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| 5654 | NCATS to Fund Next Phase of Tissue Chip for Drug Screening Program | On Oct. 18, 2016, NCATS announced a new funding opportunity for the next phase of the Tissue Chip for Drug Screening program. For the Tissue Chips for Disease Modeling and Efficacy Testing initiative, the Center and its collaborators plan to commit an estimated total of $13.5 million in fiscal year 2017 for 10 to 12 awards. The new support will enable researchers to create models of human disease using tissue chip technology for testing the effectiveness of candidate drugs. Failure to demonstrate efficacy accounts for approximately 65 percent of drug failures during clinical trials. Ultimately, these disease models will help scientists to better assess biomarkers, bioavailability, efficacy and toxicity of candidate therapeutics prior to entry into clinical trials. This image shows mature cardiac cells properly aligned and functional on the heart chip. (Columbia University Photo/Gordana Vunjak-Novakovic) NCATS funds its Tissue Chip for Drug Screening program through the Cures Acceleration Network. NIH Institutes, Centers and Offices also contributing funding, expertise and resources include the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Dental and Craniofacial Research, the National Institute of Diabetes and Digestive and Kidney Diseases, the National Institute of Environmental Health Sciences, the National Institute of Neurological Disorders and Stroke, and the Office of Research on Women’s Health. Learn more about RFA-TR-16-017 and other Tissue Chip for Drug Screening funding opportunities. Posted October 2016 | NCATS released a funding opportunity to enable researchers to create models of human disease using tissue chip technology for testing the effectiveness of candidate drugs. | /sites/default/files/heart-chip-835px_0.png | NCATS to Fund Next Phase of Tissue Chip for Drug Screening Program | NCATS released a funding opportunity to enable researchers to create models of human disease using tissue chip technology for testing the effectiveness of candidate drugs. | /sites/default/files/heart-chip-835px_1.png | NCATS to Fund Next Phase of Tissue Chip for Drug Screening Program | ||
| 5645 | NCATS to Support Tissue Chip for Drug Screening Testing Centers | On Oct. 13, 2016, NCATS announced approximately $6 million in new awards for fiscal year 2016 to establish three testing centers for the Tissue Chip for Drug Screening program. The goals of the Tissue Chip Testing Centers (TCTCs) include: Providing the means for scientists funded by NCATS’ tissue chip program to test and validate tissue chip platforms independently; Promoting adoption of this technology by the broad research community, such as pharmaceutical partners and the Food and Drug Administration (FDA); and Ensuring wide-ranging availability of tissue chip technology. NCATS issued awards through its Cures Acceleration Network to the Massachusetts Institute of Technology and Texas A&M University who will be conducting the independent validation of the tissue chip platforms, and to the University of Pittsburgh to set up the tissue chip database for each organ platform. View project details. Kidney-on-a-chip. (University of Washington Photo) Over the past four years, NCATS and its Tissue Chip for Drug Screening program collaborators — the Defense Advanced Research Projects Agency and the FDA — supported the development of human tissue chips that accurately model the structure and function of human organs, such as the lung, liver and heart, to help predict drug safety in humans more rapidly. NCATS-funded TCTC scientists will use a reference set of validation compounds vetted by pharmaceutical representatives through an NCATS partnership with the IQ Consortium and the FDA, and will run tests to determine functionality, reproducibility, robustness and reliability in these organ platforms. In addition, TCTC staff will work directly with the Tissue Chip Consortium, which includes tissue chip technology developers, government officials and industry representatives, to test tissue chip devices; acquire, store and use standard tissue chip resources; test compounds for device validation; and share the data and methodologies with the consortium. In collaboration with stakeholders and regulatory agencies, organ chip testing will determine whether the technology can be used as a better predictive model for assessing safety and efficacy of promising therapies than current cell and animal models. Learn more about the Tissue Chip for Drug Screening program. Posted October 2016 | NCATS announced new awards, issued through the Cures Acceleration Network, to establish Tissue Chip Testing Centers. | /sites/default/files/tissue-chip-hands-closeup-900px_0.jpg | NCATS to Support Tissue Chip for Drug Screening Testing Centers | NCATS announced new awards, issued through the Cures Acceleration Network, to establish Tissue Chip Testing Centers. | /sites/default/files/tissue-chip-hands-closeup-900px_1.jpg | NCATS to Support Tissue Chip for Drug Screening Testing Centers | ||
| 5623 | Tissue Chip Development | In 2012, we partnered with the Defense Advanced Research Projects Agency and the U.S. Food and Drug Administration to lead the development of 3-D platforms engineered to support living human tissues and cells, called tissue chips or organs-on-chips. Through the Tissue Chip for Drug Screening program, staff awarded 11 two-year projects that supported the development of 3-D cellular microsystems designed to represent a number of human organ systems. We also awarded eight two-year projects that explored the use of stem and progenitor cells to differentiate into multiple cell types that represent the cellular architecture within the organ.Renewable cell sources and bioengineered microsystems that successfully demonstrated physiological function then moved into the second phase (2014–2017). The goal for this phase was to further refine the technology and begin organ chip integration. By combining all major organ systems to form a human body-on-a-chip, we aim to speed up the translation of basic discoveries into the clinic.View the 2014 projects to integrate tissue chips.View the 2012 projects on model systems.View the 2012 projects on cell resources. | Tissue Chip Development | Tissue Chip Development | ||||||
| 5622 | NCATS, CASIS Announce Funding Opportunity for Tissue Chip Research in Space | NCATS and the Center for the Advancement of Science in Space (CASIS) are collaborating to use tissue chip technology for translational research at the International Space Station U.S. National Laboratory (ISS-NL). Through its Tissue Chip for Drug Screening program, NCATS announced a new funding opportunity on Oct. 5, 2016, to leverage recent tissue-on-chip advances to modify and deploy these devices at the ISS-NL. The goal of the Tissue Chips in Space initiative is to further refine tissue- and organ-on-chip platforms for in-flight experiments at the ISS-NL so that scientists can better understand the role of microgravity (diminished gravity relative to Earth, often called “zero gravity”), on human health and disease and translate those findings to affect human health on Earth. Sunrise for the International Space Station as captured by an STS-129 crew member in 2009. (NASA Photo) “To be able to conduct biomedical research in space using tissue chip technology provides us with unprecedented opportunities to study the effects of microgravity and reduced-gravity environments at the ISS-NL on many of the human body’s systems,” said Danilo A. Tagle, Ph.D., M.S., NCATS associate director for special initiatives and head of the Tissue Chip for Drug Screening program. “For example, it is now widely known that accelerated aging takes place in space, due to muscle wasting, osteoporosis, reduced cardiopulmonary function and immune response, but that these conditions are reversible when astronauts return to Earth.” NCATS and CASIS intend to commit an estimated total of $3 million to fund four to five awards in fiscal year 2017. Learn more about RFA-TR-16-019 and other Tissue Chip funding opportunities. Posted October 2016 | NCATS and the Center for the Advancement of Science in Space are collaborating to use tissue chip technology for translational research at the International Space Station. | /sites/default/files/iss-rising-sun-900px_0.jpg | New Funding Opportunity to Conduct Tissue Chip Research in Space | NCATS and CASIS are collaborating to use tissue chip technology for translational research at the International Space Station. | /sites/default/files/iss-rising-sun-900px_1.jpg | New Funding Opportunity to Conduct Tissue Chip Research in Space | ||
| 5423 | NCATS Announces Funding Opportunity for New Bench-to-Clinic Repurposing Initiative | A novel drug can take about 14 years and more than $1 billion to develop, with a failure rate exceeding 95 percent. To help combat these challenges, NCATS has announced the Bench-to-Clinic Repurposing initiative and related funding opportunity. The goal is to support investigators to repurpose ― or identify new uses for — existing experimental drugs or biologics, as well as Food and Drug Administration-approved therapies already on the market. Multi-color image of whole brain for brain imaging research. This image was created using a computer image processing program (called SUMA), which is used to make sense of data generated by functional Magnetic Resonance Imaging (fMRI). (Credit: National Institute of Mental Health, National Institutes of Health) NCATS seeks applications to support preclinical (bench) studies to test the effectiveness of using an independent crowdsourcing effort, computational algorithm or big dataset from patient records to predict new uses of a drug or biologic. A key goal is to identify systematic approaches for predicting which existing drug or biologic might be effective in treating a disease or condition. Using existing therapeutics means positive findings could rapidly lead to testing in humans, and the translational approach can be adopted by the scientific community to improve other drug repurposing efforts. Researchers interested in applying should submit a letter of intent by Oct. 14, 2016, and applications are due Nov. 14, 2016. In addition, NCATS plans to issue a complementary funding opportunity in fiscal year 2017 to support clinical studies for projects that are further along in the development pipeline. The Bench-to-Clinic Repurposing initiative represents an expansion of NCATS’ Discovering New Therapeutic Uses for Existing Molecules (New Therapeutic Uses) program, which supports research on new indications or uses for therapeutic assets that already have been clinically tested. These assets have already cleared several key steps along the development path, thereby providing scientists with a strong starting point for contributing their expertise and, ultimately, accelerating the pace of therapeutics development. To learn more about the new funding opportunity, contact therapeutics.discovery@nih.gov or view frequently asked questions. Posted September 2016 | NCATS announced the Bench-to-Clinic Repurposing initiative and funding opportunity to help investigators repurpose or find new uses for experimental or approved therapies. | /sites/default/files/ntu_brain_900px_0.jpg | NCATS Announces Funding Opportunity for New Bench-to-Clinic Initiative | NCATS announced the Bench-to-Clinic Repurposing initiative and funding opportunity to help investigators repurpose or find new uses for experimental or approved therapies. | /sites/default/files/ntu_brain_900px.jpg | NCATS Announces Funding Opportunity for New Bench-to-Clinic Initiative | ||
| 5420 | RFA-TR-16-015 Frequently Asked Questions | NCATS is seeking applications for rigorous, preclinical research projects that are based on repurposing existing drugs or biologics (therapeutics). Preclinical studies funded through this initiative will demonstrate the utility of an independent crowdsourcing effort or of a computational algorithm to predict new therapeutic uses of an existing drug or biologic. The goal of an individual project must be to explore the potential new use of an existing investigational therapeutic or one already approved by the Food and Drug Administration (FDA) to treat another disease. Applications are due November 14, 2016, by 5:00 PM local time of applicant organization. General Information How does NCATS define "published or publicly available method" for identifying a therapeutic/indication pair or combination therapy? How does NCATS define "computational algorithm"? How does NCATS define "crowdsourcing"? What is an example of a successful crowdsourcing approach? How does NCATS define "rigorous" preclinical studies? Project Approaches Are any research areas of higher interest to NCATS than others? Can applicants request funding to conduct a virtual screen to identify the therapeutic/indication pair? Literature indicates that the proposed drug or biologic of interest would be effective in treating a disease different than that for which it was developed. Can one submit an application to conduct the preclinical studies to test this? Are there any restrictions on the type of drugs or biologics that can be repurposed? Why is that important to start with therapeutics that have been in Phase I clinical trials? Can applicants access assets from companies that participated in prior NCATS crowdsourcing initiatives? Does this opportunity support reformulation of existing drugs? Is the inclusion of proprietary information in an application considered disclosure that would disqualify my company from applying for patents? NEW (Nov. 2016): Do I need to submit a methods manuscript if the method used to identify the new therapeutic/indication pair is publicly available? Budget/Funding How does the consortium budget affect the direct cost limit? Can asset providers offer supplemental funding and resources if needed to complete the project? Can applicants include cost for manufacturing the active pharmaceutical ingredient? How many awards does NCATS anticipate making? How much money is available? NEW (Nov. 2016): The instructions ask for details on the UH3 portion of the grant in the specific aims and research strategy, which to my understanding, is just one year of clinical trial planning ($100,000 direct costs). However, the budget asks for a listing of resources for the entire clinical trial, which clearly would go far beyond $100,000 and multiple years (far beyond the UH3 phase). Application Review Will reviewers assess the novelty of the method to identify the therapeutic/indication pair? General Information How does NCATS define "published or publicly available method" for identifying a therapeutic/indication pair or combination therapy? Investigators may submit ideas to test new therapeutic uses on projects for which the hypothesis originates from use of a published or publicly available computational strategy or a published or publicly available crowdsourcing site. A published method is generally one that is in a peer-reviewed publication. A publicly available method could be available via a website or a commercially available product. The publicly available strategy does not need to be free, but it should be available to investigators that would like to use it. How does NCATS define "computational algorithm"? NCATS is interested in applications that have an identified therapeutic/indication pair for repurposing, using an existing computational algorithm. A computational algorithm is the business end of bioinformatics. A computational algorithm will mine existing data and in this case identify candidate therapeutic/indication pairs for experimental investigation. NCATS is particularly interested in demonstrating the value of computational algorithms for repurposing due to the potential uptake of successful approaches by the broader research community to subsequently identify additional therapeutic/indication pairs. NCATS is not interested in applications that seek to develop or test a new computational algorithm. NCATS seeks use cases that test methods with the potential to improve prediction of successful therapeutic/indication pairs, which can be demonstrated fully at the clinical testing stage. How does NCATS define "crowdsourcing"? Crowdsourcing occurs when an investigational drug is publicly posted for investigators to propose ideas for new therapeutic uses. Generally, crowdsourcing is an approach used for investigational therapeutics, not therapeutics approved by the FDA, since approved drugs already are known to the public. An example of crowdsourcing is how NCATS matches researchers with a selection of pharmaceutical industry assets to test ideas for new therapeutic uses, with the ultimate goal of identifying promising new treatments for patients. Another example of a crowdsourcing approach is AstraZeneca's Open Innovation program or any independent website that lists investigational drugs available for repurposing. What is an example of a successful crowdsourcing approach? NCATS has demonstrated that public posting of industry assets to crowdsource ideas for new therapeutic uses from the academic community is an effective way to launch new collaborations. NCATS serves as a matchmaker between academic experts and pharmaceutical partners, enabling successful projects like one at Yale University that demonstrated a compound originally developed as a cancer therapy could be used to treat Alzheimer's disease. The Yale scientists gave the compound to mice that model Alzheimer's disease. After four to six weeks, the mice showed reversal of Alzheimer's symptoms such as spatial learning impairments and memory loss. The drug already was tested for safety in humans and passed key steps in the development process before the project began. By repurposing an existing drug, investigators began testing the drug in humans within three months; it typically would take a decade from the discovery of a promising compound to a drug ready for clinical trials. How does NCATS define "rigorous" preclinical studies? Rigor ensures robust and unbiased experimental design, methodology, analysis, interpretation and reporting of results. When a result can be reproduced by multiple scientists, it validates the original results and readiness to progress to the next phase of research. Reproducibility is especially important for clinical trials involving humans; these trials are built on studies that have demonstrated a particular effect or outcome. Learn more about rigor and reproducibility. In October 2015, NIH published guidance about rigor and reproducibility for grant applications due on or after Jan. 25, 2016. Back to top Project Approaches Are any research areas of higher interest to NCATS than others? NCATS is "disease agnostic." Rather than focusing on a single disease or biological system, NCATS focuses on improving the translational science process. Therefore, NCATS is interested in funding applications that demonstrate an approach to identifying the therapeutic/indication pair that, if successful, could be applied to other diseases and improve the efficiency of predicting new repurposing targets. This funding opportunity supports projects that scientifically have supported rationales with measurable, objective, quantifiable effects of the drug or biologic (therapeutic). NCATS will consider funding projects that address diseases that have no available treatment or an inadequate treatment, with strong scientific rationale for the new therapeutic use. Use cases that repurpose a drug or biologic originally developed or approved for a completely different disease indication are of high interest. For example, a computational prediction that a drug originally developed to treat melanoma may be effective in treating rheumatoid arthritis would be of greater interest than if that same drug may be effective in a different solid tumor cancer. Can applicants request funding to conduct a virtual screen to identify the therapeutic/indication pair? No. Applicants must identify a therapeutic/indication pair in the application. Literature indicates that the proposed drug or biologic of interest would be effective in treating a disease different than that for which it was developed. Can one submit an application to conduct the preclinical studies to test this? Although repurposing projects that are solely the result of traditional experimental methods and literature searches are important, they would not demonstrate the utility of a method for repurposing that ultimately could be broadly disseminated and, therefore, would not be responsive to this funding opportunity. However, if a drug is available through independent crowdsourcing, it may be eligible. Are there any restrictions on the type of drugs or biologics that can be repurposed? Applicants may propose to test an experimental or an FDA-approved drug or biologic. Additionally, the drug or biologic should have been tested in a Phase I clinical trial. Applicants can propose testing a drug or biologic combination for which the combination therapy was identified through an innovative process. However, this funding mechanism can support only proof-of-concept testing, rather than all the required preclinical testing to determine toxicity as a combination product. Applications for testing the effectiveness of a dietary supplement are not of interest. Why is that important to start with therapeutics that have been in Phase I clinical trials? Starting with investigational or FDA-approved drugs and biologics that already have passed key steps in the therapeutics development process speeds the pace of development. These compounds already have advanced to clinical studies with established pharmacokinetics and a safety profile, which enable further clinical investigation for other potential therapeutic uses. Can applicants access assets from companies that participated in prior NCATS crowdsourcing initiatives? Potentially. Companies that participated in the Discovering New Therapeutic Uses for Existing Molecules program are not obligated to provide access to assets from that program. However, if the company is willing to consider making the asset available, NCATS can connect interested applicants with representatives from the company. To find out more, refer to the tables on the Industry-Provided Assets page. Refer to the FOA section "Letters of Support" for confirmation of drug access assurance. Does this opportunity support reformulation of existing drugs? Because investigational therapies explored through this funding opportunity must already have been in a Phase I clinical trial, NCATS expects that applicants already will have determined a drug or biologic's toxicity through Investigational New Drug-enabling preclinical studies. Changes in formulation that require additional Phase I studies would not be supported through this opportunity. If applicants have existing proof that the FDA would accept the available preclinical and Phase I data despite the formulation change, NCATS would consider the proposed therapeutic Phase II-ready. Is the inclusion of proprietary information in an application considered disclosure that would disqualify my company from applying for patents? Refer to the NIH Small Business Innovation Research program website for more information about intellectual property and applications. Do I need to submit a methods manuscript if the method used to identify the new therapeutic/indication pair is publicly available? If the method used to identify the new therapeutic/indication pair is publicly available, you only need to provide a citation or website for the published or publicly available method. If the method has not yet been published and will be by the time an award is made, provide the manuscript that has been submitted for publication. Back to top Budget/Funding How does the consortium budget affect the direct cost limit? Pursuant to the NIH Grants Policy Statement, the direct cost limit excludes the consortium indirect costs. Questions about consortium budget should be directed to the grants management specialist identified as the point of contact in the FOA. Can asset providers offer supplemental funding and resources if needed to complete the project? Yes. NCATS encourages multiparty collaborations to maximize the use of federal funds; however, such additional support is not required and will not be used as a factor during the application review. Can applicants include cost for manufacturing the active pharmaceutical ingredient? Yes. Application budgets are limited to $200,000 in direct costs per year in year 1 and 2. How many awards does NCATS anticipate making? How much money is available? NCATS anticipates funding up to 10 awards, for a total level of support of $3.5 million in fiscal year 2017. The actual number of applications funded depends on the quality of applications received, budgets required for individual applications, and programmatic priorities. The instructions ask for details on the UH3 portion of the grant in the specific aims and research strategy, which to my understanding, is just one year of clinical trial planning ($100,000 direct costs). However, the budget asks for a listing of resources for the entire clinical trial, which clearly would go far beyond $100,000 and multiple years (far beyond the UH3 phase). The UH3 portion of the award is intended for planning the clinical trial. The information listed in the budget section was provided in error. Applicants should provide a budget and budget justification that includes the resources needed to accomplish the activities proposed for clinical trial planning. Back to top Application Review Will reviewers assess the novelty of the method to identify the therapeutic/indication pair? Reviewers will assess the proposed project according to the review criteria as stated in the FOA. | RFA-TR-16-015 Frequently Asked Questions | RFA-TR-16-015 Frequently Asked Questions | ||||||
| 5419 | 2014 Industry-Provided Assets | Assets in this table are alphabetized by mechanism of action. These compounds and biologics have undergone significant preclinical and safety testing in humans. 2014 Table of Assets for Adult Indications 2014 Table of Assets for Pediatric Indications 2014 Table of Assets for Adult Indications Code Number & Link to More Information Mechanism of Action Original Development Indication(s) Route of Administration Formulation Available (CNS Penetrant+) AZD4017 (PDF - 155KB) 11-beta hydroxysteroid dehydrogenase type 1 inhibitor Diabetes Oral (Low) RWJ-445380 (PDF - 108KB) Cathepsin S inhibitor Psoriasis Rheumatoid arthritis Oral SAR114137 (PDF - 179KB) Cathepsin S inhibitor Chronic pain (osteoarthritis, neuropathic, low back) Oral (Maybe) CNTO-888 (PDF - 141KB) Carlumab Chemokine (C-C motif) ligand 2 selective human IgG1 kappa monoclonal antibody Idiopathic pulmonary fibrosis Intravenous (No) AZD9291 (PDF - 108KB) Epidermal growth factor receptor (EGFR) tyrosine kinase sensitizing and T790M resistance mutations inhibitor Non-small cell lung cancer Oral (Unknown) JNJ-31001074 (PDF - 109KB) Bavisant Histamine type 3 receptor antagonist Attention deficit hyperactivity disorder Oral (Yes) SAR110894 (PDF - 112KB) Histamine type 3 receptor antagonist Symptomatic treatment of Alzheimer's disease Oral (Yes) AZD2014 (PDF - 126KB) Mammalian target of rapamycin serine/ threonine kinase (dual TORC1 and TORC2) inhibitor Solid tumors Oral (Unknown) AZD8529 (PDF - 108KB) Metabotropic glutamate receptor 2 positive allosteric modulator Schizophrenia Oral (Yes) PF-03882845 (PDF - 314KB) Mineralocorticoid receptor antagonist Diabetic nephropathy Oral AZD6765 (PDF - 129KB) Lanicemine N-methyl-D-aspartate receptor open-channel blocker Major depressive disorder Intravenous (Yes) AZD2624 (PDF - 133KB) Neurokinin-3 receptor, tachykinin receptor 3 antagonist Schizophrenia Oral (Low) AZD9668 (PDF - 126KB) Neutrophil elastase inhibitor Chronic obstructive pulmonary disease Cystic fibrosis Oral (Low) PF-03049423 (PDF - 143KB) Phosphodiesterase type 5 inhibitor Stroke recovery Oral (Yes) AZD1208 (PDF - 135KB) Proviral integration Moloney virus serine/threonine kinase family inhibitor Acute myeloid leukemia Advanced solid tumors Malignant lymphoma Oral (Yes) CE-224535 (PDF - 203KB) Purinergic receptor 2 antagonist Rheumatoid arthritis Osteoarthritis Oral AZD9150 (PDF - 97KB) Signal transducer and activator of transcription 3 antisense Hepatocellular carcinoma Intravenous (Low) AZD1775 (PDF - 183KB) Wee1 G2 checkpoint kinase inhibitor Advanced solid tumors Oral (Unknown) +CNS penetrant: Yes, no,maybe, low or unknown. 2014 Table of Assets for Pediatric Indications Code Number & Link to More Information Mechanism of Action Original Development Indication(s) Route of Administration Formulation Available (CNS Penetrant+) AVE5530 (PDF - 128KB) Canosimibe Acyl-coenzyme A: cholesterol O-acyltransferase inhibitor Hypercholesterolemia Oral (No) SSR149744 (PDF - 125KB) Celivarone Cation channel blocker Supraventricular (atrial fibrillation) and ventricular arrhythmia Oral AZD1981 (PDF - 115KB) Chemoattractant receptor-homologous molecule expressed on Th2 cells antagonist (prostaglandin D2 receptor antagonist) Asthma Chronic obstructive pulmonary disease Oral (Low) AZD7325 (PDF - 153KB) Gamma-aminobutyric acid receptor A alpha 2 & 3 positive modulator General anxiety disorder Oral (Yes) AZD3355 (PDF - 167KB) Lesogaberan Gamma-aminobutyric acid receptor B agonist Gastroesophageal reflux disease Oral (Low) JNJ-31001074 (PDF - 109KB) Bavisant Histamine type 3 receptor antagonist Attention deficit hyperactivity disorder Oral (Yes) PF-03654746 (PDF - 192KB) Histamine type 3 receptor antagonist Tourette syndrome Narcolepsy Cognition Attention deficit hyperactivity disorder Allergic rhinitis Oral (Yes) SAR152954 (PDF - 94KB) Histamine type 3 receptor antagonist Excessive daytime sleepiness Oral (Yes) AZD6765 (PDF - 129KB) Lanicemine N-methyl-D-aspartate receptor open-channel blocker Major depressive disorder Intravenous (Yes) AZD9668 (PDF - 126KB) Neutrophil elastase inhibitor Chronic obstructive pulmonary disease Cystic fibrosis Oral (Low) JNJ-39393406 (PDF - 118KB) Nicotinic acetylcholine receptor, α7 positive allosteric modulator Cognitive impairment associated with schizophrenia Oral (Yes) AZD1775 (PDF - 183KB) Wee1 G2 checkpoint kinase inhibitor Advanced solid tumors Oral (Unknown) +CNS penetrant: Yes, no,maybe, low or unknown. | 2014 Industry-Provided Assets | 2014 Industry-Provided Assets | ||||||
| 5354 | NCATS Small Business Award Seeds App to Improve Medication Adherence | April 2017 Update Seven years ago, health care technology expert Adam Hanina, M.B.A., and his colleagues recognized a major problem in clinical trials and outpatient care settings: Too many individuals take their medications incorrectly or do not take them at all. This can reduce the accuracy of clinical studies, make drug development less efficient and be detrimental to patient health. To combat this problem, Hanina joined forces with Laura Shafner, M.Sc., a health policy expert with a finance background, and Gordon Kessler, J.D., M.B.A., an intellectual property attorney. They set out to develop an artificial intelligence smartphone application that would visually confirm medication ingestion. In other words, it would help ensure the right patient takes the right medication at the right time. To develop and test the app, the team’s startup company, AiCure, received a Small Business Innovation Research (SBIR) Phase 1 grant in 2011 from the National Center for Research Resources (NCRR), which, under congressional authorization, reorganized into NCATS later that year. A patient takes medication while using the AiCure application on her smartphone. (AiCure Photo) The SBIR and Small Business Technology Transfer (STTR) programs help NCATS speed innovation in translational science. Often, small startup companies lack the early-stage funding to carry an idea through further investment and into commercial markets, where new interventions can be developed and delivered to patients. The NCATS SBIR and STTR programs bridge this translational gap by awarding grants, contracts and technical assistance to small businesses and research organizations focused on advancing translational research and technologies that will improve disease prevention, detection and treatment. “We had a potentially revolutionary idea to reduce risk in clinical research and improve patient health, and we needed the resources to develop it to the point of commercialization,” Hanina said. “NCATS’ goals align with our company’s mission: to improve translational science and accelerate the drug development process to get high-quality therapies into the hands of more patients more quickly.” Tackling the Adherence Problem Hospitalizations and poor health outcomes due to medication nonadherence cost the U.S. approximately $290 billion each year. In addition, poor adherence prevents researchers from properly assessing a drug in clinical trials, which contributes to a high failure rate. Clinical trials can cost $1 billion or more, and they most often fail because researchers cannot prove a therapy’s effectiveness or safety. These pitfalls ultimately can be harmful to patient health and quality of life. Although researchers already have several options for estimating adherence, such as pill counting and medication containers that record and track administration, these methods cannot confirm actual intake. Direct observation of patients is costly, invasive and impractical, and self-reporting of medication behaviors by patients can be imprecise and unreliable. The AiCure group devised the artificial intelligence adherence technology to address these translational barriers and provide a more efficient and accurate way to measure adherence. “Most existing adherence monitoring methods are geared toward either clinical research or clinical practice but not both,” Shafner said. “Our technology is designed to fill this gap by providing a gold standard method to measure data in a standardized way across all settings.” Automating Direct Observation With the initial SBIR funding, the AiCure team hired an artificial intelligence engineer to develop the monitoring app. Using a mobile device’s camera, software algorithms confirm the identities of the patient and the medication and verify intake. The video to the right describes how the app works. The app sends this information to a cloud-based dashboard that researchers or health care providers can use to monitor adherence and identify issues in real time. Providers can communicate with patients through the dashboard to offer immediate assistance. The application also gives interactive instructions, reminders and suggestions to patients to further increase adherence. For now, the technology monitors pill intake, but it can be adapted to recognize any form of administration, such as injections or oral liquids. “The AiCure application acts as an intelligent, mobile medical assistant to guide a patient through the health care journey, providing improved quality of care that would have been otherwise inaccessible,” Hanina said. With the Phase 1 grant, the AiCure team successfully demonstrated that the platform was technically feasible and able to confirm that patients have taken medication. Based on this success, NCATS awarded AiCure a Phase 2 SBIR award in 2013. This funding enabled validation of the technology against blood levels of medications and showed that the app improves adherence rates in schizophrenia and stroke patient populations. The group expects to publish study results later in 2016. An Expanding Enterprise “The initial two SBIR awards were instrumental to the development of our company and have led to additional NIH grants,” Hanina said. “Together, the NIH support has enabled our company to attract and leverage an additional $12.25 million in financing from venture capital investors.” AiCure also has entered contracts with five of the top 12 global pharmaceutical companies to provide the adherence monitoring app for clinical trials of experimental drugs. One of these companies, Takeda Pharmaceuticals U.S.A., Inc., is testing the technology in a clinical trial for patients with psychiatric illnesses. “Noncompliance is a major issue in clinical trials,” said Atul R. Mahableshwarkar, M.D., senior medical director at Takeda. “The AiCure platform may help improve our ability to detect a drug’s effectiveness as well as help us reduce costs by decreasing the number of patients needed in studies.” In addition to their work with the drug development industry, the AiCure team is continuing to test the platform in NIH studies of substance abuse and is partnering with government organizations and insurance companies on population health contracts in infectious and cardiovascular disease. Ultimately, the team envisions deploying the technology globally to assist in care for high-risk patients, for whom missed doses could lead to serious outcomes such as hospitalization or death. “In keeping with NCATS’ disease-agnostic philosophy, the SBIR awards facilitated the development of the AiCure technology and approach for translation across every therapeutic area and route of drug administration,” said Lili Portilla, M.P.A., director of strategic alliances at NCATS and program lead for SBIR and STTR. “In this way, the technology holds promise for generating a multiplier effect of benefits in translational research and for patients.” April 2017 Update AiCure’s artificial intelligence smartphone application, described in the story above, was recently evaluated in an NCATS-supported clinical trial of adults with ischemic stroke. The study was designed to test whether using the application — which visually confirms medication ingestion — would improve adherence in patients taking anticoagulation therapy to help prevent blood clots. As published April 6 in Stroke, the researchers found that patients who used the AiCure application had a 50 percent improvement in adherence. Posted August 2016 | This artificial intelligence app will help to ensure that the right patient takes the right medication at the right time. | NCATS Small Business Award Seeds App to Improve Medication Adherence | This artificial intelligence app will help to ensure that the right patient takes the right medication at the right time. | NCATS Small Business Award Seeds App to Improve Medication Adherence | ||||
| 5353 | Doctoral Students Use NCATS Resources to Investigate Promising Disease Therapies | Since 2012, the NIH Oxford-Cambridge Scholars Program (OxCam) has enabled future scientists to work with NCATS researchers to explore the translation of promising new therapies for cancers and tuberculosis. Most recently, OxCam — an accelerated, individualized doctoral training program for outstanding students committed to biomedical research careers — has supported the work of three M.D./Ph.D. students in NCATS’ Division of Preclinical Innovation.Unlike traditional U.S. doctoral programs, which require two years of courses and research training prior to the start of thesis work, OxCam enables scholars to begin thesis research immediately upon starting the program. The trainees split their research time over four years with scientific mentors at NIH and at Oxford University or Cambridge University in the U.K.NCATS mentors share their translational science expertise with the scholars, enabling them not only to focus on a specific scientific question but also to learn how to apply translation approaches to research more broadly.“A key part of NCATS’ mission is to work collaboratively with disease and biology experts on projects designed to demonstrate ways to improve translational research processes and ultimately speed development of new treatments,” said Anton Simeonov, Ph.D., NCATS scientific director. “Mentoring OxCam students in translational science helps form collaborations between NIH and Oxford or Cambridge.”Probing Health and DiseaseDeveloping a new therapy for patients is a multistage process in which the potential therapy is translated from basic research, preclinical research, clinical research and clinical implementation to affect public health. As such, multidisciplinary collaborations are crucial for successful translation; no individual or organization can succeed alone. NCATS studies the science of translation to understand the scientific and operational principles underlying each step of the translational process and develops innovative approaches to make the process more efficient. One major area of collaboration at NCATS involves working with disease experts to generate chemical probes for studying human biology, focusing specifically on new therapeutic targets.Chemical probes are small molecule compounds that can be used to increase or decrease the activity of a biological target in cells or animals. Investigators use these compounds to “probe” the function of molecules such as proteins to understand their roles in health and disease. If appropriate, probes can be optimized to become potential drug candidates. Generating these probes requires the specialized expertise and facilities that NCATS can provide.The OxCam program provided a new avenue for launching collaborations. With their U.K. mentors and lead mentor Craig Thomas, Ph.D., who heads NCATS’ Chemistry Technology program, three students — Monica Kasbekar, Michael Gormally and Ian Goldlust — have harnessed NCATS’ assay development and high-throughput screening capabilities to identify potential new therapeutics.Investigating an Infectious DiseaseMonica KasbekarFor her thesis project, Kasbekar set out to develop a small molecule to probe the metabolism of Mycobacterium tuberculosis, the bacterium that causes tuberculosis, a potentially life-threatening infectious lung disease. In her lab at Cambridge, under the mentorship of biological chemist Chris Abell, FRS, FMedSci, Kasbekar developed an assay to look for the activity of an enzyme called fumarate hydratase, which is involved in the bacterium’s metabolism. She then took the assay to Thomas’ lab to find an inhibitor to block fumarate hydratase. Kasbekar used NCATS’ robotic technology to perform high-throughput screens of a library containing more than 400,000 small molecules.Unexpectedly, Kasbekar found an inhibitor that was selective for the bacterial version of fumarate hydratase but not the human version. The compound’s selective nature makes it an ideal tuberculosis drug candidate because it would be unlikely to cause toxic side effects in patients. Kasbekar published the results of this work in the July 5, 2016, issue of the Proceedings of the National Academy of Sciences.“The OxCam program enabled me to leverage the differing expertise of the Cambridge and NCATS labs to approach problems from different angles, which ultimately led to this discovery,” Kasbekar explained.Repurposing a Cancer DrugIan GoldlustThe same year that Kasbekar began her work at Cambridge, Goldlust arrived at NCATS to perform high-throughput screens for potential ovarian cancer drugs, using the NCATS Pharmaceutical Collection and the Mechanism Interrogation PlatE (MIPE) library of approved and investigational drugs. Goldlust was searching for agents that could kill ovarian tumor spheroids, tiny clusters of cancer cells that often remain and spread (metastasize) throughout the body after surgical removal of an ovarian tumor.The screens identified a possible match called elesclomol, a drug originally developed to treat metastatic skin cancer. GoldIust brought the compound to his Cambridge lab and worked with cancer research physician and mentor James Brenton, FRS, FMedSci, to determine the mechanisms by which elesclomol kills ovarian cancer spheroids.Goldlust noted that these discoveries might not have been possible in a traditional training program. “The OxCam program provides a level of independence that many scientists do not achieve until they are assistant professors,” he said. “We were given almost unlimited access to the resources we needed to answer questions that interested us. That freedom was indispensable.”Targeting a Problem ProteinMichael GormallyGormally used the OxCam learning environment to explore an even broader research objective: He wanted to find a drug to block FOXM1, a protein that is overactive in many types of cancer. At Cambridge, under the mentorship of biological chemist Shankar Balasubramanian, FRS, FMedSci, Gormally designed an assay to test for FOXM1 activity. Then he brought the assay to NCATS to run a high-throughput screen of a library of more than 54,000 drug-like small molecules.The experiment yielded several promising inhibitors of FOXM1. Gormally returned to Cambridge and continued to study and characterize the compounds, ultimately generating new insights into how FOXM1 and similar proteins work in cancer cells. He published the results in the Nov. 12, 2014, issue of Nature Communications.“NCATS’ resources for high-throughput screening are second to none, and the automation and robotics enabled me to perform many more experiments than would have been possible otherwise,” Gormally said. “And, the training from the OxCam program provided excellent preparation for leading my own research lab in the future.”Training for the Next GenerationAll three students currently are finishing their Ph.D. work and will start medical school in fall 2016 to complete the second portion of their doctoral programs. Each anticipates establishing a clinically focused research career, through which they can continue the drug discovery efforts they began in the OxCam program. Meanwhile, their former Ph.D. labs will continue to pursue the therapeutic leads these students uncovered.“These three students perfectly exemplify what the NIH OxCam Scholars Program aims to produce: young, ambitious and independent investigators who have achieved a high-quality, impactful and collaborative research experience — one they can take with them wherever they go next,” said Rick Fairhurst, M.D., Ph.D., director of the NIH M.D./Ph.D. Partnership Training Program. “I have no doubt that Kasbekar, Goldlust and Gormally each will develop and trial a new therapeutic for human disease at some point in their careers.”Participation in the OxCam program is just one of the ways that NCATS prioritizes drug discovery collaborations. The focus on training future scientists — in the OxCam program and through other NCATS efforts — provides the nation with a pipeline of promising translational investigators. These critical thinkers will have the skills, experience and knowledge to transform groundbreaking basic research discoveries into therapeutic innovations that benefit more patients more quickly.“The students who qualify for the OxCam program are remarkable,” Thomas added. “It has been a great experience for NCATS, largely due to their combined efforts and talents.” Posted August 2016 | Since 2012, the NIH Oxford-Cambridge Scholars Program has enabled future scientists to work with NCATS researchers to explore the translation of promising new therapies. | Students Use NCATS Resources to Investigate Disease Therapies | Since 2012, the NIH Oxford-Cambridge Scholars Program has enabled future scientists to work with NCATS researchers to explore the translation of promising new therapies. | Students Use NCATS Resources to Investigate Disease Therapies | ||||
| 5352 | CTSA Program-Supported Research Uncovers Genetic Components of Healthy Aging | Older adults often face aging-related ailments such as heart disease, dementia and high blood pressure, all of which can be costly and shorten lifespans. However, some people live long lives without encountering these common health problems. What sets apart healthy agers from their peers? To find out, Scripps Translational Science Institute (STSI) researchers led efforts to sequence and compare the genomes of 511 healthy agers — whom they deemed the “Wellderly” — and a representative group of 686 older adults. The STSI scientists defined the Wellderly as those aged 80 and older who had no chronic diseases and were not taking medications for chronic illnesses. Study results, published in Cell, reveal that the Wellderly had reduced genetic susceptibility to Alzheimer’s disease, suggesting that protection against cognitive decline is at least one genetic feature of healthy aging. Ali Torkamani, Ph.D. (left), and Galina Erikson, authors on the Wellderly study by Scripps Translational Science Institute. (Scripps Research Institute Photo) “Teasing apart the genetics of natural disease resistance could help us identify therapeutic targets to help prevent or treat age-associated diseases,” said Ali Torkamani, Ph.D., assistant professor and director of drug discovery at STSI and senior author of the article. Torkamani’s group found that the Wellderly had fewer genetic variants linked to Alzheimer’s and had a genetic modification that potentially helped protect them against this disease. This finding suggests that protection against cognitive decline could be at least one genetic feature of healthy aging. The Wellderly also had decreased genetic risk for coronary artery disease and a marginal, statistically not significant, decrease in stroke risk, which might be more significant in a larger group of participants. The researchers are continuing to recruit additional Wellderly participants to validate their initial findings. The STSI scientists say these findings represent only a fraction of the potential information that can be gleaned from the results, so they have publicly released the study’s genomic data to help promote additional discoveries by other investigators. This exemplifies one of NCATS’ key priorities: to foster collaboration and accelerate translation by publicly sharing data and resources. STSI is funded in part through NCATS’ Clinical and Translational Science Awards (CTSA) Program. STSI houses an arsenal of facilities, expertise and services that are available to its investigators to accelerate clinical and translational research. The Wellderly researchers used several STSI resources, including clinical trial coordinators to recruit participants* and biostatisticians and computational biologists to analyze and interpret the genomic data. The team also used REDCap, a CTSA Program-wide software tool, to collect participant data. *Inova Health Systems contributed DNA from the control group of older adults. Posted August 2016 | CTSA Program-funded researchers are studying natural disease resistance to identify therapeutic targets that help prevent or treat age-associated diseases. | /sites/default/files/ctsa-wellderly-authors_900px_0.jpg | CTSA Program-Supported Research Uncovers Genetic Components of Healthy | CTSA Program-funded researchers are studying natural disease resistance to identify therapeutic targets that help prevent or treat age-associated diseases. | /sites/default/files/ctsa-wellderly-authors_900px_1.jpg | CTSA Program Research Uncovers Genetic Components of Healthy Aging |
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