Investment Highlights

• IVIVA Medical is a Harvard-based spin-out addressing the organ donor shortage by developing biomimetic artificial organs
• First products are a bio-artificial blood purification device mimicking nephrons to create a kidney replacement to treat ESRD and a bio-artificial islet organ device for Type 1 Diabetes
• Highly experienced team of industry leaders from Massachusetts General Hospital, Harvard Stem Cell Institute, United Therapeutics, the United Network for Organ Sharing, USC, and more
• Initial $5M round is oversubscribed and being upsized to $9-$10M based on strong demand by institutional investors
• Already raised from leading healthcare investors and institutions including AstraZeneca, Johnson & Johnson, the Department of Defense, United Therapeutics,  BOLD Capital, WI Harper and more

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.

Organdonor.gov

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. 

CDC.gov

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: 

1. Blood filtration

2. Solute reabsorption

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.

Development Progress

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.

Market Opportunity

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.

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