across the united states , united kingdom , germany , france , spain , italy , and japan , there are an estimated 160,000 patients each year who have progressed on first line therapy and are eligible for subsequent treatment of non-small cell lung adenocarcinoma . approximately 90,000 of these eligible patients are estimated to be chemosensitive and negative for both egfr mutation and alk translocation . in addition , over 500,000 patients receive taxanes each year ( docetaxel or paclitaxel ) , across all cancer indications . ganetespib mechanism of action hsp90 is required for the structural and functional maturation of numerous client proteins , many of which play critical roles in cell growth , differentiation and survival . preclinical and clinical results have shown that ganetespib is a selective inhibitor of hsp90 , supporting the potential for treating a broad range of malignancies . relative to their normal counterparts , cancer cells are more reliant on elevated levels of the active hsp90 complex and as such , appear to be selectively sensitive to hsp90 inhibitors , including ganetespib . recent published work has shown that cancer cells overexpress an active form of hsp90 that preferentially binds hsp90 inhibitors , providing a mechanistic explanation for this selectivity . in contrast to therapies that target a single oncogene driver , such as alk or her2 , inhibition of hsp90 results in the simultaneous disruption of numerous oncogenic signaling pathways that are critical for tumor cell proliferation and survival . the biological effects of ganetespib can be divided into three categories : deactivate driver oncogenes . certain genetically defined cancers , such as alk+ lung cancer or her2+ breast cancer , show a strong dependence on a single mutated or overexpressed hsp90 client protein . hsp90 inhibition , by leading to the destabilization of these client proteins , offers an approach to treating these cancers that is distinct from kinase inhibitors or antibodies , which bind to the oncogene driver directly . strong hsp90 clients that drive certain oncogene-addicted cancers include alk , her2 , mutant braf and egfr , androgen receptor ( ar ) , estrogen receptor ( er ) , and jak2 . reduce tumor spread . in advanced stage disease , tumors develop properties that allow them to spread throughout the body . these include the activation of pathways that regulate new blood vessel formation ( angiogenesis ) and those that enable cancer cell separation from primary tumors and establishment of new tumor lesions ( metastasis ) . many hsp90 client proteins play key roles in these processes . these include hif-1alpha , vegfr , pdfgr , and vegf in angiogenesis ; and met , raf , akt , mmps , hif-1alpha , and igf-1r in metastasis . in preclinical models , ganetespib has shown ability to inhibit these proteins and suppress angiogenesis and metastasis . enhance chemotherapy and targeted agents . cancer cells often develop resistance to commonly used anti-cancer treatments such as chemotherapy , targeted agents , and radiation therapy . many 58 of the resistance mechanisms to chemotherapy or radiation therapy involve cell-cycle checkpoint , dna repair , and anti-apoptosis pathways , which rely on hsp90 client proteins including atr , bcl2 , brca1/2 , cdk1/4 , chk1 , survivin , and wee1 . inhibition of these client proteins by ganetespib provides rationale to add ganetespib to chemotherapy or radiation treatment in order to reduce resistance and improve clinical activity . recently identified resistance mechanisms to targeted agents such as vegf inhibitors or mtor inhibitors also rely on hsp90 client proteins . in preclinical models of cancer , ganetespib has shown synergistic activity with chemotherapies including docetaxel , paclitaxel , pemetrexed , gemcitabine , cytarabine , irinotecan , etoposide , doxorubicin , carboplatin , cisplatin , and vincristine ; with targeted agents including alk inhibitors , her2 inhibitors , mtor inhibitors , braf inhibitors , mek inhibitors , egfr inhibitors , and proteasome inhibitors ; and with radiation therapy . ganetespib is being evaluated in several randomized clinical trials across multiple cancer types , both by synta and by our collaborators . the galaxy program : ganetespib in lung cancer galaxy-1 phase 2b trial in 2011 , we initiated the galaxy-1 trial in patients with advanced nsclc who received one prior treatment for advanced disease , i.e . , a second-line treatment setting . galaxy-1 compares treatment with docetaxel alone , which is approved for second-line treatment , vs. treatment with ganetespib plus docetaxel . the aims of this study were to : evaluate clinical benefit and establish the safety profile of ganetespib in combination with docetaxel relative to docetaxel alone ; identify the patient populations , by biomarker or other disease characteristics , which may be most responsive to combination treatment ; and build the clinical and operational experience needed to optimize the design and execution of the pivotal galaxy-2 phase 3 trial . patients in both arms of galaxy-1 receive a standard regimen of docetaxel 75 mg/m2 on day 1 of a 21-day treatment cycle . patients in the combination arm also receive ganetespib 150 mg/m2 on days 1 and 15. treatment continues until disease progression or until treatment intolerance . to ensure balance of prognostic factors between the two arms , patients were stratified by ecog performance status , baseline lactate dehydrogenase ( ldh ) level , smoking status , and time since diagnosis of advanced disease . galaxy-1 was originally designed to enroll 240 second-line advanced nsclc patients of all histologies in order to evaluate several hypotheses on which patients might be most responsive to combination treatment . co-primary endpoints were pfs in all patients ( the itt population ) and os in patients with elevated baseline level of serum ldh ( eldh ) . during the course of the trial , the co-primary endpoints were changed to pfs in patients with eldh and pfs in patients with mutant kras ( mkras ) . story_separator_special_tag gannet53 , a seventh framework programme ( fp7 ) research project funded by the european commission , is a pan-european randomized trial designed to evaluate the combination of ganetespib and paclitaxel vs. paclitaxel alone in over 200 patients with metastatic , predominantly p53 mutant , platinum-resistant ovarian cancer . preclinical models have shown that mutant p53 is critical to the growth and proliferation of these cancers . many mutations render p53 unable to fold appropriately , leaving the protein highly dependent on hsp90 for stability . inhibition of hsp90 destroys the complex between hsp90 and mutant p53 , leading to the degradation of the protein and cancer cell death . this anti-cancer activity is substantially stronger in cells with mutant p53 than in cells with non-mutated p53 , suggesting potential as a predictive biomarker for hsp90 inhibitors such as ganetespib . the safety lead-in phase 1 portion of gannet53 is expected to begin enrollment in mid-2014 , with centers in austria , belgium , france , and germany will participating . the study 's consortium consists of national clinical trial groups in gynecological oncology and high-volume university centers as well as noted p53 scientists and three innovative small and medium sized companies ( smes ) . 64 elesclomol ( mitochondria-targeting agent ) elesclomol is a first-in-class , investigational drug candidate that triggers programmed cell death ( apoptosis ) , in cancer cells through a novel mechanism : disrupting cancer cell mitochondrial metabolism . in preclinical experiments , anti-cancer activity of elesclomol has been shown to correlate with certain biomarkers , including ldh , which can distinguish between active mitochondria ( sufficient oxygen present ) and inactive mitochondria ( insufficient oxygen present ) . consistent with these findings in three randomized clinical trials , ldh was an important predictor of elesclomol treatment outcome . we are evaluating the use of elesclomol in combination with paclitaxel in ovarian cancer . in march 2011 , the gynecological oncology group ( gog ) initiated a phase 2 clinical trial of elesclomol in combination with paclitaxel for the treatment of persistent or recurrent ovarian , fallopian tube or primary peritoneal cancer for patients with total baseline serum ldh level less than 0.8 times the upper limit of normal ( uln ) . the gog is a non-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies . the national cancer institute is providing financial support of up to approximately $ 300,000 for the trial through its cancer therapy evaluation program . the ovarian cancer trial met the pre-specified efficacy requirement to advance to stage 2 and full enrollment of the phase 2 study , indicating potential activity in this difficult-to-treat patient population with limited treatment options . hsp90-inhibitor drug conjugate ( hdc ) platform : improving the delivery to tumors of small molecule anti-cancer therapies in september 2013 , we announced the launch of a novel , proprietary small molecule cancer drug development program : the hdc platform . this innovative approach to tumor targeted delivery capitalizes on the prolonged retention of hsp90 inhibitors by tumors to trap any active agent of interest inside cancer cells and builds on our extensive expertise in the science of hsp90 . the hdc platform stemmed from the observation that small molecule inhibitors of hsp90 are retained in tumors for as much as 20 times longer than in blood or normal tissue . our researchers have shown that ganetespib can persist in tumor cells for over a week , while it is cleared from blood and normal tissues in a matter of hours . several other research groups have published results demonstrating this characteristic is shared by first-generation inhibitors such as 17-aag and its derivatives , as well as other classes of hsp90 inhibitors . one group in particular has provided clinical validation of the observation by imaging tumors in patients using an 124 i radiolabeled form of their hsp90 inhibitor ( puh-71 ) . this property of the hsp90 inhibitor class is believed to be due to overexpression of an active form of hsp90 in cancer cells that preferentially binds hsp90 inhibitors , as compared to normal tissues . remarkably , even weak hsp90 inhibitors that do not engage degredation of hsp90 client proteins can be retained for days by cancer cells , enabling use of this property purely as a targeting mechanism to deliver an anticancer drug into cancer cells . hdcs are drug candidates consisting of an hsp90 inhibitor ( targeting moiety ) joined to an anti-cancer agent ( payload ) via a cleavable chemical linker optimized for controlled release of payload drug inside cancer cells . unlike antibody-drug conjugates ( adcs ) , hdcs are small molecules that do not require cell surface antigens for targeting or endocytosis for cellular uptake . instead , hdcs home in on an intracellular target ( hsp90 ) that is present in a wide range of cancers . hdcs can deliver micromolar concentrations of an active payload to tumor cells for extended periods of time eliminating the need for using high potency toxins in the conjugates and opening the door to a wide range of possibilities for enhancement of approved anticancer agents and promising development candidates . by directing sustained , high concentrations of active payload drug to cancer 65 cells , hdcs enable greater cancer cell killing than can be achieved with administration of unconjugated chemotherapy or other payloads . the hdc platform enables the rapid creation of an extensive proprietary pipeline of novel anticancer drugs that we may elect to develop independently or co-develop with selected partners . figure 2 : the hdc platform : using the preferential retention of hsp90 inhibitors by tumor cells to selectively deliver anti-cancer payloads . we have developed over 550 hd-conjugated chemotherapeutics , kinase inhibitors , hormone therapies , immunomodulators , and epigenetic modifiers , creating the potential for next-generation compounds in each of these categories

cash flows the following table provides information regarding our cash position , cash flows and capital expenditures for the years ended december 31 , 2013 , 2012 and 2011. replace_table_token_9_th our operating activities used cash of $ 77.4 million , $ 54.1 million and $ 47.3 million in 2013 , 2012 and 2011 , respectively . the use of cash in these periods principally resulted from our losses from operations , as adjusted for non-cash charges for depreciation and stock-based compensation , and changes in our working capital accounts . in 2013 , our investing activities used cash of $ 24.7 million , including the purchases of marketable securities of $ 114.2 million and purchases of property and equipment of $ 0.8 million , offset by maturities of marketable securities in our investment portfolio in the amount of $ 90.3 million . in 2012 , our investing activities used cash of $ 9.9 million , including the purchases of marketable securities of $ 50.0 million and purchases of property and equipment of $ 0.5 million , offset by maturities of marketable securities in our investment portfolio of $ 40.6 million . in 2011 , our investing activities provided cash of $ 9.3 million , including maturities of marketable securities in our investment portfolio 75 of $ 60.7 million , offset by the purchases of marketable securities of $ 50.7 million and purchases of property and equipment of $ 0.7 million . our financing activities provided cash of $ 69.0 million , $ 115.5 million and $ 36.7 million in 2013 , 2012 and 2011 , 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 position , cash flows and capital expenditures for the years ended december 31 , 2013 , 2012 and 2011. replace_table_token_9_th our operating activities used cash of $ 77.4 million , $ 54.1 million and $ 47.3 million in 2013 , 2012 and 2011 , respectively . the use of cash in these periods principally resulted from our losses from operations , as adjusted for non-cash charges for depreciation and stock-based compensation , and changes in our working capital accounts . in 2013 , our investing activities used cash of $ 24.7 million , including the purchases of marketable securities of $ 114.2 million and purchases of property and equipment of $ 0.8 million , offset by maturities of marketable securities in our investment portfolio in the amount of $ 90.3 million . in 2012 , our investing activities used cash of $ 9.9 million , including the purchases of marketable securities of $ 50.0 million and purchases of property and equipment of $ 0.5 million , offset by maturities of marketable securities in our investment portfolio of $ 40.6 million . in 2011 , our investing activities provided cash of $ 9.3 million , including maturities of marketable securities in our investment portfolio 75 of $ 60.7 million , offset by the purchases of marketable securities of $ 50.7 million and purchases of property and equipment of $ 0.7 million . our financing activities provided cash of $ 69.0 million , $ 115.5 million and $ 36.7 million in 2013 , 2012 and 2011 , respectively .
```    
 Suspicious Activity Report : across the united states , united kingdom , germany , france , spain , italy , and japan , there are an estimated 160,000 patients each year who have progressed on first line therapy and are eligible for subsequent treatment of non-small cell lung adenocarcinoma . approximately 90,000 of these eligible patients are estimated to be chemosensitive and negative for both egfr mutation and alk translocation . in addition , over 500,000 patients receive taxanes each year ( docetaxel or paclitaxel ) , across all cancer indications . ganetespib mechanism of action hsp90 is required for the structural and functional maturation of numerous client proteins , many of which play critical roles in cell growth , differentiation and survival . preclinical and clinical results have shown that ganetespib is a selective inhibitor of hsp90 , supporting the potential for treating a broad range of malignancies . relative to their normal counterparts , cancer cells are more reliant on elevated levels of the active hsp90 complex and as such , appear to be selectively sensitive to hsp90 inhibitors , including ganetespib . recent published work has shown that cancer cells overexpress an active form of hsp90 that preferentially binds hsp90 inhibitors , providing a mechanistic explanation for this selectivity . in contrast to therapies that target a single oncogene driver , such as alk or her2 , inhibition of hsp90 results in the simultaneous disruption of numerous oncogenic signaling pathways that are critical for tumor cell proliferation and survival . the biological effects of ganetespib can be divided into three categories : deactivate driver oncogenes . certain genetically defined cancers , such as alk+ lung cancer or her2+ breast cancer , show a strong dependence on a single mutated or overexpressed hsp90 client protein . hsp90 inhibition , by leading to the destabilization of these client proteins , offers an approach to treating these cancers that is distinct from kinase inhibitors or antibodies , which bind to the oncogene driver directly . strong hsp90 clients that drive certain oncogene-addicted cancers include alk , her2 , mutant braf and egfr , androgen receptor ( ar ) , estrogen receptor ( er ) , and jak2 . reduce tumor spread . in advanced stage disease , tumors develop properties that allow them to spread throughout the body . these include the activation of pathways that regulate new blood vessel formation ( angiogenesis ) and those that enable cancer cell separation from primary tumors and establishment of new tumor lesions ( metastasis ) . many hsp90 client proteins play key roles in these processes . these include hif-1alpha , vegfr , pdfgr , and vegf in angiogenesis ; and met , raf , akt , mmps , hif-1alpha , and igf-1r in metastasis . in preclinical models , ganetespib has shown ability to inhibit these proteins and suppress angiogenesis and metastasis . enhance chemotherapy and targeted agents . cancer cells often develop resistance to commonly used anti-cancer treatments such as chemotherapy , targeted agents , and radiation therapy . many 58 of the resistance mechanisms to chemotherapy or radiation therapy involve cell-cycle checkpoint , dna repair , and anti-apoptosis pathways , which rely on hsp90 client proteins including atr , bcl2 , brca1/2 , cdk1/4 , chk1 , survivin , and wee1 . inhibition of these client proteins by ganetespib provides rationale to add ganetespib to chemotherapy or radiation treatment in order to reduce resistance and improve clinical activity . recently identified resistance mechanisms to targeted agents such as vegf inhibitors or mtor inhibitors also rely on hsp90 client proteins . in preclinical models of cancer , ganetespib has shown synergistic activity with chemotherapies including docetaxel , paclitaxel , pemetrexed , gemcitabine , cytarabine , irinotecan , etoposide , doxorubicin , carboplatin , cisplatin , and vincristine ; with targeted agents including alk inhibitors , her2 inhibitors , mtor inhibitors , braf inhibitors , mek inhibitors , egfr inhibitors , and proteasome inhibitors ; and with radiation therapy . ganetespib is being evaluated in several randomized clinical trials across multiple cancer types , both by synta and by our collaborators . the galaxy program : ganetespib in lung cancer galaxy-1 phase 2b trial in 2011 , we initiated the galaxy-1 trial in patients with advanced nsclc who received one prior treatment for advanced disease , i.e . , a second-line treatment setting . galaxy-1 compares treatment with docetaxel alone , which is approved for second-line treatment , vs. treatment with ganetespib plus docetaxel . the aims of this study were to : evaluate clinical benefit and establish the safety profile of ganetespib in combination with docetaxel relative to docetaxel alone ; identify the patient populations , by biomarker or other disease characteristics , which may be most responsive to combination treatment ; and build the clinical and operational experience needed to optimize the design and execution of the pivotal galaxy-2 phase 3 trial . patients in both arms of galaxy-1 receive a standard regimen of docetaxel 75 mg/m2 on day 1 of a 21-day treatment cycle . patients in the combination arm also receive ganetespib 150 mg/m2 on days 1 and 15. treatment continues until disease progression or until treatment intolerance . to ensure balance of prognostic factors between the two arms , patients were stratified by ecog performance status , baseline lactate dehydrogenase ( ldh ) level , smoking status , and time since diagnosis of advanced disease . galaxy-1 was originally designed to enroll 240 second-line advanced nsclc patients of all histologies in order to evaluate several hypotheses on which patients might be most responsive to combination treatment . co-primary endpoints were pfs in all patients ( the itt population ) and os in patients with elevated baseline level of serum ldh ( eldh ) . during the course of the trial , the co-primary endpoints were changed to pfs in patients with eldh and pfs in patients with mutant kras ( mkras ) . story_separator_special_tag gannet53 , a seventh framework programme ( fp7 ) research project funded by the european commission , is a pan-european randomized trial designed to evaluate the combination of ganetespib and paclitaxel vs. paclitaxel alone in over 200 patients with metastatic , predominantly p53 mutant , platinum-resistant ovarian cancer . preclinical models have shown that mutant p53 is critical to the growth and proliferation of these cancers . many mutations render p53 unable to fold appropriately , leaving the protein highly dependent on hsp90 for stability . inhibition of hsp90 destroys the complex between hsp90 and mutant p53 , leading to the degradation of the protein and cancer cell death . this anti-cancer activity is substantially stronger in cells with mutant p53 than in cells with non-mutated p53 , suggesting potential as a predictive biomarker for hsp90 inhibitors such as ganetespib . the safety lead-in phase 1 portion of gannet53 is expected to begin enrollment in mid-2014 , with centers in austria , belgium , france , and germany will participating . the study 's consortium consists of national clinical trial groups in gynecological oncology and high-volume university centers as well as noted p53 scientists and three innovative small and medium sized companies ( smes ) . 64 elesclomol ( mitochondria-targeting agent ) elesclomol is a first-in-class , investigational drug candidate that triggers programmed cell death ( apoptosis ) , in cancer cells through a novel mechanism : disrupting cancer cell mitochondrial metabolism . in preclinical experiments , anti-cancer activity of elesclomol has been shown to correlate with certain biomarkers , including ldh , which can distinguish between active mitochondria ( sufficient oxygen present ) and inactive mitochondria ( insufficient oxygen present ) . consistent with these findings in three randomized clinical trials , ldh was an important predictor of elesclomol treatment outcome . we are evaluating the use of elesclomol in combination with paclitaxel in ovarian cancer . in march 2011 , the gynecological oncology group ( gog ) initiated a phase 2 clinical trial of elesclomol in combination with paclitaxel for the treatment of persistent or recurrent ovarian , fallopian tube or primary peritoneal cancer for patients with total baseline serum ldh level less than 0.8 times the upper limit of normal ( uln ) . the gog is a non-profit organization with the purpose of promoting excellence in the quality and integrity of clinical and basic scientific research in the field of gynecologic malignancies . the national cancer institute is providing financial support of up to approximately $ 300,000 for the trial through its cancer therapy evaluation program . the ovarian cancer trial met the pre-specified efficacy requirement to advance to stage 2 and full enrollment of the phase 2 study , indicating potential activity in this difficult-to-treat patient population with limited treatment options . hsp90-inhibitor drug conjugate ( hdc ) platform : improving the delivery to tumors of small molecule anti-cancer therapies in september 2013 , we announced the launch of a novel , proprietary small molecule cancer drug development program : the hdc platform . this innovative approach to tumor targeted delivery capitalizes on the prolonged retention of hsp90 inhibitors by tumors to trap any active agent of interest inside cancer cells and builds on our extensive expertise in the science of hsp90 . the hdc platform stemmed from the observation that small molecule inhibitors of hsp90 are retained in tumors for as much as 20 times longer than in blood or normal tissue . our researchers have shown that ganetespib can persist in tumor cells for over a week , while it is cleared from blood and normal tissues in a matter of hours . several other research groups have published results demonstrating this characteristic is shared by first-generation inhibitors such as 17-aag and its derivatives , as well as other classes of hsp90 inhibitors . one group in particular has provided clinical validation of the observation by imaging tumors in patients using an 124 i radiolabeled form of their hsp90 inhibitor ( puh-71 ) . this property of the hsp90 inhibitor class is believed to be due to overexpression of an active form of hsp90 in cancer cells that preferentially binds hsp90 inhibitors , as compared to normal tissues . remarkably , even weak hsp90 inhibitors that do not engage degredation of hsp90 client proteins can be retained for days by cancer cells , enabling use of this property purely as a targeting mechanism to deliver an anticancer drug into cancer cells . hdcs are drug candidates consisting of an hsp90 inhibitor ( targeting moiety ) joined to an anti-cancer agent ( payload ) via a cleavable chemical linker optimized for controlled release of payload drug inside cancer cells . unlike antibody-drug conjugates ( adcs ) , hdcs are small molecules that do not require cell surface antigens for targeting or endocytosis for cellular uptake . instead , hdcs home in on an intracellular target ( hsp90 ) that is present in a wide range of cancers . hdcs can deliver micromolar concentrations of an active payload to tumor cells for extended periods of time eliminating the need for using high potency toxins in the conjugates and opening the door to a wide range of possibilities for enhancement of approved anticancer agents and promising development candidates . by directing sustained , high concentrations of active payload drug to cancer 65 cells , hdcs enable greater cancer cell killing than can be achieved with administration of unconjugated chemotherapy or other payloads . the hdc platform enables the rapid creation of an extensive proprietary pipeline of novel anticancer drugs that we may elect to develop independently or co-develop with selected partners . figure 2 : the hdc platform : using the preferential retention of hsp90 inhibitors by tumor cells to selectively deliver anti-cancer payloads . we have developed over 550 hd-conjugated chemotherapeutics , kinase inhibitors , hormone therapies , immunomodulators , and epigenetic modifiers , creating the potential for next-generation compounds in each of these categories

