Instylla Secures $30M Series C Funding to Advance Embrace™ Hydrogel Embolic System for Rapid and Durable Vascular Embolization

Data from the American Association for the Surgery of Trauma (AAST) shows that trauma is a major public health issue, causing more than 150,000 deaths and over 3 million non-fatal injuries each year. According to the "Summary and Interpretation of the European Guidelines for the Management of Severe Trauma Bleeding and Coagulopathy (5th Edition)," globally, trauma results in approximately 5.8 million deaths annually, accounting for about 10% of total deaths. Uncontrolled post-traumatic bleeding is the leading cause of death in these patients.

Patients with severe traumatic hemorrhage may develop hemorrhagic shock or even death if not treated promptly. Therefore, the ability to quickly and effectively stop bleeding is a matter of life and death for trauma patients.

Instylla, Inc. has found that current liquid embolic agents often lack deep penetration, water-based properties, and absorbability. This leads to several shortcomings in existing embolization therapies, such as insufficient targeting accuracy, incomplete embolization, and prolonged embolization time for patients with impaired blood clotting function. To address these issues, the company has developed a new generation of liquid embolic agents for interventional radiology, aimed at treating highly vascularized tumors and peripheral bleeding.

Instylla, Inc., headquartered in Bedford, Massachusetts, is dedicated to improving treatment outcomes by adopting innovative embolization solutions. The company’s first product, the Embrace™ Hydrogel Embolization System (hereinafter referred to as Embrace HES), is a novel water-based liquid embolic agent capable of embolizing highly vascularized tumors by filling the tumor vasculature and solidifying into a hydrogel, offering a new approach for minimally invasive vascular embolization therapy.

Embrace HES is intended for embolization of highly vascularized tumors in vessels ≤5 mm or peripheral arterial bleeding in vessels ≤6 mm. It is formed from a functionalized polyethylene glycol precursor and an initiator that rapidly self-reacts to form a hydrogel in situ.

During the treatment process, the doctor inserts a double-lumen catheter into the femoral artery or another suitable artery and advances it along the blood vessel to the target position. The double-lumen catheter has two independent channels, each connected to a separate syringe containing functionalized polyethylene glycol precursor and initiator, respectively. Subsequently, the doctor simultaneously presses both syringes, injecting the contents at the same rate and pressure into the double-lumen catheter. The two substances mix inside the catheter and rapidly polymerize into a soft, water-based PEG hydrogel upon reaching the blood vessel. The coaxial catheter configuration ensures that the precursors do not mix before entering the bloodstream, thereby preventing catheter blockage.

The formed hydrogel can fill the vascular cavity, block damaged or bleeding blood vessels, or cut off the blood supply to tumors. Within approximately 6 months, the hydrogel will liquefy through hydrolysis, and the hydrolyzed products will be filtered, absorbed, and eliminated by the kidneys.

Traditional embolization therapy may inadvertently deliver embolic agents to normal blood vessels, resulting in non-target embolization and damage to healthy tissue. In contrast, the HES precursor injected by Embrace HES exhibits dilution-sensitive properties, which can reduce the formation of hydrogel embolic material when transferred to high-flow shunts or reflux occurs, thereby minimizing non-target embolization.

Moreover, Embrace HES can mix the precursor with commercially available iodinated contrast agents to make it radioactive, enabling real-time visualization of reagent delivery. This allows doctors to observe the formation and distribution of the hydrogel and adjust the injection speed and dosage as needed until complete and lasting embolization is achieved. This effectively enhances the precision of embolization and reduces the risk of non-target embolization.

As a minimally invasive vascular embolization treatment, Embrace HES enables interventional radiologists to achieve immediate, comprehensive, and lasting embolization. With its ability to achieve deep, distal penetration and reduce recanalization, Embrace HES can be used to treat highly vascularized tumors.

Highly Vascularized Tumors: A Challenge in Surgical Resection and Treatment

The first-in-human study of Embrace HES demonstrated that it effectively embolizes both malignant and benign hypervascular tumors by blocking their blood supply, achieving technical success in all patients. Follow-up imaging at 30 days showed sustained embolization with rapid and durable effects.

In an article published in the Journal of Vascular and Interventional Radiology, Dr. Gandras and colleagues evaluated the hemostatic capability of Embrace HES in a porcine mesenteric artery bleeding model that replicates human injuries. The results showed that Embrace HES achieved complete, rapid, and durable embolization in all injured arteries, with an average delivery time of 5.3 minutes and no occurrence of non-target embolization.

Embrace HES adopts a biocompatible hydrophilic hydrogel with aqueous-based chemistry, which avoids catheter adhesion and effectively prevents compatibility issues with glue and organic solvent embolic agents. Meanwhile, Embrace HES can also adjust the delivery rate, making it suitable not only for diffuse embolization treatment of highly vascularized tumors but also for proximal embolization.

Previous embolization therapies often relied on blood coagulation to achieve embolization. Therefore, for patients with impaired coagulation function, the embolization time would be prolonged and the hemostatic effect significantly reduced. However, Embrace hydrogel can achieve embolization without relying on the patient’s coagulation function, making the treatment process and outcomes unaffected by the patient’s coagulation status.

Dr. Kauvar and colleagues induced splenic injury and hemorrhage in pigs in a standalone study. The trial compared a control group without embolization therapy to groups treated with Embrace HES, gelatin sponge slurry, or coil hemostasis. Results showed that under coagulopathic conditions, Embrace HES demonstrated longer survival times and significantly greater reduction in bleeding compared to the other groups.

On August 15, 2023, Instylla announced the completion of a $30 million Series C financing round. This round was led by Delos Capital, with participation from Sparta Group, Incept LLC, Excelestar Ventures, and other companies. The funds will help Instylla complete its ongoing prospective clinical trials and early commercialization of Embrace HES. Currently, Embrace HES is undergoing clinical trials and has not yet received approval from the U.S. FDA.

Instylla Recently Launched the "HALT" Study in the United States. The HALT study is a prospective, multi-center, single-arm study led by Dr. Suvranu Ganguli, Chief of Interventional Radiology at Boston Medical Center. The study aims to evaluate the safety and efficacy of Embrace HES in embolizing organ and peripheral arterial bleeding. On January 10, 2023, Embrace HES announced the enrollment of the first patient in the HALT study for the treatment of peripheral arterial bleeding. The study is expected to recruit 118 patients across up to 25 sites in the United States and conclude by December 2024.

According to the "2020-2024 China Liquid Embolic Agents Industry Market Supply and Demand Status and Development Trend Prediction Report" released by VCBeat Research, the current liquid embolic agents market in China is mainly dominated by foreign enterprises, with Medtronic and GEM occupying the majority of the market share, and there is a lack of domestically produced products. However, in recent years, domestic medical companies have been continuously making efforts in the independent research and development of liquid embolic agents.

Sciencells Biotech Co., Ltd. mainly engages in the research, production, and sales of implantable biological material-based medical devices. The company's non-adhesive liquid embolic agent (EverFlow) is primarily used for endovascular embolization treatment of cerebral vascular malformations and is China's first non-adhesive liquid embolic material for BAVM treatment.

Beijing Guanhe Medical Technology Co., Ltd. mainly engages in the design, research and development, production, and sales of Class III medical devices in China. For many years, the company has focused on the field of tumor interventional therapy. Its core product, the "temperature-sensitive liquid embolic agent," is a globally pioneering new material, suitable for the embolization treatment of hypervascular benign and malignant tumors. The product is soluble in aqueous solution at room temperature. During interventional therapy surgery, after being implanted into the human body, the material's temperature rises to 36°C along with body temperature. In this process, it gradually dehydrates and precipitates a white, soft solid, which serves to block blood vessels, thereby achieving the embolic function.

Currently, China's liquid embolic agents market is still in the early stage of development. However, with the clinical promotion of vascular embolization, the increasing demand from patients, and the continuous emergence of innovative enterprises, the research, development, and production vitality of liquid embolic agents will be continuously unleashed. In the future, it is expected to fill the market gap in China and achieve substitution by domestically produced alternatives.