enVVeno Medical Stock

enVVeno Medical Corporation operates as a late stage clinical med-tech company.

The company is focused on the advancement of innovative bioprosthetic (tissue-based) solutions to improve the standard of care for the treatment of venous disease. The company is developing surgical and non-surgical replacement venous valves for patients suffering from severe CVI of the deep venous system of the leg.

The company's lead product is the VenoValve, which is a first-in-class surgical replacement venous valve that is being evaluated in a U.S. pivotal study. The company is also developing a second product called enVVe, which is a first-in-class, non-surgical, transcatheter based replacement venous valve. The company is waiting for regulatory approval to begin a first-in-human study for enVVe. Both the VenoValve and enVVe are designed to act as one-way valves, to help assist in propelling blood up the veins of the leg, and back to the heart and lungs.

The VenoValve and enVVe are being developed first for approval by the U.S. Food and Drug Administration (FDA). The company expects the VenoValve to be eligible for FDA approval first, followed two to three years later by enVVe. Once approved, the company expects the VenoValve and enVVe to co-exist, with the VenoValve as a surgical replacement venous valve option and enVVe as a non-surgical replacement venous valve option. There are no devices approved as surgical or non-surgical replacement venous valves, and there are no effective treatments for deep venous CVI caused by incompetent valves.

VenoValve

The VenoValve is a porcine based replacement venous valve developed at enVVeno Medical to be surgically implanted in the deep venous system of the leg to treat severe CVI. By reducing reflux and lowering pressure (venous hypertension) within the deep venous system of the leg, the VenoValve has the potential to reduce or eliminate the symptoms of severe deep venous CVI, including the potential to heal recurring venous leg ulcers. The VenoValve is implanted into the femoral vein of the patient in an open surgical procedure via a 5-to-6-inch incision in the upper thigh. As the company's planned initial entrant to the replacement venous valve market, the company estimates that approximately 2.5 million people with severe deep venous CVI in the U.S. would be candidates for the VenoValve.

VenoValve Clinical Status

After consultation with the FDA, and as a precursor to the U.S. pivotal trial, in 2020 the company conducted a small first-in-human study for the VenoValve in Colombia, which included eleven (11) patients. In addition to providing safety and efficacy data, the purpose of the first-in-human study was to provide proof of concept, and to provide feedback to make any necessary product modifications or adjustments to the company's surgical implantation procedure for the VenoValve prior to conducting the SAVVE (Surgical Anti-reflux Venous Valve Endoprosthesis) U.S. pivotal trial. Endpoints for the VenoValve first-in-human study included safety (device related adverse events), reflux, measured by Duplex Ultrasound, a rVCSS score used by the clinician to measure disease severity and progress, a VAS score used by the patient to measure pain, and quality of life measurements.

Related safety incidences during the one year first-in-human study for the VenoValve included one (1) fluid pocket (which was aspirated), intolerance from Coumadin anticoagulation therapy, three (3) minor wound infections (treated with antibiotics), and one occlusion due to patient non-compliance with anti-coagulation therapy.

On August 3, 2020, the company announced that the FDA granted Breakthrough Device Designation status to the VenoValve. The FDA's Breakthrough Devices Program was established to enable priority review for devices that provide more effective treatment or diagnosis of life threatening or irreversibly debilitating diseases or conditions. The goal of the FDA's Breakthrough Devices Program is to provide patients and health care providers with timely access to medical devices by speeding up their development, assessment, and review, while preserving the FDA's mission to protect and promote public health.

In March 2021, the company submitted an IDE application with the FDA and in April 2021, the company received notification from the FDA that the company's IDE application was approved. An investigational device exemption or IDE from the FDA is required before a medical device company can proceed with a pivotal trial for a class III medical device. This approval allowed the company to proceed with its SAVVE study, a prospective, non-blinded, single arm, multi-center study of seventy-five (75) CVI patients to be enrolled at up to 20 U.S. sites. The company later received permission from the FDA to increase the number of clinical sites to up to 30.

At the end of the VenoValve first-in-human study, eight (8) study participants agreed to additional monitoring. In November of 2022, three-year follow-up data was presented at the 49th Annual VEITH Symposium in New York city for this cohort of patients. That data indicated no recurrences of the severe CVI that was present pre-VenoValve, including no ulcer recurrences for those patients who had venous ulcers (C6 patients) prior to receiving the VenoValve. There were no reported safety issues from the end of one (1) year first-in-human study to the end of the three (3) year reporting period. In addition, the patients continued to show improvements compared to pre-surgery levels, reporting 62%, 64%, and 84%, average improvements in reflux, VCSS, and VAS scores, respectively, at an average of three (3) years post VenoValve surgery. One DVT occurred between year 2 and year 3 due to patient non-compliance with anti-coagulation medication. In addition to presenting at leading academic and vascular conferences around the world, results from the VenoValve first-in-human study and following observational period have been published in the Journal of Vascular Surgery Venous and Lymphatic Disorders, the Journal of Vascular and Endovascular Surgery, and JAMA Surgery Journal.

In November of 2022, the company had passed a preliminary safety review by the FDA for the first twenty (20) patients enrolled in the SAVVE trial. The FDA had requested that the company submits preliminary safety data at thirty (30) days post VenoValve implantation for the first twenty (20) patients enrolled in the study. The preliminary safety data included one (1) device related (mild) and two (2) procedure related (moderate) adverse events. After review by the FDA, the study was cleared to continue without modification or interruption.

As widely reported in the media, the lasting impact from the COVID-19 pandemic has put an enormous strain on hospital resources including their clinical staff. Hospitals continue to be severely understaffed, which impacts the rate at which clinical trials enroll and progress. The company has taken several steps to help address the hospital staffing shortages, including the company's hiring of 4 Clinical Technologists, with extensive and specialized experience in duplex sonography of the deep venous system, to assist in training site personnel, proctoring Duplex Ultrasound examinations, and providing assistance for the SAVVE study.

As of December 31, 2022, the company had twenty (20) clinical trial sites activated and eligible to enroll patients in the SAVVE trial and have completed forty-three (43) successful surgeries. The company's guidance is to reach full enrollment in the SAVVE study by the end of the second quarter of 2023.

enVVe

On September 21, 2022, the company announced the development of a non-surgical transcatheter based replacement venous valve called enVVe, for the treatment of CVI of the deep veins of the leg. Preliminary bench testing and animal testing for enVVe were completed before the company's announcement. The company also filed an application seeking approval to begin first-in-human (FIH) testing in Columbia, which the company expects to receive by the end of the first quarter of 2023.

The enVVe first-in-human trial will be known as the Transcatheter Anti-reflux, Venous Valve Endoprosthesis first-in-human (TAVVE-FIH) study. The initial phase of the TAVVE-FIH study will seek to enroll 3 to 5 patients across multiple sites. Several parameters will be evaluated over the course of the study, including safety and technical success of the enVVe venous valve delivery system, and the safety and clinical performance of the enVVe venous valve.

enVVe is delivered into the femoral vein of the patient via a minimally invasive procedure requiring no general anesthesia and no overnight hospital stay. Due to the minimally invasive nature of the procedure, the company expects to be able to reach patients with less severe CVI or who are otherwise not good candidates for a surgical device, and estimate the U.S. market for enVVe to be approximately 3.5 million patients.

Government Regulation

The company's product candidates and the company's operations are subject to extensive regulation by the FDA, and other federal and state authorities in the United States, as well as comparable authorities in foreign jurisdictions. The company's product candidates are subject to regulation as medical devices in the United States under the Federal Food, Drug, and Cosmetic Act ('FDCA'), as implemented and enforced by the FDA.

Class III devices, such as the VenoValve and enVVe generally require pre-market approval (PMA) before they can be marketed in the U.S.

In December of 2018, the company received regulatory approval from Instituto Nacional de Vigilancia de Medicamentos y Alimentos, the Colombian equivalent of the U.S. Food and Drug Administration, for the company's first-in-human study for the VenoValve in Colombia.

Intellectual Property

The company has filed numerous patent applications for the VenoValve with the U.S. Patent and Trademark Office (USPTO) and throughout the world. The company has seventeen (17) patents granted from agencies around the world, including four (4) from the USPTO.

Research and Development

For the year ended December 31, 2022, the company's research and development expenses were $9.9 million.

History

The company was founded in 1999. It was incorporated in the state of Delaware in 1999. The company was formerly known as Hancock Jaffe Laboratories, Inc. and changed its name to enVVeno Medical Corporation in 2021.