the secondary endpoints of the 312 study included evaluating the proportion of subjects achieving culture conversion ( defined in the same way as the convert study ) by month 6 and the proportion of subjects achieving culture conversion by month 12 , which was the end of treatment . the 312 study has completed . as a condition of accelerated approval , we must conduct a post-approval confirmatory clinical trial . the required confirmatory trial , which is currently under discussion with the fda , is proposed to be a randomized , double-blind , placebo-controlled clinical trial to assess and describe the clinical benefit of arikayce in patients with mac lung disease . the trial will evaluate the effect of arikayce on a clinically meaningful endpoint , as compared to an appropriate control , in the intended patient population of patients with mac lung disease . pursuant to the timetable agreed upon with the fda , the study protocol is expected to be finalized during the first half of 2019 , with trial results to be reported by 2024. continued approval of arikayce will be contingent upon verification and description of clinical benefit in this study . pipeline progress ins1007 54 ins1007 is a small molecule , oral , reversible inhibitor of dpp1 , which we licensed from astrazeneca in october 2016. dpp1 is an enzyme responsible for activating neutrophil serine proteases in neutrophils when they are formed in the bone marrow . neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation . neutrophils contain the neutrophil serine proteases ( including neutrophil elastase , proteinase 3 , and cathepsin g ) that have been implicated in a variety of inflammatory diseases . in chronic inflammatory lung diseases , neutrophils accumulate in the airways and release active neutrophil serine proteases in excess that cause lung destruction and inflammation . ins1007 may decrease the damaging effects of inflammatory diseases , such as non-cf bronchiectasis , by inhibiting dpp1 and its activation of neutrophil serine proteases . non-cf bronchiectasis is a progressive pulmonary disorder in which the bronchi become permanently dilated due to chronic inflammation and infection . currently , there is no cure , and we are not aware of any fda-approved therapies specifically indicated for non-cf bronchiectasis . the willow study the willow study is a global phase 2 , randomized , double-blind , placebo-controlled , parallel group , multi-center clinical study to assess the efficacy , safety and tolerability , and pharmacokinetics of ins1007 administered once daily for 24 weeks in subjects with non-cf bronchiectasis . we commenced enrollment in the willow study in december 2017 and we expect to complete enrollment in mid-2019 . in addition , we are exploring the potential of ins1007 in various neutrophil-driven inflammatory conditions . ins1009 ins1009 is an investigational inhaled treprostinil prodrug formulation that has the potential to address certain of the current limitations of existing prostanoid therapies . we believe that ins1009 prolongs duration of effect and may provide pah patients with greater consistency in pulmonary arterial pressure reduction over time . current inhaled prostanoid therapies must be dosed four to nine times per day for the treatment of pah . reducing dose frequency has the potential to ease patient burden and improve compliance . additionally , we believe that ins1009 may be associated with fewer side effects , including elevated heart rate , low blood pressure , and severity and or frequency of cough , associated with high initial drug levels and local upper airway exposure when using current inhaled prostanoid therapies . we believe ins1009 may offer a differentiated product profile for rare pulmonary disorders , including pah , and we are currently evaluating our options to advance its development , including exploring its use as an inhaled dry powder formulation . other development activities our earlier-stage pipeline includes preclinical compounds that we are evaluating in multiple rare diseases of unmet medical need , including gram positive pulmonary infections in cf , ntm lung disease and refractory localized infections involving biofilm . to complement our internal research and development , we actively evaluate in-licensing and acquisition opportunities for a broad range of rare diseases . key components of our results of operations revenues product revenues consist primarily of net sales of arikayce in the us . in october 2018 , we began shipping arikayce to our customers in the us , which include specialty pharmacies and specialty distributors . we recognize revenue for product received by our customers net of allowances for customer credits , including estimated rebates , chargebacks , prompt pay discounts , returns , service fees , and government rebates , such as medicaid rebates and medicare part d coverage gap reimbursements in the us . we also began recognizing revenue from sales to the french national agency for medicines and health products safety ( ansm ) , which granted arikayce a temporary authorizations for use ( autorisation temporaire d'utilisation or atu ) . cost of product revenues ( excluding amortization of intangible assets ) cost of product revenues ( excluding amortization of intangible assets ) consist primarily of direct and indirect costs related to the manufacturing of arikayce sold , including third-party manufacturing costs , packaging services , freight , allocation of overhead costs , and inventory adjustment charges , in addition to royalty expenses due to pari . we began capitalizing inventory upon fda approval of arikayce . research and development ( r & d ) expenses r & d expenses consist of salaries , benefits and other related costs , including stock-based compensation , for personnel serving in our research and development functions , including medical affairs . expenses also include other internal operating 55 expenses , the cost of manufacturing our drug candidate ( s ) for clinical study , the cost of conducting clinical studies , and the cost of conducting preclinical and research activities . story_separator_special_tag in 2019 , we plan to continue to support the commercial launch of arikayce in the us , to fund further clinical development of arikayce and ins1007 , and support efforts to obtain regulatory approvals for arikayce outside the us . our cash requirements in 2019 will be impacted by a number of factors , the most significant of which are expenses related to the commercialization efforts for arikayce , and to a lesser extent , expenses related to ins1007 and future arikayce clinical trials . cash flows as of december 31 , 2018 , we had cash and cash equivalents of $ 495.1 million , as compared with $ 381.2 million as of december 31 , 2017 . the $ 113.9 million increase was due primarily to the net cash proceeds from our issuance of convertible notes in january 2018 , partially offset by cash used in operating activities and , to a lesser extent , cash used in investing activities . our working capital was $ 439.2 million as of december 31 , 2018 as compared with $ 344.8 million as of december 31 , 2017 . story_separator_special_tag collaborated with therapure to construct a production area for the manufacture of arikayce in therapure 's existing manufacturing facility in canada . the agreement has an initial term of five years from the first date on which therapure delivers arikayce to us after we obtain permits related to the manufacture of arikayce , and will renew automatically for successive periods of two years each , unless terminated by either party by providing the required two years ' prior written notice to the other party . under the agreement , we are obligated to pay certain minimum amounts for the batches of arikayce produced each calendar year . in september 2015 , we entered into a commercial fill/finish services agreement ( the fill/finish agreement ) with althea , for althea to produce , on a non-exclusive basis , arikayce in finished dosage form at a 50 kg scale . under the fill/finish agreement , we are obligated to pay a minimum of $ 2.7 million for the batches of arikayce produced each calendar year during the term of the fill/finish agreement . the fill/finish agreement became effective as of january 1 , 2015 , and following an extension in 2018 , the agreement remains in effect through december 31 , 2021. the fill/finish agreement may be extended for additional two -year periods upon mutual written agreement of the company and althea at least one year prior to the expiration of its then-current term . we currently have a licensing agreement with pari for the use of the optimized lamira nebulizer system for delivery of arikayce in treating patients with ntm lung infections , cf and bronchiectasis . under the licensing agreement , we have rights under several us and foreign issued patents , and patent applications involving improvements to the optimized lamira nebulizer system , to exploit such system with arikayce for the treatment of such indications , but we can not manufacture such nebulizers except as permitted under our commercialization agreement with pari . under the licensing 61 agreement , we paid pari an upfront license fee and milestone payments . upon fda acceptance of our new drug application and the subsequent fda approval of arikayce , we paid pari additional milestone payments of 1.0 million and 1.5 million , respectively . in addition , pari is entitled to receive a future milestone payment of 0.5 million in cash based on achievement of first receipt of marketing approval in a major eu country for arikayce and the device . in october 2017 , we exercised an option to buy-down the royalties payable to pari , which was included within selling , general and administrative expenses in the fourth quarter of 2017. pari is now entitled to receive royalty payments in the mid-single digits on the annual global net sales of arikayce , pursuant to the licensing agreement , subject to certain specified annual minimum royalties . in july 2014 , we entered into a commercialization agreement with pari for the manufacture and supply of the lamira nebulizer systems and related accessories ( the device ) as optimized for use with arikayce . under the commercialization agreement , pari manufactures the device except in the case of certain defined supply failures , when the company will have the right to make the device and have it made by third parties ( but not certain third parties deemed under the commercialization agreement to compete with pari ) . the commercialization agreement has an initial term of 15 years that began in october 2018 ( the initial term ) . the term of the commercialization agreement may be extended by us for an additional five years by providing written notice to pari at least one year prior to the expiration of the initial term . in october 2017 , we entered into certain agreements with patheon related to the increase of our long-term production capacity for arikayce . the agreements provide for patheon to manufacture and supply arikayce for our anticipated commercial needs . under these agreements , we are required to deliver to patheon the required raw materials , including active pharmaceutical ingredients , and certain fixed assets needed to manufacture arikayce . patheon 's supply obligations will commence once certain technology transfer and construction services are completed . our manufacturing and supply agreement with patheon will remain in effect for a fixed initial term , after which it will continue for successive renewal terms unless either we or patheon have given written notice of termination . the technology transfer agreement will expire when the parties agree that the technology transfer services have been completed . the agreements may also be terminated under certain other circumstances , including by either party due to a material uncured breach of the other party or the other party 's insolvency . these early termination clauses

net cash used in operating activities was $ 258.0 million and $ 159.6 million for the years ended december 31 , 2018 and 2017 , respectively . the net cash used in operating activities during the years ended december 31 , 2018 and 2017 was primarily for the pre-commercialization efforts and clinical activities related to arikayce , as well as general and administrative expenses . in addition , net cash used in operating activities during the year ended december 31 , 2018 and 2017 included commercialization efforts and clinical trial expenses related to ins1007 . net cash used in investing activities was $ 14.8 million and $ 3.0 million for the years ended december 31 , 2018 and 2017 , respectively . the net cash used in investing activities during 2018 was primarily related to the investment in our long-term production capacity build-out at patheon . the net cash used in investing activities during 2017 was primarily related to the investment in our long-term production capacity build-out at patheon and for the build out of our lab facility in bridgewater , 60 new jersey . we expect our net cash used in investing activities will increase in 2019 as compared to 2018 as a result of our continuing investment in the build-out of patheon and our new headquarters facility . net cash provided by financing activities was $ 386.7 million and $ 381.1 million for the years ended december 31 , 2018 and 2017 , 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.
     ```net cash used in operating activities was $ 258.0 million and $ 159.6 million for the years ended december 31 , 2018 and 2017 , respectively . the net cash used in operating activities during the years ended december 31 , 2018 and 2017 was primarily for the pre-commercialization efforts and clinical activities related to arikayce , as well as general and administrative expenses . in addition , net cash used in operating activities during the year ended december 31 , 2018 and 2017 included commercialization efforts and clinical trial expenses related to ins1007 . net cash used in investing activities was $ 14.8 million and $ 3.0 million for the years ended december 31 , 2018 and 2017 , respectively . the net cash used in investing activities during 2018 was primarily related to the investment in our long-term production capacity build-out at patheon . the net cash used in investing activities during 2017 was primarily related to the investment in our long-term production capacity build-out at patheon and for the build out of our lab facility in bridgewater , 60 new jersey . we expect our net cash used in investing activities will increase in 2019 as compared to 2018 as a result of our continuing investment in the build-out of patheon and our new headquarters facility . net cash provided by financing activities was $ 386.7 million and $ 381.1 million for the years ended december 31 , 2018 and 2017 , respectively .
```    
 Suspicious Activity Report : the secondary endpoints of the 312 study included evaluating the proportion of subjects achieving culture conversion ( defined in the same way as the convert study ) by month 6 and the proportion of subjects achieving culture conversion by month 12 , which was the end of treatment . the 312 study has completed . as a condition of accelerated approval , we must conduct a post-approval confirmatory clinical trial . the required confirmatory trial , which is currently under discussion with the fda , is proposed to be a randomized , double-blind , placebo-controlled clinical trial to assess and describe the clinical benefit of arikayce in patients with mac lung disease . the trial will evaluate the effect of arikayce on a clinically meaningful endpoint , as compared to an appropriate control , in the intended patient population of patients with mac lung disease . pursuant to the timetable agreed upon with the fda , the study protocol is expected to be finalized during the first half of 2019 , with trial results to be reported by 2024. continued approval of arikayce will be contingent upon verification and description of clinical benefit in this study . pipeline progress ins1007 54 ins1007 is a small molecule , oral , reversible inhibitor of dpp1 , which we licensed from astrazeneca in october 2016. dpp1 is an enzyme responsible for activating neutrophil serine proteases in neutrophils when they are formed in the bone marrow . neutrophils are the most common type of white blood cell and play an essential role in pathogen destruction and inflammatory mediation . neutrophils contain the neutrophil serine proteases ( including neutrophil elastase , proteinase 3 , and cathepsin g ) that have been implicated in a variety of inflammatory diseases . in chronic inflammatory lung diseases , neutrophils accumulate in the airways and release active neutrophil serine proteases in excess that cause lung destruction and inflammation . ins1007 may decrease the damaging effects of inflammatory diseases , such as non-cf bronchiectasis , by inhibiting dpp1 and its activation of neutrophil serine proteases . non-cf bronchiectasis is a progressive pulmonary disorder in which the bronchi become permanently dilated due to chronic inflammation and infection . currently , there is no cure , and we are not aware of any fda-approved therapies specifically indicated for non-cf bronchiectasis . the willow study the willow study is a global phase 2 , randomized , double-blind , placebo-controlled , parallel group , multi-center clinical study to assess the efficacy , safety and tolerability , and pharmacokinetics of ins1007 administered once daily for 24 weeks in subjects with non-cf bronchiectasis . we commenced enrollment in the willow study in december 2017 and we expect to complete enrollment in mid-2019 . in addition , we are exploring the potential of ins1007 in various neutrophil-driven inflammatory conditions . ins1009 ins1009 is an investigational inhaled treprostinil prodrug formulation that has the potential to address certain of the current limitations of existing prostanoid therapies . we believe that ins1009 prolongs duration of effect and may provide pah patients with greater consistency in pulmonary arterial pressure reduction over time . current inhaled prostanoid therapies must be dosed four to nine times per day for the treatment of pah . reducing dose frequency has the potential to ease patient burden and improve compliance . additionally , we believe that ins1009 may be associated with fewer side effects , including elevated heart rate , low blood pressure , and severity and or frequency of cough , associated with high initial drug levels and local upper airway exposure when using current inhaled prostanoid therapies . we believe ins1009 may offer a differentiated product profile for rare pulmonary disorders , including pah , and we are currently evaluating our options to advance its development , including exploring its use as an inhaled dry powder formulation . other development activities our earlier-stage pipeline includes preclinical compounds that we are evaluating in multiple rare diseases of unmet medical need , including gram positive pulmonary infections in cf , ntm lung disease and refractory localized infections involving biofilm . to complement our internal research and development , we actively evaluate in-licensing and acquisition opportunities for a broad range of rare diseases . key components of our results of operations revenues product revenues consist primarily of net sales of arikayce in the us . in october 2018 , we began shipping arikayce to our customers in the us , which include specialty pharmacies and specialty distributors . we recognize revenue for product received by our customers net of allowances for customer credits , including estimated rebates , chargebacks , prompt pay discounts , returns , service fees , and government rebates , such as medicaid rebates and medicare part d coverage gap reimbursements in the us . we also began recognizing revenue from sales to the french national agency for medicines and health products safety ( ansm ) , which granted arikayce a temporary authorizations for use ( autorisation temporaire d'utilisation or atu ) . cost of product revenues ( excluding amortization of intangible assets ) cost of product revenues ( excluding amortization of intangible assets ) consist primarily of direct and indirect costs related to the manufacturing of arikayce sold , including third-party manufacturing costs , packaging services , freight , allocation of overhead costs , and inventory adjustment charges , in addition to royalty expenses due to pari . we began capitalizing inventory upon fda approval of arikayce . research and development ( r & d ) expenses r & d expenses consist of salaries , benefits and other related costs , including stock-based compensation , for personnel serving in our research and development functions , including medical affairs . expenses also include other internal operating 55 expenses , the cost of manufacturing our drug candidate ( s ) for clinical study , the cost of conducting clinical studies , and the cost of conducting preclinical and research activities . story_separator_special_tag in 2019 , we plan to continue to support the commercial launch of arikayce in the us , to fund further clinical development of arikayce and ins1007 , and support efforts to obtain regulatory approvals for arikayce outside the us . our cash requirements in 2019 will be impacted by a number of factors , the most significant of which are expenses related to the commercialization efforts for arikayce , and to a lesser extent , expenses related to ins1007 and future arikayce clinical trials . cash flows as of december 31 , 2018 , we had cash and cash equivalents of $ 495.1 million , as compared with $ 381.2 million as of december 31 , 2017 . the $ 113.9 million increase was due primarily to the net cash proceeds from our issuance of convertible notes in january 2018 , partially offset by cash used in operating activities and , to a lesser extent , cash used in investing activities . our working capital was $ 439.2 million as of december 31 , 2018 as compared with $ 344.8 million as of december 31 , 2017 . story_separator_special_tag collaborated with therapure to construct a production area for the manufacture of arikayce in therapure 's existing manufacturing facility in canada . the agreement has an initial term of five years from the first date on which therapure delivers arikayce to us after we obtain permits related to the manufacture of arikayce , and will renew automatically for successive periods of two years each , unless terminated by either party by providing the required two years ' prior written notice to the other party . under the agreement , we are obligated to pay certain minimum amounts for the batches of arikayce produced each calendar year . in september 2015 , we entered into a commercial fill/finish services agreement ( the fill/finish agreement ) with althea , for althea to produce , on a non-exclusive basis , arikayce in finished dosage form at a 50 kg scale . under the fill/finish agreement , we are obligated to pay a minimum of $ 2.7 million for the batches of arikayce produced each calendar year during the term of the fill/finish agreement . the fill/finish agreement became effective as of january 1 , 2015 , and following an extension in 2018 , the agreement remains in effect through december 31 , 2021. the fill/finish agreement may be extended for additional two -year periods upon mutual written agreement of the company and althea at least one year prior to the expiration of its then-current term . we currently have a licensing agreement with pari for the use of the optimized lamira nebulizer system for delivery of arikayce in treating patients with ntm lung infections , cf and bronchiectasis . under the licensing agreement , we have rights under several us and foreign issued patents , and patent applications involving improvements to the optimized lamira nebulizer system , to exploit such system with arikayce for the treatment of such indications , but we can not manufacture such nebulizers except as permitted under our commercialization agreement with pari . under the licensing 61 agreement , we paid pari an upfront license fee and milestone payments . upon fda acceptance of our new drug application and the subsequent fda approval of arikayce , we paid pari additional milestone payments of 1.0 million and 1.5 million , respectively . in addition , pari is entitled to receive a future milestone payment of 0.5 million in cash based on achievement of first receipt of marketing approval in a major eu country for arikayce and the device . in october 2017 , we exercised an option to buy-down the royalties payable to pari , which was included within selling , general and administrative expenses in the fourth quarter of 2017. pari is now entitled to receive royalty payments in the mid-single digits on the annual global net sales of arikayce , pursuant to the licensing agreement , subject to certain specified annual minimum royalties . in july 2014 , we entered into a commercialization agreement with pari for the manufacture and supply of the lamira nebulizer systems and related accessories ( the device ) as optimized for use with arikayce . under the commercialization agreement , pari manufactures the device except in the case of certain defined supply failures , when the company will have the right to make the device and have it made by third parties ( but not certain third parties deemed under the commercialization agreement to compete with pari ) . the commercialization agreement has an initial term of 15 years that began in october 2018 ( the initial term ) . the term of the commercialization agreement may be extended by us for an additional five years by providing written notice to pari at least one year prior to the expiration of the initial term . in october 2017 , we entered into certain agreements with patheon related to the increase of our long-term production capacity for arikayce . the agreements provide for patheon to manufacture and supply arikayce for our anticipated commercial needs . under these agreements , we are required to deliver to patheon the required raw materials , including active pharmaceutical ingredients , and certain fixed assets needed to manufacture arikayce . patheon 's supply obligations will commence once certain technology transfer and construction services are completed . our manufacturing and supply agreement with patheon will remain in effect for a fixed initial term , after which it will continue for successive renewal terms unless either we or patheon have given written notice of termination . the technology transfer agreement will expire when the parties agree that the technology transfer services have been completed . the agreements may also be terminated under certain other circumstances , including by either party due to a material uncured breach of the other party or the other party 's insolvency . these early termination clauses

