however , we will continue our efforts to seek to discover , research and develop additional product candidates and seek regulatory approvals in additional regions for xipere for the treatment of macular edema associated with uveitis . we have advanced our proprietary suspension of axitinib , which we refer to as cls-ax , into clinical development , and if these trials are successful , we anticipate an increase in clinical trial expenses as we continue further development of that product candidate . components of operating results revenue we have not generated any revenue from the sale of any drugs , and we do not expect to generate any product revenue unless or until we obtain regulatory approval of and commercialize our product candidates , either on our own or with a third party . our revenue in recent years has been generated primarily from our license agreements . we are seeking to enter into additional license and other agreements with third parties to evaluate the potential use of our proprietary scs microinjector with the third party 's product candidates for the treatment of various eye diseases . these agreements may include payments to us for technology access , upfront license payments , regulatory and commercial milestone payments and royalties . 58 research and development since our inception , we have focused on our development programs . research and development expenses consist primarily of costs incurred for the research and development of our preclinical and clinical product candidates , which include : employee-related expenses , including salaries , benefits , travel and share-based compensation expense for research and development personnel ; expenses incurred under agreements with contract research organizations , or cros , as well as contract manufacturing organizations and consultants that conduct clinical trials and preclinical studies ; costs associated with preclinical activities and clinical trials ; costs associated with submitting regulatory approval applications for our product candidates ; costs associated with training physicians on the suprachoroidal injection procedure and educating and providing them with appropriate product candidate information ; costs associated with technology and intellectual property licenses ; costs for our research and development facility ; and depreciation expense for assets used in research and development activities . we expense research and development costs to operations as incurred . these costs include preclinical activities , such as manufacturing and stability and toxicology studies , that are supportive of a product candidate itself . in addition , there are expenses related to clinical trials and similar activities for each program , including costs associated with cros . clinical costs are recognized based on the terms of underlying agreements , as well as an evaluation of the progress to completion of specific tasks using data such as patient enrollment , clinical site activations and additional information provided to us by our vendors about their actual costs occurred . expenses related to activities that support more than one development program or activity , such as salaries , share-based compensation and depreciation , are not classified as direct preclinical costs or clinical costs and are separately classified as unallocated . the following table shows our research and development expenses by type of activity for the years ended december 31 , 2020 , 2019 and 2018. replace_table_token_0_th our expenses related to clinical trials are based on estimates of patient enrollment and related expenses at clinical investigator sites as well as estimates for the services received and efforts expended under contracts with research institutions , consultants and cros that conduct and manage clinical trials on our behalf . we generally accrue expenses related to clinical trials based on contracted amounts applied to the level of patient enrollment and activity according to the protocol . if future timelines or contracts are modified based upon changes in the clinical trial protocol or scope of work to be performed , we would modify our estimates of accrued expenses accordingly on a prospective basis . research and development activities are central to our business model . product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development , primarily due to the increased size and duration of later-stage clinical trials . however , it is difficult to determine with certainty the duration and completion costs of our current or future preclinical programs and clinical trials of our product candidates , or if , when or to what extent we will generate revenues from the commercialization and sale of any of our product candidates that obtain regulatory approval . we may never succeed in achieving regulatory approval for any of our product candidates . 59 the duration , costs and timing of clinical trials and development of our product candidates will depend on a variety of factors that include the following : the costs associated with process development , scale-up and manufacturing of xipere and the scs microinjector for clinical trials and for requirements associated with regulatory filings associated with approval ; the number of trials required for approval and any requirement for extension trials ; per patient trial costs ; the number of patients that participate in the trials ; the number of sites included in the trials ; the countries in which the trials are conducted ; the length of time required to enroll eligible patients ; the number of doses that patients receive ; the potential impact of the covid-19 pandemic on the enrollment in , and timing of , our clinical trials ; the drop-out or discontinuation rates of patients ; potential additional safety monitoring or other studies requested by regulatory agencies ; the duration of patient follow-up ; and the efficacy and safety profiles of the product candidates . in addition , the probability of success for each product candidate will depend on numerous factors , including competition , manufacturing capability and commercial viability . story_separator_special_tag in the year ended december 31 , 2019 we recognized $ 2.1 million of revenue associated with our license agreements . in the years ended december 31 , 2019 and 2018 , we recognized $ 0.1 million and $ 30,000 , respectively , of revenue associated with other agreements . research and development . research and development expense decreased by $ 52.6 million , from $ 68.3 million for the year ended december 31 , 2018 to $ 15.7 million for the year ended december 31 , 2019. this was primarily attributable to a $ 42.1 million decrease due to closing down the sapphire and topaz trials . additionally , there was a $ 4.6 million decrease due to the completion of the peachtree trial during the first quarter of 2018 , a $ 3.2 million decrease in costs related to our dme program , as the tybee trial was completed in the second quarter of 2018 , a $ 1.2 million decrease in costs related to device and drug manufacturing , a $ 0.6 million decrease in costs related to quality assurance as audits related to our nda filing were completed during 2018 and a $ 1.4 million decrease in regulatory expenses as the nda submission for xipere was completed in the fourth quarter of 2018. these decreases were partially offset by a $ 0.4 million increase in employee-related costs and a $ 0.5 million increase in nonclinical activities . general and administrative . general and administrative expenses increased by $ 2.1 million , from $ 14.7 million for the year ended december 31 , 2018 to $ 16.8 million for the year ended december 31 , 2019. the increase was primarily attributable to a $ 1.9 million increase in employee-related costs , including accrued expenses related to the resignation of our former ceo , and an increase of $ 0.9 million in professional fees . these increases were partially offset by a $ 0.4 million decrease that was primarily attributable to marketing-related expenses related to the change of our business strategy to seek partners for xipere rather than commercialize it on our own . other ( expense ) income . the decrease from other income of $ 0.1 million in 2018 to other expense of $ 0.5 million in 2019 was the result of higher interest income on short-term investment balances in the first quarter of 2018 following our public offering of common stock , which balances decreased over time . liquidity and capital resources sources of liquidity we have funded our operations primarily through the proceeds of public offerings of our common stock , sales of convertible preferred stock and the issuance of long-term debt . as of december 31 , 2020 , we had cash and cash equivalents of $ 17.3 million . we invest any cash in excess of our immediate requirements primarily with a view to liquidity and capital preservation . as of december 31 , 2020 , our funds were held in cash and money market funds . on january 6 , 2021 , we entered into a securities purchase agreement with certain institutional purchasers pursuant to which we issued and sold 4.2 million shares of our common stock in a registered direct offering at a price of $ 2.851 per share . we raised net cash proceeds of $ 11.1 million after deducting offering expenses . during the year ended december 31 , 2020 , we sold 6.2 million shares of our common stock for net proceeds of $ 12.0 million under the at-the-market , or atm , agreement , cowen and company llc , or cowen . under the atm agreement , we may offer and 64 sell , from time to time at our sole discretion , shares of our common stock through cowen acting as our sales agent . as of december 31 , 2020 , there was $ 27.0 million available for future sales under the atm agreement . subsequent to december 31 , 2020 , we sold 1.2 million shares of our common stock for net proceeds of $ 3.3 million . in september 2020 , we received $ 3.0 million in milestone payments under the regenxbio agreement . on april 20 , 2020 , we entered into a loan agreement with silicon valley bank under the terms of which silicon valley bank loaned us $ 1.0 million , or the ppp loan , pursuant to the paycheck protection program , or ppp , under the coronavirus aid , relief , and economic security act , or cares act . in accordance with the requirements of the cares act , we used the proceeds primarily for payroll costs and other eligible expenses . the cares act and the ppp provided a mechanism for forgiveness of up to the full amount borrowed . on january 11 , 2021 , we received notification from silicon valley bank that the full amount borrowed under the ppp loan and approximately $ 7,000 of accrued interest was forgiven . on march 10 , 2020 , we entered into the arctic license agreement , under which arctic vision has agreed to pay us up to a total of $ 35.5 million . this amount includes an upfront payment of $ 4.0 million , which we received in march 2020 , as well as an aggregate of up to $ 31.5 million in potential development milestone payments for specified events prior to and including receipt of regulatory approval of xipere in the united states and potential sales milestone payments for achievement of specified levels of net sales . further , during the applicable royalty term , we will also be entitled to receive tiered royalties of 10-12 % of net sales in the arctic territory , subject to customary reductions . we previously entered into a loan and security agreement with silicon valley bank and midcap financial services , or collectively the lenders , under which we borrowed $ 10.0 million in may 2018

cash flows the following is a summary of the net cash flows provided by ( used in ) our operating , investing and financing activities : replace_table_token_3_th 66 during the years ended december 31 , 2020 , 2019 and 2018 , our operating activities used net cash of $ 13.0 million , $ 27.1 million and $ 79.2 million , respectively . the use of cash in each period primarily resulted from our net losses . the decrease in the net loss for the year ended december 31 , 2020 as compared to the year ended december 31 , 2019 was primarily attributable to lower research and development expenses as a result of the discontinuation of the sapphire and topaz trials and ceasing of commercialization activities in 2019. the losses were partially offset by non-cash items , made up primarily of share-based compensation , of $ 3.6 million and $ 4.6 million for the years ended december 31 , 2020 and 2019 , respectively . the decrease in net loss for the year ended december 31 , 2019 as compared to the year ended december 31 , 2018 was primarily attributable to lower research and development expenses as a result of the completion of the peachtree and tybee trials in the prior year and the discontinuation of the sapphire and topaz trials . the year ended december 31 , 2019 also included a net cash outflow of $ 5.1 million from a decrease in accounts payable , which was the result of payments we made in connection with winding down the clinical trials .


 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 the net cash flows provided by ( used in ) our operating , investing and financing activities : replace_table_token_3_th 66 during the years ended december 31 , 2020 , 2019 and 2018 , our operating activities used net cash of $ 13.0 million , $ 27.1 million and $ 79.2 million , respectively . the use of cash in each period primarily resulted from our net losses . the decrease in the net loss for the year ended december 31 , 2020 as compared to the year ended december 31 , 2019 was primarily attributable to lower research and development expenses as a result of the discontinuation of the sapphire and topaz trials and ceasing of commercialization activities in 2019. the losses were partially offset by non-cash items , made up primarily of share-based compensation , of $ 3.6 million and $ 4.6 million for the years ended december 31 , 2020 and 2019 , respectively . the decrease in net loss for the year ended december 31 , 2019 as compared to the year ended december 31 , 2018 was primarily attributable to lower research and development expenses as a result of the completion of the peachtree and tybee trials in the prior year and the discontinuation of the sapphire and topaz trials . the year ended december 31 , 2019 also included a net cash outflow of $ 5.1 million from a decrease in accounts payable , which was the result of payments we made in connection with winding down the clinical trials .
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 Suspicious Activity Report : however , we will continue our efforts to seek to discover , research and develop additional product candidates and seek regulatory approvals in additional regions for xipere for the treatment of macular edema associated with uveitis . we have advanced our proprietary suspension of axitinib , which we refer to as cls-ax , into clinical development , and if these trials are successful , we anticipate an increase in clinical trial expenses as we continue further development of that product candidate . components of operating results revenue we have not generated any revenue from the sale of any drugs , and we do not expect to generate any product revenue unless or until we obtain regulatory approval of and commercialize our product candidates , either on our own or with a third party . our revenue in recent years has been generated primarily from our license agreements . we are seeking to enter into additional license and other agreements with third parties to evaluate the potential use of our proprietary scs microinjector with the third party 's product candidates for the treatment of various eye diseases . these agreements may include payments to us for technology access , upfront license payments , regulatory and commercial milestone payments and royalties . 58 research and development since our inception , we have focused on our development programs . research and development expenses consist primarily of costs incurred for the research and development of our preclinical and clinical product candidates , which include : employee-related expenses , including salaries , benefits , travel and share-based compensation expense for research and development personnel ; expenses incurred under agreements with contract research organizations , or cros , as well as contract manufacturing organizations and consultants that conduct clinical trials and preclinical studies ; costs associated with preclinical activities and clinical trials ; costs associated with submitting regulatory approval applications for our product candidates ; costs associated with training physicians on the suprachoroidal injection procedure and educating and providing them with appropriate product candidate information ; costs associated with technology and intellectual property licenses ; costs for our research and development facility ; and depreciation expense for assets used in research and development activities . we expense research and development costs to operations as incurred . these costs include preclinical activities , such as manufacturing and stability and toxicology studies , that are supportive of a product candidate itself . in addition , there are expenses related to clinical trials and similar activities for each program , including costs associated with cros . clinical costs are recognized based on the terms of underlying agreements , as well as an evaluation of the progress to completion of specific tasks using data such as patient enrollment , clinical site activations and additional information provided to us by our vendors about their actual costs occurred . expenses related to activities that support more than one development program or activity , such as salaries , share-based compensation and depreciation , are not classified as direct preclinical costs or clinical costs and are separately classified as unallocated . the following table shows our research and development expenses by type of activity for the years ended december 31 , 2020 , 2019 and 2018. replace_table_token_0_th our expenses related to clinical trials are based on estimates of patient enrollment and related expenses at clinical investigator sites as well as estimates for the services received and efforts expended under contracts with research institutions , consultants and cros that conduct and manage clinical trials on our behalf . we generally accrue expenses related to clinical trials based on contracted amounts applied to the level of patient enrollment and activity according to the protocol . if future timelines or contracts are modified based upon changes in the clinical trial protocol or scope of work to be performed , we would modify our estimates of accrued expenses accordingly on a prospective basis . research and development activities are central to our business model . product candidates in later stages of clinical development generally have higher development costs than those in earlier stages of clinical development , primarily due to the increased size and duration of later-stage clinical trials . however , it is difficult to determine with certainty the duration and completion costs of our current or future preclinical programs and clinical trials of our product candidates , or if , when or to what extent we will generate revenues from the commercialization and sale of any of our product candidates that obtain regulatory approval . we may never succeed in achieving regulatory approval for any of our product candidates . 59 the duration , costs and timing of clinical trials and development of our product candidates will depend on a variety of factors that include the following : the costs associated with process development , scale-up and manufacturing of xipere and the scs microinjector for clinical trials and for requirements associated with regulatory filings associated with approval ; the number of trials required for approval and any requirement for extension trials ; per patient trial costs ; the number of patients that participate in the trials ; the number of sites included in the trials ; the countries in which the trials are conducted ; the length of time required to enroll eligible patients ; the number of doses that patients receive ; the potential impact of the covid-19 pandemic on the enrollment in , and timing of , our clinical trials ; the drop-out or discontinuation rates of patients ; potential additional safety monitoring or other studies requested by regulatory agencies ; the duration of patient follow-up ; and the efficacy and safety profiles of the product candidates . in addition , the probability of success for each product candidate will depend on numerous factors , including competition , manufacturing capability and commercial viability . story_separator_special_tag in the year ended december 31 , 2019 we recognized $ 2.1 million of revenue associated with our license agreements . in the years ended december 31 , 2019 and 2018 , we recognized $ 0.1 million and $ 30,000 , respectively , of revenue associated with other agreements . research and development . research and development expense decreased by $ 52.6 million , from $ 68.3 million for the year ended december 31 , 2018 to $ 15.7 million for the year ended december 31 , 2019. this was primarily attributable to a $ 42.1 million decrease due to closing down the sapphire and topaz trials . additionally , there was a $ 4.6 million decrease due to the completion of the peachtree trial during the first quarter of 2018 , a $ 3.2 million decrease in costs related to our dme program , as the tybee trial was completed in the second quarter of 2018 , a $ 1.2 million decrease in costs related to device and drug manufacturing , a $ 0.6 million decrease in costs related to quality assurance as audits related to our nda filing were completed during 2018 and a $ 1.4 million decrease in regulatory expenses as the nda submission for xipere was completed in the fourth quarter of 2018. these decreases were partially offset by a $ 0.4 million increase in employee-related costs and a $ 0.5 million increase in nonclinical activities . general and administrative . general and administrative expenses increased by $ 2.1 million , from $ 14.7 million for the year ended december 31 , 2018 to $ 16.8 million for the year ended december 31 , 2019. the increase was primarily attributable to a $ 1.9 million increase in employee-related costs , including accrued expenses related to the resignation of our former ceo , and an increase of $ 0.9 million in professional fees . these increases were partially offset by a $ 0.4 million decrease that was primarily attributable to marketing-related expenses related to the change of our business strategy to seek partners for xipere rather than commercialize it on our own . other ( expense ) income . the decrease from other income of $ 0.1 million in 2018 to other expense of $ 0.5 million in 2019 was the result of higher interest income on short-term investment balances in the first quarter of 2018 following our public offering of common stock , which balances decreased over time . liquidity and capital resources sources of liquidity we have funded our operations primarily through the proceeds of public offerings of our common stock , sales of convertible preferred stock and the issuance of long-term debt . as of december 31 , 2020 , we had cash and cash equivalents of $ 17.3 million . we invest any cash in excess of our immediate requirements primarily with a view to liquidity and capital preservation . as of december 31 , 2020 , our funds were held in cash and money market funds . on january 6 , 2021 , we entered into a securities purchase agreement with certain institutional purchasers pursuant to which we issued and sold 4.2 million shares of our common stock in a registered direct offering at a price of $ 2.851 per share . we raised net cash proceeds of $ 11.1 million after deducting offering expenses . during the year ended december 31 , 2020 , we sold 6.2 million shares of our common stock for net proceeds of $ 12.0 million under the at-the-market , or atm , agreement , cowen and company llc , or cowen . under the atm agreement , we may offer and 64 sell , from time to time at our sole discretion , shares of our common stock through cowen acting as our sales agent . as of december 31 , 2020 , there was $ 27.0 million available for future sales under the atm agreement . subsequent to december 31 , 2020 , we sold 1.2 million shares of our common stock for net proceeds of $ 3.3 million . in september 2020 , we received $ 3.0 million in milestone payments under the regenxbio agreement . on april 20 , 2020 , we entered into a loan agreement with silicon valley bank under the terms of which silicon valley bank loaned us $ 1.0 million , or the ppp loan , pursuant to the paycheck protection program , or ppp , under the coronavirus aid , relief , and economic security act , or cares act . in accordance with the requirements of the cares act , we used the proceeds primarily for payroll costs and other eligible expenses . the cares act and the ppp provided a mechanism for forgiveness of up to the full amount borrowed . on january 11 , 2021 , we received notification from silicon valley bank that the full amount borrowed under the ppp loan and approximately $ 7,000 of accrued interest was forgiven . on march 10 , 2020 , we entered into the arctic license agreement , under which arctic vision has agreed to pay us up to a total of $ 35.5 million . this amount includes an upfront payment of $ 4.0 million , which we received in march 2020 , as well as an aggregate of up to $ 31.5 million in potential development milestone payments for specified events prior to and including receipt of regulatory approval of xipere in the united states and potential sales milestone payments for achievement of specified levels of net sales . further , during the applicable royalty term , we will also be entitled to receive tiered royalties of 10-12 % of net sales in the arctic territory , subject to customary reductions . we previously entered into a loan and security agreement with silicon valley bank and midcap financial services , or collectively the lenders , under which we borrowed $ 10.0 million in may 2018

