A Kiwi biotechnology company which has found a way to grow bigger-than-A5 sheets of replacement human skin says the product might be ready to start clinical trials on burn patients in 2020 or 2021.
Upside Biotechnologies, a company which spun out of the University of Auckland's immunology research area, announced this week it has raised $2 million in a convertible notes issue from existing investors.
And it is preparing for a $10m to $15m capital raising later this year, which will hopefully take it into clinical trials 12-15 months after that.
As with all medical breakthroughs, there are plenty of things that could delay or even halt the project, but Upside Biotechnologies chief executive Robert Feldman said commercial production could possibly begin in the mid-2020s.
There are few things more terrible than major burn injuries. The pain is excruciating, the recovery hideously slow, and victims have to cope with months in hospital, multiple surgeries over several years, and often the trauma of disfigurement.
Jonathan Heather is a specialist burns surgeon at the National Burns Centre at Middlemore Hospital. He said New Zealand has 20-30 major burns casualties a year, most of them adults.
Victims tend to end up in Middlemore. A burn is classified as "major" when more than 30 per cent of someone's body is affected.
Heather said advances in skin technology have not kept up with what's happening in the wider medical field in terms of tissue engineering. Many scientists have tried and failed to come up with a skin substitute that really works. In the meantime, patients suffer.
"At the moment if your skin is badly burnt the only real option in the long term is to cut off the burnt skin and replace it with skin grafts from your own skin," Heather said.
"If you have, say, burns to 60-80 per cent of your body, that means having to use the available 20-40 per cent that's left as skin grafts to cover the injured area."
Basically that means shaving off the top layers of skin from a healthy area and using it to cover some of the burn site. Then waiting until the layers of skin from the graft site grow back, and then shaving them off again and covering another area of burns.
Over and over again, sometimes.
"Unfortunately our bodies are not much use without skin," Heather said. "[Until the skin graft process is completed] it's about lots of bandages, lots of pain relief and many trips to the operating room. That's one of the reasons patients with major burns are in hospital for many months - four-to-six months is not uncommon."
Patient, heal thyself
Feldman says there have been a number of advances in skin grafts over the last few years.
And scientists around the world have been trying to grow skin in a lab. There have even been some commercial releases, but nothing has really worked.
The Upside product is a significant improvement on what is available or in development elsewhere, he said.
Starting with a piece of the patient's own skin, Upside's technology grows the new tissue in a series of special chambers - each one about 20cm x 20cm in size and making one piece of skin. To put it in perspective, 20cm x 20cm is slightly bigger than a half a sheet of A4 paper.
The process takes just 16 days. The new skin is around 0.1mm thick and contains two layers - the epidermis or outer layer and the dermis layer below it.
An adult victim with severe burns might need upwards of 40 skin sheets.
"No one has managed to grow the skin this fast. No one has managed to grow big sheets, and other products have been flimsy, and difficult to handle," Feldman said.
With the Upside skin, doctors prepare the wound, including making sure it's extremely clean, and then fasten the new skin on top.
"It should then heal. It needs to recognise itself and attach itself."
The holy grail of burns treatment
Feldman said Upside's scientists are still working on the final parameters to get a consistent, workable product. But 10 years after the company was first formed, the end is in sight.
"It's a complicated product and there are an awful lot of parameters. Like the temperature and the concentration of all the chemicals and the time we need for incubation. But we have only two parameters left before we have completely defined the product."
Then testing and measurement can begin. Then later, clinical trials.
These are more likely to happen in the US, Feldman said, because New Zealand's small size means there just aren't enough patients to progress a trial quickly.
Upside has been working with Medical Technology Enterprise Consortium (MTEC) a US government-owned body tasked with speeding up delivery of US military technology, and earlier this year received a US$300,000 ($427,000) research grant for its work. Soldiers get some horrible burns, from bombs and chemicals warfare.
Heather said it's taken far too long for someone to develop a viable skin substitute and the Upside product looks promising.
"Their ideas are solid. Someone's going to crack this sooner or later and I'd like it to be them.
"It would make a massive difference to have options to cover a patient with skin that doesn't have to be stripped in layers from their body."
Heather said even with smaller burns, having a manufactured skin product would be a godsend.
In New Zealand alone, an average of 475 children are admitted to hospital as a result of burns or scalds; 80 per cent of them are five or under. The skin graft process is extremely painful - in fact often the wound from the area of grafted skin is more painful than from the deeper burn site because in the shallower wound all the nerve endings are exposed.
"There's also an upside for other injuries that might require reconstruction," Heather said.
"Bad vehicle accidents where someone has lost a lot of skin on the road, or some kinds of tumour reconstruction. People can end of up short of reasonable quantity of skin, so if that can be manufactured in the lab grown from an individual's own skin, they wouldn't need to harvest other skin grafts."
A new funding round
Like so many medical breakthroughs, Upside Biotechnologies' skin treatment research started with scientists looking at something quite different.
Professor Rod Dunbar, now Upside's chief scientific officer, was at Auckland University studying the immune processes in skin. He and his team decided they needed to grow skin to do their research and as they worked on making skin they realised they were working on something important.
Upside's previous funding round was in March 2017, when it raised $2.3m.
The company's investors are almost exclusively high net worth New Zealanders or small funds - Ice Angels has 14 per cent, Stephen Tindall's K One W One owns 2.7 per cent, and NZVIF Investments has 5.4 per cent. Medical research funder Cure Kids Ventures owns 14.4 per cent of the company, after providing funding in the early stages, and Auckland University's commercialisation arm Uniservices is a 12 per cent shareholder.
Feldman said the $2m of convertible notes released in May were all taken up either by existing shareholders or by people who had shown an interest in the company in the past.
But he's already started the process of travelling overseas to generate interest for a significant $10m to $15m round, likely by the end of the year.
"Most of my efforts are focused on the US. [Capital raisings] always take time and lot of effort, but you use your networks. Luckily I've been doing biotech internationally for over two decades and I've also worked in business and product development, and venture capital."
How would the final system work if Upside did get a commercial product?
Feldman said he envisages having one or two labs, possibly in the US or Australia, which would grow the skin.
If a burns victim arrived in a hopsital in, say, Canada, the surgeons would send a piece of healthy skin - 10cm x 20cm is ideal, he said, but they can work with less - by plane to the Upside lab. Then Upside would grow the squares of skin, and fly them back 16 days later.