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News Article | May 12, 2017
Site: globenewswire.com

HALLE (SAALE), Germany, 12 May 2017 - Probiodrug AG (Euronext Amsterdam: PBD), a biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer's disease (AD), today announces its first quarter business update for the period ending 31 March 2017, in the form of an interim management report. The interim management report for the first quarter 2017 is available for download on the company website (http://www.probiodrug.de/investors/reports-and-presentations/). Commenting on the first quarter, Dr Konrad Glund, Chief Executive Officer of Probiodrug, said: "In the first quarter of 2017 we successfully continued to execute on our corporate strategy. The Last Patient Last Visit (LPLV) represents an important step towards the conclusion of our first patient trial with PQ912. The promising data obtained with PQ912 and PBD-C06 in AD animal models further demonstrates the potential of the pGlu-Abeta treatment concept. Positive treatment results with PQ912 in a Huntington's disease animal model provide support for evaluating PQ912 in patients with Huntington`s disease (HD) in the future, another neurological disease based on misfolded proteins." Pipeline update Probiodrug`s therapeutic approach targets pyroglutamate-Abeta (pGlu-Abeta, also called N3pG Abeta) as a therapeutic strategy to fight Alzheimer's disease. This modified Abeta is considered to be linked with disease initiation and progression by seeding the formation of soluble neurotoxic amyloid oligomers. Probiodrug is developing proprietary product candidates to target toxic pGlu-Abeta via two modes of action: by (i) inhibiting the production of pGlu-Abeta; and (ii) clearing existing pGlu-Abeta from the brain. Probiodrug's innovative approach is based on the development of specific inhibitors for the enzyme Glutaminyl Cyclase (QC), which is instrumental in the creation of pGlu-Abeta. In addition, the company is developing a monoclonal antibody targeting pGlu-Abeta to enhance its clearance. To date, Probiodrug's pipeline consists of two small molecule inhibitors of the QC-enzyme, PQ912 and PQ1565, and a monoclonal antibody, PBD-C06, targeting pGlu-Abeta. PQ912 Probiodrug is running a Phase 2a trial, the "SAPHIR" study, of its lead product candidate PQ912. In a preceding Phase 1 study with healthy young and elderly volunteers, PQ912 was shown to be safe and well tolerated and revealed high QC-inhibition. PQ912 is the first QC-inhibitor being tested in patients. The Phase 2a study is a randomized, double-blind multi-center study which plans to enrol a total of 110 patients with early stage Alzheimer's disease. The study is led by internationally renowned experts in AD in seven European countries at 21 sites, with the Alzheimer Center, VU Medical Center (VUmc), Amsterdam being the lead center. The primary endpoint of the trial is the safety and tolerability of PQ912 compared with placebo over a three-month treatment period. Additionally, a set of exploratory read-outs comprising cognitive tests, functional assessments by EEG and functional MRI and new molecular biomarkers in CSF will be used to evaluate the compound's effect on the pathology of the disease. In this study Mini-Mental State Examination (MMSE) and the Cogstate neuro-psychological test battery (NTB) are monitored blindly every 30 patients to ensure consistency and reliability of ratings. First blinded results at baseline show that the mean MMSE scores from the 120 randomised patients is 25.3, the mean age is 73 years and gender distribution is 64 female and 56 male. Current results indicate a low variability and therefore the high quality of the assessments being used. Recruitment has been completed in mid-December 2016. A total of 120 patients have been randomised, surpassing the 110 patients planned in the study protocol. Full unblinded results of the SAPHIR study are expected in the second quarter of 2017. PBD-C06 PBD-C06 is a monoclonal antibody, currently in preclinical stage. PBD-C06 targets pGlu-Abeta, aiming to selectively clear the brain of pGlu-Abeta while leaving non-toxic forms of Abeta untouched. PBD-C06 has been successfully humanized and also de-immunized to avoid detection by the patient's endogenous immune system. For the first time for an anti-pGlu-Abeta approach PBD-C06 has not only shown the ability to reduce Abeta/plaques but also to significantly improve cognitive deficits in aged Alzheimer's mice. Moreover, no evidence was found of increased microhemorrhages after treatment with PBD-C06. The development of the manufacturing process of this molecule is running. PQ1565 PQ1565 is a QC-inhibitor, currently in preclinical stage. The product candidate has shown attractive drug-like properties in preclinical studies. The GMP process for this molecule is being implemented. The next development steps are in preparation and respective decisions would be made in connection with the readout of the SAPHIR trial. New promising results from pharmacological studies with PQ912 and PBD-C06 in AD animal models and an evaluation of new biomarkers in cerebrospinal fluid (CSF) from AD patients presented Three updates on the advancement of its product candidates and the results of a Biomarker research collaboration have been presented at the 13th International Conference on Alzheimer's and Parkinson's Diseases (AD/PDTM 2017), Vienna, Austria. The conference took place from 29th March to 2nd April 2017. Financials The first quarter of 2017 showed an increase of research and development expenses to EUR 2,268k compared to EUR 1,974k in the first quarter of 2016, reflecting mainly the costs for the Phase 2 trial (SAPHIR Study) of PQ912. General and administrative expenses amounted to EUR 507k compared to EUR 597k in the first quarter of 2016, reflecting more intrayear shifts than actual savings. In the first quarter 2017 the Company has not generated any revenues, also in line with the corporate planning. Correspondingly, the comprehensive loss of the reporting period was EUR 2,798k, compared to EUR 2,596k in the first quarter of 2016. All results are in line with management expectations. Probiodrug held EUR 18.7 million in cash and cash equivalents as of 31 March 2017. Last Patient Last Visit (LPLV) accomplished in the SAPHIR Study On 07 April 2017 Probiodrug announced that the Last Patient's Last Visit (LPLV) occurred on 05 April 2017 in the currently running Phase 2a SAPHIR study investigating the QC-inhibitor PQ912. PQ912 demonstrates beneficial effects in a preclinical Huntington`s disease model On 10 April 2017 Probiodrug announced results of a preclinical study targeting Glutaminyl Cyclases (QCs) in Huntington`s disease (HD). The results have been presented at the 12th Annual HD Therapeutics Conference of the CHDI Foundation on 23rd of April in St. Julian's, Malta. HD is the most common inherited neurodegenerative disorder where, due to a mutation, the poly-glutamine amino acid sequence is expanded in a protein called huntingtin (HTT). There is currently no disease modifying therapy for this condition. PQ912 clearly improved several signs of the disease in a well characterized BACHD mouse model of HD. BACHD mice carry the human gene for mutant HTT (mHTT). At six weeks old, parallel to the onset of first behavioral, metabolic and neuropathological signs of the disease, the BACHD mice were treated for 18 weeks with food pellets containing PQ912. PQ912 treatment for 18 weeks caused a significant reduction (approximately 30%) in brain mHTT levels. These lowered mHTT levels were associated with reduced levels of the inflammation/gliosis marker GFAP-protein, a striking normalization of the abnormal body weight gain and energy metabolism as well as a normalization of several mRNA levels coding for HSPs in BACHD mice at 24 weeks of age. Data were generated in collaboration with Stephan von Hörsten of the University Hospital Erlangen, part of Friedrich-Alexander-University (FAU), Erlangen, Germany. Invitation to Probiodrug`s Ordinary General Meeting of Shareholders on 13 June 2017 On 03 May 2017 Probiodrug invited its shareholders to its ordinary general meeting of shareholders to be held on Tuesday, 13 June 2017 at 11:00 am (CEST), at the Mercure Hotel MOA Berlin, Stephanstraße 41, 10559 Berlin, Germany. The relevant documents can be found at http://www.probiodrug.de/investors/annual-shareholders-meeting-2017/. For more information, please contact: Notes to Editors: About Probiodrug AG Headquartered in Halle (Saale), Germany, Probiodrug AG (Euronext Amsterdam: PBD) is a biopharmaceutical company focused on the development of new therapeutic products for the treatment of Alzheimer's disease. Founded in 1997, the company successfully developed a novel therapeutic concept for diabetes - the DP4 inhibitors - which provided the basis for a novel class of antidiabetics - the gliptins. Its core capabilities are based on its long-standing expertise in the elucidation of the structure and function of enzymes involved in the modification of proteins and peptides, which play a central role in pathological conditions. Today Probiodrug's aim is to become a leading company in the development of Alzheimer's disease treatments and to thereby provide a better life for Alzheimer's disease patients. It has identified a new therapeutic concept linked to disease initiation and progression. The development approaches are targeting pyroglutamate-Abeta (pGlu-Abeta) as a therapeutic strategy to fight Alzheimer's disease. The Company has medical use and composition of matter patents related to the inhibition of Glutaminyl Cyclase (QC) and anti-pGlu-Abeta- specific monoclonal antibodies, providing it, in the Company's view, with a leading position in this field of research. Probiodrug's lead product candidate, PQ912, is a highly specific and potent inhibitor of Glutaminyl Cyclase (QC), which has shown therapeutic effects in Alzheimer's animal models. PQ912 is currently in a Phase 2a study, the SAPHIR trial. In a preceding Phase 1 study with healthy young and elderly volunteers, PQ912 has shown to be safe and well tolerated and also revealed high QC-inhibition. About Alzheimer's disease Alzheimer's disease is a neurological disorder, which is the most common form of dementia, and ultimately leads to death. Because Alzheimer's disease cannot be cured and is degenerative, the affected patients must increasingly rely on others for assistance. . Today, 47 million people live with dementia worldwide, and this number is projected to treble to more than 131 million by 2050, as populations age. Dementia also has a huge economic impact. Alzheimer's has an estimated, global societal cost of US$ 818 billion, and it will become a trillion dollar disease by 2018. (World Alzheimer Report 2016). Forward Looking Statements Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgment of Probiodrug AG as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.


News Article | May 12, 2017
Site: globenewswire.com

HALLE (SAALE), Germany, 12 May 2017 - Probiodrug AG (Euronext Amsterdam: PBD), a biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer's disease (AD), today announces its first quarter business update for the period ending 31 March 2017, in the form of an interim management report. The interim management report for the first quarter 2017 is available for download on the company website (http://www.probiodrug.de/investors/reports-and-presentations/). Commenting on the first quarter, Dr Konrad Glund, Chief Executive Officer of Probiodrug, said: "In the first quarter of 2017 we successfully continued to execute on our corporate strategy. The Last Patient Last Visit (LPLV) represents an important step towards the conclusion of our first patient trial with PQ912. The promising data obtained with PQ912 and PBD-C06 in AD animal models further demonstrates the potential of the pGlu-Abeta treatment concept. Positive treatment results with PQ912 in a Huntington's disease animal model provide support for evaluating PQ912 in patients with Huntington`s disease (HD) in the future, another neurological disease based on misfolded proteins." Pipeline update Probiodrug`s therapeutic approach targets pyroglutamate-Abeta (pGlu-Abeta, also called N3pG Abeta) as a therapeutic strategy to fight Alzheimer's disease. This modified Abeta is considered to be linked with disease initiation and progression by seeding the formation of soluble neurotoxic amyloid oligomers. Probiodrug is developing proprietary product candidates to target toxic pGlu-Abeta via two modes of action: by (i) inhibiting the production of pGlu-Abeta; and (ii) clearing existing pGlu-Abeta from the brain. Probiodrug's innovative approach is based on the development of specific inhibitors for the enzyme Glutaminyl Cyclase (QC), which is instrumental in the creation of pGlu-Abeta. In addition, the company is developing a monoclonal antibody targeting pGlu-Abeta to enhance its clearance. To date, Probiodrug's pipeline consists of two small molecule inhibitors of the QC-enzyme, PQ912 and PQ1565, and a monoclonal antibody, PBD-C06, targeting pGlu-Abeta. PQ912 Probiodrug is running a Phase 2a trial, the "SAPHIR" study, of its lead product candidate PQ912. In a preceding Phase 1 study with healthy young and elderly volunteers, PQ912 was shown to be safe and well tolerated and revealed high QC-inhibition. PQ912 is the first QC-inhibitor being tested in patients. The Phase 2a study is a randomized, double-blind multi-center study which plans to enrol a total of 110 patients with early stage Alzheimer's disease. The study is led by internationally renowned experts in AD in seven European countries at 21 sites, with the Alzheimer Center, VU Medical Center (VUmc), Amsterdam being the lead center. The primary endpoint of the trial is the safety and tolerability of PQ912 compared with placebo over a three-month treatment period. Additionally, a set of exploratory read-outs comprising cognitive tests, functional assessments by EEG and functional MRI and new molecular biomarkers in CSF will be used to evaluate the compound's effect on the pathology of the disease. In this study Mini-Mental State Examination (MMSE) and the Cogstate neuro-psychological test battery (NTB) are monitored blindly every 30 patients to ensure consistency and reliability of ratings. First blinded results at baseline show that the mean MMSE scores from the 120 randomised patients is 25.3, the mean age is 73 years and gender distribution is 64 female and 56 male. Current results indicate a low variability and therefore the high quality of the assessments being used. Recruitment has been completed in mid-December 2016. A total of 120 patients have been randomised, surpassing the 110 patients planned in the study protocol. Full unblinded results of the SAPHIR study are expected in the second quarter of 2017. PBD-C06 PBD-C06 is a monoclonal antibody, currently in preclinical stage. PBD-C06 targets pGlu-Abeta, aiming to selectively clear the brain of pGlu-Abeta while leaving non-toxic forms of Abeta untouched. PBD-C06 has been successfully humanized and also de-immunized to avoid detection by the patient's endogenous immune system. For the first time for an anti-pGlu-Abeta approach PBD-C06 has not only shown the ability to reduce Abeta/plaques but also to significantly improve cognitive deficits in aged Alzheimer's mice. Moreover, no evidence was found of increased microhemorrhages after treatment with PBD-C06. The development of the manufacturing process of this molecule is running. PQ1565 PQ1565 is a QC-inhibitor, currently in preclinical stage. The product candidate has shown attractive drug-like properties in preclinical studies. The GMP process for this molecule is being implemented. The next development steps are in preparation and respective decisions would be made in connection with the readout of the SAPHIR trial. New promising results from pharmacological studies with PQ912 and PBD-C06 in AD animal models and an evaluation of new biomarkers in cerebrospinal fluid (CSF) from AD patients presented Three updates on the advancement of its product candidates and the results of a Biomarker research collaboration have been presented at the 13th International Conference on Alzheimer's and Parkinson's Diseases (AD/PDTM 2017), Vienna, Austria. The conference took place from 29th March to 2nd April 2017. Financials The first quarter of 2017 showed an increase of research and development expenses to EUR 2,268k compared to EUR 1,974k in the first quarter of 2016, reflecting mainly the costs for the Phase 2 trial (SAPHIR Study) of PQ912. General and administrative expenses amounted to EUR 507k compared to EUR 597k in the first quarter of 2016, reflecting more intrayear shifts than actual savings. In the first quarter 2017 the Company has not generated any revenues, also in line with the corporate planning. Correspondingly, the comprehensive loss of the reporting period was EUR 2,798k, compared to EUR 2,596k in the first quarter of 2016. All results are in line with management expectations. Probiodrug held EUR 18.7 million in cash and cash equivalents as of 31 March 2017. Last Patient Last Visit (LPLV) accomplished in the SAPHIR Study On 07 April 2017 Probiodrug announced that the Last Patient's Last Visit (LPLV) occurred on 05 April 2017 in the currently running Phase 2a SAPHIR study investigating the QC-inhibitor PQ912. PQ912 demonstrates beneficial effects in a preclinical Huntington`s disease model On 10 April 2017 Probiodrug announced results of a preclinical study targeting Glutaminyl Cyclases (QCs) in Huntington`s disease (HD). The results have been presented at the 12th Annual HD Therapeutics Conference of the CHDI Foundation on 23rd of April in St. Julian's, Malta. HD is the most common inherited neurodegenerative disorder where, due to a mutation, the poly-glutamine amino acid sequence is expanded in a protein called huntingtin (HTT). There is currently no disease modifying therapy for this condition. PQ912 clearly improved several signs of the disease in a well characterized BACHD mouse model of HD. BACHD mice carry the human gene for mutant HTT (mHTT). At six weeks old, parallel to the onset of first behavioral, metabolic and neuropathological signs of the disease, the BACHD mice were treated for 18 weeks with food pellets containing PQ912. PQ912 treatment for 18 weeks caused a significant reduction (approximately 30%) in brain mHTT levels. These lowered mHTT levels were associated with reduced levels of the inflammation/gliosis marker GFAP-protein, a striking normalization of the abnormal body weight gain and energy metabolism as well as a normalization of several mRNA levels coding for HSPs in BACHD mice at 24 weeks of age. Data were generated in collaboration with Stephan von Hörsten of the University Hospital Erlangen, part of Friedrich-Alexander-University (FAU), Erlangen, Germany. Invitation to Probiodrug`s Ordinary General Meeting of Shareholders on 13 June 2017 On 03 May 2017 Probiodrug invited its shareholders to its ordinary general meeting of shareholders to be held on Tuesday, 13 June 2017 at 11:00 am (CEST), at the Mercure Hotel MOA Berlin, Stephanstraße 41, 10559 Berlin, Germany. The relevant documents can be found at http://www.probiodrug.de/investors/annual-shareholders-meeting-2017/. For more information, please contact: Notes to Editors: About Probiodrug AG Headquartered in Halle (Saale), Germany, Probiodrug AG (Euronext Amsterdam: PBD) is a biopharmaceutical company focused on the development of new therapeutic products for the treatment of Alzheimer's disease. Founded in 1997, the company successfully developed a novel therapeutic concept for diabetes - the DP4 inhibitors - which provided the basis for a novel class of antidiabetics - the gliptins. Its core capabilities are based on its long-standing expertise in the elucidation of the structure and function of enzymes involved in the modification of proteins and peptides, which play a central role in pathological conditions. Today Probiodrug's aim is to become a leading company in the development of Alzheimer's disease treatments and to thereby provide a better life for Alzheimer's disease patients. It has identified a new therapeutic concept linked to disease initiation and progression. The development approaches are targeting pyroglutamate-Abeta (pGlu-Abeta) as a therapeutic strategy to fight Alzheimer's disease. The Company has medical use and composition of matter patents related to the inhibition of Glutaminyl Cyclase (QC) and anti-pGlu-Abeta- specific monoclonal antibodies, providing it, in the Company's view, with a leading position in this field of research. Probiodrug's lead product candidate, PQ912, is a highly specific and potent inhibitor of Glutaminyl Cyclase (QC), which has shown therapeutic effects in Alzheimer's animal models. PQ912 is currently in a Phase 2a study, the SAPHIR trial. In a preceding Phase 1 study with healthy young and elderly volunteers, PQ912 has shown to be safe and well tolerated and also revealed high QC-inhibition. About Alzheimer's disease Alzheimer's disease is a neurological disorder, which is the most common form of dementia, and ultimately leads to death. Because Alzheimer's disease cannot be cured and is degenerative, the affected patients must increasingly rely on others for assistance. . Today, 47 million people live with dementia worldwide, and this number is projected to treble to more than 131 million by 2050, as populations age. Dementia also has a huge economic impact. Alzheimer's has an estimated, global societal cost of US$ 818 billion, and it will become a trillion dollar disease by 2018. (World Alzheimer Report 2016). Forward Looking Statements Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgment of Probiodrug AG as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.


News Article | May 12, 2017
Site: globenewswire.com

HALLE (SAALE), Germany, 12 May 2017 - Probiodrug AG (Euronext Amsterdam: PBD), a biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer's disease (AD), today announces its first quarter business update for the period ending 31 March 2017, in the form of an interim management report. The interim management report for the first quarter 2017 is available for download on the company website (http://www.probiodrug.de/investors/reports-and-presentations/). Commenting on the first quarter, Dr Konrad Glund, Chief Executive Officer of Probiodrug, said: "In the first quarter of 2017 we successfully continued to execute on our corporate strategy. The Last Patient Last Visit (LPLV) represents an important step towards the conclusion of our first patient trial with PQ912. The promising data obtained with PQ912 and PBD-C06 in AD animal models further demonstrates the potential of the pGlu-Abeta treatment concept. Positive treatment results with PQ912 in a Huntington's disease animal model provide support for evaluating PQ912 in patients with Huntington`s disease (HD) in the future, another neurological disease based on misfolded proteins." Pipeline update Probiodrug`s therapeutic approach targets pyroglutamate-Abeta (pGlu-Abeta, also called N3pG Abeta) as a therapeutic strategy to fight Alzheimer's disease. This modified Abeta is considered to be linked with disease initiation and progression by seeding the formation of soluble neurotoxic amyloid oligomers. Probiodrug is developing proprietary product candidates to target toxic pGlu-Abeta via two modes of action: by (i) inhibiting the production of pGlu-Abeta; and (ii) clearing existing pGlu-Abeta from the brain. Probiodrug's innovative approach is based on the development of specific inhibitors for the enzyme Glutaminyl Cyclase (QC), which is instrumental in the creation of pGlu-Abeta. In addition, the company is developing a monoclonal antibody targeting pGlu-Abeta to enhance its clearance. To date, Probiodrug's pipeline consists of two small molecule inhibitors of the QC-enzyme, PQ912 and PQ1565, and a monoclonal antibody, PBD-C06, targeting pGlu-Abeta. PQ912 Probiodrug is running a Phase 2a trial, the "SAPHIR" study, of its lead product candidate PQ912. In a preceding Phase 1 study with healthy young and elderly volunteers, PQ912 was shown to be safe and well tolerated and revealed high QC-inhibition. PQ912 is the first QC-inhibitor being tested in patients. The Phase 2a study is a randomized, double-blind multi-center study which plans to enrol a total of 110 patients with early stage Alzheimer's disease. The study is led by internationally renowned experts in AD in seven European countries at 21 sites, with the Alzheimer Center, VU Medical Center (VUmc), Amsterdam being the lead center. The primary endpoint of the trial is the safety and tolerability of PQ912 compared with placebo over a three-month treatment period. Additionally, a set of exploratory read-outs comprising cognitive tests, functional assessments by EEG and functional MRI and new molecular biomarkers in CSF will be used to evaluate the compound's effect on the pathology of the disease. In this study Mini-Mental State Examination (MMSE) and the Cogstate neuro-psychological test battery (NTB) are monitored blindly every 30 patients to ensure consistency and reliability of ratings. First blinded results at baseline show that the mean MMSE scores from the 120 randomised patients is 25.3, the mean age is 73 years and gender distribution is 64 female and 56 male. Current results indicate a low variability and therefore the high quality of the assessments being used. Recruitment has been completed in mid-December 2016. A total of 120 patients have been randomised, surpassing the 110 patients planned in the study protocol. Full unblinded results of the SAPHIR study are expected in the second quarter of 2017. PBD-C06 PBD-C06 is a monoclonal antibody, currently in preclinical stage. PBD-C06 targets pGlu-Abeta, aiming to selectively clear the brain of pGlu-Abeta while leaving non-toxic forms of Abeta untouched. PBD-C06 has been successfully humanized and also de-immunized to avoid detection by the patient's endogenous immune system. For the first time for an anti-pGlu-Abeta approach PBD-C06 has not only shown the ability to reduce Abeta/plaques but also to significantly improve cognitive deficits in aged Alzheimer's mice. Moreover, no evidence was found of increased microhemorrhages after treatment with PBD-C06. The development of the manufacturing process of this molecule is running. PQ1565 PQ1565 is a QC-inhibitor, currently in preclinical stage. The product candidate has shown attractive drug-like properties in preclinical studies. The GMP process for this molecule is being implemented. The next development steps are in preparation and respective decisions would be made in connection with the readout of the SAPHIR trial. New promising results from pharmacological studies with PQ912 and PBD-C06 in AD animal models and an evaluation of new biomarkers in cerebrospinal fluid (CSF) from AD patients presented Three updates on the advancement of its product candidates and the results of a Biomarker research collaboration have been presented at the 13th International Conference on Alzheimer's and Parkinson's Diseases (AD/PDTM 2017), Vienna, Austria. The conference took place from 29th March to 2nd April 2017. Financials The first quarter of 2017 showed an increase of research and development expenses to EUR 2,268k compared to EUR 1,974k in the first quarter of 2016, reflecting mainly the costs for the Phase 2 trial (SAPHIR Study) of PQ912. General and administrative expenses amounted to EUR 507k compared to EUR 597k in the first quarter of 2016, reflecting more intrayear shifts than actual savings. In the first quarter 2017 the Company has not generated any revenues, also in line with the corporate planning. Correspondingly, the comprehensive loss of the reporting period was EUR 2,798k, compared to EUR 2,596k in the first quarter of 2016. All results are in line with management expectations. Probiodrug held EUR 18.7 million in cash and cash equivalents as of 31 March 2017. Last Patient Last Visit (LPLV) accomplished in the SAPHIR Study On 07 April 2017 Probiodrug announced that the Last Patient's Last Visit (LPLV) occurred on 05 April 2017 in the currently running Phase 2a SAPHIR study investigating the QC-inhibitor PQ912. PQ912 demonstrates beneficial effects in a preclinical Huntington`s disease model On 10 April 2017 Probiodrug announced results of a preclinical study targeting Glutaminyl Cyclases (QCs) in Huntington`s disease (HD). The results have been presented at the 12th Annual HD Therapeutics Conference of the CHDI Foundation on 23rd of April in St. Julian's, Malta. HD is the most common inherited neurodegenerative disorder where, due to a mutation, the poly-glutamine amino acid sequence is expanded in a protein called huntingtin (HTT). There is currently no disease modifying therapy for this condition. PQ912 clearly improved several signs of the disease in a well characterized BACHD mouse model of HD. BACHD mice carry the human gene for mutant HTT (mHTT). At six weeks old, parallel to the onset of first behavioral, metabolic and neuropathological signs of the disease, the BACHD mice were treated for 18 weeks with food pellets containing PQ912. PQ912 treatment for 18 weeks caused a significant reduction (approximately 30%) in brain mHTT levels. These lowered mHTT levels were associated with reduced levels of the inflammation/gliosis marker GFAP-protein, a striking normalization of the abnormal body weight gain and energy metabolism as well as a normalization of several mRNA levels coding for HSPs in BACHD mice at 24 weeks of age. Data were generated in collaboration with Stephan von Hörsten of the University Hospital Erlangen, part of Friedrich-Alexander-University (FAU), Erlangen, Germany. Invitation to Probiodrug`s Ordinary General Meeting of Shareholders on 13 June 2017 On 03 May 2017 Probiodrug invited its shareholders to its ordinary general meeting of shareholders to be held on Tuesday, 13 June 2017 at 11:00 am (CEST), at the Mercure Hotel MOA Berlin, Stephanstraße 41, 10559 Berlin, Germany. The relevant documents can be found at http://www.probiodrug.de/investors/annual-shareholders-meeting-2017/. For more information, please contact: Notes to Editors: About Probiodrug AG Headquartered in Halle (Saale), Germany, Probiodrug AG (Euronext Amsterdam: PBD) is a biopharmaceutical company focused on the development of new therapeutic products for the treatment of Alzheimer's disease. Founded in 1997, the company successfully developed a novel therapeutic concept for diabetes - the DP4 inhibitors - which provided the basis for a novel class of antidiabetics - the gliptins. Its core capabilities are based on its long-standing expertise in the elucidation of the structure and function of enzymes involved in the modification of proteins and peptides, which play a central role in pathological conditions. Today Probiodrug's aim is to become a leading company in the development of Alzheimer's disease treatments and to thereby provide a better life for Alzheimer's disease patients. It has identified a new therapeutic concept linked to disease initiation and progression. The development approaches are targeting pyroglutamate-Abeta (pGlu-Abeta) as a therapeutic strategy to fight Alzheimer's disease. The Company has medical use and composition of matter patents related to the inhibition of Glutaminyl Cyclase (QC) and anti-pGlu-Abeta- specific monoclonal antibodies, providing it, in the Company's view, with a leading position in this field of research. Probiodrug's lead product candidate, PQ912, is a highly specific and potent inhibitor of Glutaminyl Cyclase (QC), which has shown therapeutic effects in Alzheimer's animal models. PQ912 is currently in a Phase 2a study, the SAPHIR trial. In a preceding Phase 1 study with healthy young and elderly volunteers, PQ912 has shown to be safe and well tolerated and also revealed high QC-inhibition. About Alzheimer's disease Alzheimer's disease is a neurological disorder, which is the most common form of dementia, and ultimately leads to death. Because Alzheimer's disease cannot be cured and is degenerative, the affected patients must increasingly rely on others for assistance. . Today, 47 million people live with dementia worldwide, and this number is projected to treble to more than 131 million by 2050, as populations age. Dementia also has a huge economic impact. Alzheimer's has an estimated, global societal cost of US$ 818 billion, and it will become a trillion dollar disease by 2018. (World Alzheimer Report 2016). Forward Looking Statements Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgment of Probiodrug AG as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.


Zonneveld H.I.,Alzheimer Center | Goos J.D.C.,Neurology | Wattjes M.P.,Alzheimer Center | Prins N.D.,Neurology | And 5 more authors.
Neurology | Year: 2014

Objective: To determine prevalence, topography, and severity of cortical superficial siderosis (SS), a recently recognized manifestation of cerebral amyloid angiopathy, and its possible association with Alzheimer disease (AD) in a memory clinic patient cohort. Methods: We included 809 patients (56% men, aged 66 6 10 years) from the Amsterdam Dementia Cohort between November 2010 and November 2012 scanned on a 3-tesla MRI system. We analyzed prevalence and topography of cortical SS according to demographic, clinical, and MRI data. Agreement for SS detection between 2 neuroradiologists was calculated by using Cohen k. Results: Agreement for detection of SS was excellent (unweighted k of 0.81). In 17 patients (2.1%), cortical SS was found without a known cause. The prevalence of idiopathic SS differed according to diagnostic groups (p , 0.001): nearly 5% (95% confidence interval [CI] 2.8%- 8.2%) in patients with AD (n 5 168) vs 2% (95%CI 0.7%-6.0%) in patients with mild cognitive impairment (n 5 143) and 2.5% (95% CI 0.7%-8.7%) in other types of dementia (n 5 80). By contrast, SS was not found in patients with subjective complaints (n 5 168) or in those with other disorders (n5157). Presence of SS was associated with APOE e4, microbleeds, and white matter hyperintensities (all p , 0.05) independent of diagnosis. Conclusion: The prevalence of cortical SS in a memory clinic setting is higher than reported in the general population but lower than reported in cerebral amyloid angiopathy. The relatively high prevalence of SS in AD suggests that SS is a relevant radiologic manifestation of amyloid pathology in AD. Presence of SS does not seem to predict severity of AD. Further longitudinal research is needed to investigate clinical relevance.


Van Der Vlies A.E.,Alzheimer Center | Goos J.D.C.,Alzheimer Center | Barkhof F.,Image Analysis Center and Alzheimer Center | Scheltens P.,Alzheimer Center | And 2 more authors.
Neurology | Year: 2012

Objective: To investigate the relationship between brain microbleeds (MBs) and the rate of cognitive decline in Alzheimer disease (AD). Methods: In this cohort study, we studied 221 patients with AD with available baseline MRI scans (1.0 or 1.5 T) and at least 2 Mini-Mental State Examinations (MMSE) scores obtained more than 1 year apart from our memory clinic. Mean ± SD follow-up time was 3 ± 1 years, and patients had a median of 4 MMSE scores (range 2-17). We used linear mixed models with sex and age as covariates to investigate whether MBs influenced the rate of cognitive decline. Results: Mean age was 68 ± 9 years, 109 (49%) patients were female, and the baseline MMSE score was 22 ± 4. There were 39 patients (18%) with MBs (median 2, range 1-27) and 182 without. Linear mixed models showed that overall patients declined 2 MMSE points per year. We found no association of the presence of MBs with baseline MMSE or change in MMSE. Adjustment for atrophy, white matter hyperintensities, lacunes, and vascular risk factors did not change the results nor did stratification for MB location, APOE ε4 carriership, or age at onset (≤65 years vs >65 years). Repeating the analyses with number of MBs as predictor rendered similar results. Conclusion: MBs did not influence the rate of cognitive decline in patients with AD. The formerly reported increased risk of mortality in patients with MBs seems not to be attributable to a steeper rate of decline per se but might be due to vascular events, including (hemorrhagic) stroke. Copyright © 2012 by AAN Enterprises, Inc.


Elias-Sonnenschein L.S.,Maastricht University | Bertram L.,Max Planck Institute for Molecular Genetics | Visser P.J.,Maastricht University | Visser P.J.,Alzheimer Center
Biomarkers in Medicine | Year: 2012

Alzheimers disease (AD) is a neurodegenerative disorder characterized by neuritic plaques (main constituent: -amyloid [A]) and neurofibrillary tangles (hyperphosphorylated tau protein) in the brain. Abnormalities in A and tau can be measured upon neuropathological examination, in cerebrospinal fluid or by PET. Etiologically, a growing body of evidence suggests that susceptibility to AD is genetically controlled. However, the precise nature of the underlying risk genes and their relation to AD biomarkers remains largely elusive. To this end, we performed a qualitative review of 17 studies (covering 47 polymorphisms in 26 genes) and investigated the potential relation between the most compelling AD risk genes and markers for A and tau in cerebrospinal fluid, PET imaging and neuropathological examination. Of all covered genes, only APOE and PICALM showed consistent effects on A but not on tau, while no obvious effects were observed for CLU, CR1, ACE, SORL and MAPT. © 2012 Future Medicine Ltd.


HALLE (SAALE), Germany,  8 December  2016 - Probiodrug AG (Euronext Amsterdam: PBD), a biopharmaceutical company developing novel therapeutic solutions to treat Alzheimer's disease (AD), announced today that the study design of the ongoing Phase IIa SAPHIR trial comparing PQ912 to placebo will be presented as a poster on Thursday, December 8, 2016 at the  9th Clinical Trials on Alzheimer's disease (CTAD) meeting in San Diego, USA. The SAPHIR study is a 3 month study in treatment naïve patients with early AD. PQ912 targets the inhibition of the Glutaminylcyclase (QC) resulting in a reduction of the production of neurotoxic pyroGlu-Abeta (pGlu-Abeta) and related oligomers. PQ912 has been extensively investigated in Phase 1 Multiple ascending dose studies (MAD) showing good tolerability and a dose dependent QC-inhibition in the spinal fluid. The SAPHIR study has been designed and is conducted in collaboration with Philip Scheltens, M.D., Ph.D., the VUmc Amsterdam (NL) and the CRO Julius Clinical ( NL). The primary objective of the SAPHIR study is to investigate the safety of PQ912 in the target population and the secondary objective is to assess the pharmacodynamic profile. The publication at CTAD reveals that the study applies a series of methodological innovations which in this combination has not been executed before in an early AD study. Specific in and exclusion criteria based on diagnostic biomarkers of Abeta and tau were required to be met by all patients to ensure a high confidence of the diagnosis of early AD. Mini-Mental State Examination (MMSE) and Cogstate test battery assessments at baseline are monitored blindly every 30 patients to ensure consistency and reliability of ratings. A number of exploratory endpoints like EEG, fMRI and a series of CSF based biomarkers including QC-activity, pGlu-Abeta, Abeta oligomers, neurogranin as well as  inflammation markers are centrally analysed. Based on an exploratory analysis of 86 randomised patients, a low standard deviation for the Neuro-psychological test battery and functional EEG at baseline has been observed. Prof Philip Scheltens, Director of the Alzheimer Center at the VUmc  in Amsterdam and Chairman of the SAPHIR study, said: "The combination of in and exclusion criteria together with the primary and innovative exploratory outcome parameter in the SAPHIR study is unique for an early AD study. We are excited to see the full results in the second quarter of 2017." For more information, please contact: Notes to Editors: About Probiodrug AG Headquartered in Halle (Saale), Germany, Probiodrug AG (Euronext Amsterdam: PBD) is a biopharmaceutical company focused on the development of new therapeutic products for the treatment of Alzheimer's disease. Founded in 1997, the company successfully developed a novel therapeutic concept for diabetes - the DP4 inhibitors - which provided the basis for a novel class of antidiabetics - the gliptins. Its core capabilities are based on its long-standing expertise in the elucidation of the structure and function of enzymes involved in the modification of proteins and peptides, which play a central role in pathological conditions. Today Probiodrug's aim is to become a leading company in the development of Alzheimer's disease treatments and to thereby provide a better life for Alzheimer's disease patients. It has identified a new therapeutic concept linked to disease initiation and progression. The development approaches are targeting pyroglutamate-Abeta (pGlu-Abeta) as a therapeutic strategy to fight Alzheimer's disease. The Company has medical use and composition of matter patents related to the inhibition of Glutaminyl Cyclase (QC) and anti-pGlu-Abeta- specific monoclonal antibodies, providing it, in the Company's view, with a leading position in this field of research. Probiodrug's lead product candidate, PQ912, is a highly specific and potent inhibitor of Glutaminyl Cyclase (QC), which has shown therapeutic effects in Alzheimer's animal models. PQ912 is currently in a Phase 2a study, the SAPHIR trial. In a preceding Phase 1 study with healthy young and elderly volunteers, PQ912 has shown to be safe and well tolerated and also revealed high QC-inhibition. About Alzheimer's disease Alzheimer's disease is a neurological disorder, which is the most common form of dementia, and ultimately leads to death. Because Alzheimer's disease cannot be cured and is degenerative, the affected patients must increasingly rely on others for assistance. . Today, 47 million people live with dementia worldwide, and this number is projected to treble to more than 131 million by 2050, as populations age. Dementia also has a huge economic impact. Alzheimer's has an estimated, global societal cost of US$ 818 billion, and it will become a trillion dollar disease by 2018. (World Alzheimer Report 2016). Forward Looking Statements Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgment of Probiodrug AG as of the date of this press release. Such forward-looking statements are neither promises nor guarantees, but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.


Fiala M.,University of California at Los Angeles | Veerhuis R.,Alzheimer Center
Experimental Gerontology | Year: 2010

The ultimate goal of diagnostic research is a blood test detecting the risk of Alzheimer disease (AD) before neuronal damage develops. Current amyloid-β (Aβ) tests do not detect the process leading to neurodegeneration. Novel immunologic and proteomics tests are based on aberrant appearance of inflammatory cytokines in the CSF and other protein biomarkers in the CSF or blood, and immune biomarkers of peripheral blood mononuclear cells (PBMC's). Cytokines, chemokines, complement factors, serum amyloid P component, and signaling proteins in the CSF or blood may be a rich source of diagnostic biomarkers, but the power of these tests will need to be examined in prospective studies. Recently-described flow cytometric test of defective Aβ phagocytosis detects patients with AD with a high sensitivity and specificity in distinct populations (confirmed AD patients vs. active University professors), but further experience is necessary for its use in general population at risk of AD. The analysis of the transcriptome of peripheral blood mononuclear cells "stressed" by Aβ is beginning to unravel the relations between specific pathways and AD. Thus novel diagnostic tests may provide biomarkers for pre-clinical detection, clarification of progression from MCI to AD, and follow-up of patients in clinical trials of immunostimulating therapies. © 2009 Elsevier Inc. All rights reserved.


Bertens D.,Alzheimer Center | Scheltens P.,Alzheimer Center | Visser P.J.,Alzheimer Center | Visser P.J.,Maastricht University
Alzheimer's and Dementia | Year: 2015

Background We investigated the pattern of disease progression in the asymptomatic, mild cognitive impairment (MCI), and dementia stage of Alzheimer's disease (AD). Methods We selected 284 subjects with AD pathology, defined as abnormal levels of amyloid beta 1-42 (Aβ1-42) in cerebrospinal fluid (CSF). Disease outcome measures included six biomarkers and five cognitive markers. We compared differences in baseline measures and decline over 4 years between the AD stages and tested whether these changes differed from subjects, without AD pathology (N = 132). Results CSF Aβ1-42 reached the maximum abnormality level in the asymptomatic stage and tau in the MCI stage. The imaging and cognitive markers started to decline in the asymptomatic stage, and decline accelerated with advancing clinical stage. Conclusion This study provides further evidence for a temporal evolution of AD biomarkers. Our findings may be helpful to determine stage specific outcome measures for clinical trials. © 2015 The Alzheimer's Association.


Perez G.,Technical University of Ambato | Perez G.,Rey Juan Carlos University | Conci A.,Federal University of Fluminense | Moreno A.B.,Rey Juan Carlos University | Hernandez-Tamames J.A.,Alzheimer Center
Integrated Computer-Aided Engineering | Year: 2014

Preprocessing stage for denoising is a crucial task in image analysis in general, and in computer-aided diagnosis using medical images in particular. Standard acquisition of Magnetic Resonance Images (MRI) presents statistical Rician noise which degrades the performance of the image analysis. This paper presents a new technique to reduce Rician noise of brain MRI. The new method for noise filtering is achieved in the discrete Wavelet Packets Transform (WPT) domain. Four methodologies for thresholding the detail coefficients in the same 2D WPT domain have been experimented considering two scenarios (with and without a previous adaptive Wiener filtering in the spatial domain). Best quantitative and qualitative results have been obtained by the new method presented in this work (specifically tailored for brain MRI), which is adaptive to each subband and dependent on the data. It has been compared with other traditional methods considering the Signal to Noise Ratio (SNR), Normalized Cross Correlation (NCC) and execution time ( 0.1 s/slice). A complete dataset of structural (T1-w) brain MRI of the BrainWeb database has been used for experiments. An important aspect is that these experiments with synthetic images proved that the common prior adaptive Wiener filtering often used by many authors is a dispensable procedure. © 2014 IOS Press.

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