In the spring of 2014, Robin Smith and Kate Blanchard launched a new venture, which they named Orig3n. They had spent the previous three years at Perkin Elmer after it acquired their last startup, Artus Labs (Smith’s third company). By the end of their tenure at Perkin Elmer, Robin was head of global R&D and Kate was running the Tibco software business. While the experience at Perkin Elmer was invaluable, they again felt the entrepreneurial drive to build a new company.
Smith and Blanchard were looking for an exciting new technology to leverage for their new venture. Just two years earlier, in 2012, the Nobel Prize for Medicine was awarded to Shinya Yamanaka and John Gurdon for their work generating stem cells from adult cells. The process they developed identified four transcription factors which, when delivered into the cell nucleus, could induce somatic cells, such as skin or blood cells, to a state similar to embryonic stem cells. Cells created using these “Yamanaka factors, are called induced pluripotent stem cells or “iPSCs” for short. Due to their pluripotent nature, iPSCs can be turned — or “differentiated” — into almost any cell type in the body, such as heart, liver, retinal and blood cells, and even neurons. Additionally, the cells can be made in quantities sufficient to serve large patient populations. To date, over 200 cell types have been produced from iPSCs.
Upon learning of this technology, Smith and Blanchard knew that they had found the concept around which they would build their new company. They quickly realized that Orig3n’s mission would be to accelerate the future of regenerative medicine by developing cell therapies that would benefit people everywhere. Along the way, they built the world’s largest crowdsourced cell bank for regenerative medicine and the largest suite of direct-to-consumer lifestyle DNA tests on the market.
One of the biggest challenges facing cell therapy companies is sourcing cells from healthy donors in order to create cell therapies. Orig3n initially believed that it could purchase a sufficient number of cells from research labs and other institutions, but quickly learned that these cells had been donated for research use only, and could not be used for commercial applications. Alternatively, iPSC cell lines could be purchased from companies like Cellular Dynamics (now owned by Fuji), but at a high cost. As a result, the company decided to build its own cell bank.
As an experiment, Orig3n sponsored the Beach to Battleship triathlon in Wilmington NC and hosted a small tent for blood donation for the purpose of advancing regenerative medicine. To the company’s pleasant surprise, people stood in line to donate blood. Orig3n repeated this experiment at several additional events and found the crowds equally as receptive to its message: that one could donate blood which could someday be used to create cells to help treat disease. Realizing that this message was resonating with event attendees, the company accelerated its blood collection efforts by attending hundreds of events such as marathons, triathlons, Spartan Races, Tough Mudders, Wizard Worlds, and Comic-Cons, across the country. As a result of this effort, Orig3n was able to quickly collect enough samples to create a cell bank for therapeutic purposes. To date, these cells are matched to the immune profiles of over 90% of the U.S. population (see “HLA Matching” section below for more information).
Direct-to-Consumer Lifestyle DNA Tests
In the course of collecting blood for its cell bank at events, Orig3n found a group of people eager to contribute to future therapies and who also wanted to learn more about themselves. The blood collection teams were consistently asked what Orig3n could tell the donors about their own health from the samples they were giving. The number and frequency of these unexpected inquiries sparked the idea of developing genetic tests that were both fun and informational. The tests were developed to not only offer direct, affordable access to genetic information to the public, which was consistent with Orig3n’s mission to help improve people’s lives via new technology but also to serve as a source of revenue for the company. Smith and Blanchard realized that the market for these products was significant and accelerating, and believed that revenues from sales of the tests could serve as a non-dilutive source of capital that could sustain, at least in part, Orig3n’s research into cell therapy programs, a unique advantage for a biotech company.
Orig3n’s initial attendance at fitness-related events attracted individuals who had an interest in their own athletic potential. This inspired the first DNA test, Fitness, which is a 27-gene profile that indicates an individual’s fitness potential with respect to endurance and strength.
As the variety of events expanded, inquiries regarding different types of genetic information emerged, and five additional tests were launched that examine genetic predispositions towards characteristics such as nutrition, beauty, behavior, and child development. The company also launched a whimsical test called Superhero for their participation at Comic-Con and Wizard World conventions, which offers information regarding genetic predispositions for speed, intelligence, and strength. Currently, Orig3n offers 18 different DNA tests on its website. A small subset of the company’s portfolio of tests is featured below.
To interpret the DNA needed for its tests, Orig3n’s customers apply a swab (similar to a Q-Tip) to the inside of their cheek for 20 seconds, register their sample online, and return it to the company via a pre-paid envelope included as part of the test kit. After 1-2 weeks (which the company believes is one of the fastest turnaround times in the industry), customers can access their results electronically, either via Orig3n’s LifeProfile iPhone app, or its lifeprofile.com website, enabling customers to quickly and easily see their results anytime, anywhere, and to share them with healthcare providers, personal trainers, friends, family, nutritionists, or anyone else they’d like. An example of results in Orig3n’s LifeProfile iPhone application is below. Data for the application is generated via Orig3n’s automation and software integration platform.
While Orig3n makes it easy for users to share their genetic information, the company has taken a unique position in the industry in stating its strong belief that privacy is essential regarding genetic information. As a result, the company will never share or sell customers’ genetic information for any reason.
Orig3n’s Guidance from Peer-Reviewed Academic Literature
Orig3n’s genetic tests target single genetic variants in DNA, known as single nucleotide polymorphisms (commonly referred to as SNPs or “snips”). The interpretations of the test results that Orig3n provides to its consumers are derived from a large library of peer-reviewed journal articles that examine the results of studies regarding the biological associations of DNA variants and associated traits among people. Each of Orig3n’s reports includes references to these scientific sources, enabling its customers to conduct their own research into the science behind the tests if they are so inclined.
While there are currently 18 tests in its product portfolio, Orig3n could potentially create hundreds of different tests based on the available published scientific research, which has examined a wide variety of individual characteristics and their related DNA markers.
Additionally, Orig3n’s unique technology platform, including its in-house lab and software team, enables the company to not only conduct its own testing but to also quickly and efficiently create customized tests for conferences and companies. These custom tests provide attendees or employees with results regarding a specific set of genes related to an event or company mission. Orig3n is also leveraging this technology to work with several consumer goods companies to create tests that will inform consumers about products that may best suit their needs based on their genetic information.
The cost of genetic testing has declined substantially over the last two decades. In 2001, when the Human Genome Project was well underway, the cost of reading the three billion DNA base pairs in our 23 chromosomes was estimated to be $100 million. By 2015, the cost had declined to approximately $1,000 and a broad variety of different types of tests have proliferated at different price points, offering increased accuracy and speed.
As a result, the number of companies in the global DNA testing market has expanded. Orig3n’s competitors in the consumer genetic testing market include 23andMe, AncestryDNA, MyHeritageDNA, Helix, Habit and many others. The industry is dominated by analyses that describe ancestral traits and regional origin, however, there are a broad variety of offerings including predictive and pre-symptomatic, nutritional, carrier, prenatal, newborn, disease risk, microbiome and pharmacogenomic testing, some of which require FDA approval before they may be sold on a direct-to-consumer basis.
Due to the increase in affordability for consumers, the global predictive genetic testing and consumer wellness genomics market is rapidly expanding. According to Research and Markets, the industry is predicted to reach USD $4.6 billion by 2025iiii.
Orig3n has stated that it will continue to launch new products in the coming months and years to meet growing consumer demand. The company already has a global presence, including a joint venture with Zhong-An Online P&C Insurance Co., an USD $8 billion public insurance company, by which it will bring its products to the Chinese market. The company also has a distributor for Central and South America and anticipates announcing expansion into Southeast Asia and Europe in 2018.
iPSC-Based Cell Therapy Applications
While the fun and excitement of Orig3n’s DNA tests garner significant attention in the public sphere, the cutting-edge science is being done in the background, working with the cell bank to develop cell therapies. Using regenerative medicine technology, Orig3n hopes to one day treat unmet medical needs in a variety of disease areas.
Regenerative medicine is the creation of living, functional cells and tissues to repair or replace damaged or poorly functioning tissues, organs, or genes. There are three primary regenerative medicine technologies: cell therapy (which is Orig3n’s focus), gene editing, and gene therapy.
Stem cells by their nature are regenerative. There are small populations of stem cells in every adult organ that can replenish mature cells as part of their natural life cycle. For example, the outer layer of our skin regenerates every 2-3 weeks; however, there are not enough stem cells in the body to compensate for significant damage and disease.
Cell therapy can be used to heal injured tissue or produce missing proteins by delivering cells and cellular material into a patient. Cells derived from iPSCs can be manufactured at the scale and with the characteristics necessary to restore the function of damaged cells and prevent, and potentially reverse, the progression of diseases.
There are hurdles to overcome with reprogramming cells to iPSCs, such as low efficiency and the use of methods for reprogramming that leave unwanted effects.
As these processes have been refined, alternative approaches have emerged to avoid these pitfalls and scientists expect that the clinical trial process will continue to reveal emerging risks and safety concerns as well as their solutions. Two companies are already in clinical trials with iPSC-derived cells, Cynata and Healios.
Using the technique developed by Dr. Yamanaka, Orig3n is able to induce pluripotency in the blood cells in its cell bank and then differentiate the iPSCs into a variety of human tissues. The company is currently performing preclinical work in unannounced programs.
The potential for iPSC-derived cell therapies is immense. There is work being conducted in numerous applications; however, scientists have only just begun to unlock the possibilities. The field has advanced tremendously since Yamanaka first derived mouse iPSCs in 2006. Below, we summarize some of the areas where research is being done and where Orig3n might contribute its assets and knowledge.
Cell Therapy: Autologous vs. Allogeneic Approaches; HLA Matching and Superdonors
The first generation of FDA approved cell therapies, such as the CAR-T programs from Novartis and Kite Pharmaceuticals, are autologous, meaning that cells are taken from the patient, modified in a lab, and then reintroduced into the patient. While this approach avoids immune rejection of the transplanted cells, producing cell therapies using an autologous approach can be problematic for many reasons, including the following:
1. A person’s own cells may not be the best cellular material to use for cell transplantation. DNA is known to accumulate errors over time (especially as we age) creating an increased risk of some diseases, such as cancer. Using a source of cells from a healthy individual is more likely to have a better outcome.
2. To produce iPSC-derived cells for each patient introduces long delays before treatment. Healios’ clinical trial for Age-related Macular Degeneration in Japan was initiated with autologous cells that took several months to produce.
3. Autologous approaches are limited in the number of cells they can produce due to the source of the cells and expense constraints.
4. If multiple doses are needed over time to address the particular indication, cost issues related to producing autologous cells repeatedly, and at scale, could be significant.
To alleviate these issues, Orig3n is developing HLA-matched, allogeneic cell therapies. This approach uses cells from healthy donors, rather than from the patient. The cells are manufactured ahead of time for “off-the-shelf” availability, and the same cell line can be used to treat any number of patients. Allogeneic iPSCs can provide essentially an unlimited supply of cells, so being able to administer the number of cells appropriate for the treatment is not an issue. The potential drawback of using allogeneic cells is that the patient’s immune system may reject them, in the same way, that organ and bone marrow transplant recipients face this issue. In order to mitigate this risk, Orig3n “HLA-matches” the cells to each patient’s unique immune profile, which is the approach favored by Shinya Yamanaka.
The human leukocyte antigen (HLA) system is a gene complex encoding the major histocompatibility complex (MHC) proteins. The HLA system functions in cells to allow the recognition of materials that originate from one’s body or are otherwise non-damaging to the body, and substances, such as invading viruses and other foreign material that can harm it. The body’s immune system will attack foreign material to combat these viruses and other substances that could cause damage. For cell therapy, similar to organ transplant, the HLA profile of the cell must be matched between donor and recipient, or the recipient’s immune system will attack the new cellular material, limiting the efficacy of the therapy and potentially causing harm to the patient. Many transplant recipients need to take immune suppression medications for the rest of their lives to address this issue. Recipients of HLA-matched, allogeneic cell therapies should be able to avoid this onerous burden. While there is always a chance of HLA-matched cells being rejected, small doses of immunosuppressive agents can be helpful in mitigating this risk.
For this reason, Orig3n built the world’s largest crowdsourced cell bank for allogeneic cell therapy. The company has identified a number of cell lines in the bank that are matched to significant HLA populations. When aggregated, these cell lines can be administered to more than 90% of the U.S. population. This achievement far surpasses even the cell bank that Professor Yamanaka is building in Japan for this same purpose.
In identifying the best cell lines to use, Orig3n looked for HLA “superdonors.” Superdonors are individuals who have HLA profiles that are a match for a larger segment of the population, and therefore can be used more broadly.
Leveraging iPSCs to Evaluate Treatment Efficacy
iPSC technology can be applied to evaluate efficacy prior to a patient even entering a clinic. To predict how a patient may respond to a therapy, iPSCs created from a patient’s blood can be differentiated into the cell type affected by the damage or disease, and cells and/or drugs can be administered to the differentiated cells in vitro. By doing so, safety and efficacy can be examined without putting the patient at risk. In the context of personalized medicine, these cells or drugs can be optimized for the individual patient. One example of success using this approach involved a child requiring electrical stimulation of his heart to maintain the proper rhythm. Following extensive testing of iPSC-derived cardiomyocytes developed from the child’s blood, an optimal drug combination was identified and arrhythmias in the child were reduced to zero.
As of the end of 2017, Orig3n has raised over $30 million through its series A-2 round of funding. In November 2017, the company acquired the remaining assets of Interleukin Genetics, including its CLIA certified laboratory and its remaining portfolio of genetic test products, including tests for nutritional needs, weight management, bone health, and periodontal health. Further allowing Orig3n to expand its array of DNA tests and empower more people to take charge of their health through genetic insights.
Founded in 2014, Orig3n is a successful and revolutionary startup that has attracted the attention of numerous investors due to its unique business model and dedication. Its goal is to advance the future of regenerative medicine through the development of iPSC-derived cells for therapy. While many in the public know the company for its fun and exciting genetic tests and its efforts to build its cell bank at events across the country, the cutting-edge science is being done in the lab, where Origin is developing cell therapies for a broad array of existing diseases. By developing iPSC-derived cells, Orig3n is not only helping to repair damaged and diseased tissues and organs, but is also assisting in the advancement and acceleration of ex vivo drug testing, which has great potential to improve patient safety and treatment efficacy in a cost-effective manner. With the identification of superdonors based on HLA typing, there is an opportunity to develop allogeneic, off-the-shelf therapies that address the medical needs of the majority of the population both rapidly and inexpensively.
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