NEWS
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The Structural Genomics Consortium (SGC) public-private partnership has launched an open-source initiative to use human-derived cells to validate targets for new medicines. Academic researchers from at least five hospitals have joined the SGC, a not-for profit organization set up to support drug discovery. The partners have agreed to waive intellectual property (IP) rights to these preclinical assays developed to validate targets. The initiative pushes against the status quo in which drug discovery researchers typically carry out target validation work under a shroud of secrecy and heavy IP protection. By pooling patient-derived cells, chemical probes, clinical insight and industry expertise, participants aim to reduce redundant research projects and speed up the identification of disease-relevant targets. The Innovative Medicines Initiative (IMI) is contributing more than €40 ($43) million over five years to develop assays and chemical and antibody-based probes for autoimmune and inflammatory diseases, including ankylosing spondylitis, polymyositis and lupus. These projects will be run out of the Karolinska Institute and Karolinska University Hospital, in Stockholm, and the Oxford University Hospitals, in the UK. The Ontario Brain Institute and other funders are contributing resources towards developing assays for neuroscience indications, including Rett syndrome, amyotrophic lateral sclerosis and Parkinson’s, and oncology indications, including glioblastoma. These projects will be run at The Hospital for Sick Children and the University Health Network, both in Toronto, as well as the Montreal Neurological Institute and Hospital in Montreal. “It’s a different way of thinking about things. For some diseases, it may be a fabulous way to go,” says Peter Dirks, a neurosurgeon at The Hospital for Sick Children in Toronto, who is participating in the project. Under the new initiative, Dirks will characterize the phenotypes of tumor cells donated by patients with glioblastoma. By setting up open-access target-validation assays with these cells, he hopes to identify chemical probes that modulate the proliferative abilities and stem-cell likeness of the patient-derived cells. Because the SGC has extensively characterized the selectivity profile of its chemical probes, hits that come out of Dirks’ assays could point to potential drug targets. At the Montreal Neurological Institute and Hospital, another team of participat436
Dr Mark J Winter/ Science Source
© 2015 Nature America, Inc. All rights reserved.
Human cell assays for new medicines now open access
The Structural Genomics Consortium facilitates drug discovery by characterizing crystal structures of human proteins, such as alcohol dehydrogenase (pictured), and generating epigenetic chemical probes to be used as reagents.
ing researchers is taking a similar approach, developing phenotypic assays to validate targets for amyotrophic lateral sclerosis and Parkinson’s disease. For both neurodegenerative disorders, they will primarily use induced pluripotent stem cell methodologies to reprogram patient-derived skin cells into neurons. Clinical researchers will initially screen their assays with SGC’s library of epigenetic chemical probes. These probes have been generated by SGC as part of its remit to solve the structures of medically relevant proteins. So far, this precompetitive structural biology research initiative, which includes ten pharma partners, has generated 30 IP-free chemical probes with high potency and selectivity for chosen epigenetic targets for use in research (http://www.thesgc.org/ chemical-probes). SGC’s industry collaborators have nominated another 30 targets against which they would like the SGC to develop small-molecule and antibody probes for use in drug discovery. “We imagine a few hubs generating these chemical tools, and we will then fan them out to a network of hospitals to test them in different target-validation assays,” says Aled Edwards, director of the SGC in Toronto. By operating in an open-access manner, adds Edwards, researchers are able to side-
step the legal wrangling that otherwise delays or prevents the setup of their experiments. “The only way to get this done is to declare it an IP-free zone and do the science,” he says. Results will be put into the public domain as quickly as possible, and the clinical researchers will be encouraged to publish their findings in academic journals. Other public-private, academic and industry groups have also been working hard in recent years to make the most of academia’s target-validation capabilities. The Academic Drug Discovery Consortium, a network of 126 academic drug discovery centers that includes the SGC, for example, established a partnership with London-based AstraZeneca in 2014 to enable academics to access industry-caliber screening decks (in this case, AstraZeneca gets the right to license compounds and data that are generated from such screens). However, many industry researchers are skeptical of academic target validation owing to problems they have had replicating research findings (Nat. Rev. Drug Discov. 10, 643–644, 2011). The Montreal team eventually plans to hire ex-industry researchers to ensure the quality and caliber of their assays. But both academic and industry partners in the new projects also hope that regular interactions and engagement between sectors will address any
volume 33 NUMBER 5 MAY 2015 nature biotechnology
npg
© 2015 Nature America, Inc. All rights reserved.
news potential problems. “We really plan to work will then come to the fore. “The IP that we with them [clinical researchers] to design want comes from the molecule that we can assays that are robust and reproducible,” says then develop,” says Perros-Huguet. Although there is a risk that the IP-free Christelle Perros-Huguet, senior vice president of inflammation and immunology at approach will mean that academic researchNew York–based Pfizer. Pfizer is contributing ers or their institutions could lose out on to the IMI-funded autoimmune and inflam- revenue from assay licensing opportunities, matory research projects, along with Bayer of the research scientists who have signed up to Leverkusen, Germany, Janssen of Titusville, date do not see this as a major sacrifice. “Our hypothesis is that this open-access approach New Jersey and Novartis of Basel. Companies will tap into their own con- will lead to increased upfront funding,” siderable expertise developing cell-based says Guy Rouleau, director of the Montreal screening assays. At Novartis, already Neurological Institute and Hospital, who around 10% of primary screens involve is participating in the pilot project, adding patient-derived cells. For this reason, says that philanthropic and disease association Dhaval Patel, head of Novartis Institutes groups are very interested by the potential to for BioMedical Research Europe, based in accelerate drug discovery through the openBasel, the company can weigh in on what access approach. And the IP on academic assays may not have phenotypes to focus on, how to handle interpatient variability and how to design much realizable financial value, for the most high-throughput assays. In exchange, he is part, anyway. Only “a rather small percentage” of the screening assays that looking forward to seeing Novartis works with are results from assays that are licensed in from academic made up of patient-derived The next step groups anyway, says Patel. cells that could otherwise could be to Although industry be difficult and costly to get raise money to remains tight-lipped on access to. “That’s where I see specific molecular targets value for us,” says Patel, who run IP-free lead of interest, Edwards and his has represented Novartis at optimization colleagues at the SGC are SGC discussions. projects hopeful that they can push “I’m excited about this the precompetitive envebecause it is one of the few types of consortia that may be a win-win lope further. In 2011, they proposed the crefor both academia and industry,” adds Patel. ation of Arch2POCM, an industry-academia partnership that would see competitors work“This is a true collaboration.” Perros-Huguet says that Pfizer—and the ing together to take validated new targets even other industry partners—already have inter- into proof-of-concept trials in human patients nal lead-optimization programs running ((Nat. Biotechnol. 29, 298, 2011). This remains against many of the proteins that the SGC’s as yet a bridge too far, but the target validation probes target. “With better patient valida- projects are a step in that direction. The next tion, we will probably put even more effort step could be to raise money to run IP-free lead into the targets that we discover are the most optimization projects on a few of the chemirelevant for a disease.” Although drug devel- cal probes to generate drug candidates that are opers will have to compete with one another ready for clinical trials. “We are getting increon a level scientific playing field, compound mentally closer,” says Edwards. optimization and development capabilities Asher Mullard Ottawa, Ontario, Canada
“The biology of disease is an away game if there ever was one. The inner workings of cells and the ways that they work together are flat-out alien compared to anything we’ve ever built ourselves…. Expecting the sorts of behavior that you get from human-built technologies, and expecting the same effects from the techniques that work to optimize them, is an expensive accident waiting to happen.” Blogger Derek Lowe comments on the notion that health is “one app away.” (In the Pipeline, 2 April 2014)
“Some people are going to freak out about this. DNA and Facebook are two words that most people do not want to hear in the same sentence.” Michelle Meyer, of the Union Graduate College–Icahn School of Medicine at Mt. Sinai Bioethics Program, on a new Facebook app, Genes for Good, which has been set up by researchers at the University of Michigan, to recruit subjects for genetic studies. What could possibly go wrong? (BuzzFeed News, 31 March 2015)
nature biotechnology volume 33 NUMBER 5 MAY 2015
Keytruda UK’s first earlyaccess drug UK patients with advanced melanoma can now access Merck’s cancer drug Keytruda (pembrolizumab), an anti-PD-1 (programmed death receptor 1) antibody, although not yet approved by the European Medicines Agency. Keytruda, a new-generation oncology therapy from Kenilworth, New Jersey–based Merck, is the first therapy accepted under the Early Access to Medicines Scheme (EAMS), a program introduced in 2014 to help patients benefit from promising, innovative treatments before a license from European regulators. In the US, Keytruda is approved for patients with metastatic melanoma whose disease has worsened after trying Yervoy (ipilimumab), another immunotherapy (Nat. Biotechnol. 32, 847–848, 2014). Both Yervoy from New York–based Bristol-Myer Squibb and Keytruda are checkpoint inhibitors, but they work through different pathways. A head-to-head trial testing Keytruda against Yervoy in 830 patients with metastatic melanoma found that 74% of patients on Keytruda were still alive one year after starting treatment, compared with 58% on Yervoy. The phase 3 study results released April 19 point at Keytruda as the better first-line therapy for advanced melanoma rather than the current Yervoy.
Epigenome drug approved after setback Novartis’ multiple myeloma drug Farydak (panobinostat), an oral histone-deacetylase (HDAC) inhibitor, gained an accelerated approval in February after the US Food and Drug Administration recommended narrowing the indication to make the benefit-risk profile more attractive. In November 2014, the Oncologic Drugs Advisory Committee had recommended not approving this epigenetictargeted therapeutic in the broad population of relapsed multiple myeloma patients owing to the drug’s toxicities. Novartis submitted a subgroup analysis of 193 patients who had received at least two prior treatments. Participants received either Farydak combined with Takeda’s Velcade (bortezomib) and dexamethasone, or Velcade and dexamethasone alone. Results showed that the Farydak combination delayed disease progression for about 11 months compared with 6 months for those receiving Velcade and dexamethasone alone.
“In the end it’s about respect. Biotech companies need to respect consumers and give them the information they need to make their own choice.” Sylvain Charlebois, of The Food Institute of the University of Guelph, on the recent approval by Health Canada of the Arctic Apple (genetically engineered not to brown), expected to evoke an uproar by anti-GMO activists, despite (or maybe because of) its consumer appeal. (The Province, 26 March 2015)
437
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The Structural Genomics Consortium (SGC) public-private partnership has launched an open-source initiative to use human-derived cells to validate targets for new medicines. Academic researchers from at least five hospitals have joined the SGC, a not-for profit organization set up to support drug discovery. The partners have agreed to waive intellectual property (IP) rights to these preclinical assays developed to validate targets. The initiative pushes against the status quo in which drug discovery researchers typically carry out target validation work under a shroud of secrecy and heavy IP protection. By pooling patient-derived cells, chemical probes, clinical insight and industry expertise, participants aim to reduce redundant research projects and speed up the identification of disease-relevant targets. The Innovative Medicines Initiative (IMI) is contributing more than €40 ($43) million over five years to develop assays and chemical and antibody-based probes for autoimmune and inflammatory diseases, including ankylosing spondylitis, polymyositis and lupus. These projects will be run out of the Karolinska Institute and Karolinska University Hospital, in Stockholm, and the Oxford University Hospitals, in the UK. The Ontario Brain Institute and other funders are contributing resources towards developing assays for neuroscience indications, including Rett syndrome, amyotrophic lateral sclerosis and Parkinson’s, and oncology indications, including glioblastoma. These projects will be run at The Hospital for Sick Children and the University Health Network, both in Toronto, as well as the Montreal Neurological Institute and Hospital in Montreal. “It’s a different way of thinking about things. For some diseases, it may be a fabulous way to go,” says Peter Dirks, a neurosurgeon at The Hospital for Sick Children in Toronto, who is participating in the project. Under the new initiative, Dirks will characterize the phenotypes of tumor cells donated by patients with glioblastoma. By setting up open-access target-validation assays with these cells, he hopes to identify chemical probes that modulate the proliferative abilities and stem-cell likeness of the patient-derived cells. Because the SGC has extensively characterized the selectivity profile of its chemical probes, hits that come out of Dirks’ assays could point to potential drug targets. At the Montreal Neurological Institute and Hospital, another team of participat436
Dr Mark J Winter/ Science Source
© 2015 Nature America, Inc. All rights reserved.
Human cell assays for new medicines now open access
The Structural Genomics Consortium facilitates drug discovery by characterizing crystal structures of human proteins, such as alcohol dehydrogenase (pictured), and generating epigenetic chemical probes to be used as reagents.
ing researchers is taking a similar approach, developing phenotypic assays to validate targets for amyotrophic lateral sclerosis and Parkinson’s disease. For both neurodegenerative disorders, they will primarily use induced pluripotent stem cell methodologies to reprogram patient-derived skin cells into neurons. Clinical researchers will initially screen their assays with SGC’s library of epigenetic chemical probes. These probes have been generated by SGC as part of its remit to solve the structures of medically relevant proteins. So far, this precompetitive structural biology research initiative, which includes ten pharma partners, has generated 30 IP-free chemical probes with high potency and selectivity for chosen epigenetic targets for use in research (http://www.thesgc.org/ chemical-probes). SGC’s industry collaborators have nominated another 30 targets against which they would like the SGC to develop small-molecule and antibody probes for use in drug discovery. “We imagine a few hubs generating these chemical tools, and we will then fan them out to a network of hospitals to test them in different target-validation assays,” says Aled Edwards, director of the SGC in Toronto. By operating in an open-access manner, adds Edwards, researchers are able to side-
step the legal wrangling that otherwise delays or prevents the setup of their experiments. “The only way to get this done is to declare it an IP-free zone and do the science,” he says. Results will be put into the public domain as quickly as possible, and the clinical researchers will be encouraged to publish their findings in academic journals. Other public-private, academic and industry groups have also been working hard in recent years to make the most of academia’s target-validation capabilities. The Academic Drug Discovery Consortium, a network of 126 academic drug discovery centers that includes the SGC, for example, established a partnership with London-based AstraZeneca in 2014 to enable academics to access industry-caliber screening decks (in this case, AstraZeneca gets the right to license compounds and data that are generated from such screens). However, many industry researchers are skeptical of academic target validation owing to problems they have had replicating research findings (Nat. Rev. Drug Discov. 10, 643–644, 2011). The Montreal team eventually plans to hire ex-industry researchers to ensure the quality and caliber of their assays. But both academic and industry partners in the new projects also hope that regular interactions and engagement between sectors will address any
volume 33 NUMBER 5 MAY 2015 nature biotechnology
npg
© 2015 Nature America, Inc. All rights reserved.
news potential problems. “We really plan to work will then come to the fore. “The IP that we with them [clinical researchers] to design want comes from the molecule that we can assays that are robust and reproducible,” says then develop,” says Perros-Huguet. Although there is a risk that the IP-free Christelle Perros-Huguet, senior vice president of inflammation and immunology at approach will mean that academic researchNew York–based Pfizer. Pfizer is contributing ers or their institutions could lose out on to the IMI-funded autoimmune and inflam- revenue from assay licensing opportunities, matory research projects, along with Bayer of the research scientists who have signed up to Leverkusen, Germany, Janssen of Titusville, date do not see this as a major sacrifice. “Our hypothesis is that this open-access approach New Jersey and Novartis of Basel. Companies will tap into their own con- will lead to increased upfront funding,” siderable expertise developing cell-based says Guy Rouleau, director of the Montreal screening assays. At Novartis, already Neurological Institute and Hospital, who around 10% of primary screens involve is participating in the pilot project, adding patient-derived cells. For this reason, says that philanthropic and disease association Dhaval Patel, head of Novartis Institutes groups are very interested by the potential to for BioMedical Research Europe, based in accelerate drug discovery through the openBasel, the company can weigh in on what access approach. And the IP on academic assays may not have phenotypes to focus on, how to handle interpatient variability and how to design much realizable financial value, for the most high-throughput assays. In exchange, he is part, anyway. Only “a rather small percentage” of the screening assays that looking forward to seeing Novartis works with are results from assays that are licensed in from academic made up of patient-derived The next step groups anyway, says Patel. cells that could otherwise could be to Although industry be difficult and costly to get raise money to remains tight-lipped on access to. “That’s where I see specific molecular targets value for us,” says Patel, who run IP-free lead of interest, Edwards and his has represented Novartis at optimization colleagues at the SGC are SGC discussions. projects hopeful that they can push “I’m excited about this the precompetitive envebecause it is one of the few types of consortia that may be a win-win lope further. In 2011, they proposed the crefor both academia and industry,” adds Patel. ation of Arch2POCM, an industry-academia partnership that would see competitors work“This is a true collaboration.” Perros-Huguet says that Pfizer—and the ing together to take validated new targets even other industry partners—already have inter- into proof-of-concept trials in human patients nal lead-optimization programs running ((Nat. Biotechnol. 29, 298, 2011). This remains against many of the proteins that the SGC’s as yet a bridge too far, but the target validation probes target. “With better patient valida- projects are a step in that direction. The next tion, we will probably put even more effort step could be to raise money to run IP-free lead into the targets that we discover are the most optimization projects on a few of the chemirelevant for a disease.” Although drug devel- cal probes to generate drug candidates that are opers will have to compete with one another ready for clinical trials. “We are getting increon a level scientific playing field, compound mentally closer,” says Edwards. optimization and development capabilities Asher Mullard Ottawa, Ontario, Canada
“The biology of disease is an away game if there ever was one. The inner workings of cells and the ways that they work together are flat-out alien compared to anything we’ve ever built ourselves…. Expecting the sorts of behavior that you get from human-built technologies, and expecting the same effects from the techniques that work to optimize them, is an expensive accident waiting to happen.” Blogger Derek Lowe comments on the notion that health is “one app away.” (In the Pipeline, 2 April 2014)
“Some people are going to freak out about this. DNA and Facebook are two words that most people do not want to hear in the same sentence.” Michelle Meyer, of the Union Graduate College–Icahn School of Medicine at Mt. Sinai Bioethics Program, on a new Facebook app, Genes for Good, which has been set up by researchers at the University of Michigan, to recruit subjects for genetic studies. What could possibly go wrong? (BuzzFeed News, 31 March 2015)
nature biotechnology volume 33 NUMBER 5 MAY 2015
Keytruda UK’s first earlyaccess drug UK patients with advanced melanoma can now access Merck’s cancer drug Keytruda (pembrolizumab), an anti-PD-1 (programmed death receptor 1) antibody, although not yet approved by the European Medicines Agency. Keytruda, a new-generation oncology therapy from Kenilworth, New Jersey–based Merck, is the first therapy accepted under the Early Access to Medicines Scheme (EAMS), a program introduced in 2014 to help patients benefit from promising, innovative treatments before a license from European regulators. In the US, Keytruda is approved for patients with metastatic melanoma whose disease has worsened after trying Yervoy (ipilimumab), another immunotherapy (Nat. Biotechnol. 32, 847–848, 2014). Both Yervoy from New York–based Bristol-Myer Squibb and Keytruda are checkpoint inhibitors, but they work through different pathways. A head-to-head trial testing Keytruda against Yervoy in 830 patients with metastatic melanoma found that 74% of patients on Keytruda were still alive one year after starting treatment, compared with 58% on Yervoy. The phase 3 study results released April 19 point at Keytruda as the better first-line therapy for advanced melanoma rather than the current Yervoy.
Epigenome drug approved after setback Novartis’ multiple myeloma drug Farydak (panobinostat), an oral histone-deacetylase (HDAC) inhibitor, gained an accelerated approval in February after the US Food and Drug Administration recommended narrowing the indication to make the benefit-risk profile more attractive. In November 2014, the Oncologic Drugs Advisory Committee had recommended not approving this epigenetictargeted therapeutic in the broad population of relapsed multiple myeloma patients owing to the drug’s toxicities. Novartis submitted a subgroup analysis of 193 patients who had received at least two prior treatments. Participants received either Farydak combined with Takeda’s Velcade (bortezomib) and dexamethasone, or Velcade and dexamethasone alone. Results showed that the Farydak combination delayed disease progression for about 11 months compared with 6 months for those receiving Velcade and dexamethasone alone.
“In the end it’s about respect. Biotech companies need to respect consumers and give them the information they need to make their own choice.” Sylvain Charlebois, of The Food Institute of the University of Guelph, on the recent approval by Health Canada of the Arctic Apple (genetically engineered not to brown), expected to evoke an uproar by anti-GMO activists, despite (or maybe because of) its consumer appeal. (The Province, 26 March 2015)
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