Patient-Driven Data Platform for Rare Disease

400 million people worldwide live with one of 7,000 rare diseases, 95% of which don’t have an FDA-approved treatment, let alone a cure. Epidermolysis Bullosa (EB), is a devastating and life-threatening genetic disorder that affects children from birth. EB is not specific to any socioeconomic status, race, ethnicity, or gender and affects an estimated 500,000 people worldwide. Like in many other rare diseases, centralized EB datasets and trusted resources for patients and investigators are sparse, hindering progress to effective therapies. For example, in 2010, EBRP established the Epidermolysis Bullosa Clinical Research Consortium (EBCRC), a group of 22 centers of excellence across North America that record EB patient data in the Epidermolysis Bullosa Clinical Characterization and Outcomes Database (EBCCOD). Unfortunately, the EBCCOD data is not easily accessible to investigators nor patients, is incomplete with only 44% of patients having undergone genetic analysis, and is not adequately built to efficiently connect patients with investigators and companies performing clinical research and trials. Our platform aims to collect comprehensive patient data, allowing patients themselves to directly contribute health information, and make it accessible to all stakeholders to accelerate therapy development. 

We set out to answer one question: How can we help Investigators and Patients quickly and easily access phenotype and genotype data? What if we could make navigating the researcher and patient journey as easy as entering a destination into GPS? Where right turns are the right treatment for the right patient at the right time and the destination is a cure. A world where siloed rare disease data is shared amongst researchers. A world where doctors can collaborate in real time. A world where patients can participate by providing their unique information and receive a curated mapped journey. Biotech and pharma companies can connect with the patients who are right for their clinical trials. A world where patients go from the fear of the unknown, to knowing exactly the best doctor within 100 miles, the best treatment based on patients just like them, and sit in the driver's seat on the road to a cure.

Built with Amazon Web Services (AWS) and Stanford Medicine, our solution is a data platform that centralizes comprehensive patient data, resources, and clinical trial information that is accessible to EB investigators, patients, and industry partners to streamline the process of discovering cures. Investigators and patients log in to separate portals on the web or app version and navigate dashboards made specifically for their needs. Investigators can use AWS’ suite of analytic tools to evaluate patient data and research new therapies, update clinical trial information, and directly interface with patients. Patients can directly contribute their health data, request at-home genetic testing kits to pinpoint their exact mutation, be matched to specialists and clinical trials applicable to their unique condition and location, and opt in to be connected to similar patients and families. This project began with a question: what if we could make navigating the researcher and patient journey as simple as entering a destination into your GPS? Except for us, that destination is a cure. 

Currently there are 500,000 people living with EB, approximately 50,000 in the United States. Individuals with EB lack proteins (collagen 7) that connect their two layers of skin, causing open external and internal wounds, disfigurement, severe pain, and more. Called “Butterfly Children” because their skin is as fragile as the wings of a butterfly, children with severe EB face shortened life expectancy, ranging from infancy to 30 years of age. There is currently no treatment or cure for EB, and parents and patients must be on constant alert for new wounds with bleach baths, drug store creams, and gauze as their only available protection against new injury and infection. Further, EB patients do not have a valid technology source for accurate information regarding their care, connection to other patients and families, and clinical trials they are eligible for. Many patients and families engage via social media groups and, while this provides a sense of community, the information is not guided by medical professionals nor is it curated to the specific needs of the individual’s disease type. EB ranges in levels of severity from life-threatening to chronic disease. Families often see information on social media that can be alarming and inaccurate without knowing how this applies to their individual condition. Additionally, these groups are not connected to trusted and easily navigable resources regarding new research and clinical trials. ClinicalTrials.gov, for example, has a wealth of information on clinical trials for EB, however its unfriendly interface and highly scientific explanations are discouraging to patients and caregivers searching for clinical trials they may be eligible to participate in, creating a barrier to study recruitment. Lastly, patients and families living with rare disease have a high willingness to partake in research and data sharing that can advance treatments and cures for their disease. However, no platform currently exists in which they can not only share data, but also receive updates that may inform their care and connection to research, clinical trials, and patients and families similar to them. 

Our data platform directly addresses these major problems facing the EB community and rare disease community at large: no effective treatments and cures, lack of access to trusted resources, and inability to partake in the research process. First, the platform will provide a comprehensive longitudinal database to doctors and researchers around the world looking to improve patient care and research therapies with potential to treat and cure this devastating disorder. Second, the platform acts as a GPS for the patient journey, connecting patients to verified information on best care practices, doctors and clinical trials near them, and similar patients to create community. Lastly, our direct-to-patient initiative allows patients to provide their own health data and even request at-home genetic testing kits, giving them agency over their care and participation in finding cures for their disease. To launch the patient-facing side of the platform, we have engaged a focus group of 25 patients and caregivers to provide feedback and frame our build to best accommodate their needs.

EBRP was founded in 2010 by a group of parents set out to save their children’s lives along with Jill and Eddie Vedder (Pearl Jam) with one bold audacious goal: cure the devastating and life-threatening genetic rare skin disease epidermolysis bullosa (EB) by 2030 and in the process pioneer an innovative business model to lead the way for 7,000 rare diseases that affect 400 million people. EB Research Partnership has a proven history and plan to scale. In under a decade, we’ve funded over 100 projects, increased the number of EB clinical trials by 20x, formed three new companies, and struck nearly 75 venture deals with businesses and universities. Since our inception, besides 107 research projects (leading to 20x more EB clinical trials - from 2 to now more than 40), for the first time there are 4 Phase III clinical trials that are in the final stage before FDA approval. Of the four Phase 3 clinical trials - Amryt's Oleogel-S10, Abeona's EB-101, Castle Creek's DeFi-RDEB, and Krystal's KB-103 - EBRP was an early investor in Abeona, Castle Creek, and Krystal (all gene therapies), as well as several promising Phase 1 and 2 trials. 

EBRP is the largest global funder of EB research. Parents of kids with EB, and their communities can trust that when they support EBRP, 90% of all funds raised go directly to fund lifesaving treatments and ultimately, a cure for EB. In addition, even with a small team, we are in constant contact with the EB community and will continue to integrate them within this project. Specifically, to launch the patient-facing side of the platform, we have engaged a focus group of 25 patients and caregivers to provide feedback and frame our build to best accommodate their needs. Our progress and our mark has been made, and we have cemented ourselves as a trusted source in the EB community. 

With the guidance of our founders and other Board and staff members who live with EB or are EB parents, the EBRP team remains driven to fulfill our mission. Additionally, expert EB clinician and researcher Dr. Jean Tang of Stanford Medicine is the principal investigator of Cure Curator. Along with her team, Dr. Tang meets with EB patients every day and is intimately aware of their medical reality and desire for a future without this devastating disorder. With Stanford Medicine as a partner, our platform will not only be effective, compliant, and poised for use by both investigators and patients, but driven by their passion to provide unmatched care to patients. Lastly, the AWS team built the architecture for Cure Curator using state-of-the-art technology, ensuring security, compliance, and innovation. Together, these three organizations ensure the mission to better patients' lives is both the primary focus and one that will be fulfilled.

400 million people live with one of 7,000 rare diseases, 95% of which don’t have an FDA-approved treatment, let alone a cure. Centralized data sets and trusted resources for rare disease patients and investigators are sparse, fragmented, and not shared among the communities they are meant to serve. Our Cure Curator platform directly addresses these problems facing the EB and rare disease communities: no effective treatments, lack of access to trusted resources, and inability to partake in the research process. First, the platform will provide a comprehensive longitudinal database to doctors and researchers around the world looking to improve patient care and research therapies to treat and cure this devastating disorder. Second, the platform acts as a GPS for the patient journey, connecting patients to verified information on best care practices, doctors and clinical trials near them, and similar patients to create community. Lastly, our direct-to-patient initiative allows patients to provide their own health data and even request at-home genetic testing kits, giving them agency over their care and participation in finding cures for their disease. 

Children with EB face excruciating pain and suffering everyday, our mission and this project seeks to urgently change that. With a shortened life expectancy ranging from infancy to 30 years old, there is currently no treatment for EB, and parents and patients must be on constant alert for new wounds with bleach baths, drug store creams, and gauze as their only available protection against new injury and infection. Called "Butterfly Children" because their skin is as fragile as the wings of a butterfly, children face severe pain, open external and internal wounds, and a grueling daily bandaging process. Daily activities such as eating, walking, and sleeping become monumental tasks. 

Together we can change this. Because EB is often caused by one-genetic mutation, and with the rapid advancement of technologies such as gene-editing, leading researchers believe we can cure EB by 2030 and lead the way for millions of people with rare diseases. EBRP has funded more than 100 projects around the world to drastically transform the landscape, from only 2 clinical trials in 2011 to nearly 40 clinical trials, including for the first time ever four Phase III clinical trials, the last phase before the first treatment is approved. Out of the active 39 clinical trials, EBRP has been involved in 19 of them, which is a testament to our innovative model, and world-class independent Scientific Advisory Board.

Our solution’s innovation comes from its power to centralize data and encourage collaboration, especially by giving patients agency over their own health information and care. Natural history studies, phenotype and genotype data, and biorepositories all exist in EB, however they are siloed in individual academic medical centers, limiting research breakthroughs. Pharmaceutical and biotech companies spend valuable time compiling their own natural history studies to prove their interventions in regulatory settings and identify eligible patients for trials, lengthening the process to gain drug approvals. And, most importantly, patients can only interact with the research process and receive quality care by visiting hospitals with trained staff that actively record EB-specific data, prohibiting significant support of the overall patient population, especially in a rare disease where patients are already scarce and scattered throughout the globe. Our platform tackles each of these difficulties by putting patients in the driver’s seat, able to dictate if they want to share their data, raise their hand to be contacted by clinical trial coordinators, and contact specialists or patients like them for care advice, all from the comfort of their own homes, wherever they may be in the world. The Patient-Driven Data Platform for Rare Disease Platform aims to democratize exceptional care and the research process to accelerate effective treatments and cures for rare disease patients.

The goals of the direct-to-patient program this year are (1) to add critical genetic data that is currently missing in patients with a clinical EB diagnosis and (2) to record and analyze genetic information and clinical events to evaluate genotype-phenotype trends. In our 50 patient pilot, we will primarily enroll patients with recessive dystrophic EB (RDEB), a severe type, as there is a pronounced unmet need for increased genetic testing in this population. Previously, diagnoses were based on immunofluorescence and electron microscopy, which included subjective analysis causing inconclusive results. An accurate diagnosis is crucial for family planning purposes and clinical surveillance. Furthermore, lack of a genetic diagnosis hinders research recruitment and participation. It is estimated that over 12,500 individuals with RDEB live within the US. Cure Curator would provide all EB patients, regardless of type or location, with an opportunity for genetic diagnosis that they otherwise may not have had and enhance participation in future clinical trials. Secondly, efforts have been made to predict milestone clinical events like G-tube insertion, complete mitten deformity, and squamous cell carcinoma onset, based on subtype diagnosis to accurately and definitively counsel families about their child’s expected disease course. Genetic testing will bolster those efforts by making patient connections at the DNA level. While our 1-year goals are EB-focused, 80% of all rare diseases are genetic and can benefit from the precision of genetic testing.

Year 1 Metrics of Success: 1. Number of Participating Patients providing Genotype & Phenotype Data: (Target: 50)  2. Number of Referrals to Clinical Trials (Target: 25) 3. Number of Surveys Completed (Target: 40) 4. Values of  Surveys (Target: 50 unique clinical and patient reported fields)  

Impact Aim 1: Add critical genetic data that is currently missing in patients with a clinical diagnosis of EB and to  collect key clinical data that is often not available in the current database.  

Impact Aim 2: To record and analyze genetic information and clinical events to evaluate genotype-phenotype trends.  Our hypothesis is that EB patients with more severe mutations (resulting in premature termination codons) will  correlate with more severe clinical features (for example, more frequent esophageal dilations, more wounding, more  severe anemia, earlier age of SCC onset).

The cloud-based Patient-Driven Data Platform for Rare Disease aims to build 6 critical outcomes as the core functionality of the product, with EB as the use case however building each feature with the capability to scale to any rare disease, given the shared necessity for this data to overcome barriers to accelerate the development of life-saving treatments and ultimately cures via patient participation and engagement.    

Patient at Home Genetic Sequencing from GeneDX

• GeneDX has a CLIA-certified gene panel test using whole exome capture and sequencing. Once a Patient/ Caregiver registers on our platform, they can consent and request an at home genetic testing kit which will be sent via GeneDX, and once received back by GeneDX can by analyzed and shared on the AWS platform for use by Investigators and Patients/ Caregivers.

• Patient/ Caregiver Connection to Clinical Trials

  • On our existing AWS Investigator Platform, we have already built an interface with ClinicalTrials.gov via their API to ingest, analyze, and organize EB clinical trials in real time . Patients/ Caregivers would be able to search EB clinical trials in a user friendly way based on location, academic medical center, disease subtype, age, and the status of the trial.

• Patient/ Caregiver Connection to other Patients/ Caregivers 

  • Once a Patient/ Caregiver registers on our platform they can choose the option to be connected to other patients and families like them, they can “match” them to one another based on criteria such as 1. Disease Subtype 2. Age 3. Location. 

• Patient/ Caregiver Connection to EB Doctors and Medical Centers  

  • Once a Patient/ Caregiver registers on our platform they can choose the option to be connected to EB Doctors and Medical Centers within a range of their location, given the choice to “Find the Best EB Center within 50 miles, 100 miles, 250 miles, 500 miles, etc”.

• Patient/ Caregiver Connection to Resources Based on Their Disease Subtype

  • Patient/ Caregivers can receive access to medical professional validated resources based on their subtype of the disease including videos on treatment resources, treatment guidelines and protocols, mental health resources, and recent publications and news. 

• Patient/ Caregiver Surveys

  • Patient/ Caregivers will complete survey information that will speed patient enrollment and build the patient voice and validate patient reported outcomes for research studies and future FDA clinical endpoints. We have already built a dashboard with analytics on a EB patient survey conducted in 2016, EBCares data.

Built on AWS architecture by Envision Engineering and the AWS ProServ team, the Cure Curator Platform touts state-of-the-art software for data ingestion (AWS Lambda, AWS Glue), analytics (BioConda/Python/R, Amazon EC2), storage (S3 servers, AWS ElasticSearch), and reporting (AWS QuickSight) with APIs for a seamless user experience. Our genomic sequencing partner is GeneDX, founded in 2000 by two scientists from the National Institutes of Health (NIH) to address the needs of patients diagnosed with rare disorders and the clinicians treating these conditions. Today, GeneDx has grown into a global industry leader in genomics, having provided testing to patients and their families in over 55 countries. Led by its world-renowned whole exome sequencing program, and an unparalleled comprehensive genetic testing menu, GeneDx has a continued expertise in rare and ultra-rare disorders. GeneDX has a CLIA-certified gene panel test specific to EB- EB XomeDX Slice- using whole exome capture and sequencing, all of the known genes for the various forms of EB (Dystrophica, Simplex, Junctional) can be analyzed at one time, achieving substantial savings in both cost and time, with little loss of sensitivity. In most cases, this should now be the test of first choice for a new patient with the diagnosis of EB and many other rare diseases.

EB is is not specific to any socioeconomic status, race, ethnicity, or gender, however often research and clinical trials is not representative of the diversity of the disease. In order to address representation and equity we would set goals for research recruitment that more accurately represent the ethnic diversity of the disease. Through our work with Harvard Business School’s Kraft Precision Medicine Accelerator, we have been introduced to the group Joy Collective, a Minority Certified owned company with experience in reaching minority communities. They have “expertise in multicultural marketing and communications, and the ability to segment (and then speak to) specific audience segments based on unique attitudes, lifestyles, and behaviors of a particular audience”. We would seek to work with Joy Collective or a similar group to prioritize participation of underrepresented communities. We also would ensure our Patient Advisory Board was composed of a diverse group or leaders.

We are currently working to enhance diversity, equity, and inclusion among our staff as well as our Board and research. We have established a Committee on our Board to address these important issues. The Committee’s focus is to ensure we are prioritizing diversity, equity, and inclusion in all aspects of our organization. Currently steps we have taken are: 1) As a member of Harvard Business School’s Kraft Precision Medicine Accelerator, a small group of CEOs of the leading medical research nonprofits, we have identified addressing disparities as a core component of our work and have brought in experts to discuss how diversity, equity, and inclusion can be reflected from research recruitments to staff and Boards 2) Our Board reflects inclusion of patients and patient parents (6+) as well as our staff representing the patient and diversity communities  3) Including Equal Opportunity Employer statements in every job posting.  While we have taken small steps, we are committed to taking larger steps to further enhance diversity, equity, and inclusion as a core principle of our company culture. 

EBRP believes that universal participation in data collection from all demographic groups is essential to embed equity into this next chapter of health care. The data will be collected for epidermolysis bullosa (EB) research, but the work will inform gene therapy research for other diseases. Specifically, this project will focus on the inclusion of demographic groups who typically do not participating in research because of barriers created by lack of access to researchers and clinicians, cultural considerations, or low levels of medical literacy. This outreach will take time and effort, but it is critical for the development of equitable health outcomes for all people through curative gene-therapies. 

EBRP funds research to discover treatments and cures for EB and, in the process, pioneer the model to cure all rare disease. Currently, no treatment or cure for EB exists like 95% of all rare diseases. EBRP rejects the standard nonprofit tradition, using a Venture Philanthropy business model to exponentially increase our impact.

At EB Research Partnership, we see our 501(c)3 nonprofit status as a tax code, not a business model. We choose to run our foundation more like a venture capital firm than a traditional nonprofit. Often medical research foundations pass through donations from patients and supporters directly into academia and industry yet have no role or financial reward in what happens to the research after that. We directly disrupt the old model by giving the patients that support us a seat at the table by only investing in projects that can result in a meaningful therapy or a potential cure in the next 3-5 years and negotiating a share of

the intellectual property, when this researcher becomes commercialized we share in the returns with pharmaceutical companies, and instead of going to executives or shareholders our returns go right back into research until we find a cure for EB, into the hands of our shareholders: patients. This also creates a more sustainable business model in which now we have a revenue stream coming from outside of traditional methods like donations and galas, we have built a new source of funds: return on venture investments.

The key goals of the Venture Philanthropy fundraising model is to:

1) Rapidly accelerate treatments and cures for EB,

2) Create an innovative and sustainable funding model,

3) Build a bridge between patients, research and industry and

4) Pioneer the model for all rare diseases.

We have established leadership and proven results in venture philanthropy, here’s a real life example of how it works for a research project we invested $500,000 in that returned $6,000,000 to our foundation in just three years:

• We’ve worked with a university to develop a gene therapy treatment for severe EB that corrects gene mutations in skin cells.

• When a public company uses that intellectual property to make a treatment, we receive stock in the company.

• That stock can grow to worth multiples beyond our original investment. Earning potentially several million dollars in

additional funds for EB Research Partnership.

• Through a venture philanthropy agreement with an academic medical center and publicly traded biopharmaceutical company,

EBRP saw a 12:1 return on investment in 3 years.

• That allows us to fund even more research now to expedite funding a cure.

• It’s a hopeful time. Thanks to partners and collaborators, more EB trials will happen in EB in the next three years than the last

ten years combined.

• The technology EB researchers are developing could be applying to thousands of other rare genetic diseases that affect 10>#/p###

of the population.

• Donations are thus able to go a really long way, giving back time to those who need it most.

EBRP’s model has been praised for its leadership by Harvard Business School, Yale University, and the Milken Institute FasterCures.

As the largest global organization funding EB research, EBRP is committed to supporting this project long-term as a key driver to accomplish our mission: accelerating life-saving treatments and cures for EB. EBRP will budget a minimum of $1 million annually to cover the cost of internal technology staffing, product development, enhancement and maintenance, cloud computing and storage costs, UX design and development, and onboarding additional medical centers and individual patients. As the product scales, costs can also be supplemented by revenue derived from biotech and pharmaceutical industry partners, who have a significant need for data to support drug discovery and regulatory applications and budget for this cost.

In addition, at EBRP we actively apply for grants for this particular project, and also discuss with our biggest donors, supporters and stakeholders, specifically those who are looking to make an impact beyond just EB.

 While we intend for academic researchers to have free access to the database, we can charge industry partners a fee to access and analyze the database when bringing new therapies to market. Additionally, we plan to license the product to other non-profit medical research foundations.

In 2021, EB Research Partnership was selected as an AWS Imagine Grant winner for the "Go Further, Faster" award, receiving up to $150,000 in unrestricted funding, up to $100,000 in AWS Promotional Credit, and engagement with AWS technical specialists. The award will support development of EBRP's first-of-its-kind collaborative data platform to unites scientists, industry, and patients to accelerate outcomes in Epidermolysis Bullosa research that will also benefit the field of rare disease research.

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