Nonprofit foundations spur translational research

Every year, hundreds of promising basic discoveries in the pharmacological field are lost and will never have a chance to be exploited for patients due to difficulties in clinical translation. This is especially true for most neurodegenerative disorders lacking disease-modifying therapies. Here we present the current scenario and our vision of a ‘collective-impact’ multistakeholder approach to expedite the development of new drugs. Every year, hundreds of promising basic discoveries in the pharmacological field are lost and will never have a chance to be exploited for patients due to difficulties in clinical translation. This is especially true for most neurodegenerative disorders lacking disease-modifying therapies. Here we present the current scenario and our vision of a ‘collective-impact’ multistakeholder approach to expedite the development of new drugs. Call to action: patients need new therapiesDespite progress in innovative therapies for several human diseases, approaches to mental and neurological disorders remain comparatively disappointing. In Europe, the burden of brain disorders was €798 billion in 2010 [1Olesen J. et al.The economic cost of brain disorders in Europe.Eur. J. Neurol. 2012; 19: 155-162Crossref PubMed Scopus (993) Google Scholar]. Other Western countries such as the USA, Canada, and Japan face similar challenges. In this scenario, the market for drugs is enormous. However, for the degenerative forms of these disorders, such as Alzheimer's and Parkinson's diseases, and progressive multiple sclerosis (MS), no disease-modifying drugs are yet available. One reason is that, in this area, R&D tools are mostly unproven. These include: (i) predictive experimental disease models; (ii) markers to assess the activity of drug candidates on targets; (iii) surrogate measures and biomarkers to detect disease initiation and progression; and (iv) sensitive and robust clinical measurements. Drug developers must make large bets on putative drug targets and perform clinical trials before knowing whether their faith has been well placed. Because of this (and because of the intrinsic chronic features of these diseases), clinical trials have been extraordinarily expensive and often unsuccessful. In the past 10–15 years, pharmaceutical companies (Pharma) have concentrated efforts and investments mainly on less risky ‘low-hanging fruits’, contributing to the so-called ‘innovation crisis’ [2Bartek R.J. Foundation–industry relationships – a new business model joint-venture philanthropy in therapy development.Curr. Top. Med. Chem. 2014; 14: 313-318Crossref PubMed Scopus (8) Google Scholar, 3Dollery C.T. Lost in Translation (LiT): IUPHAR Review 6.Br. J. Pharmacol. 2014; 171: 2269-2290Crossref PubMed Scopus (6) Google Scholar]. To meet the challenge, it is mandatory to revitalize innovation and become far more effective in building relationships along the entire drug-discovery and -development pathway with all involved stakeholders including, academia, government and regulatory agencies, patient and health foundations, biotechnological companies (Biotechs), and Pharma [2Bartek R.J. Foundation–industry relationships – a new business model joint-venture philanthropy in therapy development.Curr. Top. Med. Chem. 2014; 14: 313-318Crossref PubMed Scopus (8) Google Scholar].New companies and academia as sources of innovationStarting in the 1990s, Biotechs based on innovative ideas mostly coming from academia started developing drugs for still-unmet medical needs. Of 252 new drugs approved by the FDA between 1998 and 2007, about half came from Biotechs or academia [4Kneller R. The importance of new companies for drug discovery: origins of a decade of new drugs.Nat. Rev. Drug Discov. 2010; 9: 867-882Crossref PubMed Scopus (191) Google Scholar]. Now, due to diminished early-stage venture capital for Biotechs and reduced public funding to academia, these two actors do not often have the required resources to sustain innovation. Moreover, due to growing early-stage research costs, Pharma and venture capitalists have started focusing on the late, Phase II/III stages of clinical research [3Dollery C.T. Lost in Translation (LiT): IUPHAR Review 6.Br. J. Pharmacol. 2014; 171: 2269-2290Crossref PubMed Scopus (6) Google Scholar]. As a consequence, a translational gap, often referred to as the ‘Valley of Death’ [5Finkbeiner S. Bridging the Valley of Death of therapeutics for neurodegeneration.Nat. Med. 2010; 16: 1227-1232Crossref PubMed Scopus (40) Google Scholar], appears between Pharma on the one hand, waiting for de-risked programs, and Biotechs/academia on the other hand, doing all they can to move their programs across the Valley.How to fill the translational gap: the role of foundationsTo foster the discovery of new therapies, nonprofit health organizations and patient foundations have taken a growing role in intervening at distinct levels in the R&D process. For example, health and patient foundations have often represented a major funding source for disease-specific basic research [2Bartek R.J. Foundation–industry relationships – a new business model joint-venture philanthropy in therapy development.Curr. Top. Med. Chem. 2014; 14: 313-318Crossref PubMed Scopus (8) Google Scholar]. In 2012 alone, patient and health foundations distributed approximately US$1.5 billion in the UK and USA ([6de Vrueh R.L. et al.Deal watch: roles and strategies for health foundations in public–private partnerships.Nat. Rev. Drug Discov. 2014; 13: 406Crossref PubMed Scopus (5) Google Scholar], see Table S2). This has represented a meritorious mechanism to keep innovation alive, as reflected by increasing numbers of high-impact-factor breakthrough publications on disease-related basic research. For example, the Italian MS Society (AISM), through its foundation (FISM, http://www.aism.it/index.aspx?codpage=intro_aism_fism_eng) has long been investing in research (€47.4 million in the past 24 years). In 2013, €6.3 million devoted to research of excellence in MS has publications with a of to foundations have a In diseases, a research has a new for and clinical development To this in a similar to the of for example, the for and in Pharmacol. PubMed Scopus Google patient organizations for neurodegenerative have funding to from to the human clinical trials for example, et the multiple sclerosis from the Society on 2012; PubMed Scopus Google Scholar, for progressive multiple 19: PubMed Scopus Google Scholar, R.J. et a research for progressive multiple the on 2012; PubMed Scopus Google have started building on the development of for and a and often drug-discovery such as and and nonprofit can with the translational to meet for a and and to be for tools such as For example, the have the and the with a to of major patient foundations have become in the clinical research by and clinical for their et the multiple sclerosis from the Society on 2012; PubMed Scopus Google Scholar]. of such foundations and efforts by the MS Society as well as the of the J. and Alzheimer's Drug the translational can be by and efforts all In multistakeholder from a to new therapies for However, stakeholders have mostly as through a to discoveries are to Biotechs or to Pharma In this scenario, to fill the translational gap, health and patient foundations have started strategies by increasing in and and by about the are Vrueh R.L. et al.Deal watch: roles and strategies for health foundations in public–private partnerships.Nat. Rev. Drug Discov. 2014; 13: 406Crossref PubMed Scopus (5) Google model is by to to this the for is and foundations this model a more role in and The and of the model in the of health research patient is Vrueh R.L. et al.Deal watch: roles and strategies for health foundations in public–private partnerships.Nat. Rev. Drug Discov. 2014; 13: 406Crossref PubMed Scopus (5) Google as in our this to keep innovation in disease-related the foundations are the by research a more role in This has been to Biotechs on the and clinical development of and to make more for Pharma and to the clinical development of therapies approach is on with other funding in research and resources to and and the of research are and In our this model has started the translational and and new clinical for et the multiple sclerosis from the Society on 2012; PubMed Scopus Google with the is to several foundations are involved in and in with other stakeholders In Europe, a of a multistakeholder is the as of the will public patient and regulatory with the of the to the patient at the for in is a disease and the most of neurological in The disease with a and to a progressive by the of major progress has been in for progressive multiple 19: PubMed Scopus Google Scholar], for progressive MS comparatively disappointing. on this a was by and from several MS to expedite the development of disease-modifying therapies R.J. et a research for progressive multiple the on 2012; PubMed Scopus Google Scholar]. this is a of a multistakeholder For the the MS is the and MS organizations to to make in progressive In through patients are the MS to and to resources the of the development of new therapies for the million with progressive is all of the in innovative and has long been investing in research through of progressive MS and research this is by of are at of brain its in et al.The as a new J. PubMed Scopus Google Scholar, et al.The is a of brain and a new for brain PubMed Scopus Google Scholar]. and biotechnological a role in is to the In and by pharmacological in to be in MS et of new for a promising for neurodegenerative PubMed Scopus Google Scholar]. is with academia in a multistakeholder model to with the multistakeholder most multistakeholder have of and to true of efforts and of To multistakeholder will have to be by a in has its of with the of developing effective therapies for patients In this model stakeholders will a and approach on and a the of the are for (i) (ii) to (iii) (iv) and and a with in and in and the entire and J. Rev. 9: Scholar, et the Med. J. 2012; Google this model is and it a and has several one of is the of is to to However, well as be one of the of is on the of the process. Moreover, to must be about its and and its the process. not and is and J. Rev. 9: with all we have to be and that, to the for breakthrough the model and Call to action: patients need new therapiesDespite progress in innovative therapies for several human diseases, approaches to mental and neurological disorders remain comparatively disappointing. In Europe, the burden of brain disorders was €798 billion in 2010 [1Olesen J. et al.The economic cost of brain disorders in Europe.Eur. J. Neurol. 2012; 19: 155-162Crossref PubMed Scopus (993) Google Scholar]. Other Western countries such as the USA, Canada, and Japan face similar challenges. In this scenario, the market for drugs is enormous. However, for the degenerative forms of these disorders, such as Alzheimer's and Parkinson's diseases, and progressive multiple sclerosis (MS), no disease-modifying drugs are yet available. One reason is that, in this area, R&D tools are mostly unproven. These include: (i) predictive experimental disease models; (ii) markers to assess the activity of drug candidates on targets; (iii) surrogate measures and biomarkers to detect disease initiation and progression; and (iv) sensitive and robust clinical measurements. Drug developers must make large bets on putative drug targets and perform clinical trials before knowing whether their faith has been well placed. Because of this (and because of the intrinsic chronic features of these diseases), clinical trials have been extraordinarily expensive and often unsuccessful. In the past 10–15 years, pharmaceutical companies (Pharma) have concentrated efforts and investments mainly on less risky ‘low-hanging fruits’, contributing to the so-called ‘innovation crisis’ [2Bartek R.J. Foundation–industry relationships – a new business model joint-venture philanthropy in therapy development.Curr. Top. Med. Chem. 2014; 14: 313-318Crossref PubMed Scopus (8) Google Scholar, 3Dollery C.T. Lost in Translation (LiT): IUPHAR Review 6.Br. J. Pharmacol. 2014; 171: 2269-2290Crossref PubMed Scopus (6) Google Scholar]. To meet the challenge, it is mandatory to revitalize innovation and become far more effective in building relationships along the entire drug-discovery and -development pathway with all involved stakeholders including, academia, government and regulatory agencies, patient and health foundations, biotechnological companies (Biotechs), and Pharma [2Bartek R.J. Foundation–industry relationships – a new business model joint-venture philanthropy in therapy development.Curr. Top. Med. Chem. 2014; 14: 313-318Crossref PubMed Scopus (8) Google Scholar]. progress in innovative therapies for several human diseases, approaches to mental and neurological disorders remain comparatively disappointing. In Europe, the burden of brain disorders was €798 billion in 2010 [1Olesen J. et al.The economic cost of brain disorders in Europe.Eur. J. Neurol. 2012; 19: 155-162Crossref PubMed Scopus (993) Google Scholar]. Other Western countries such as the USA, Canada, and Japan face similar challenges. In this scenario, the market for drugs is enormous. However, for the degenerative forms of these disorders, such as Alzheimer's and Parkinson's diseases, and progressive multiple sclerosis (MS), no disease-modifying drugs are yet available. One reason is that, in this area, R&D tools are mostly unproven. These include: (i) predictive experimental disease models; (ii) markers to assess the activity of drug candidates on targets; (iii) surrogate measures and biomarkers to detect disease initiation and progression; and (iv) sensitive and robust clinical measurements. Drug developers must make large bets on putative drug targets and perform clinical trials before knowing whether their faith has been well placed. Because of this (and because of the intrinsic chronic features of these diseases), clinical trials have been extraordinarily expensive and often unsuccessful. In the past 10–15 years, pharmaceutical companies (Pharma) have concentrated efforts and investments mainly on less risky ‘low-hanging fruits’, contributing to the so-called ‘innovation crisis’ [2Bartek R.J. Foundation–industry relationships – a new business model joint-venture philanthropy in therapy development.Curr. Top. Med. Chem. 2014; 14: 313-318Crossref PubMed Scopus (8) Google Scholar, 3Dollery C.T. Lost in Translation (LiT): IUPHAR Review 6.Br. J. Pharmacol. 2014; 171: 2269-2290Crossref PubMed Scopus (6) Google Scholar]. To meet the challenge, it is mandatory to revitalize innovation and become far more effective in building relationships along the entire drug-discovery and -development pathway with all involved stakeholders including, academia, government and regulatory agencies, patient and health foundations, biotechnological companies (Biotechs), and Pharma [2Bartek R.J. Foundation–industry relationships – a new business model joint-venture philanthropy in therapy development.Curr. Top. Med. Chem. 2014; 14: 313-318Crossref PubMed Scopus (8) Google Scholar]. companies and academia as sources of innovationStarting in the 1990s, Biotechs based on innovative ideas mostly coming from academia started developing drugs for still-unmet medical needs. Of 252 new drugs approved by the FDA between 1998 and 2007, about half came from Biotechs or academia [4Kneller R. The importance of new companies for drug discovery: origins of a decade of new drugs.Nat. Rev. Drug Discov. 2010; 9: 867-882Crossref PubMed Scopus (191) Google Scholar]. Now, due to diminished early-stage venture capital for Biotechs and reduced public funding to academia, these two actors do not often have the required resources to sustain innovation. Moreover, due to growing early-stage research costs, Pharma and venture capitalists have started focusing on the late, Phase II/III stages of clinical research [3Dollery C.T. Lost in Translation (LiT): IUPHAR Review 6.Br. J. Pharmacol. 2014; 171: 2269-2290Crossref PubMed Scopus (6) Google Scholar]. As a consequence, a translational gap, often referred to as the ‘Valley of Death’ [5Finkbeiner S. Bridging the Valley of Death of therapeutics for neurodegeneration.Nat. Med. 2010; 16: 1227-1232Crossref PubMed Scopus (40) Google Scholar], appears between Pharma on the one hand, waiting for de-risked programs, and Biotechs/academia on the other hand, doing all they can to move their programs across the in the 1990s, Biotechs based on innovative ideas mostly coming from academia started developing drugs for still-unmet medical needs. Of 252 new drugs approved by the FDA between 1998 and 2007, about half came from Biotechs or academia [4Kneller R. The importance of new companies for drug discovery: origins of a decade of new drugs.Nat. Rev. Drug Discov. 2010; 9: 867-882Crossref PubMed Scopus (191) Google Scholar]. Now, due to diminished early-stage venture capital for Biotechs and reduced public funding to academia, these two actors do not often have the required resources to sustain innovation. Moreover, due to growing early-stage research costs, Pharma and venture capitalists have started focusing on the late, Phase II/III stages of clinical research [3Dollery C.T. Lost in Translation (LiT): IUPHAR Review 6.Br. J. Pharmacol. 2014; 171: 2269-2290Crossref PubMed Scopus (6) Google Scholar]. As a consequence, a translational gap, often referred to as the ‘Valley of Death’ [5Finkbeiner S. Bridging the Valley of Death of therapeutics for neurodegeneration.Nat. Med. 2010; 16: 1227-1232Crossref PubMed Scopus (40) Google Scholar], appears between Pharma on the one hand, waiting for de-risked programs, and Biotechs/academia on the other hand, doing all they can to move their programs across the to fill the translational gap: the role of foundationsTo foster the discovery of new therapies, nonprofit health organizations and patient foundations have taken a growing role in intervening at distinct levels in the R&D process. For example, health and patient foundations have often represented a major funding source for disease-specific basic research [2Bartek R.J. Foundation–industry relationships – a new business model joint-venture philanthropy in therapy development.Curr. Top. Med. Chem. 2014; 14: 313-318Crossref PubMed Scopus (8) Google Scholar]. In 2012 alone, patient and health foundations distributed approximately US$1.5 billion in the UK and USA ([6de Vrueh R.L. et al.Deal watch: roles and strategies for health foundations in public–private partnerships.Nat. Rev. Drug Discov. 2014; 13: 406Crossref PubMed Scopus (5) Google Scholar], see Table S2). This has represented a meritorious mechanism to keep innovation alive, as reflected by increasing numbers of high-impact-factor breakthrough publications on disease-related basic research. For example, the Italian MS Society (AISM), through its foundation (FISM, http://www.aism.it/index.aspx?codpage=intro_aism_fism_eng) has long been investing in research (€47.4 million in the past 24 years). In 2013, €6.3 million devoted to research of excellence in MS has publications with a of to foundations have a In diseases, a research has a new for and clinical development To this in a similar to the of for example, the for and in Pharmacol. PubMed Scopus Google patient organizations for neurodegenerative have funding to from to the human clinical trials for example, et the multiple sclerosis from the Society on 2012; PubMed Scopus Google Scholar, for progressive multiple 19: PubMed Scopus Google Scholar, R.J. et a research for progressive multiple the on 2012; PubMed Scopus Google have started building on the development of for and a and often drug-discovery such as and and nonprofit can with the translational to meet for a and and to be for tools such as For example, the have the and the with a to of major patient foundations have become in the clinical research by and clinical for their et the multiple sclerosis from the Society on 2012; PubMed Scopus Google Scholar]. of such foundations and efforts by the MS Society as well as the of the J. and Alzheimer's Drug To foster the discovery of new therapies, nonprofit health organizations and patient foundations have taken a growing role in intervening at distinct levels in the R&D process. For example, health and patient foundations have often represented a major funding source for disease-specific basic research [2Bartek R.J. Foundation–industry relationships – a new business model joint-venture philanthropy in therapy development.Curr. Top. Med. Chem. 2014; 14: 313-318Crossref PubMed Scopus (8) Google Scholar]. In 2012 alone, patient and health foundations distributed approximately US$1.5 billion in the UK and USA ([6de Vrueh R.L. et al.Deal watch: roles and strategies for health foundations in public–private partnerships.Nat. Rev. Drug Discov. 2014; 13: 406Crossref PubMed Scopus (5) Google Scholar], see Table S2). This has represented a meritorious mechanism to keep innovation alive, as reflected by increasing numbers of high-impact-factor breakthrough publications on disease-related basic research. For example, the Italian MS Society (AISM), through its foundation (FISM, http://www.aism.it/index.aspx?codpage=intro_aism_fism_eng) has long been investing in research (€47.4 million in the past 24 years). In 2013, €6.3 million devoted to research of excellence in MS has publications with a of to foundations have a In diseases, a research has a new for and clinical development To this in a similar to the of for example, the for and in Pharmacol. PubMed Scopus Google patient organizations for neurodegenerative have funding to from to the human clinical trials for example, et the multiple sclerosis from the Society on 2012; PubMed Scopus Google Scholar, for progressive multiple 19: PubMed Scopus Google Scholar, R.J. et a research for progressive multiple the on 2012; PubMed Scopus Google have started building on the development of for and a and often drug-discovery such as and and nonprofit can with the translational to meet for a and and to be for tools such as For example, the have the and the with a to of major patient foundations have become in the clinical research by and clinical for their et the multiple sclerosis from the Society on 2012; PubMed Scopus Google Scholar]. of such foundations and efforts by the MS Society as well as the of the J. and Alzheimer's Drug the translational can be by and efforts all In multistakeholder from a to new therapies for However, stakeholders have mostly as through a to discoveries are to Biotechs or to Pharma In this scenario, to fill the translational gap, health and patient foundations have started strategies by increasing in and and by about the are Vrueh R.L. et al.Deal watch: roles and strategies for health foundations in public–private partnerships.Nat. Rev. Drug Discov. 2014; 13: 406Crossref PubMed Scopus (5) Google model is by to to this the for is and foundations this model a more role in and The and of the model in the of health research patient is Vrueh R.L. et al.Deal watch: roles and strategies for health foundations in public–private partnerships.Nat. Rev. Drug Discov. 2014; 13: 406Crossref PubMed Scopus (5) Google as in our this to keep innovation in disease-related the foundations are the by research a more role in This has been to Biotechs on the and clinical development of and to make more for Pharma and to the clinical development of therapies approach is on with other funding in research and resources to and and the of research are and In our this model has started the translational and and new clinical for et the multiple sclerosis from the Society on 2012; PubMed Scopus Google with the is to several foundations are involved in and in with other stakeholders In Europe, a of a multistakeholder is the as of the will public patient and regulatory with the of the to the patient at the for the translational can be by and efforts all In multistakeholder from a to new therapies for However, stakeholders have mostly as through a to discoveries are to Biotechs or to Pharma In this scenario, to fill the translational gap, health and patient foundations have started strategies by increasing in and and by about the are Vrueh R.L. et al.Deal watch: roles and strategies for health foundations in public–private partnerships.Nat. Rev. Drug Discov. 2014; 13: 406Crossref PubMed Scopus (5) Google The model is by to to this the for is and foundations this model a more role in and The and of the model in the of health research patient is Vrueh R.L. et al.Deal watch: roles and strategies for health foundations in public–private partnerships.Nat. Rev. Drug Discov. 2014; 13: 406Crossref PubMed Scopus (5) Google as in our this to keep innovation in disease-related research. the foundations are the by research a more role in This has been to Biotechs on the and clinical development of and to make more for Pharma and to the clinical development of therapies The approach is on with other funding in research and resources to and and the of research are and In our this model has started the translational and and new clinical for et the multiple sclerosis from the Society on 2012; PubMed Scopus Google Scholar]. with the is to several foundations are involved in and in with other stakeholders In Europe, a of a multistakeholder is the as of the will public patient and regulatory with the of the to the patient at the for in is a disease and the most of neurological in The disease with a and to a progressive by the of major progress has been in for progressive multiple 19: PubMed Scopus Google Scholar], for progressive MS comparatively disappointing. on this a was by and from several MS to expedite the development of disease-modifying therapies R.J. et a research for progressive multiple the on 2012; PubMed Scopus Google Scholar]. this is a of a multistakeholder For the the MS is the and MS organizations to to make in progressive In through patients are the MS to and to resources the of the development of new therapies for the million with progressive is all of the in innovative and has long been investing in research through of progressive MS and research this is by of are at of brain its in et al.The as a new J. PubMed Scopus Google Scholar, et al.The is a of brain and a new for brain PubMed Scopus Google Scholar]. and biotechnological a role in is to the In and by pharmacological in to be in MS et of new for a promising for neurodegenerative PubMed Scopus Google Scholar]. is with academia in a multistakeholder model to with the MS is a disease and the most of neurological in The disease with a and to a progressive by the of major progress has been in for progressive multiple 19: PubMed Scopus Google Scholar], for progressive MS comparatively disappointing. on this a was by and from several MS to expedite the development of disease-modifying therapies R.J. et a research for progressive multiple the on 2012; PubMed Scopus Google Scholar]. this is a of a multistakeholder For the the MS is the and MS organizations to to make in progressive In through patients are the MS to and to resources the of the development of new therapies for the million with progressive is all of the in innovative and has long been investing in research through of progressive MS and research this is by of are at of brain its in et al.The as a new J. PubMed Scopus Google Scholar, et al.The is a of brain and a new for brain PubMed Scopus Google Scholar]. and biotechnological a role in is to the In and by pharmacological in to be in MS et of new for a promising for neurodegenerative PubMed Scopus Google Scholar]. is with academia in a multistakeholder model to with the The multistakeholder most multistakeholder have of and to true of efforts and of To multistakeholder will have to be by a in has its of with the of developing effective therapies for patients In this model stakeholders will a and approach on and a the of the are for (i) (ii) to (iii) (iv) and and a with in and in and the entire and J. Rev. 9: Scholar, et the Med. J. 2012; Google this model is and it a and has several one of is the of is to to However, well as be one of the of is on the of the process. Moreover, to must be about its and and its the process. not and is and J. Rev. 9: with all we have to be and that, to the for breakthrough the model and most multistakeholder have of and to true of efforts and of To multistakeholder will have to be by a in has its of with the of developing effective therapies for patients In this model stakeholders will a and approach on and a In the of the are for (i) (ii) to (iii) (iv) and and a with in and in and the entire and J. Rev. 9: Scholar, et the Med. J. 2012; Google Scholar]. this model is and it a and has several one of is the of is to to However, well as be one of the of is on the of the process. Moreover, to must be about its and and its the process. not and is and J. Rev. 9: Scholar]. with all we have to be and that, to the for breakthrough the model and The are to for and in to for in of and to and of for and on the

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