Despite remarkable medical advances, many conditions lack safe and effective therapies. More than 90% of drug candidates fail to make it to market [1, 2], and those that are successful gain Food and Drug Administration (FDA) approval after an average of 13 years in development and a cost of ∼$1 billion for a single drug [2]. Novel approaches to drug development would greatly facilitate the discovery of therapies for unmet medical needs. One such novel approach is drug repositioning, or finding new uses for existing compounds [3, 4]. By starting with compounds that have already undergone significant testing, drug repositioning dramatically cuts the time and cost necessary to bring a drug to market. This strategy is particularly applicable to therapeutics discovery for rare or neglected diseases, whose limited commercial potential attracts scarce funding from industry.

The Clinical Translational Science Awards (CTSA) Pharmaceutical Assets Portal was created with the goal of facilitating collaborative partnerships between industry and academic investigators for discovery of new indications for discontinued compounds [5]. The project focused on providing a mechanism for academic researchers to access compounds that are no longer being actively developed by pharmaceutical companies. De novo drug development is a lengthy, expensive process during which compounds are progressively evaluated for their therapeutic potential. Compounds can be discontinued at any stage for a variety of reasons, including lack of efficacy, insufficient therapeutic index, lack of commercial potential, and strategy-driven changes. Although it is difficult to estimate the exact number of shelved, discontinued compounds, clinical trial attrition rates suggest that, collectively, thousands of such compounds from decades of clinical trials may exist in industry repositories worldwide. Discontinued compounds that have been tested in humans represent a valuable scientific resource; however, to date, many of these compounds remain unknown to the academic research community.

The NIH Chemical Genomics Center (NCGC) has embraced the concept of drug repurposing by creating a comprehensive list of small-molecule drugs as well as a physical collection of these entities [6]. This invaluable resource encompasses FDA-approved compounds known through publicly available sources. The CTSA Pharmaceutical Assets Portal complements the NCGC’s approach by focusing on making available compounds that are unknown to the public because they were discontinued prior to FDA approval. Historically, identifying new indications for existing drugs has occurred through serendipity or chance observation. Notable examples include the blockbuster drugs sildenafil (Viagra) and minoxidil (Rogaine) [3]. Drug repositioning is significantly less costly than de novo drug development and has an estimated success rate of 30% [4]. However, fully exploiting this opportunity relies on collaboration between pharmaceutical companies and the researchers interested in testing these compounds.

Through public outreach, the Pharmaceutical Assets Portal brought multiple parties to the table, including academic institutions, pharmaceutical companies, government entities, and disease-specific nonprofit organizations. To date, the Pharma Portal has established an infrastructure capable of supporting future public–private partnerships in drug repositioning, including a national database of principal investigators with their respective biological models and delivery systems; a collaboration browser tool; a facility to house and maintain a compound repository; and a funding partner for repositioning studies. While the ultimate goal of creating a shared repository accessible to the academic community remains to be achieved, the CTSA Pharmaceutical Assets Portal has created a strategy and a mechanism to facilitate future opportunities for drug repositioning.

The CTSA Pharmaceutical Assets Portal

The CTSA Pharmaceutical Assets Portal (http://www.ctsapharmaportal.org) was initiated by the consortium of universities linked by the CTSA [5, 7]. The project’s mission was to create a public–private partnership based on collaboration among academic, government, foundation, and industry scientists to facilitate repositioning efforts by effectively leveraging the knowledge/expertise important to drug discovery and development. These matches are envisioned to ultimately result in an increased number of approved drugs for new indications and considerable public benefit.

In collaboration with Pfizer’s Indications Discovery Unit (IDU) and the National Center for Research Resources (NCRR), the Pharma Portal has made significant progress in establishing the infrastructure for such partnerships. Specifically, key elements comprising the Portal include (1) membership from 50 universities, (2) a tool for connecting partners and members (Foci-of-Expertise, [FoX]), (3) a funding arm (Partnership for Cures), (4) an Intellectual Property (IP) arm (the University-Industry Demonstration Partnership, UIDP), and (5) facilities/resources to house, maintain, and distribute the discontinued compounds (the Center for World Health and Medicine, CWHM) (Figure 9.1). Establishing an infrastructure with these elements was considered important to minimize barriers to collaboration. The resulting infrastructure provides a platform for promoting shelved compounds for further investigation and medical use. This chapter describes the evolution of the CTSA Pharmaceutical Assets Portal, the real and perceived barriers to creating public–private partnerships, and potential opportunities for moving forward.

The Pharma Portal Members

The success of the Pharmaceutical Assets Portal rests both with industry partners who provide access to compounds and the Pharma Portal members who seek access to these compounds. In an online, 28-question survey to recruit members, the “Portal” was described as a tool that would connect investigators to researchers with complementary knowledge and skills, as well as to pharmaceutical companies wishing to explore new indications for their active or discontinued drug programs. The survey was divided into categories related to demographics, research interests (by MeSH headings), and previous experience with transfer of compounds. It also tracked the sources from which investigators obtain information about investigational compounds. In addition, respondents were asked to provide their primary reason for seeking compounds, for example, for use in vitro or in animal models, to conduct clinical trials, or a combination of these reasons, and probed the success rates of obtaining compounds from industry. Finally, the survey sought to identify the barriers to such collaborations.

Between 2008 and 2011, a total of 696 individuals from 47 (85%) CTSA institutions, industry, and the NIH responded to the survey. The majority of respondents were physicians, with most self-identifying as institutional leaders or senior faculty. The primary focus of respondents was on clinical applications, with 80% stating that they would conduct clinical trials if the compounds of interest were made available. This response underscores the overwhelming interest in gaining access to compounds for clinical testing rather than for basic research purposes. The four most commonly reported diseases of interest included cancer and noncancerous diseases of the nervous, cardiovascular, and immune systems (Table 9.1). Approximately half of those surveyed had access to unique experimental models supporting their clinical research hypotheses, including animal models of disease; high-throughput, cell-based screening assays; or assays for specific molecular targets in the nucleus and cytoplasm. Many investigators expressed an interest in new routes of administration, novel delivery systems, and compounds/delivery systems that can cross the blood–brain barrier (Table 9.2).

Most respondents (58%) had previously requested compounds directly from the pharmaceutical industry (Table 9.3). More than half of the respondents had been “successful” (57%), while another 37% reported being “sometimes successful.” The relatively small fraction (4%) of those who had prior experience requesting compounds but were “unsuccessful” often reported that their success was limited primarily by contractual issues. Importantly, those who sought compounds desired a more efficient process by streamlining the negotiation process. The survey did not seek specific details of the contractual limitations, although our experience suggests that intellectual property and publication language are typically the most contentious. Lack of sufficient compound quantities or lack of a compelling business case were also frequently cited as reasons for refusal. Most investigators identified compounds of interest through public sources, such as the scientific literature, professional conferences, web searches, or by word of mouth. Fewer than 40% reported using commercial drug information databases—the subscription fees associated with these services may discourage their use. Our own informal research revealed that commercial databases capture only a portion of the potentially useful shelved compounds, perhaps 50%. This underscores the importance of projects such as the Pharma Portal, which aims to make available compounds not described in publicly accessible literature. The goals of the Portal project appear to be in alignment with the needs of this community, as evidenced by the fact that the majority of respondents (82%, 570/696) signed on to become members of the Pharma Portal.

One barrier to forming productive public–private partnerships is the difficulty in identifying companies and academic investigators with complementary interests. We specifically developed the Foci-of-Expertise (FoX) Synergy Browser, a graphical scientific search tool, to address this challenge. The browser extracts information from online biomedical resources and visually displays the relationships between researchers, diseases, and gene/protein targets. Moreover, search results specifically “highlight” members of the Pharmaceutical Assets Portal, allowing easy identification of researchers who wish to establish collaborative drug repositioning partnerships (Figure 9.2).

Currently existing browsers, such as BiomedExpert’s Collexis (http://www.biomedexperts.com/

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