Home Blog ORIEN:  Drug Discovery and Development Collaboration

ORIEN:  Drug Discovery and Development Collaboration

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The pursuit of a cancer cure represents a truly collaborative effort requiring both altruistic cooperation and the profit motive of self-interest and entrepreneurial ingenuity.  Worldwide a myriad of collaborative, team-oriented pursuits have materialized—in participation with entrepreneurial and commercial interests–holding tremendous promise.  It is needed. In the United States alone the specter of cancer is terrifying for anyone that has felt the pain, sorrow and personal calamity associated with the loss of a loved one to this terminal disease. This author has lost multiple family members to cancer—from a grandfather to an adopted sister. In one case it was at an older age but as a youth the view the rapid deterioration and death of a wise, sage was an awakening.  Some years later, an adopted sister who cared for me through the formative years of childhood died nearly as soon as she was diagnosed with a deadly form of brain cancer–her life ended so quickly.  Frankly that latter loss has never fully been processed to this day.

This life is precious and anyone of us has a number; cancer is actively seeking to steal those years in seemingly an indiscriminate fashion.  Time flies by and from one vantage, we don’t have much time left.  We covet our loved ones as long as we can enjoy them.  This primary and basic human need crosses all walks of life, demographic segments—all stations of life—we are all the same. And the fight against the assortment of ever-present cancer threats, represents a fundamental human project.

Grim Cancer Numbers

The Cancer reaper is busy at work in the United States. The National Cancer Institute (NCI) reports that close to 1.8 million people will be diagnosed with cancer and just about 610,000 will die. The most common forms of cancer include the following in ascending order:

  • Breast cancer
  • Lung & bronchus cancer
  • Prostate cancer
  • Colon cancer
  • Rectum cancer
  • Melanoma
  • Bladder cancer
  • Non-Hodgkin lymphoma
  • Kidney & renal cancer

Emerging Treatment Hopes

Cancer fighting technologies, platforms and treatments are rapidly advancing thanks to a dynamic, innovative and entrepreneurially-driven drug development marketplace.  Cancer treatments are advancing– and in some cases, in profound and revolutionary ways. New targeted breakthrough therapies such as various immunotherapy approaches are making a material difference.  From new monoclonal antibodies and checkpoint inhibitors to cytokines and CAR-T cell therapy to advancement in radiation and proton therapies to innovative combination treatments the blossoming  of new discoveries and breakthroughs to commercialization milestones, frankly, at least for this author, is nearly a miracle in and of itself—as compared to the reality of the 1970s or 1980s from what I remember was available as a child experiencing the loss of loved ones.

The breakthroughs have been made possible by a confluence of factors and forces including the dynamic fundamentals of both altruistic and self-interested forces. Put differently, a market-based economic culture offering vast economic rewards to those that succeed alongside the necessary co-partner (the collective and altruistic nature of humans) that from an evolutionary standpoint has been necessary for survival itself. The fight to cure cancer; or at least extend the survival period (so enabling the enjoyment of loved) ones company for at least some additional time–is a fundamental and universal need we all share worldwide. Most of us are altruistic– we sincerely want to save each and every person when we can; and possess self-interest—we can appreciate that material success goes to those that can create cures.

Enter ORIEN

A new and innovative collaborative initiative has emerged as part of the cancer cure advancement movement: ORIEN—the Oncology Research Information Exchange Network.  Founded in 2014, in just four short years and some change has evolved into a unique collaborative partnership including many of North America’s top cancer centers.  These preeminent institutions understand that collective, altruistic-driven behavior paired with self-interested, entrepreneurial pursuits—represent a fundamental underpinning and prerequisite for success in complex, scientific and technological pursuits. Members form a shared mission and directive to collaborate and share data to ultimately match patients to leading targeted treatments in the ongoing pursuit of cures. Those that can actually commercialize cures face the prospect of substantial returns.

ORIEN Founders include:

Key Members include:

The Value Proposition (Use and Exchange Value)

With a powerful ensemble of some of world’s top tier academic research centers (and minds) at work, core offerings make ORIEN stand out separate from others—they include:

  • The Common Protocol
    • All OIREN members use a single protocol—Total Cancer Care® (TCC). To date over 200,000 TCC consented patients have agreed to donate their tissue and clinical data for research to understand cancer at the molecular level. It represents one of the world’s largest observational research studies in cancer. These underlying consents enable collaborative members to share de-identified data to accelerate the development of precision medicine and treatments. This provides the intelligence powering the trial matching service. Because of the comprehensive patient data, access to member research programs as well as shared trial data, ORIEN facilitates a powerfully sophisticated and accurate way for researchers and clinicians to more expeditiously match eligible patients to clinical trials to ultimately conduct longer, more comprehensive and hence more valuable analyses.

With each new member comes exponential value with scale.  With precision methods (and advancements) comes the need for greater sharing. Molecular profiling of tumors shrinks the number of patients eligible for clinical trials of an agent that targets a specific mutation. As ORIEN has expanded, so does the addition of cancer patients to the TCC registry which adds cumulative value to ORIEN to speed clinical research and provide more cancer patients access to matching trials targeting their specific cancers.

  • National Clinical Trial Matching Service
    • ORIEN leverages M2Gen to analyze data from all participating ORIEN centers to quickly and precisely connect patients with clinical trials based on their molecular profile. ORIEN provides the information and tools needed to study the long-term effects of disease, while assisting cancer center member institutions in their development of precision medicine. M2Gen is Moffit Cancer Center’s wholly owned, for-profit, informatics solution subsidiary advancing personalized medicine. Using a rapid learning approach, M2Gen helps accelerate precision medicine research pursuits by creating evidence and knowledge-based solutions that identify a patient’s susceptibility to disease, offer prediction services as to how any one patient will respond to a particular drug and includes a matching engine—bringing specific patient condition to the best therapies for optimal treatment outcomes. ORIEN offers via M2Gen, a huge, cancer-focused biorepository linked to incredibly value-added clinical and molecular data.
    • M2Gen was founded in 2006 at the Moffit Cancer Center to “operationalize the Total Cancer Care Protocol”—the unique approach to studying patients throughout their lifetime. M2Gen forms a fundamental technology and operational component to ORIEN. The Avatar™ offering is built on the M2Gen engine.
  • Powerful Shared Continuous Learning Platform
    • ORIEN participants have unrivaled access to the collective’s large, shared data warehouse. An treasure trove for scientists, researchers and investigators to ask new questions, formulate new, improved hypothesis, develop superior, competitive grant submissions and participate in cross-institutional collaborations and biomarker discovery programs with not only academic partners but also commercial sponsors. Truly establishing the conditions for two fundamental elements necessary for complex, technological and scientific progress to occur—collective, altruistic-based sharing affords the opportunities for individuals and organizations to develop competitive advantage for either non-profit fund raising, academic scientific pursuit or private sector advantage. We all likely benefit when the system unfolds in such a manner.
  • Patient Access Opportunity
    • A growing number of initiatives, from federal funding in precision medicine to foundation and university and commercial grants—produces a collective spotlight on new cancer treatments. The more ORIEN leadership promotes and supports growing collaboration the greater the benefits to patients (and family members) struggling with various forms of cancer affliction. A growing array of targeted investigational therapies become available for those facing dire situations. With the growth of ORIEN membership means new participating centers and not only more targeted investigational potential investigational opportunity but also more geographic choices.  The expansion of ORIEN means patients have closer access to an ORIEN participating site. Imagine has new technologies become organically included—from connected, GcP validated smart phone apps to telehealth platforms facilitating even enhanced patient engagement.

 The World Starts to Notice

The world began to notice with active deal making starting a year or so after inception.  The evolution of this intriguing and important collaborative structure has continued—how it will evolve will be influenced by both the need for ongoing altruistic cooperation as well as successful entrepreneurial conversion and execution.  A core technology component, M2Gen, for example, recently received a $75 million capital infusion from the venture arm of Heart Corporation. The capital infusion was raised to support the expansion of ORIEN to support data sharing among the participating members. A brief digression of interest. Hearst’s origins are publishing—in fact—one of greatest films of all time—Citizen Kane—depicted Orson Wells playing what was really Hearst as the powerful and isolated mogul and the building of the famous Hearst Castle in California.  Ultimately, Hearst (portrayed a Foster Kane) sought only one thing—his home and his parents love who were long gone—reflected in the symbolic burning of his childhood sled—Rosebud.  All his money couldn’t buy that basic need back. We desire our loved ones to be around as long as possible! Truly interesting to anyone with historical perspective that Hearst made the funding happen.

According to a GenoneWeb article, Hearst Business Media president Richard Malloch noted “M2Gen’s unique ability to pair a person’s clinical and genetic data for analysis puts it at the leading edge of genetics-based oncology research, and we are eager to extend Hearst Health’s reach and make an important contribution to this new area of science.”  Hearst not only has a quest for a robust ROI—they also understand the collective need we all have to fight cancer.

The Introduction of Avatar™

In 2016 M2Gen announced the launch of Avatar™ with oncology-focused biopharma Celgene to leverage the ORIEN TCC protocol– the prospective observational study enrolling patients with various cancers and the valuable insights and information this collaborative is producing. Japanese pharma Takeda joined shortly thereafter. During 2016 M2Gen structured a deal with DNAnexus to manage the molecular data for the Avatar program. The parties established a technology foundation to unite the participating academic cancer centers with commercial biopharmaceutical sponsors in pursuit of the shared goal to develop more precise cancer treatments for patients.

Industry Sponsors Take Notice

By 2017, a growing number of industry sponsors (e.g. biopharma) were approaching ORIEN (and M2Gen) to contribute financial support in exchange for access to deidentified genetic and disease information utilized to inform the discovery and clinical development of novel cancer therapeutics.  Industry sponsors understood that collaborative undertaking participation wasn’t a luxury—but rather a necessity. With the cost of bringing drugs to market at $2.6+ billion (along with 10 to 15 years and a high probability of failure) industry sponsors increasingly accepted that their projects would continue to fold when investigators simply couldn’t identify sufficient numbers of cancer patient sample size for a trial.  They must tap into initiatives such as ORIEN. The Cancer Letter reported, for example, Celgene’s Michael Pehl, president of hematology and oncology noted “The ORIEN Avatar program is a standout in its approach to patient information gathering and sharing to form a more efficient system.” Pehl continued “this wealth of clinical and molecular data will potentially lead to a better understanding of molecular properties that are involved in patient’s disease and what treatment designs might be most successful in battling their cancer. Building this resource in a multi-partner collaboration creates a wealth of data, which will potentially lead to better outcomes for patients.”  American giant Merck & Co joined the collaborative in 2017 understanding what Celgene and Takeda has already figured out. Of course Merck could infuse synergistic intelligence and energies into the collaborative–it learned something about developing cancer therapies in a unorthodox kind of way. They were smart enough to buy Schering Plough—which had picked up Organon. It was there that researchers Gregory Carven, Hans van Eenennaam and John Dulos invented pembrolizumab. Schering Plough lost interest and then so did Merck—nor did Merck have much oncology expertise.  However, Bristol Myers Squibb published a paper in NEMJ evidencing the strong promise of a checkpoint inhibitor—ipilimumab—that it could treat metastatic melanoma and that another investigational target—nivolumab (OPDIVO) showed great promise. Upon an intellectual deep-dive into the paper, Merck’s entrepreneurial instinct and scientific pedigree kicked-in—and thereafter they promptly reactivated the pembrolizumab program and filed for an IND in 2010. They mobilized a key oncology expert in management—Martin Huber—to drive the development of pembrolizumab. The rest is history. Known as Keytruda, it is an immensely successful humanized antibody used in cancer immunotherapy—it’s sales will cross $9 billion in 2019 making it one of the world’s most successful drugs. Merck’s entry, participation and dynamic engagement with the ORIEN collective will only make it better in so long as it remains true to the underlying altruistic principles driving health care while pairing with entrepreneurial R&D and commercialization ingenuity.

Big Data Affords New Opportunity

ORIEN continues to invest and expand its big data capabilities.  One account reveals by incorporating broad molecular analyses to facilitate research of targeted therapies whole exome sequencing (WES) and RNA sequencing are performed on a tumor and WES is performed on germline tissue by the HudsonAlpha Institute for Biotechnology in Huntsville, Alabama. In another example, patients and clinicians can benefit in myriad ways. A physician caring for a patient with pancreatic cancer in the ORIEN program can secure molecular data on that specific individual. This empowers the patient’s physician to potentially personalize the patient’s treatment plans by following them retrospectively noted Daniel M. Sullivan, MD Associate Center Director for Clinical Science at Moffit Cancer Center (ORIEN founder) and Chief Medical Officer for M2Gen.

Precision data leads to the potential ability to address health inequities. For example the American Association for Cancer Research (AACR) recently launched a collaborative initiative to address cancer health disparities in the African American population of the United States. Known as the 2020 initiative, its principals will facilitate the sequencing of cancer genomes from 2,020 African American patients by the year 2020. ORIEN represents a key infrastructure partner for this most important health equity initiative.  After all, blacks have the highest death rate and shortest survival of any racial/ethnic group in the U.S. for most cancers. The causes of such inequities can be considered “social determinants of health” and include a complex array of social, economic disparities perhaps more than biological differences. Overall, the racial disparity in cancer death rates is coming down but death rates are still considerably higher when compare to whites, for example. ORIEN data accessibility and insights, undoubtedly will provide a fundamental role in supporting this important program.

Challenges 

In 2018 ORIEN participant investigators published an academic report titled “Patient Enrichment for Precision-Based Cancer Clinical Trials: Using Prospective Cohort Surveillance as an Approach to Improve Trials.” The ORIEN authors summarize that while technological advanced have led to compelling identification of biomarkers and development of novel target-based therapies, new challenges have emerged from the prevalence and diversity of biomarkers and targets in patient populations—especially for cancer patients—in the design and performance of traditional clinical trials. The authors propose that a prospective cohort surveillance of patients could represent a solution to support and facilitate the more effective and efficient pairing of cancer patients in dire need with the right targeted clinical trial. Undoubtedly the findings and recommendations that arise from the continuous accumulation of data sharing at scale will lead to both more challenges and opportunities.  New breakthroughs will emerge.

Conclusion

This article is meant to be an upbeat introduction to ORIEN. It represents a transformational collaborative effort, at scale, that undoubtedly will produce considerable contribution to the fight against cancer. It is founded on a fundamental principle that collaboration and sharing can, combined with support for entrepreneurial pursuits can lead to new cancer cure discovery.  It rests upon an age- old premise that human survival requires altruistic and self-interested forces. Founded, in 2014, it is but a baby when considering the lengthy timelines associated with drug development–it is still in its infancy. After all, the average time to develop and commercialize a drug may be 10 to 15 years and over $2.6 billion dollars.  Yet in just 4 years they are approaching 200,000 patients in what has become one of the most comprehensive observational studies worldwide.  The patient base expands—by some reports adding 50,000 patients per year. It certainly will be exciting to start seeing new outcomes that will help loved ones enjoy each other—at least for a while longer.

Author

Daniel O’Connor

Mr. O’Connor has spent nearly 20 years providing technology and value-added services to the clinical trials and health technology industry. An entrepreneur, he has been instrumental in building different ventures focusing on FDA 21 Part 11 enterprise document management, technology-enabled patient recruitment services, clinical safety data exchange, as well as population health and community care coordination for at-risk populations with Eccovia Solutions. He is a co-founder of a public benefit corporation launching a global clinical research site accreditation standard–ACRES ReServ. At TrialSite News Mr. O’Connor and team have developed a comprehensive clinical research site data base and intelligent clinical news curation engine to contribute to clinical research transparency with a focus on sites and investigators. He earned his combined MA and JD from the University of California (Los Angeles and Hastings College of the Law) and undergraduate from San Francisco State University.

 

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