Monitoring the Health of Transplanted Organs
TAI Diagnostics, Inc. is a biotechnology company focused on providing a non-invasive and highly sensitive diagnostic test to monitor the health of transplanted organs in patients who have received solid organ transplants.
The Clinical Need for
Monitoring Transplant Patients
Rejection is the major cause of transplant failure, and transplant recipients require lifelong rejection surveillance to guide modulation of immunosuppressant dosage and frequently require clinical interventions to improve organ function. Our initial test offering will be for cardiac transplant patients. The current gold standard surveillance test for these patients is the endomyocardial biopsy with histological interpretation by a pathologist, a procedure that is invasive, subject to sampling error, and expensive for both the patient and the healthcare system.
TAI Diagnostics has developed a proprietary noninvasive assay which utilizes patent-pending cf-DNA technology as a direct measurement of organ injury through quantitation of donor-specific cf-DNA released into the bloodstream from injured cells of a transplanted organ. The Quantitative Genotyping Assay requires only a small blood sample for processing in our accredited clinical reference laboratory. Scientific data to date indicates that the quantitative genotyping technique has a high degree of sensitivity and specificity, a rapid turnaround time, and can be offered at a very competitive price point.
The standard of care in the surveillance of cardiac allograft rejection remains catheter-based endomyocardial biopsy (EMB). To detect rejection early, surveillance biopsies must be performed at regular intervals; however, EMB is both expensive and invasive. Furthermore, organ rejection is a “patchy” process, and biopsy samples can fail to sample small patches of rejection, leading to the dangerous potential for false negative biopsy results and undiagnosed graft rejection.
Biopsies remain the standard of care in allograft monitoring largely because other options have major limitations that diminish their value in clinical practice. Alternative non-invasive transplant monitoring tests do exist that measure gene products present in blood related to the immune response to a transplanted organ, but all such tests on the market suffer from limited positive predictive value and cannot be used until months after transplant, missing the most clinically critical, highest-risk period for transplant rejection. The limitations of currently available technologies leave crucial unmet needs in the field of organ transplant surveillance that the Quantitative Genotyping Assay is designed to address.
Cell Free DNA Technology
All people have “self-specific” cf-DNA released into the bloodstream by their own cells as a product of natural cell turnover or injury by illness, such as infection. In transplant recipients, “donor-specific” cf-DNA is present in the blood in addition to self-specific cf-DNA. Donor-specific cf-DNA is released by the transplanted organ and has the genotype of the organ donor, distinct from the recipient’s native genotype. Our test, through quantitative genotyping, can discriminate “self-specific” cf-DNA from “donor-specific” cf-DNA, which originates specifically from the transplanted organ and proportionally increases in the bloodstream of the recipient during transplant rejection as the cells of the transplant are injured by the recipient’s immune system. We previously published a pilot study in a cohort of pediatric and adult heart transplant patients utilizing a novel, highly accurate approach which precisely quantifies the amount of donor specific cf-DNA in recipient plasma. Further research by TAI Diagnostics has strengthened this evidence.
The Quantitative Genotyping Assay is performed in a highly-controlled environment within our CLIA-certified TAI Diagnostics state of the art clinical reference laboratory (College of American Pathologists accreditation pending). Continuing analytical studies demonstrate the assay’s capacity to generate precise, highly reproducible results even in early stages of transplant rejection, backed by correlation with clinical presentation and biopsy results. A multicenter prospective clinical study for cardiac transplant monitoring funded by the NIH/National Heart Lung and Blood Institute and by TAI Diagnostics, Inc. is also underway, and additional studies in lung, liver, and kidney are planned.
Peer Reviewed Scientific Publications and Presentations
1. Hidestrand M, Tomita-Mitchell A, Hidestrand P, et al. Journal of the American College of Cardiology. 2014 Apr; 63(12):1224-1226
2. Hidestrand M, Stokowski R, Song K et al. Fetal Diagn Ther. 2012 Mar; 31(2):122-128
3. Wagner A, Mitchell M, Tomita-Mitchell A. Clin Perinatol. 2014 Dec;41(4):957-66
4. Castleberry C, Hidestrand M, Tomita Mitchell A, et al. ISHLT 31st Annual Meeting and Scientific Sessions, April 13-16, 2011, San Diego CA.
5. Hidestrand M, Zangwill S, Tomita-Mitchell A. Journal of Heart and Lung Transplantation. 2012 Apr; 31(4): S91-S92
6. Hidestrand P, Hidestrand M, Stamm K, et al. ISHLT 33rd Annual Meeting and Scientific Sessions, April 24-27, 2013, Montreal QC.
7. Mitchell M, Hidestrand P, Simpson P et al. The Journal of Heart and Lung Transplantation. 2015 Apr; 34(4):S53
About the Company
TAI Diagnostics is committed to bringing its life-changing new technology to the transplant surveillance market. The company is headquartered in the Milwaukee County Research Park adjacent to the Medical College of Wisconsin, Blood Research Institute, and Milwaukee Regional Medical Center.
TAI Diagnostics is led by a team of healthcare professionals and executives with decades of experience committed to developing cell-free DNA technology for better clinical outcomes.
CEO and Board Director
Frank Langley has over 30 years of Life Sciences experience, and has spent over a decade in executive management in the Transplant Diagnostics industry. Prior to joining TAI Diagnostics as CEO, Mr. Langley was Vice President & General Manager of Immucor Transplant Diagnostics in Stamford, Connecticut. He previously served as President and CEO of Pel-Freez Clinical Systems in Brown Deer, Wisconsin. Under his leadership, the company developed a complete line of Human Leukocyte Antigen Typing (HLA) transplant diagnostic products. Mr. Langley was instrumental in the strategic sale of Pel-Freez to Dynal Biotech (now part of Thermo Fisher) after an extended period of robust growth.
Mr.Langley has deep experience in the functional areas of Product Management, Sales, Marketing, and Business Development. He has worked in startups to Fortune 500 companies and has also served as an advisor, board member, and investor in numerous Life Science industry organizations. This includes his involvement with the Wisconsin Biotechnology Association (now BioForward) where he served as board member and President. He also served on the Research Foundation Board and Technology Innovation Council of the Medical College of Wisconsin. Mr. Langley has a Master’s degree in Business Administration from the University of St. Thomas and an undergraduate degree in Business Administration from the University of Wisconsin.
Aoy Tomita-Mitchell, PhD
Chief Scientific Officer, Co-founder, Board Director
Dr. Aoy Tomita-Mitchell brings her experience and expertise in rare variant detection to the development of cell free DNA technology for TAI Diagnostics. A co-founder of TAI, Dr. Tomita-Mitchell was also a co-founder of Ariosa Diagnostics, a leading global molecular diagnostics company that was acquired by Roche in 2015.
Dr. Tomita-Mitchell is an investigator at the Children’s Research Institute at the Children’s Hospital of Wisconsin as well as an Associate Professor at the Medical College of Wisconsin. She has conducted pioneering research on circulating donor specific cell free DNA and on fetal cell free DNA, along with an ongoing investigation into the genetic etiology of congenital heart disease. Dr. Tomita-Mitchell’s work at TAI supports a passion for utilizing genetic tests to improve patient outcome.
Prior to postdoctoral work in Pediatric Cardiology at The Children’s Hospital of Philadelphia, Aoy received her BS in Mechanical Engineering, her PhD in Genetic Toxicology and Bioengineering, and a postdoctoral fellowship from the Massachusetts Institute of Technology.
Michael Mitchell, MD
Chief Clinical Advisor, Co-founder, Board Director
Dr. Michael E. Mitchell MD is a pediatric cardiothoracic surgeon at the Children’s Hospital of Wisconsin and is a Professor of Surgery in the Department of Surgery, Division of Pediatric Cardiothoracic Surgery at MCW. He is a member of the American Surgical Association and has held numerous national leadership positions. Prior to founding TAI Diagnostics, Dr. Mitchell was a co-founder of Ariosa Diagnostics, a leading global molecular diagnostics company (San Jose, CA), and a co-founder of MDinteractive (Framingham, MA), a company that provides a Physician Quality Reporting System.
Dr. Mitchell has a number of medically related patents with several resulting in FDA approved devices. He earned his B.A. in chemistry from Princeton University, and M.D. Magna Cum Laude from Harvard University. He completed his clinical training in surgery at the Brigham and Women’s Hospital, Boston Children’s Hospital, and the Children’s Hospital of Philadelphia.
Paula North, MD, PhD
Dr. Paula North has over 20 years of experience directing clinical diagnostic laboratories and is board-certified by the American Board of Pathology in Anatomic, Clinical, and Pediatric Pathology. She is a Fellow of the College of American Pathologists (CAP) and a member of the United States and Canadian Academy of Pathology, the Society for Pediatric Pathology, and the American Society for Investigational Pathology. Prior to joining TAI Diagnostics as Chief Medical Officer and Laboratory Medical Director, she was Medical Director of the Department of Pathology and Laboratory Medicine at Children’s Hospital of Wisconsin for 10 years, after a decade of experience as Director of Clinical Pathology at Arkansas Children’s Hospital. She has been a pioneer in bringing molecular diagnostics into clinical practice, ranging from PCR assays to whole genome sequencing, founding and directing two academic hospital-based, CAP-accredited Molecular Diagnostic Laboratories, the first in 1996.
Dr. North is Professor of Pathology at the Medical College of Wisconsin and continues to practice pathology at Children’s Hospital of Wisconsin (CHW). She has been placed by her peers on the Best Doctors in America list since 2008, and was named Physician of the Year by the Vascular Birthmarks Foundation in 2015. She has authored over 100 peer-reviewed scientific publications, books, and chapters and is an advisor for several patient-oriented organizations in the field of vascular anomalies. Dr. North received an undergraduate degree from the University of Virginia, an MD from the University of Arkansas and a PhD in Molecular Biology from Vanderbilt University.
Chairman, Board of Directors
John Fowler is Vice Chairman & Executive Vice President of Quad/Graphics, a global provider of print and multichannel solutions with more than 50 print-production facilities on three continents. He oversees global strategic planning and business development with a concentrated focus on overall business strategy and investment opportunities.
Quad/Graphics is the parent company of QuadMed, a national provider of employer-sponsored health and wellness solutions. Mr. Fowler has worked closely with QuadMed since inception in 1990 and continued exponential growth from the beginnings of an on-site medical facility for Quad/Graphics’ employees to serving over 90 clients with more than 100 clinics in 22 states. This includes 350,000 lives served by over 700 employees. Mr. Fowler is one of two directors for the QuadMed internal board.
Mr. Fowler has worked with Quad/Graphics since 1980. Prior to joining Quad/Graphics, he worked with the company as an audit and tax manager with Arthur Andersen. John attended Tufts University and Iowa State University, graduating summa cum laude with bachelor’s degrees in both economics and business/accounting. He also serves on the board of directors for Quad/Graphics, Manipal Technologies Ltd. , the Left Bank Wine Company and the University Club Tower and is a past board member of Stat Doctors (prior to its sale to Teledoc) and Creative Forming and Coatings Excellence International (both Mason Wells portfolio companies prior to their sale).
John Neis is the Executive Managing Director at Venture Investors LLC, where he has been a Managing Director since 1997. John brings considerable expertise in biotechnology startups to TAI Diagnostics, including his current directorships at Venture Investors portfolio companies Deltanoid Pharmaceuticals, Cellectar BioSciences, Delphinus Medical Technologies, Virent, and Great Lakes Pharmaceuticals.
John’s experience includes assisting multiple ventures from inception through successful product deployment and exit to public markets. He joined the Board of Third Wave Technologies when they had three employees and served through the initial public offering (they were subsequently acquired by Hologic for $580 million), and also joined the Board of TomoTherapy when they had one employee and served through their public offering, which was the fourth largest healthcare IPO in the first decade of the millennium. Other notable past directorships included NimbleGen Systems, which was acquired by Roche for $272.5 million, and Inviragen, which was acquired by Takeda for up to $250 million.
John is a Chartered Financial Analyst who received his MS in Marketing and Finance from the University of Wisconsin – Madison, and his BS magna cum laude in Finance from the University of Utah.
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ContactTAI Diagnostics, Inc.
10101 Innovation Drive
Milwaukee WI, 53226
Phone: (414) 831-9970