Over the past century, many diseases that previously would have been fatal are now almost entirely curable. However, the prognosis and treatment for end-stage organ failure is still bleak.
Chronic diseases lead to wear and tear in organs such as the liver, lungs, kidneys, and more. Eventually, the damage builds up to a point where the organs stop working - at this point, patients currently have relatively few options. The current standard of care for patients with end-stage organ failure is an organ transplant. However, the demand for a transplant greatly exceeds the supply of organs.
Organ donor infographic (Fast Company)
When you check off “organ donor” on your driver’s license, you are opting in to have your organs donated in the event of your death. However, the process is much more complicated than it seems.
Upon closer examination of the stringent organ donation requirements, you will find you must die in a hospital, be free of any diseases that could cause organ damage such as cancer or serious injections, and much more.
This makes 99.7% of all registered donors ineligible for actually donating their organs.
Although there are 165 million organ donors in the US, only 3 in 1,000 meet the criteria, creating a huge backlog in the organ waitlist of over 100,000 people. With additional requirements for transplants such as matching blood and tissue types, it is incredibly difficult for patients to receive an organ donation.
Without a transplant, these people waiting on a donation have a much poorer prognosis, resulting in 17 people dying on the organ waitlist every day.
As seen in the chart above, of the different requested and donated organs, the kidney is by far being the most common and makes up about 80% of organ requests.
Kidney failure, also called end-stage renal disease, is the last stage of chronic kidney disease and is the number 9 killer in the US. At this point, the kidneys don’t function well enough for the patient to survive without constant dialysis or a kidney transplant.
Kidney disease is also very common, with 1 in 3 Americans being at risk and over 15% of Americans having chronic kidney disease. However, only 1 out of 10 people know that they have it since symptoms may not be apparent until the disease progresses.
Stages of Kidney Disease (kidneyfund.org)
Older adults with ESRD are a rapidly growing group and they have a mortality rate that is twice that of older adults with cancer. There are several risk factors for chronic kidney disease, with the most common being diabetes and high blood pressure. Kidney failure is also far from being a rare disease and affects 700,000 Americans and over 2 million people internationally.
Currently, there are only two treatments for end-stage kidney disease: dialysis at least 3 times a week or a kidney transplant. At age 60, a healthy individual is expected to live 20 more years, while an individual on hemodialysis has a life expectancy of only 4 more years.
Aside from a kidney transplant, dialysis is the only method for treating kidney failure. The goal of dialysis is to do the work of the kidney by purifying blood and removing wastes and extra fluid from your blood. One type of dialysis - hemodialysis - is performed 3-4 times a week either at home or at a dialysis center, where your blood is pumped through a dialysis machine to be cleaned and returned to your body.
Hemodialysis (About Kids Health)
The other type of dialysis is peritoneal dialysis, where your blood is cleaned daily inside your body through your stomach lining. A fluid is injected and then removed after filtering is finished.
Peritoneal Dialysis Infographic (La Isla Network)
Survival rates for both of these dialysis options have improved over time, however, the numbers are still not promising. The 5-year dialysis survival rate is under 50%.
If the patient is able to receive a transplant, the 5-year survival rate jumps from under 50% to around 80%.
Living with End-Stage Renal Disease/Diabetes
As you can imagine, living with end-stage renal disease takes a huge emotional and physical toll on both the patient and the family.
Once a patient is diagnosed, they must undergo dialysis treatments every other day unless they are able to get a kidney transplant. Without dialysis, the life expectancy for a patient with ESRD can range from days to weeks, making the procedure crucial to prolonging life.
Every other day, you would have to drive to the dialysis center to undergo the procedure, which takes between 3-5 hours each session. Side effects are also pretty nasty, including low blood pressure, cramps, nausea, fatigue, and more, and. The diagnosis will likely have significant impacts on the patient's ability to work, as well as their home and social life.
Patient undergoing hemodialysis (Stellar Transportation)
The Austin Diagnostic Clinic documented the experience of patients with chronic and end stage renal disease (ESRD). You can find the story of one such patient, Teresa, here:
Now, imagine finding out that you or a family member has been diagnosed with kidney failure. However, instead of having to go into a dialysis center every other day or waiting in the organ donation line for years, you’re able to opt for a biologic device that is implanted and consistently operates in the background, much like a real kidney.
This is what the biomedical startup IVIVA is aiming to do: create an artificial implantable organ that allows the patient to bypass the traditional treatment avenues. The technology will have the potential to impact hundreds of thousands of lives across the country.
IVIVA was founded by Dr. Brock Reeve, the director of Harvard’s Stem Cell Institute, and Dr. Harald Ott, a surgeon at Massachusetts General Hospital and an associate professor of surgery at Harvard Medical School.
Dr. Harald Ott has spent much of his academic career working on organ engineering with patients before and after organ transplants. Throughout his years working in the field, he was able to see first hand the devastating impacts of ESRD and the difficulties that patients going through dialysis almost every day have to face. He was inspired after working with a pediatric ESRD patient to create a better solution and founded IVIVA.
IVIVA’s goal is to build a replacement for vital kidney function and thereby replace hemodialysis and renal transplantation. For the past 50 years, no significant strides have been made in treatment options for ESRD patients, however, IVIVA’s current work in this area is groundbreaking.
The team’s goal is to create a fully biologic implantable technology that does not require dialysate, mechanical pumps, or be subject to fibrosis and fouling typical of devices based on synthetic materials. By doing this, they essentially create an artificial model of a kidney, removing the need for constant dialysis or a kidney transplant. This has the potential to significantly improve the quality of life in the patients and improve disease prognosis.
To understand how this implant works, we first have to take a look at the functional unit of a healthy kidney - the nephron. Solutes from the blood are filtered through the nephron, necessary solutes as reabsorbed, and waste and excess water are flushed out.
Nephron Functional Diagram (Research Gate)
There is currently no biologic device that can mimic both the filtration and reabsorption functions of the nephrons within a kidney. The fully biologic nature of the device is a huge differentiator for IVIVA - this approach removes many major modes of failure stemming from current mechanical devices (e.g., power loss, driveline infections, blood material interface, embolic stroke, etc.).
The product performs two main functions:
IVIVA’s thin-film membrane offers a natural basement membrane for the proper functioning of cells. Cells in the reabsorption component actively uptake solutes (e.g., glucose) from the filtrate back into the blood supply much like the native kidney. With natural materials it will not experience the fouling and fibrosis challenges of synthetic materials.
IVIVA has unique hydrogel scaffolds created using computer-designed architecture to achieve the architecture and stability required to mimic native kidney function.
What sets IVIVA apart from the rest
IVIVA’s technology presents a significant advantage over the existing solutions. Patients on hemodialysis are tethered to a large unit for multiple hours, three times per week to achieve adequate toxin removal and fluid balance compatible with survival. When not in session, patients experience dramatic fluid shifts throughout a given week as they are typically water-heavy before a hemodialysis session, water drained after a session, and then balanced only for a day or so following a session.
Due to the lack of cellular functions, many toxins gradually accumulate, and patients are stuck in an inflamed state, a condition that eventually leads to the observed decrease in life expectancy.
In contrast, IVIVA’s grafts will function continuously, in the background. Patients would not experience these dramatic fluid shifts seen in intermittent treatment. Additionally, the device would not tether patients in a single place as it would be either implanted or small enough to be a wearable extracorporeal device.
The table below delineates how IVIVA’s product addresses the weaknesses of the most commonly used current treatment methods and devices.
They are currently in a pre-clinical phase, and have successfully tested IVIVA’s prototype in a porcine animal model. Below is an outline depicting R&D developments from IVIVA’s founding to the end of 2019.
Below are IVIVA’s development timelines for their kidney project. Their team will continue following a milestone-based development plan, first with a wearable (extracorporeal) device and then an implant, with the goal of starting pre-clinical trials by 2023.
IVIVA also has 3 filed patents for:
Filing #1 – Thin Film Interposition of Basement Membrane Scaffolds
Filing #2 – Cell Enhanced Peritoneal Dialysis
Filing #3 – Biological Fluid Purification with Biocompatible Membranes
And has another provisional filing in process.
Their team is currently working on replacing the functionality of the kidney and pancreas. However, their technological platform has a multitude of other applications such as local delivery of cells, expanding to other organs and tissue types, and more. For example, they have shown they can use their system to model functional behavior of the lung.
IVIVA’s initial target market is patients with ESRD, which has a prevalence of over 700,000 patients and an annual growth rate of about 4.2% according to the United States Renal Data System. Out of these, 70% are treated with dialysis while the remaining 30% have functional renal grafts. IVIVA will initially target delayed graft failure patients, which has an incidence of about 4,700 patients.
After the initial launch into this market, they will address the broader ESRD population by being an alternative to traditional hemodialysis. According to the USRDS, $35.9B was spent caring for ESRD patients in 2017, with the number being even larger internationally, a market that IVIVA can also target down the road.
In addition to having a strong core team, IVIVA has an advisory board with extensive industry leadership and experience.
As CEO, Brock Reeve has overall responsibility for leading IVIVA Medical and is excited to be working with a world-class team to solve the major medical challenge and clinical need for kidney repair. Brock is also the Executive Director of the Harvard Stem Cell Institute, whose mission is to use stem cells, both as tools and as therapies, to understand and treat the root causes of leading degenerative diseases. HSCI invests in scientific research and its faculty has grown to include over 350 Principal and Affiliated members. The Institute engages with several leading pharmaceutical companies and foundations in joint research projects and its faculty have founded over 25 stem cell-related startup companies and serve on leading Scientific Advisory Boards.
Prior to HSCI, Brock’s background was in the commercial sector with extensive experience in both management consulting and operations for technology-based companies, with a focus on life sciences. Brock was COO and Managing Director of Life Science Insights, an IDC company, a consulting and market research firm specializing in information technology in life sciences. As a consultant, Brock has additional experience in IT and the healthcare/life sciences market with IBM, Viant Corp. and SRI Consulting, where his clients included some of the leading pharmaceutical, biotechnology and medical device companies.
Brock received a BA and MPhil from Yale University and an MBA from Harvard Business School.
Harald Ott is a thoracic surgeon at the Massachusetts General Hospital and an Associate Professor in Surgery at Harvard Medical School, where he built one of the leading laboratory groups in organ engineering and regeneration. He discovered and perfected the method of stripping an organ of its own cells and then infusing the remaining scaffold with new progenitor cells. To date, his technology has been successfully applied to heart, liver, lung, kidney, pancreas, and composite tissue regeneration.
The approach of reseeding and engraftment of native cells to generate personalized organ grafts potentially eliminates donor organ shortage and the need for life-long immunosuppression in transplant patients, and thus lays the path for effective solutions for the millions of people in need of organ repair or replacement. Harald’s background is in surgery (M.D.; University Innsbruck in Austria, 2000) and this training has been an asset for his chosen field of scientific research and development.
The privilege to work with patients suffering from end organ failure provides the motivation to continue to push boundaries in organ regeneration. Inspired by a pediatric patient suffering from end stage kidney disease, he founded IVIVA Medical to develop novel treatment solutions for this devastating disease.
Charles currently leads research and development efforts as vice president of engineering at IVIVA Medical. His work includes developing tissue engineering and imaging systems, bioreactors, and novel whole-organ disease modeling platforms for internal use and for industry and academic partners. Charles has extensive experience in artificial bioscaffold design and fabrication, 3D printing, and tissue regeneration.
Charles received an M.S. degree in Biomedical Engineering from Johns Hopkins University in 2014 after conducting research focused on regeneration of liver tissue using perfusion decellularized scaffolds as a platform. In addition to tissue regeneration he worked on the development and refinement of bioreactor systems to serve as platforms for stem cell-based regeneration of tissue scaffolds and whole organ constructs.
Daniel is a senior scientist at IVIVA. Daniel has extensive experience in 3D printing and the fabrication of 3D vascularized tissues. Daniel received a BS in Biomedical Engineering from Brown University and a PhD in Biomedical Engineering from Boston University.
Thomas’ expertise is in kidney development. Thomas received a BS in Biology from New Mexico State University and a PhD in Biomedical Science from the University of California, San Diego. He also completed research fellowships at UCSD, the Salk Institute for Biological Studies, and Massachusetts General Hospital.
Gita received a PharmD from the Tehran University of Medical Sciences and an MS in Biomedical Engineering from Tufts University.