithelioid sarcoma in the ongoing phase 2 study , we are targeting submission of our first nda for accelerated approval of tazemetostat for the treatment of epithelioid sarcoma in the second quarter of 2019. in connection with this submission , we will need to conduct a confirmatory program to verify clinical benefit and support the full approval of tazemetostat . we plan to explore with the fda utilizing the natural history study in epithelioid sarcoma that we are conducting to serve as confirmatory evidence required in connection with any accelerated approval . the cohort of patients in the phase 2 study of chordoma patients is ongoing , and we are evaluating tazemetostat in the dose-expansion portion of a phase 1 study in pediatric patients with ini1-negative tumors , with plans to report updated data in 2019. we own the global development and commercialization rights to tazemetostat outside of japan . eisai co. ltd , or eisai , holds the rights to develop and commercialize tazemetostat in japan . we intend to build a focused field presence and marketing capabilities to commercialize tazemetostat for the epithelioid sarcoma and follicular lymphoma indications in the united states . we have begun building the infrastructure necessary to support the launch and marketing of tazemetostat for epithelioid sarcoma , and believe we can adequately address this patient population through a modest field force of less than 25 professionals . for geographies outside the united states , we are evaluating the most efficient path to reach patients , including through potential collaborations . tazemetostat is covered by claims of u.s. and european composition of matter patents , which are expected to expire in 2032 , exclusive of any patent term or other extensions . tazemetostat has been granted fast track designation by the fda in patients with relapsed or refractory fl , with or without activating ezh2 mutations , relapsed or refractory dlbcl with ezh2 activating mutations and metastatic or locally advanced epithelioid sarcoma who have progressed on or following an anthracycline-based treatment regimen . the fda has also granted orphan drug designation to tazemetostat for the treatment of patients with fl , malignant rhabdoid tumors , or mrt , soft tissue sarcoma , or sts , and mesothelioma . the orphan drug designation for the treatment of mrt applies to ini1-negative mrt as well as smarca4-negative malignant rhabdoid tumor of ovary , or mrto . beyond tazemetostat , we are building an early pipeline to further support our leadership in epigenetics . we are developing our wholly-owned g9a candidate , ezm8266 , for the treatment of people with sickle cell disease . we have completed ind-enabling studies for this program and plan to begin clinical evaluation with a safety and dose-finding study in the second half of 2019. in november 2018 , we entered a strategic collaboration with boehringer ingelheim international gmbh , or boehringer ingelheim , focused on the research , development and commercialization of novel small molecule inhibitors , discovered by us , directed toward two previously unaddressed epigenetic targets as potential therapies for people with cancer . specifically , these targets are enzymes within the helicase and histone acetyltransferase , or hat , families that when dysregulated have been linked to the development of cancers that currently lack therapeutic options . we also have collaborations with glaxo group limited ( an affiliate of glaxosmithkline ) , or gsk , focused on the development of prmt inhibitors discovered by us , and with celgene corporation and celgene rivot ltd. , an affiliate of celgene corporation , which we collectively refer to as celgene , focused on the development of pinometostat and small molecule inhibitors directed to three hmt targets . through december 31 , 2018 , we have raised an aggregate of $ 988.2 million to fund our operations , of which $ 232.8 million was non-equity funding through our collaboration agreements , $ 679.4 million was from the sale of common stock in our public offerings and $ 76.0 story_separator_special_tag 87 liquidity and capital resources through december 31 , 2018 , we have raised an aggregate of $ 988.2 million to fund our operations , of which $ 232.8 million was non-equity funding through our collaboration agreements , $ 679.4 million was from the sale of common stock in our public offerings and $ 76.0 million was from the sale of redeemable convertible preferred stock . as of december 31 , 2018 , we had $ 240.3 million in cash , cash equivalents and marketable securities . in october 2018 , we raised approximately $ 81.6 million in net proceeds ( after deducting underwriting discounts and commissions and estimated offering expenses , but excluding any expenses and other costs reimbursed by the underwriters ) from the sale of 9,583,334 shares of our common stock in a public offering at a price of $ 9.00 per share . in september 2017 , we raised $ 151.3 million , net of underwriting discounts and commissions , but before direct and incremental costs from the sale of 10,557,000 shares of our common stock in a public offering at a price to the public of $ 15.25 per share . on april 15 , 2016 , we entered into a sales agreement with cowen and company , llc , or cowen , to sell , from time to time , shares of our common stock having an aggregate sales price of up to $ 50.0 million through an “ at the market offering ” as defined in rule 415 under the securities act of 1933 , as amended , under which cowen would act as sales agent , which we refer to as the atm offering . through march 10 , 2017 , we sold 155,834 shares of common stock under the sales agreement , resulting in net proceeds of $ 1.9 million related to the atm offering . we terminated the sales agreement with cowen , effective march 10 , 2017. in addition to our existing cash , cash equivalents and marketable securities , we may receive research and development co-funding and are eligible to earn a significant amount of option exercise and milestone payments under our collaboration agreements . our ability to earn these payments and the timing of earning these payments is dependent upon the outcome of our research and development activities and is uncertain at this time . funding requirements our primary uses of capital are , clinical trial costs , third-party research and development services , expenses related to preparation for commercialization , compensation and related expenses , laboratory and related supplies , our potential future milestone payment obligations to eisai and roche molecular under the amended eisai collaboration agreement and roche molecular companion diagnostic agreement , legal and other regulatory expenses and general overhead costs . because our product candidates are in various stages of clinical and preclinical development and the outcome of these efforts is uncertain , we can not estimate the actual amounts necessary to successfully complete the development and commercialization of our product candidates or whether , or when , we may achieve profitability . until such time , if ever , as we can generate substantial product revenues , we expect to finance our cash needs through a combination of equity or debt financings and collaboration arrangements . except for any obligations of our collaborators to make license , milestone or royalty payments under our agreements with them , we do not have any committed external sources of liquidity . to the extent that we raise additional capital through the future sale of equity or debt , the ownership interest of our stockholders may be diluted , and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing common stockholders . debt financing and preferred equity financing , if available , may involve agreements that include covenants limiting or restricting our ability to take specific actions , such as incurring additional debt , making capital expenditures or declaring dividends . if we raise additional funds through collaboration arrangements in the future , we may have to relinquish valuable rights to our technologies , future revenue streams or product candidates or grant licenses on terms that may not be favorable to us . if we are unable to raise any additional funds that may be needed through equity or debt financings when needed , we may be required to delay , limit , reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves . 88 outlook based on our research and development plans and our timing expectations related to the progress of our programs , we expect that our existing cash , cash equivalents and marketable securities as of december 31 , 2018 , will be sufficient to fund our planned operating expenses and capital expenditure requirements into the second quarter of 2020 , without giving effect to any potential option exercise fees or milestone payments we may receive under our collaboration agreements . we have based this estimate on assumptions that may prove to be wrong , particularly as the process of testing product candidates in clinical trials is costly and the timing of progress in these trials is uncertain . as a result , we could use our capital resources sooner than we expect . story_separator_special_tag 2018 , we have committed to fund $ 8.4 million of remaining development costs payable to roche molecular , expected to be paid through 2020 upon certain development and regulatory milestones , under an amended companion diagnostic agreement . the agreement was amended in march 2018. under the amended agreement , we are responsible for remaining development costs of $ 10.4 million due under the agreement as of march 2018 and eisai has agreed to reimburse us for $ 0.9 million of this amount related to a regulatory milestone

cash flows the following is a summary of cash flows for the years ended december 31 , 2018 , 2017 and 2016 : replace_table_token_16_th replace_table_token_17_th net cash used in operating activities net cash used in operating activities was $ 121.6 million during the year ended december 31 , 2018 compared to $ 120.4 million during the year ended december 31 , 2017. the increase in net cash used in operating activities primarily relates to the decrease in net loss in the period compared to 2017 , a net increase in non-cash stock-based compensation , partially offset by a decrease in net depreciation and amortization and changes in working capital . the most significant items affecting working capital in the year ended december 31 , 2018 includes accounts receivable related to the milestone revenue recognized under the gsk agreement and current deferred revenue associated with the bi agreement . net cash used in operating activities was $ 120.4 million during the year ended december 31 , 2017 compared to $ 96.4 million during the year ended december 31 , 2016. the increase in net cash used in operating activities primarily relates to the increase in net loss in the period compared to 2016 , partially offset by changes in working capital .


 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 is a summary of cash flows for the years ended december 31 , 2018 , 2017 and 2016 : replace_table_token_16_th replace_table_token_17_th net cash used in operating activities net cash used in operating activities was $ 121.6 million during the year ended december 31 , 2018 compared to $ 120.4 million during the year ended december 31 , 2017. the increase in net cash used in operating activities primarily relates to the decrease in net loss in the period compared to 2017 , a net increase in non-cash stock-based compensation , partially offset by a decrease in net depreciation and amortization and changes in working capital . the most significant items affecting working capital in the year ended december 31 , 2018 includes accounts receivable related to the milestone revenue recognized under the gsk agreement and current deferred revenue associated with the bi agreement . net cash used in operating activities was $ 120.4 million during the year ended december 31 , 2017 compared to $ 96.4 million during the year ended december 31 , 2016. the increase in net cash used in operating activities primarily relates to the increase in net loss in the period compared to 2016 , partially offset by changes in working capital .
```    
 Suspicious Activity Report : we intend to review our proposed confirmatory program with the fda , and to finalize its design in the first half of 2019. we hope to leverage the confirmatory program to expand tazemetostat into the second-line treatment setting for patients with fl , both with and without ezh2 activating mutations . in addition , we plan to evaluate tazemetostat treatment in combination with other therapies . in mid-2019 , we anticipate initiating a combination study that would compare tazemetostat plus rituximab and revlimid , a chemotherapeutic-free treatment regimen referred to as r 2 , versus r 2 with placebo in patients with relapsed or refractory fl , both with and without ezh2 activating mutations . in addition , we are finalizing plans for a trial of tazemetostat in combination with rituxan for the treatment of patients with relapsed and refractory fl . based on clinical activity observed with tazemetostat in combination with r-chop as a front-line treatment for 80 patients with diffuse large b-cell lymphoma , or dlbcl , we are evaluating the opportunity to investigate this combination as a front-line treatment for patients with fl . in collaboration with the lymphoma study association , or lysa , we are continuing to evaluate tazemetostat with r-chop as a front-line treatment for high-risk patients with dlbcl . in addition , genentech inc. , or genentech , is evaluating the combination of tazemetostat with its checkpoint inhibitor , tecentriq ( atezolizumab ) , for the treatment of patients with relapsed or refractory dlbcl , with preliminary data expected from that study in 2019. in our solid tumor program , we are evaluating tazemetostat 's treatment potential in adults and children with molecularly defined solid tumors , including ini1- and smarca4-negative tumors , which we collectively refer to as ini1-negative tumors . we are conducting a multi-cohort global phase 2 trial of tazemetostat in adults with ini1-negative tumors , including epithelioid sarcoma or chordoma . based on positive data that we have observed in patients with epithelioid sarcoma in the ongoing phase 2 study , we are targeting submission of our first nda for accelerated approval of tazemetostat for the treatment of epithelioid sarcoma in the second quarter of 2019. in connection with this submission , we will need to conduct a confirmatory program to verify clinical benefit and support the full approval of tazemetostat . we plan to explore with the fda utilizing the natural history study in epithelioid sarcoma that we are conducting to serve as confirmatory evidence required in connection with any accelerated approval . the cohort of patients in the phase 2 study of chordoma patients is ongoing , and we are evaluating tazemetostat in the dose-expansion portion of a phase 1 study in pediatric patients with ini1-negative tumors , with plans to report updated data in 2019. we own the global development and commercialization rights to tazemetostat outside of japan . eisai co. ltd , or eisai , holds the rights to develop and commercialize tazemetostat in japan . we intend to build a focused field presence and marketing capabilities to commercialize tazemetostat for the epithelioid sarcoma and follicular lymphoma indications in the united states . we have begun building the infrastructure necessary to support the launch and marketing of tazemetostat for epithelioid sarcoma , and believe we can adequately address this patient population through a modest field force of less than 25 professionals . for geographies outside the united states , we are evaluating the most efficient path to reach patients , including through potential collaborations . tazemetostat is covered by claims of u.s. and european composition of matter patents , which are expected to expire in 2032 , exclusive of any patent term or other extensions . tazemetostat has been granted fast track designation by the fda in patients with relapsed or refractory fl , with or without activating ezh2 mutations , relapsed or refractory dlbcl with ezh2 activating mutations and metastatic or locally advanced epithelioid sarcoma who have progressed on or following an anthracycline-based treatment regimen . the fda has also granted orphan drug designation to tazemetostat for the treatment of patients with fl , malignant rhabdoid tumors , or mrt , soft tissue sarcoma , or sts , and mesothelioma . the orphan drug designation for the treatment of mrt applies to ini1-negative mrt as well as smarca4-negative malignant rhabdoid tumor of ovary , or mrto . beyond tazemetostat , we are building an early pipeline to further support our leadership in epigenetics . we are developing our wholly-owned g9a candidate , ezm8266 , for the treatment of people with sickle cell disease . we have completed ind-enabling studies for this program and plan to begin clinical evaluation with a safety and dose-finding study in the second half of 2019. in november 2018 , we entered a strategic collaboration with boehringer ingelheim international gmbh , or boehringer ingelheim , focused on the research , development and commercialization of novel small molecule inhibitors , discovered by us , directed toward two previously unaddressed epigenetic targets as potential therapies for people with cancer . specifically , these targets are enzymes within the helicase and histone acetyltransferase , or hat , families that when dysregulated have been linked to the development of cancers that currently lack therapeutic options . we also have collaborations with glaxo group limited ( an affiliate of glaxosmithkline ) , or gsk , focused on the development of prmt inhibitors discovered by us , and with celgene corporation and celgene rivot ltd. , an affiliate of celgene corporation , which we collectively refer to as celgene , focused on the development of pinometostat and small molecule inhibitors directed to three hmt targets . through december 31 , 2018 , we have raised an aggregate of $ 988.2 million to fund our operations , of which $ 232.8 million was non-equity funding through our collaboration agreements , $ 679.4 million was from the sale of common stock in our public offerings and $ 76.0 story_separator_special_tag 87 liquidity and capital resources through december 31 , 2018 , we have raised an aggregate of $ 988.2 million to fund our operations , of which $ 232.8 million was non-equity funding through our collaboration agreements , $ 679.4 million was from the sale of common stock in our public offerings and $ 76.0 million was from the sale of redeemable convertible preferred stock . as of december 31 , 2018 , we had $ 240.3 million in cash , cash equivalents and marketable securities . in october 2018 , we raised approximately $ 81.6 million in net proceeds ( after deducting underwriting discounts and commissions and estimated offering expenses , but excluding any expenses and other costs reimbursed by the underwriters ) from the sale of 9,583,334 shares of our common stock in a public offering at a price of $ 9.00 per share . in september 2017 , we raised $ 151.3 million , net of underwriting discounts and commissions , but before direct and incremental costs from the sale of 10,557,000 shares of our common stock in a public offering at a price to the public of $ 15.25 per share . on april 15 , 2016 , we entered into a sales agreement with cowen and company , llc , or cowen , to sell , from time to time , shares of our common stock having an aggregate sales price of up to $ 50.0 million through an “ at the market offering ” as defined in rule 415 under the securities act of 1933 , as amended , under which cowen would act as sales agent , which we refer to as the atm offering . through march 10 , 2017 , we sold 155,834 shares of common stock under the sales agreement , resulting in net proceeds of $ 1.9 million related to the atm offering . we terminated the sales agreement with cowen , effective march 10 , 2017. in addition to our existing cash , cash equivalents and marketable securities , we may receive research and development co-funding and are eligible to earn a significant amount of option exercise and milestone payments under our collaboration agreements . our ability to earn these payments and the timing of earning these payments is dependent upon the outcome of our research and development activities and is uncertain at this time . funding requirements our primary uses of capital are , clinical trial costs , third-party research and development services , expenses related to preparation for commercialization , compensation and related expenses , laboratory and related supplies , our potential future milestone payment obligations to eisai and roche molecular under the amended eisai collaboration agreement and roche molecular companion diagnostic agreement , legal and other regulatory expenses and general overhead costs . because our product candidates are in various stages of clinical and preclinical development and the outcome of these efforts is uncertain , we can not estimate the actual amounts necessary to successfully complete the development and commercialization of our product candidates or whether , or when , we may achieve profitability . until such time , if ever , as we can generate substantial product revenues , we expect to finance our cash needs through a combination of equity or debt financings and collaboration arrangements . except for any obligations of our collaborators to make license , milestone or royalty payments under our agreements with them , we do not have any committed external sources of liquidity . to the extent that we raise additional capital through the future sale of equity or debt , the ownership interest of our stockholders may be diluted , and the terms of these securities may include liquidation or other preferences that adversely affect the rights of our existing common stockholders . debt financing and preferred equity financing , if available , may involve agreements that include covenants limiting or restricting our ability to take specific actions , such as incurring additional debt , making capital expenditures or declaring dividends . if we raise additional funds through collaboration arrangements in the future , we may have to relinquish valuable rights to our technologies , future revenue streams or product candidates or grant licenses on terms that may not be favorable to us . if we are unable to raise any additional funds that may be needed through equity or debt financings when needed , we may be required to delay , limit , reduce or terminate our product development or future commercialization efforts or grant rights to develop and market product candidates that we would otherwise prefer to develop and market ourselves . 88 outlook based on our research and development plans and our timing expectations related to the progress of our programs , we expect that our existing cash , cash equivalents and marketable securities as of december 31 , 2018 , will be sufficient to fund our planned operating expenses and capital expenditure requirements into the second quarter of 2020 , without giving effect to any potential option exercise fees or milestone payments we may receive under our collaboration agreements . we have based this estimate on assumptions that may prove to be wrong , particularly as the process of testing product candidates in clinical trials is costly and the timing of progress in these trials is uncertain . as a result , we could use our capital resources sooner than we expect . story_separator_special_tag 2018 , we have committed to fund $ 8.4 million of remaining development costs payable to roche molecular , expected to be paid through 2020 upon certain development and regulatory milestones , under an amended companion diagnostic agreement . the agreement was amended in march 2018. under the amended agreement , we are responsible for remaining development costs of $ 10.4 million due under the agreement as of march 2018 and eisai has agreed to reimburse us for $ 0.9 million of this amount related to a regulatory milestone

