Concept Medical Inc. Files IPO Prospectus: Pioneering Drug Delivery Innovations to Combat Vascular Restenosis

More than forty years ago, Andreas Gruentzig, known as the "father of interventional cardiology," performed the world's first percutaneous transluminal coronary angioplasty (PTCA), achieving a groundbreaking milestone in the field of interventional cardiology. However, the rate of restenosis caused by simple balloon dilation was as high as 30% to 50%.

As a result, bare-metal stents that can provide lasting support for blood vessels have emerged. However, this type of stent tends to cause damage to the inner walls of blood vessels, leading to issues such as thrombosis and inflammation. The restenosis rate of these stents is 20%–30%, which clearly yields unsatisfactory outcomes.

The third revolution was marked by the advent of drug-eluting stents (DES). These stents are capable of carrying drugs that inhibit vascular intimal hyperplasia, reducing the risk of restenosis to less than 10%. However, permanent stent implantation can affect normal vascular elasticity and does not completely resolve issues of in-stent restenosis and thrombosis. Coronary intervention once again encounters a bottleneck.

How to minimize the negative impact of stents while reducing the rate of in-stent restenosis? The answer is "Leave nothing behind." Drug-coated balloons (DCB) are a product of this concept. Currently, in the treatment of in-stent restenosis and small vessel disease, DCB has almost become the preferred treatment option.

Looking back at the development logic of the past five decades, it is not difficult to see that the history of coronary intervention development is an exploration history of continuously reducing the restenosis rate of stents, and also a struggle history of minimizing stent-induced damage to blood vessel walls.

Go with the flow, act at the right time. Concept Medical is an innovative company that emerged during the fourth revolution in coronary intervention. Headquartered in Tampa, Florida, USA, it focuses on the development of drug-coated balloons and innovations in drug-eluting stents, committed to solving the problem of restenosis in cardiovascular and peripheral arteries through innovative drug delivery technologies. Currently, its product areas cover cardiology, nephrology, urology, oncology, and vascular surgery.

Sirolimus can inhibit the proliferation of vascular endothelial cells, thereby reducing the risk of restenosis. However, compared with paclitaxel, sirolimus and its derivatives have a lower transfer rate and need to be retained in the tissue for a longer period. Meanwhile, the drug itself has relatively low lipophilicity, making it more difficult to enter cells and the vascular wall.

Concept Medical has achieved innovation in the delivery methods of sirolimus and its derivatives. Using Nanolute technology, the company employs a nanocarrier composed of phospholipids to encapsulate sirolimus, enhancing its lipophilicity.

First, sirolimus is cut into submicron-sized particles. It is then encapsulated in a tiny spherical structure composed of phospholipids known as a nanocarrier. The nanocarrier can protect sirolimus from degradation or premature release and deliver it to the target site. Next, the sirolimus and nanocarrier are coated onto a stent and balloon, after which the balloon is positioned at the target site and inflated. During the balloon expansion process, the surface of the nanocarrier becomes hydrophilic upon contact with blood and transfers to the vessel wall according to the principle of coefficient diffusion. In response to changes in pH within the body, the nanocarrier mimics endogenous lipids and releases sirolimus. After some time, sirolimus will penetrate to the deepest layers of the blood vessel.

At the same time, Nanolute technology can also enhance the bioavailability of sirolimus.

Bioavailability refers to the amount of drug that reaches the target site. Sirolimus has poor bioavailability, which affects the efficiency of drug utilization. However, the coating of nanocarriers enables sirolimus to adhere better to the balloon surface, minimizing its loss during transportation, better promoting its diffusion, and increasing its retention time in arteries, thereby achieving maximum drug delivery during balloon expansion.

Based on the Nanolute technology platform, Concept Medical has launched the "MagicTouch" series of products for the treatment of various types of vascular restenosis.

MagicTouch SCB is a novel sirolimus-coated balloon catheter for the treatment of coronary artery disease. It is suitable for in-stent restenosis, small vessels, bifurcation lesions, and de novo lesions.

During the coating process, the balloon is first inflated with low-pressure gas, and then sirolimus and a drug carrier are applied to the unfolded balloon surface. This ensures that the coating is evenly distributed on the balloon surface, with drug coverage reaching 100%. Additionally, this balloon catheter has a unique refolding mechanism that allows the balloon to maintain a smaller diameter after deflation, facilitating easier passage through blood vessels. The balloon catheter is inserted via a guidewire to the narrowed section of the coronary artery, then inflated to expand and release sirolimus onto the vessel wall to prevent restenosis.

In addition, Concept Medical has launched other "MagicTouch" products, all of which follow roughly the same usage process as the MagicTouch SCB: First, the balloon catheter is delivered to the narrowed or blocked area of the target vessel via a guidewire. Then, the balloon is inflated and the time is controlled between 30 to 60 seconds to achieve optimal drug delivery. Finally, the balloon is deflated and the balloon catheter is removed.

Among them, MagicTouch PTA is a sirolimus-coated balloon catheter used for the treatment of peripheral artery disease (PAD). It can treat restenosis of the superficial femoral artery and popliteal artery in patients with peripheral artery disease and has received Breakthrough Device Designation from the FDA in the field of below-the-knee (BTK) arterial disease. MagicTouch AVF aims to treat dysfunctional arteriovenous fistulas and stenotic lesions in synthetic grafts in patients with end-stage renal failure, providing them with functional dialysis access. MagicTouch ED is used to treat vasculogenic erectile dysfunction (ED). By delivering a balloon via a catheter to the narrowed or occluded site of the penile artery and releasing sirolimus, it improves penile blood flow and restores normal erectile function.

Envisolution Technology is an innovative coating technology, with distal membrane coating technology, fusion coating technology, edge coating technology, and biodegradable membrane as its four key tools, capable of achieving unidirectional, uniform, and efficient drug delivery.

Based on Envisolution technology, Concept Medical has developed ABLUMINUS DES+. It is a drug-eluting stent (DES) for the treatment of coronary artery disease (CAD), aiming to meet the unmet clinical needs of patients with diabetes and acute myocardial infarction combined with coronary artery disease.

Seeing the name "ABLUMINUS DES+", you might have a question: Why is there a "+" at the end? What special meaning does it hold? Does it indicate that it's different from ordinary drug-eluting stents (DES)?

The answer is yes, the biggest highlight of this system lies in this "+". "DES+" actually stands for "DES+DCB", reflecting two characteristics of the system: first, the system is a combination of a drug-eluting stent (DES) and a drug-coated balloon (DCB); second, the drug coating of the system covers both the stent surface and the exposed part of the balloon.

ABLUMINUS DES+ Utilizes "Fusion Coating" Technology. It not only applies a drug coating to the stent surface but also covers the exposed balloon portion with a drug coating. This allows the drug to be distributed more evenly and comprehensively onto the vessel wall, avoiding issues of excessive or insufficient drug concentration that could impact efficacy and safety. Moreover, the drug coating can inhibit cell proliferation on the vessel wall and reduce inflammatory responses, addressing two common types of restenosis diseases: diffuse proliferative disease (referring to overall thickening of the vessel wall) and focal restenosis.

At the same time, ABLUMINUS DES+ adopts the "Far Membrane Coating" technology. The system uses a unidirectional drug release coating, applying the drug only to the stent surface on the side away from the vascular lumen. The purpose of this is to control the drug release solely towards the blood vessel wall, avoiding its entry into the bloodstream which could cause adverse reactions, while promoting the repair of vascular endothelial cells and reducing the risk of thrombosis.

"Edge Coating" refers to the additional 0.5mm of the balloon edge being coated with a drug coating, apart from the stent surface and the exposed part of the balloon. This ensures that the drug coating extends beyond the edges of the stent to cover the vessel wall, preventing restenosis in the vessel walls at both ends of the stent due to lack of drug coating influence.

Biodegradable film is a circular film formed from biodegradable polymers, which helps maximize drug delivery under bloody and wet conditions. It is uniformly textured and tightly adheres to the inner side of the stent, preventing the drug from diffusing or being lost too quickly in the blood. This complements the "far-membrane coating" technology that releases drugs only to the vessel wall. Together, they achieve the optimal rate of drug delivery. Moreover, biodegradable polymers can be naturally decomposed by the human body, so the film does not cause foreign body reactions or inflammation.

Concept Medical has operational offices in the Netherlands, Singapore, and Brazil, with a production unit in India. Among them, Envision Scientific is an affiliate of Concept Medical and the sole factory producing all drug delivery devices for Concept Medical.

Envision Scientific, established in 2008 and located in Surat, Gujarat, India, is a company engaged in the research, development, and manufacturing of innovative products for the treatment of cardiovascular diseases. The company is committed to pioneering advancements in the application of nanotechnology and has developed a novel polymer-free nano-carrier drug delivery system. Envision Scientific has obtained ISO certification and set up manufacturing units in Hazira and the Sachin Special Economic Zone (SEZ) in Surat to meet the needs of both international and domestic markets.

Envision Scientific and Concept Medical jointly own more than 100 patents for their products, technologies, and equipment, providing Concept Medical with a platform to transform innovative ideas into real products.

On April 25, 2023, the FDA granted the third Investigational Device Exemption (IDE) for MagicTouch SCB. The current IDE approval will allow Concept Medical to initiate a pivotal clinical trial to evaluate the safety and efficacy of MagicTouch SCB in small vessel coronary artery disease. The data generated from this trial will support the company’s future PMA submission in the United States.

Just a month later, on May 24, Concept Medical announced again that the company's fourth Investigational Device Exemption (IDE) application had been approved by the FDA for the treatment of superficial femoral artery (SFA) disease. To date, the company has received four Investigational Device Exemption (IDE) approvals from the U.S. FDA, respectively for the treatment of small vessel indications, in-stent restenosis (ISR) in coronary arteries, below-the-knee (BTK) arterial disease, and superficial femoral artery (SFA) disease. These clinical trials will lay the foundation for Concept Medical to apply for final approval and market launch from the U.S. FDA.

Currently, MagicTouch SCB has obtained CE certification and has been put into commercial sales. It has wide commercial applications in major markets in Europe, Asia, and the Middle East, and has provided treatment for more than 100,000 patients. The next step for the company is to continue conducting clinical trials to demonstrate the safety and efficacy of its products, while seeking more partners and distributors to further expand into international markets.

References:

[1]Jeger RV,Eccleshall S,Wan Ahmad WA,et al. Drug-coated balloons for coronary artery disease:third report of the international DCB consensus group[J]. JACC Cardiovasc Interv,2020,13(12):1391-1402.

[2] VCBeat. Review: The Fourth Revolution in Interventional Treatment of Coronary Heart Disease [EB/OL]. (2016-01-22) [2023-09-07]. https://circ.cmt.com.cn/detail/1092781.html.