“When our inventors discovered that fat had prodigious effects in plastic surgery when placed under the skin, they thought of applying it to other areas.”
It is Giorgio Ninzoli, CEO of Lipogems, who tells us how the device that could be the game changer against one of the most widespread disabling diseases in the world, arthrosis, was born and developed. And not only that.
How did you come to lead Lipogems?
“I come from 17 years at Tyco/Covidien, now Medtronic where for the last six years I was President EMEA of the whole group and then moved to Smith & Nephew in the field of orthopaedics for 4 years, until 2012, as President Europe of Recon, i.e. the whole prosthetics and trauma area. I then decided to take on new challenges outside the multinational context by dedicating myself to consulting and therefore supported the start-up of Lipogems first from outside and then in 2014 as CO. This is where I started on this fascinating new path.”
What were the main stages?
“In the first two years, from 2014 to 2015, we engineered the device. It’s a product that looks very simple but instead has some peculiar features that are based on the mathematical principles of Fibonacci. There are in fact precise rules both in the size of the spheres and in the proportions of the device and filters that allow the reduction of fat. And there was no shortage of technical problems in the beginning, but at the end of 2015, we were able to officially put it on the market, with an ad hoc focus on some of the world’s most disabling diseases such as osteoarthritis. In America alone, the market attributable to this disease is around $14 billion and the five multinationals selling prostheses have a turnover of $60 billion.“
How does the device actually work?
“I would divide the use of the device into three parts. The disposable kit we sell contains everything needed for harvesting the fat tissue, processing it, and infiltrating it into the patient’s ‘joints’ that need to pursue therapy for OA or to support cartilage regeneration of the knee, shoulder, hip, and ankle.
The kit,’ Ninzoli explains, ‘contains cannulas that allow the removal of 100-150 cc of adipose tissue under local anaesthesia, with a virtually painless action through a small incision. The fat thus harvested is placed in a syringe; this adipose tissue contains adipocytes and mesenchymal cells, but also oil and blood, highly inflammatory material. After 3-4 minutes of decanting, the harvested adipose tissue is inserted through an initial filter into the ‘device’ inside of which saline solution flows continuously, ‘washing’ away blood and oil, i.e. the pro-inflammatory material that should not be inserted into the cavity of a knee shoulder hip or ankle. Blood and oil go directly into a waste material bag. Inside the device there are 5 steel spheres floating in the saline solution, which are ‘shaken’ by the operating personnel with the aim of emulsifying the fatty tissue, gently micro-fragmenting it. The saline solution goes from cloudy and hazy to clear by virtue of the removal of oil and blood. The residual adipocytes and mesenchymal cells move upwards, while the saline solution moves downwards.”
And we come to Lipogems, after which the company is named.
“Exactly. Adipocytes and mesenchymal cells pass through a second filter that further reduces the size of the tissue. The result is Lipogems a substance that turns from the initial red colour to golden yellow. Once taken with a syringe, it is injected directly into the knee. The entire procedure takes between 30 and 45 minutes from the time the fat is taken out, and in one surgical time. The patient, who is on a couch, is then injected with Lipogems and then has his leg moved so that it is well distributed in the cavity and can return with his own legs. It is a very short operation, the only side effect is some soreness and some blue marks where the fat was taken. For a couple of days the patient will have the knee a bit stiff, but as they walk the Lipogems will expand and stay in place. “
But how did this discovery come about?
“The basic premise stems from the observation that pericytes, the small ‘polyps’ that surround our kilometres of blood vessels, have two major functions: the first is physiological, because they regulate arterial and venous pressure, widening or narrowing the vessels as needed. The second is that when you have a small wound, it closes within two days thanks to the fact that the pericytes detach themselves from the vessels, transform into mesenchymal cells and go on to close the wound, regenerating the tissue. Lipogems works in the same way: when we take the adipose tissue, pass it through a first filter, wash it and then through a second filter, we create tissue damage; in this way countless pericytes detach themselves from the vessels and turn into mesenchymal cells.”
A part that did not originally concern the knees…
“As is often the case, great discoveries arise from a mix of factors, intuition and coincidence. When one of our inventors, Dr Tremolada, a maxillofacial surgeon with extensive international experience in the world of general surgery, discovered that fat had prodigious effects in cosmetic surgery when injected subcutaneously (the skin became like that of a doll, glowing and homogenous, with a long-lasting effect), he thought of applying it to other areas. So in 2010, with Prof Ricordi, they invented a prototype that was progressively engineered until they obtained the current kit, which includes everything from harvesting the adipose tissue to processing and infiltrating it into the patient.”The added value of Lipogems is the vascularisation of the cells that allows them to continue living for months. Only Lipogems manages to keep the ‘stromal vascular fraction’, i.e. the ‘little house’ that each mesenchymal cell has, intact and vascularised.
What is the added value of Lipogems?
“The vascularisation of the cells allows them to continue living for months. Only Lipogems manages to keep the ‘stromal vascular fraction’, i.e. the ‘little house’ that each mesenchymal cell has, intact and vascularised. Once injected into the patient’s knee or shoulder or hip or ankle, therefore, the mesenchymal cell does not die, but remains active for months because it has its own vascularisation. This is the ‘method of action’ of Lipogems that we have demonstrated in vitro and on animals and through clinical studies to the FDA. The FDA also asked us that the Lipogems device should not turn the harvested adipose tissue into something ‘different’ otherwise it would be considered a ‘drug’. Lipogems, in fact, simply takes the adipose tissue, ‘washes’ it, reduces its size so that it can be infiltrated through a very thin needle into the knee or shoulder in the hip or ankle, while keeping the architecture of the original adipose tissue intact.”
Is the issue of reimbursement crucial to the growth of your business?
“Absolutely. Obtaining authorisation from the Food and Drug Administration is a crucial step in the US to access reimbursement for medical expenses. To be eligible for reimbursement, the FDA requires the company to conduct a study on 200 patients in 20 US hospitals and to demonstrate the absolute superiority of Lipogems over the ‘standard of care’, which in America is cortisone, i.e. steroid injections into the knee. Lipogems already has studies showing its clear superiority over cortisone (which has a maximum efficacy of 30 days as a painkiller and anti-inflammatory)”.
For this real ‘turning point’ you therefore turned to professional investors.
“It was the right time to do it: the study for the FDA costs between EUR 6 and 8 million and rises, considering another complementary study, to a figure of around EUR 10 million in total. Large sums that led us to look for partners with whom we could share our project, and so we got in touch with LIFTT. This is a clear win/win operation: our US advisor Back Bay pointed out that in the hands of a major company the revenue that could be achieved by 2031 is close to $5-600 million in the US alone and for knee pathology alone. Unlocking the issue of reimbursability would open up very wide horizons: consider that, without reimbursement, we have sales targets of 5 million euros, but in Italy in the ‘only’ regions that have reimbursement, Veneto and Emilia Romagna, we have a revenue of 1.5 million, i.e. 1,500 kits at a unit cost per patient of 1,000 euros, while in Lombardy, which has twice the population but does not have reimbursement, we only sell 300 kits a year, because the patient is only private and has to spend an amount of up to 3,000 euros.”
A project with high potential.
“Yes. This is a project that has the strength and cohesion of a team behind it – the one I brought to Lipogems – and that has been working together with me for 30 years: we have all personally invested in this company and we are all working with the same goal. The feedback is not lacking: many surgeons have appreciated the initiative so much that they have carried out independent studies completely independently, buying the kits and allowing us to have over 100 case-studies demonstrating the effectiveness of Lipogems not only in orthopaedics. In fact, the potential areas of intervention are enormous and we have studies involving two pathologies without solutions such as ‘non-healing’ diabetic foot ulcers, leading to minor amputation, and complex perianal fistulas from Chron’s disease, a disruptive pathology leading to colostomy. In particular, ‘non-healin’g diabetic foot ulcers affect 30-40% of diabetic patients. A ‘non-healing’ ulcer evolves in 80% of cases into a minor amputation (amputation of the toes down to the metatarsal). In 54% of cases after minor amputation it goes to a major amputation; in 5 years 80% of people who have undergone major amputation die (official data). Lipogems carried out a randomised study with 114 patients who were to undergo minor amputation: all 114 were amputated, 57 post amputation were treated with Lipogems and 57 treated with the ‘standard of care’. Eighty per cent of the patients treated with Lipogems did not evolve into a major amputation while only 46% of the patients treated with the standard of care did not evolve into a major amputation. This (explosive) result attracted the attention of Boston-based Alira Health Grupp and leading advisor in the world of ‘wound’, which has involved us in a summit to be held on 13 July in Boston where it will present Lipogems to the top 4 US wound care companies, 3M, Coloplast, Mölnlycke and Johnson & Johnson. With regard to complex perianal fistulas from Chron’s disease, a pathology currently still without a real solution, Lipogems has demonstrated with 2 very important studies that in 67% the treatment with micro-fragmented adipose tissue resolves the pathology.”
Your goal, however, is even more ambitious…
“Yes, the applications are really endless but our real £dream is to be able to use Lipogems as a ‘scaffold’ to transport anti-tumours into solid tumours. Our research is absolutely at a preliminary study in the lab and on animals but the results are such that we think the prospects are really something amazing.”
