Over Dr. Igal Kushnir’s 74 years, two tendencies stand out. One is getting injured while riding his bike and the other is thinking of ideas for new start-ups. The two came together one day while he was riding his bike up Mount Hurshan and conceived of a product for healing chronic wounds. “Actually, it was when I managed to pick myself up from the ground after falling. You see, I’m that kind of person, very involved in sports, but also someone who hits walls, gets cut, battered. It was when I was injured that I had a crazy idea,” Kushnir recalls.
RedDress, the start-up that arose from that incident, has developed a method for treating deep chronic wounds that don’t heal and don’t respond to medical treatment. Such wounds tend to develop in older people suffering from diabetes or poor blood flow, or people who sit or lie down for long periods of time. Often they are very painful, cause dysfunction and can lead to amputation.
Kushnir knew that the injuries he had suffered in the accident were going away through the body’s process of natural healing. But the deep wounds that he saw in patients as the medical director of a nursing home are simply forgotten by the body at a certain point of the process. All that needs to be done, he figured, is remind the body of the wound and cause it to restart the process of natural healing.
“In an ordinary situation, you have a blood clot that consists of red blood cells, platelets and fibers of the protein fibrin, and they signal the body that it has an injury. The clot prevents loss of blood and accompanies the healing process until, in the end, you grow new skin tissue and the clot falls off,” explains Kushnir.
The body has a mechanism that signals when the injury was created, but not when it has healed. But what if a clot from the sufferer’s own blood could be created outside the body and placed on the open wound?
“I believed, and in hindsight I was right, that it would cause the body to think it has just incurred a large acute wound, which creates a lot of blood, and that it has to start taking care of it. When I place that [clot] on you once a week, I cause it to think that every week a new wound is formed and that awakens it.”
At present, RedDress sells “wound kits” under the name ActiGraft to prepare a blood clot outside the body, or in the professional jargon, autologous [self] tissue. The kit includes syringes, test tubes for taking blood, clotting substances, a concave pan to create a blood clot six centimeters in diameter, and additional equipment such as bandages, a tourniquet and gloves – “everything you need in order to administer the treatment anywhere,” he says. Preparation is simple and enables the treatment team to carry out the procedure after half an hour of virtual training.
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Preparing the blood clot with ActiGraft takes seven minutes and can be done in the patient’s home. After it is attached, the patient walks around with it for a week, and then repeats the process. Complete healing takes four to eight weeks. The success rate in the trials the company submitted to the U.S. Food and Drug Administration is 78%, a very high rate since patients who used the product previously used other treatments unsuccessfully. The company received FDA approval last November. In December, it received approval from the European CE and about four months ago, from the Israeli Health Ministry.
Daas Shukry, 57, likes to introduce himself as the product’s “No. 1 patient in Israel.” Shukry, who suffers from diabetes and a serious vascular disease, has lost his right leg above the knee. He arrived at Hillel Yaffeh Medical Center in Hadera with a necrotic left heel as a result of a particularly severe pressure wound. Nothing succeeded in improving the blood supply to his foot.
He underwent surgery for a partial amputation of his heel, but the wound remained large and couldn’t be closed by any existing treatment. He was not a suitable candidate for plastic surgery and transplants due to his underlying illnesses. The doctors explained to him that his left leg would also have to be amputated.
“I told the doctors that I would absolutely not amputate my leg – try whatever you like,” he recounts in a phone interview from a hospital where he is now being treated for the coronavirus. “And then came these guys [Igal and his son Alon, the CEO of RedDress]. I don’t know where they came from. It’s a miracle.”
For Shukry, it really was the closest thing to a miracle. That same week the Health Ministry had approved ActiGraft and Alon Kushnir was at a meeting with Shukry’s physician, Dr. Maxim Gurevich.
Gurevich, an orthopedic surgeon who is also in charge of treatments for diabetic foot problems at Hillel Yaffeh, says he was skeptical about the product. “In general I’m very conservative, but I told Alon and his guys, ‘Let’s try it on the most severe case, where the patient has nothing left to lose.’ We began treatments on Daas, and the huge wound, who had exposed his bone, gradually healed before my eyes, and became a small hole. Had he not contracted COVID-19, we could have continued until complete healing. But there is no question that we have already scored a tremendous achievement that we couldn’t have accomplished it any other way.”
Yael Isaacson, the owner of two private wound clinics, is widely regarded as having the most experience using ActiGraft treatments. She has been treating eight patients and all of them are now in an advanced stage of healing. A registered nurse, Isaacson has 25 years of clinical experience in hospitals in the United States and Israel.
The first time she tried the product was 13 weeks ago, on an elderly man who had a wound on his shin for seven years. “It’s a Stage 4 ulcer due to severe venous insufficiency, which had spread over 70% of his leg,” she says. “When he came to my clinic in Bnei Brak two years ago, we tried everything – advanced ointments and bandages – but nothing worked.”
In such situations, Isaacson explains, you simply bandage the wound very frequently and try to ensure that it doesn’t get infected and open even more. She says sufferers have severe pains that they describe as “a cigarette on your leg.”
A week after she administered ActiGraft on her elderly patient, she examined the wound for the first time. “I jumped out of my chair and started dancing, I felt as though I had won the lottery,” she says.
Kushnir senior is a serial inventor. He was the entrepreneur and inventor of DeepBreeze, an acoustic simulator using Vibration Response Imaging to monitor the flow of air into the lungs. He also developed MTRE, a device for regulating body temperature during surgery and brain traumas, which is now found in operating rooms around the world.
Because of his many years of experience in medical devices, he knew it would take a long time for his wound-healing solution to reach the market. In fact, 11 years have passed since that fateful bike trip on Mount Hurshan. But Kushnir was already on the phone with his son Alon to discuss the idea as he was loading his bicycle into his car.
Alon Kushnir had two decades of experience in medical equipment. For years he specialized in regulation and constructing clinical trials. He was a partner in startups that originated with his father’s earlier ideas. His most recent job was as vice president for regulation, clinical trials and marketing at Circ MedTech, which developed a device for circumcision without surgery. (The company shut down in 2019.)
“At first we said, let’s take blood and try to create a blood clot,” says Alon Kushnir. “And for two years we took blood from ourselves and our friends and experimented in the kitchen. My mother was alarmed when she discovered that we had borrowed all the souffle bowls in the house for the experiments.”
They admit that there is a lot of hard work in empirical tests, but it also takes common sense and a lot of luck. The two claim that they prepared hundreds of blood clots in the souffle bowls until they were satisfied with the clotting time and the strength, shape and color of the clot.
Because a test tube for taking blood contains anti-coagulants, RedDress uses a substance called calcium gluconate, free calcium ions that clot the blood when they are introduced into the syringe. But the blood itself clotted very slowly. In order to clot it inside a concave form and create the desired tissue from it, they added a substance called kaolin.
Kaolin is a mineral used for ceramics as well as in manufacturing drugs, bricks and toothpaste. Kushnir senior knew that the substance is used for testing blood clotting in the laboratory, but he says that no one had clotted blood for therapeutic purposes. “Our kaolin is three microns in diameter, and that’s significant: It’s the only reason that it doesn’t sink and can float for almost 10 minutes inside the liquid, which enables us to create a homogeneous clot.”
“We conducted several experiments, such as hanging the clot on a clothesline for a week to check whether it would stink, and then we discovered that kaolin has several other anti-bacterial characteristics that affect the smell, but that was a total coincidence,” says Alon Kushnir. “Afterward we put it on my leg and I went to sleep with it for three days in order to see what happens, that it isn’t harmful. We started laboratory tests that proved that the product is safe for trials and we received permission for trials on human beings.”
An experiment to prove the effectiveness of the product, submitted to the FDA, treated 20 patients in three American medical centers. It was led by two wound specialists, Drs. Thomas E. Serena and Robert J. Snyder.
RedDress now employs about 17 people, five of them in Pardes Hannah in Israel and the rest in Jacksonville, Florida. RedDress’ advantage over a large variety of wound products is the ease of use and low manufacturing costs. Because the company is based on the patient’s self-healing mechanism, it’s easier for it to send doctors kits free of charge for testing purposes.
“There are a lot of companies that make blood products, there is a company that made wound glue from the fibrin protein in the blood; there was an Israeli company called MacroCure that took white blood cells from the blood called macrophages, synthesized them and injected them into the wounds. But no one takes the blood ‘as is,’” says Alon Kushnir. “Our treatment can be completed even without electricity or water. It is the only biological product in the United States that can be used at home or in a nursing home. Other products need to be ‘cared for,’ for example freezing at -60 degrees and thawing.”
For the patients, the cost of a single-use kit is $300 in the United States and 800 shekels ($235) in Israel, compared with $700 to $2,500 for competing biological products. The U.S. government’s Medicare program for the elderly provides coverage for the product.
RedDress’ trials have shown that as a rule, patients who have seen their wounds heal by 50% after the first three treatments will probably be completely healed. The company’s researchers at present can’t explain why treatments don’t always work, but they assume it’s related to nutrition and the protein level in the blood.
“In order to heal serious wounds you need a professional team that knows how to treat a wound. The important things are reducing pressure on the wound, cleanliness and debridement [removing dead tissue] and treating infection,” says Alon Kushnir.
In May, RedDress completed a $11.5 million fundraising round, adding to the $5 million it previous raised. Unusually for a startup, the company has no venue capital fund investors nor does it raise capital unless it needs it. The Registrar of Companies reveals it has over 85 shareholders, with Igal and Alon Kushnir each with a 20% stake. Among its main investors are international investor Peter Kadas, the consulting firm Aston Partners and Israeli investor Zohar Gilon.
The first investor was the man who received the first phone call from the Kushnirs: Ilan Cohen, a partner with the Tel Aviv firm Reinhold Cohn Group. A patent attorney, he has a Ph.D. in biology and has worked with Igal Kushnir for 25 years.
“Most inventions today are an incremental improvement of other things,” he says. “For example, they improve the effectiveness of a product or the speed of a process, or combine things that are familiar in themselves, in a new way. Only few of them seem to come out of nowhere and create dramatic change.”
After first hearing the idea, he agreed to put his private money into the firm. Today he even serves as chairman. “Even then I realized that it was a unique idea. Many doctors who hear about it now are thinking to themselves, ‘Why didn’t I think of that?’”
To laypeople, RedDress’ solution sounds more like a discovery than an invention, which makes patenting it more challenging. “Patents are a tool for attaining ownership of a product, a kind of technological land registry that builds fences around the invention and says: ‘It’s mine, and anyone who enters is trespassing,’” explains Cohen. “One of the considerations that determine whether its can be protected by a patent is whether it’s possible to enforce these rights.
“If I have a patent on an algorithm that’s in the core of software that runs on the cloud, it’s almost impossible to discover whether it’s being used, and therefore the economic significance of the right [of ownership] is likely to be small and it’s unlikely that the investment in [patent] registration is worthwhile. It’s a cost that is could reach tens of thousands of dollars if it’s a matter of protection on a global scale.
“If a doctor in a hospital creates a blood clot using his own methods and places it on a wound, it’s impossible to do much about that. After all, there really isn’t any way to block a doctor sitting in his laboratory and carrying out a medical procedure,” says Cohen. “But medical practice and medical insurance don’t work like that. Doctors and medical institutions purchase ready-made kits, which are approved for use by regulators. That’s why RedDress’ patents protect the kit and the method for creating the clot, along with the items inside it.”
The company has registered patents in Israel, the United States, Canada, Europe, Australia, South America, South Africa, Brazil, India, Japan, Korea and China. The Chinese patent office was especially demanding. It was a Chinese patent examiner who found a century-old article in a scientific journal in which an American doctor describes treating an ulcer resulting from a tooth extraction by creating an incision and a blood clot inside the wound that triggered the healing mechanism.
“We had to prove to the patent office that RedDress’ technology is completely different, and emphasize the differences compared to this publication and others, and we succeeded,” says Cohen. “It’s unimportant, but it makes it clear that a patent … is not automatic. A patent application usually goes through a difficult examination, where you need to prove to the different patent offices around the world that you have a new and non-obvious product.”