Vascular Dynamics Files IPO Prospectus Highlighting MobiusHD System for Heart Failure Treatment via Natural Baroreflex Activation

According to the "Prevalence and Incidence of Heart Failure Among Urban Patients in China" published in 2021, the number of heart failure patients aged 25 and above in China was approximately 12.1 million in 2017, with about 3 million new cases each year and approximately 1.7 heart failure-related hospitalizations per year.

Heart Failure: Heart failure refers to a syndrome caused by various structural or functional heart diseases that impair ventricular filling or ejection capacity. It can cause symptoms such as chest tightness, fatigue, dizziness, lower limb edema, and paroxysmal nocturnal dyspnea, and may also increase the probability of complications like cardiogenic shock and sudden death.

In order to help heart failure patients improve cardiac function and gain more treatment options, Vascular Dynamics has been focusing on developing innovative endovascular device therapies for heart failure patients.

Vascular Dynamics, Inc. is a private medical device company founded in 2008, with its headquarters located in Mountain View, California, USA. Its core product, the MobiusHD system, is a novel endovascular device. It leverages the body's natural baroreflex mechanism to modulate the autonomic nervous system and help restore the balance between the sympathetic and parasympathetic nerves, thereby achieving the goal of reducing the cardiac burden in heart failure patients through a minimally invasive transcatheter approach.

Due to reduced cardiac output and elevated ventricular filling pressure, sympathetic nervous system activity is enhanced in symptomatic heart failure patients with reduced ejection fraction (HFrEF), which in turn increases myocardial oxygen demand and afterload, further exacerbating the cardiac burden.

Reducing the activity of the sympathetic nervous system can be achieved through medication, but it comes with a series of side effects, such as difficulty in dosage adjustment, multiple adverse reactions, poor compliance, and rebound effects after discontinuation.

β-Blockers can reduce sympathetic activity and myocardial oxygen consumption, and are often used clinically as a method to prevent perioperative cardiovascular events. However, long-term use of β-blockers, if suddenly discontinued, can lead to increased sympathetic activity, causing elevated blood pressure and heart rate, and may even induce hypertensive emergencies and acute coronary syndrome. A large observational study has shown that for patients who have been using β-blockers long-term, temporarily discontinuing the medication before surgery increases long-term mortality.

ACE inhibitors, ARBs, calcium channel blockers and other drugs can also reduce the activity of the sympathetic nerve, thereby lowering heart rate, blood pressure, and myocardial oxygen consumption. However, these drugs may cause side effects such as dry cough, hyperkalemia, fatigue, dizziness, and headache.

Compared with traditional drug therapy, the innovative therapy of Vascular Dynamics does not require long-term medication, avoiding adverse reactions and dependence on drugs. It uses the MobiusHD system to perform Endovascular Baroreflex Amplification (EVBA), which can activate the body's natural reflex mechanism, restore the balance of the autonomic nervous system, thereby reducing the burden on the heart.

Endovascular Baroreflex Amplification (EVBA) is a novel minimally invasive procedure for treating resistant hypertension, offering a less traumatic and faster recovery therapy for heart failure patients with reduced ejection fraction (HFrEF). During the procedure, the MobiusHD is implanted into the patient via a transcatheter approach. The MobiusHD is a stent-like device implanted in the internal carotid artery to enhance vascular baroreflex amplification, aiming to reduce excessive sympathetic nerve activity in heart failure patients.

The principle of this therapy is to regulate the autonomic nervous system by stimulating the baroreceptors of the carotid sinus, reducing sympathetic activity and increasing parasympathetic activity, thereby lowering blood pressure.

The MobiusHD system consists of two parts: an implant and a delivery catheter introduced through the femoral artery. The implant is available in three sizes and can be implanted into non-atherosclerotic carotid arteries with a lumen diameter ranging from 5.0 mm to 11.75 mm.

Before performing the surgery, clinicians will conduct a detailed preoperative imaging examination of the patient to assess the adaptability of placing an implant in the carotid artery, select an appropriately sized implant, and precisely determine the implant location.

Then, the clinician will use a minimally invasive method to introduce a 0.014-inch (0.04 mm) guidewire into the distal internal carotid artery under local anesthesia, allowing the delivery catheter to be inserted along the guidewire. Once properly positioned, the protective sheath of the delivery catheter will be retracted to allow for the expansion, fixation, and apposition of the implant with the vascular intima. After the catheter is removed, the implant will remain in the position of the carotid sinus.

MobiusHD is a self-expanding rectangular nitinol implant with excellent shape memory and superelasticity, capable of adjusting its shape and size according to the diameter of the blood vessel at different temperatures. During insertion, MobiusHD assumes a spear-like form and, once placed, can self-expand and anchor within the carotid sinus.

Percutaneous EVBA surgery enhances the effect of arterial baroreflex by implanting the MobiusHD device, thereby reducing blood pressure and cardiac load in heart failure patients.

The Baroreceptor Reflex: A Neural Mechanism Regulating Blood Pressure and Heart Rate

The design of MobiusHD closely revolves around the unique property of arterial baroreflex. It can alter the geometry of the carotid sinus, causing greater deformation with each heartbeat, increasing the stretching of the vascular wall, stimulating baroreceptors to a greater extent, and amplifying the signals transmitted to the brain.

In this process, the frequency of peripheral afferent nerve impulses increases, leading to the excitation of neurons in the nucleus tractus solitarius. The projection from the nucleus tractus solitarius to the sympathetic center is inhibitory, while its projection to the vagal center is excitatory. Therefore, when this excitation reaches these two efferent nerves, it results in the inhibition of neurons in the sympathetic center and the excitation of neurons in the vagal center. These excitatory effects act on the heart and blood vessels as effectors, causing reduced myocardial contractility, slower heart rate, decreased cardiac output, thereby lowering blood pressure and reducing cardiac load. During this process, the implanted device does not dilate the carotid sinus like traditional balloons or stents but maintains its pulsatility, ensuring normal blood flow and oxygen delivery.

As early as 2016, Vascular Dynamics announced that its MobiusHD system received CE certification for the treatment of resistant hypertension. Currently, the company has conducted the first-in-human trials of the MobiusHD system in Europe and the United States (CALM-FIM_EUR and CALM-FIM_USA), primarily evaluating the safety and efficacy of the system in patients with resistant hypertension. According to the European study results published in The Lancet, the average 24-hour ambulatory systolic blood pressure of 30 European patients decreased by 21 mmHg six months after the implantation of the MobiusHD device.

In addition, the study authors reported a 100% implantation success rate for MobiusHD, with a total operation time of 27.2 ± 11.8 minutes, device implantation time of 4.9 ± 1.9 minutes, and fluoroscopy time of 6.9 ± 5.5 minutes. MobiusHD demonstrated short implantation time, ease of operation, and high implantation success rates in this study. Whether during the perioperative period or the 1-year follow-up, EVBA did not cause hypotension or bradycardia. In the 6-month and 12-month analyses of this study, nearly all patients showed improvements in quality of life, 6MWD (6-minute walking distance, a standard measure of exercise tolerance in heart failure patients), and NT-proBNP results. The findings support the potential beneficial effects of EVBA and the MobiusHD device in HFrEF.

The MobiusHD device has also undergone feasibility studies in heart failure patients. This is a prospective, open-label clinical trial. The trial results showed a significant improvement in the 6MWD of patients, with an average increase of 108 meters in walking distance during the 24-month follow-up, which is three times the minimum clinically important difference of 30 meters. Before treatment, the average %LVEF (left ventricular ejection fraction) of the study patients was 35.3%. After EVBA with the MobiusHD device and maintaining HF medication therapy, the average %LVEF at the 24-month follow-up was 41.1%, and it was found that EVBA treatment could promote reverse remodeling of the heart.

On July 12, 2022, Vascular Dynamics announced the completion of a $20 million financing round. This round was led by Rainbow Medical, with participation from Invus, HBM Healthcare Investments AG, and others. The proceeds will drive Vascular Dynamics to further expand pilot studies and lay the groundwork for upcoming pivotal research. According to Crunchbase, after 10 rounds of funding, the company's total financing has reached $105.1 million.

The MobiusHD system has not yet received FDA approval but has obtained Investigational Device Exemption (IDE) from the FDA and is currently conducting its pivotal trial (CALM 2) in the United States. This is a controlled, multi-center, randomized, double-blind clinical trial aimed at evaluating the efficacy of the MobiusHD system in reducing blood pressure levels in patients with resistant hypertension. Currently, the patient enrollment for this trial has been completed in the United States. The next step for Vascular Dynamics will be to explore the potential application of the MobiusHD system in other cardiovascular diseases, such as pulmonary arterial hypertension and atrial fibrillation, while optimizing the design and functionality of the MobiusHD system to enhance its biocompatibility and durability.

References：
[1] ZHAO Menglin, XU Weixian, XU Yuan, et al. Research Progress and Guideline Changes on the Application of β-Adrenergic Receptor Blockers in the Perioperative Period of Non-cardiac Surgery[J]. Chinese Journal of Cardiology, 2021.
[2]Piayda K, Sievert K, Sievert H, et al. Endovascular Baroreflex Amplification With the MobiusHD Device in Patients With Heart Failure and Reduced Ejection Fraction: Interim Analysis of the First-in-Human Results[J]. Structural Heart, 2022, 6(5): 100086.