based on the substantial reductions from baseline to weeks 4 to 12 in both uox and plasma oxalate , or pox , observed in subjects with enteric hyperoxaluria and advanced ckd , we obtained feedback from the fda on potential expedited approval pathways for reloxaliase in this patient population . the fda recognized that the high oxalate burden in these patients represents a serious , life-threatening condition , which is a requirement for considering an expedited approval pathway . however , the fda advised us that reloxaliase would not currently qualify for breakthrough designation in this patient population based on the lack of placebo-controlled data from open-label study 206. in this setting , and given our current financial resources , we remain focused on executing urirox-2 and plan to evaluate potential clinical development of reloxaliase in patients with enteric hyperoxaluria and advanced ckd in the future . in addition , we have designed our second product candidate , alln-346 , an orally administered , novel , urate degrading enzyme , for patients with hyperuricemia and gout in the setting of advanced ckd . hyperuricemia , or elevated levels of uric 107 acid in the blood , results from overproduction or insufficient excretion of urate , or often a combination of the two . we have conducted two preclinical proof-of-concept studies that support the potential of alln-346 as an oral therapy for the treatment of hyperuricemia in patients with gout and associated ckd . we filed an ind for alln-346 with the fda in december 2019. in july 2020 , we initiated a single-ascending dose ( sad ) phase 1 clinical trial of alln-346 in healthy volunteers and announced initial data from this study in november 2020. alln-346 was well-tolerated with no clinically significant safety signals and no dose-limiting toxicities observed in any cohort up to the highest administered dose . subject to feedback from the fda , we expect to initiate a phase 1b multiple-ascending dose ( mad ) trial in healthy volunteers in the second quarter of 2021 and a phase 2a program in patients with hyperuricemia and ckd in the third quarter of 2021 , with initial data from the phase 1b mad study expected in the third quarter of 2021 and initial phase 2a data in the fourth quarter of 2021 . on june 28 , 2019 , we completed a registered direct offering in which we issued and sold 2,632,092 shares of our common stock , at a purchase price of $ 3.80 per share , for net proceeds of $ 9.4 million , after deducting issuance costs , through a securities purchase agreement with the investors . the shares of common stock sold in this offering were being offered pursuant to our shelf registration statement on form s-3 , or form s-3 , filed with the securities and exchange commission , or sec , which was declared effective on december 26 , 2018. on december 30 , 2019 , we completed an at-the-market , offering in which we issued and sold 1,243,756 shares of our common stock , at a purchase price of $ 2.15 per share , for net proceeds of $ 2.6 million , after deducting issuance costs , through an at-the-market equity offering sales agreement , or atm agreement . the shares of common stock sold in this offering were also being offered pursuant to our shelf registration statement on form s-3 filed with the sec , which was declared effective on december 26 , 2018. on june 5 , 2020 , we completed a registered direct offering , in which we issued and sold 7,317,074 shares of our common stock , at a purchase price of $ 2.05 per share , for net proceeds of $ 13.7 million through a securities purchase agreement with certain institutional and accredited investors . the shares of common stock sold in this offering were being offered by us pursuant to our shelf registration statement on form s-3 filed with the sec , which was declared effective on december 26 , 2018 and a prospectus supplement thereunder filed on june 5 , 2020. on july 30 , 2020 , we completed a public underwritten offering of 5,894,191 shares of our common stock , including the exercise in full of the underwriter 's option to purchase an additional 768,807 shares of common stock , at a price to the public of $ 1.30 per share , for net proceeds of $ 6.7 million . on december 4 , 2020 , we completed a public underwritten offering of 11,960,000 shares of our common stock , including the exercise in full of the underwriter 's option to purchase an additional 1,560,000 shares of common stock , at a price to the public of $ 1.25 per share , for net proceeds of $ 13.5 million . during the first quarter of 2021 until the filing date of this annual report , we issued and sold 6,058,318 shares of our common stock under the atm agreement at a weighted average price of $ 1.99 per share for net proceeds of $ 11.7 million . our operations to date have been primarily focused on organizing and staffing our company , business planning , raising capital , developing our technology , identifying potential product candidates , manufacturing our product candidates and conducting preclinical studies and clinical trials of reloxaliase and alln-346 . we do not have any products approved for sale and have not generated any revenue to date . as of december 31 , 2020 , we had cash and cash equivalents totaling $ 35.0 million . we have incurred significant net operating losses in every year since our inception and expect to continue to incur significant expenses and increasing operating losses for the foreseeable future . our net losses may fluctuate significantly from quarter to quarter and year to year . story_separator_special_tag for options granted in 2020 , we placed a higher weighting on the historical volatility of our own stock price over the historical volatility of a representative group of public companies for the computation of expected volatility used for estimating the fair value of option grants . we will continue to increase the weighting on the historical volatility of our own stock price over the historical volatility of a representative group of public companies until such time as we have a sufficient amount of historical information regarding the volatility of our own stock . we use the simplified method as prescribed by the sec staff accounting bulletin no . 107 , share-based payment , to calculate the expected term for options granted to employees as we do not have sufficient historical exercise data to provide a reasonable basis upon which to estimate the expected term . under this approach , the weighted-average expected option term is presumed to be the average of the contractual term ( ten years ) and the vesting term ( generally four years ) of our stock options . we utilize this method due to lack of historical exercise data and the “ plain-vanilla ” nature of our stock-based awards . the expected term is applied to the stock option grant group as a whole , as we do not expect substantially different exercise or post-vesting termination behavior among our employee population . for options granted to non-employees , we utilize the contractual term of the arrangement as the basis for the expected term assumption . the risk-free interest rate is based on a treasury instrument whose term is consistent with the expected term of the stock options . the expected dividend yield is assumed to be zero as we have never paid dividends and have no current plans to pay any dividends on our common stock . we recognize forfeitures as they occur as allowed per asu no . 2016-09 , compensation – stock compensation . 112 the fair value of stock options granted to employees and directors for their services on the board of directors was estimated on the date of grant using the black-scholes option-pricing model , with the following range of assumptions for the years ended december 31 , 2020 , 2019 and 2018 : replace_table_token_1_th the following table summarizes the classification of our stock-based compensation expense recognized in our statements of operations and comprehensive loss ( in thousands ) : replace_table_token_2_th as of december 31 , 2020 , we had $ 4.4 million of unrecognized compensation expense related to stock option awards , which is expected to be recognized over weighted-average remaining vesting periods of approximately 2.1 years and $ 0.8 million of unrecognized compensation expense related to restricted stock units , which is expected to be recognized during 2021. in future periods , we expect stock-based compensation expense to increase , due in part to our existing unrecognized stock-based compensation expense , potential increases in the value of our common stock and expected additional stock-based awards to continue to attract and retain our employees . results of operations comparison of years ended december 31 , 2020 and 2019 the following table summarizes our results of operations for the years ended december 31 , 2020 and 2019 ( in thousands ) : replace_table_token_3_th 113 research and development expenses research and development expense decreased by $ 16.9 million from $ 37.2 million for the year ended december 31 , 2019 to $ 20.4 million for the year ended december 31 , 2020. the following table summarizes our research and development expenses for the years ended december 31 , 2020 and 2019 ( in thousands ) : replace_table_token_4_th the $ 16.9 million decrease in research and development expense was primarily attributable to the following : our clinical development external costs decreased by $ 7.4 million from $ 14.7 million for the year ended december 31 , 2019 to $ 7.2 million for the year ended december 31 , 2020 : our urirox-1 costs decreased $ 4.5 million from $ 5.0 million for the year ended december 31 , 2019 to $ 0.5 million for the year ended december 31 , 2020. this study was completed in the fourth quarter of 2019 and we released top-line data in november 2019. the costs incurred during the year ended december 31 , 2020 were related to closeout activities ; our urirox-2 costs decreased $ 1.6 million from $ 7.0 million for the year ended december 31 , 2019 to $ 5.4 million for the year ended december 31 , 2020. during the first half of 2020 , we limited the opening of new trial sites for the ongoing urirox-2 trial while we assessed revisions to the study design and sought additional funds to support the development of reloxaliase . a significant portion of the proceeds from sales of our common stock during 2020 are being used to activate additional clinical trial sites and increase investment in the urirox-2 trial . during the second half of 2020 we began expanding urirox-2 to additional geographies and clinical trial sites ; during 2019 , we incurred costs of $ 0.4 million with an independent third party to perform an independent analysis of the results of the urirox-1 study to assist in the assessment of revisions and redesign of the urirox-2 study ; costs related to our study 206 of reloxaliase decreased $ 0.8 million from $ 1.3 million for the year ended december 31 , 2019 to $ 0.5 million for the year ended december 31 , 2020. this study was also completed in the fourth quarter of 2019 and we reported top-line data in november 2019. the costs incurred during the year ended december 31 , 2020 were related to closeout activities ; we incurred consulting costs of $ 0.4 million during the year ended december 31 , 2019 to support our urirox-1 , urirox-2 and 206 studies . in conjunction with the completion of the urirox-1 study

cash flows the following table provides information regarding our cash flows for the years ended december 31 , 2020 , 2019 and 2018 ( in thousands ) : replace_table_token_9_th net cash used in operating activities the cash used in operating activities resulted primarily from our net losses adjusted for non-cash charges and changes in components of working capital . net cash used in operating activities was $ 28.2 million for the year ended december 31 , 2020 compared to $ 43.6 million for the year ended december 31 , 2019. the decrease in cash used in operating activities of $ 15.4 million was attributable to : a decrease in net loss of $ 14.4 million ; an increase in non-cash items of $ 1.2 million resulting primarily from increases in stock-based compensation expense ; and a decrease of $ 0.2 million due to changes in the components of working capital , including decreases in accounts payable , other assets and operating lease liabilities , partially offset by an increase in prepaid expenses and other current assets , accrued expenses and other liabilities . net cash used in operating activities was $ 43.6 million for the year ended december 31 , 2019 compared to $ 31.8 million for the year ended december 31 , 2018. the increase in cash used in operating activities of $ 11.8 million was attributable to : a n increase in net loss of $ 11.7 million ; an increase in non-cash items of $ 0.7 million resulting primarily from increases in stock-based compensation expense , partially offset by our loss on extinguishment of debt recognized for the year ended december 31 , 2018 ; and a decrease of $ 0.8 million in changes in the components of working capital , including decreases in accrued expenses partially offset by increases in prepaid expenses and other current assets and accounts payable . net cash used in investing activities net cash used in investing activities was $ 0.6 million , $ 0.1 million and $ 0.3 million for the years ended december 31 , 2020 , 2019 and 2018 , respectively .


 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 provides information regarding our cash flows for the years ended december 31 , 2020 , 2019 and 2018 ( in thousands ) : replace_table_token_9_th net cash used in operating activities the cash used in operating activities resulted primarily from our net losses adjusted for non-cash charges and changes in components of working capital . net cash used in operating activities was $ 28.2 million for the year ended december 31 , 2020 compared to $ 43.6 million for the year ended december 31 , 2019. the decrease in cash used in operating activities of $ 15.4 million was attributable to : a decrease in net loss of $ 14.4 million ; an increase in non-cash items of $ 1.2 million resulting primarily from increases in stock-based compensation expense ; and a decrease of $ 0.2 million due to changes in the components of working capital , including decreases in accounts payable , other assets and operating lease liabilities , partially offset by an increase in prepaid expenses and other current assets , accrued expenses and other liabilities . net cash used in operating activities was $ 43.6 million for the year ended december 31 , 2019 compared to $ 31.8 million for the year ended december 31 , 2018. the increase in cash used in operating activities of $ 11.8 million was attributable to : a n increase in net loss of $ 11.7 million ; an increase in non-cash items of $ 0.7 million resulting primarily from increases in stock-based compensation expense , partially offset by our loss on extinguishment of debt recognized for the year ended december 31 , 2018 ; and a decrease of $ 0.8 million in changes in the components of working capital , including decreases in accrued expenses partially offset by increases in prepaid expenses and other current assets and accounts payable . net cash used in investing activities net cash used in investing activities was $ 0.6 million , $ 0.1 million and $ 0.3 million for the years ended december 31 , 2020 , 2019 and 2018 , respectively .
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 Suspicious Activity Report : based on the substantial reductions from baseline to weeks 4 to 12 in both uox and plasma oxalate , or pox , observed in subjects with enteric hyperoxaluria and advanced ckd , we obtained feedback from the fda on potential expedited approval pathways for reloxaliase in this patient population . the fda recognized that the high oxalate burden in these patients represents a serious , life-threatening condition , which is a requirement for considering an expedited approval pathway . however , the fda advised us that reloxaliase would not currently qualify for breakthrough designation in this patient population based on the lack of placebo-controlled data from open-label study 206. in this setting , and given our current financial resources , we remain focused on executing urirox-2 and plan to evaluate potential clinical development of reloxaliase in patients with enteric hyperoxaluria and advanced ckd in the future . in addition , we have designed our second product candidate , alln-346 , an orally administered , novel , urate degrading enzyme , for patients with hyperuricemia and gout in the setting of advanced ckd . hyperuricemia , or elevated levels of uric 107 acid in the blood , results from overproduction or insufficient excretion of urate , or often a combination of the two . we have conducted two preclinical proof-of-concept studies that support the potential of alln-346 as an oral therapy for the treatment of hyperuricemia in patients with gout and associated ckd . we filed an ind for alln-346 with the fda in december 2019. in july 2020 , we initiated a single-ascending dose ( sad ) phase 1 clinical trial of alln-346 in healthy volunteers and announced initial data from this study in november 2020. alln-346 was well-tolerated with no clinically significant safety signals and no dose-limiting toxicities observed in any cohort up to the highest administered dose . subject to feedback from the fda , we expect to initiate a phase 1b multiple-ascending dose ( mad ) trial in healthy volunteers in the second quarter of 2021 and a phase 2a program in patients with hyperuricemia and ckd in the third quarter of 2021 , with initial data from the phase 1b mad study expected in the third quarter of 2021 and initial phase 2a data in the fourth quarter of 2021 . on june 28 , 2019 , we completed a registered direct offering in which we issued and sold 2,632,092 shares of our common stock , at a purchase price of $ 3.80 per share , for net proceeds of $ 9.4 million , after deducting issuance costs , through a securities purchase agreement with the investors . the shares of common stock sold in this offering were being offered pursuant to our shelf registration statement on form s-3 , or form s-3 , filed with the securities and exchange commission , or sec , which was declared effective on december 26 , 2018. on december 30 , 2019 , we completed an at-the-market , offering in which we issued and sold 1,243,756 shares of our common stock , at a purchase price of $ 2.15 per share , for net proceeds of $ 2.6 million , after deducting issuance costs , through an at-the-market equity offering sales agreement , or atm agreement . the shares of common stock sold in this offering were also being offered pursuant to our shelf registration statement on form s-3 filed with the sec , which was declared effective on december 26 , 2018. on june 5 , 2020 , we completed a registered direct offering , in which we issued and sold 7,317,074 shares of our common stock , at a purchase price of $ 2.05 per share , for net proceeds of $ 13.7 million through a securities purchase agreement with certain institutional and accredited investors . the shares of common stock sold in this offering were being offered by us pursuant to our shelf registration statement on form s-3 filed with the sec , which was declared effective on december 26 , 2018 and a prospectus supplement thereunder filed on june 5 , 2020. on july 30 , 2020 , we completed a public underwritten offering of 5,894,191 shares of our common stock , including the exercise in full of the underwriter 's option to purchase an additional 768,807 shares of common stock , at a price to the public of $ 1.30 per share , for net proceeds of $ 6.7 million . on december 4 , 2020 , we completed a public underwritten offering of 11,960,000 shares of our common stock , including the exercise in full of the underwriter 's option to purchase an additional 1,560,000 shares of common stock , at a price to the public of $ 1.25 per share , for net proceeds of $ 13.5 million . during the first quarter of 2021 until the filing date of this annual report , we issued and sold 6,058,318 shares of our common stock under the atm agreement at a weighted average price of $ 1.99 per share for net proceeds of $ 11.7 million . our operations to date have been primarily focused on organizing and staffing our company , business planning , raising capital , developing our technology , identifying potential product candidates , manufacturing our product candidates and conducting preclinical studies and clinical trials of reloxaliase and alln-346 . we do not have any products approved for sale and have not generated any revenue to date . as of december 31 , 2020 , we had cash and cash equivalents totaling $ 35.0 million . we have incurred significant net operating losses in every year since our inception and expect to continue to incur significant expenses and increasing operating losses for the foreseeable future . our net losses may fluctuate significantly from quarter to quarter and year to year . story_separator_special_tag for options granted in 2020 , we placed a higher weighting on the historical volatility of our own stock price over the historical volatility of a representative group of public companies for the computation of expected volatility used for estimating the fair value of option grants . we will continue to increase the weighting on the historical volatility of our own stock price over the historical volatility of a representative group of public companies until such time as we have a sufficient amount of historical information regarding the volatility of our own stock . we use the simplified method as prescribed by the sec staff accounting bulletin no . 107 , share-based payment , to calculate the expected term for options granted to employees as we do not have sufficient historical exercise data to provide a reasonable basis upon which to estimate the expected term . under this approach , the weighted-average expected option term is presumed to be the average of the contractual term ( ten years ) and the vesting term ( generally four years ) of our stock options . we utilize this method due to lack of historical exercise data and the “ plain-vanilla ” nature of our stock-based awards . the expected term is applied to the stock option grant group as a whole , as we do not expect substantially different exercise or post-vesting termination behavior among our employee population . for options granted to non-employees , we utilize the contractual term of the arrangement as the basis for the expected term assumption . the risk-free interest rate is based on a treasury instrument whose term is consistent with the expected term of the stock options . the expected dividend yield is assumed to be zero as we have never paid dividends and have no current plans to pay any dividends on our common stock . we recognize forfeitures as they occur as allowed per asu no . 2016-09 , compensation – stock compensation . 112 the fair value of stock options granted to employees and directors for their services on the board of directors was estimated on the date of grant using the black-scholes option-pricing model , with the following range of assumptions for the years ended december 31 , 2020 , 2019 and 2018 : replace_table_token_1_th the following table summarizes the classification of our stock-based compensation expense recognized in our statements of operations and comprehensive loss ( in thousands ) : replace_table_token_2_th as of december 31 , 2020 , we had $ 4.4 million of unrecognized compensation expense related to stock option awards , which is expected to be recognized over weighted-average remaining vesting periods of approximately 2.1 years and $ 0.8 million of unrecognized compensation expense related to restricted stock units , which is expected to be recognized during 2021. in future periods , we expect stock-based compensation expense to increase , due in part to our existing unrecognized stock-based compensation expense , potential increases in the value of our common stock and expected additional stock-based awards to continue to attract and retain our employees . results of operations comparison of years ended december 31 , 2020 and 2019 the following table summarizes our results of operations for the years ended december 31 , 2020 and 2019 ( in thousands ) : replace_table_token_3_th 113 research and development expenses research and development expense decreased by $ 16.9 million from $ 37.2 million for the year ended december 31 , 2019 to $ 20.4 million for the year ended december 31 , 2020. the following table summarizes our research and development expenses for the years ended december 31 , 2020 and 2019 ( in thousands ) : replace_table_token_4_th the $ 16.9 million decrease in research and development expense was primarily attributable to the following : our clinical development external costs decreased by $ 7.4 million from $ 14.7 million for the year ended december 31 , 2019 to $ 7.2 million for the year ended december 31 , 2020 : our urirox-1 costs decreased $ 4.5 million from $ 5.0 million for the year ended december 31 , 2019 to $ 0.5 million for the year ended december 31 , 2020. this study was completed in the fourth quarter of 2019 and we released top-line data in november 2019. the costs incurred during the year ended december 31 , 2020 were related to closeout activities ; our urirox-2 costs decreased $ 1.6 million from $ 7.0 million for the year ended december 31 , 2019 to $ 5.4 million for the year ended december 31 , 2020. during the first half of 2020 , we limited the opening of new trial sites for the ongoing urirox-2 trial while we assessed revisions to the study design and sought additional funds to support the development of reloxaliase . a significant portion of the proceeds from sales of our common stock during 2020 are being used to activate additional clinical trial sites and increase investment in the urirox-2 trial . during the second half of 2020 we began expanding urirox-2 to additional geographies and clinical trial sites ; during 2019 , we incurred costs of $ 0.4 million with an independent third party to perform an independent analysis of the results of the urirox-1 study to assist in the assessment of revisions and redesign of the urirox-2 study ; costs related to our study 206 of reloxaliase decreased $ 0.8 million from $ 1.3 million for the year ended december 31 , 2019 to $ 0.5 million for the year ended december 31 , 2020. this study was also completed in the fourth quarter of 2019 and we reported top-line data in november 2019. the costs incurred during the year ended december 31 , 2020 were related to closeout activities ; we incurred consulting costs of $ 0.4 million during the year ended december 31 , 2019 to support our urirox-1 , urirox-2 and 206 studies . in conjunction with the completion of the urirox-1 study

