NASDAQ: NVNO

enVVe
is being developed for approval by the FDA. We cannot provide any assurance that enVVe will receive approval from the FDA (see the section entitled “Risk Factors”
in this Annual Report on Form 10-K). There are currently no devices approved as surgical or non-surgical replacement venous valves, and
there are currently no effective treatments for deep venous CVI caused by incompetent valves.

We
develop and manufacture our products in a 14,507 sq. ft. leased manufacturing facility in Irvine, California, which has been ISO 13485-2016
certified for the design, development and manufacturing of tissue based implantable medical devices.

CVI
Background

Chronic
venous disease (“CVD”) is the world’s most prevalent chronic disease. CVD is clinically classified using a standardized
system known as CEAP (clinical, etiological, anatomical, and pathophysiological). The CEAP system consists of seven clinical classifications
(C0 to C6) with C4, C5 and C6 being the most severe categories of CVD.

Chronic
Venous Insufficiency (“CVI”) is a large subset of CVD and is generally used to describe patients with C4 to C6 CVD. CVI is
a debilitating condition that affects the venous system of the leg causing pain, swelling, edema, skin changes, and ulcerations.

The
human leg contains three vein systems: the deep vein system, the superficial vein system, and the perforator vein system which connects
the deep system to the superficial system. The deep venous system is located below the muscle and facia in the center portion of the
leg and is responsible for approximately 90% of the blood flow. In order for blood to return to the heart from the foot, ankle, and lower
leg, the calf muscle serves as a pump and pushes the blood up the veins of the leg against gravity and through a series of one-way valves.
Each valve is supposed to open as blood passes through, and then close as blood progresses up the veins of the leg to the next valve.
CVI occurs when the one-way valves in the veins of the leg fail and become incompetent. When the valves fail, gravity causes the blood
to flow backwards and in the wrong direction (reflux). As blood pools in the lower leg, pressure inside the veins increases (venous hypertension).
Reflux, and the resulting venous hypertension, causes the leg to swell, resulting in debilitating pain, and in the most severe cases,
venous ulcers.

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Severe
CVI sufferers experience a significantly reduced quality of life. Daily activities such as preparing meals, housework, and personal hygiene
(washing and bathing) become difficult due to reduced mobility. For many severe CVI sufferers, intense pain, which frequently occurs
at night, prevents them from getting adequate sleep. Severe CVI sufferers are known to miss approximately 40% more workdays than the
average worker. A high percentage of venous ulcer patients also experience severe itching, leg swelling, and an odorous discharge. Wound
dressing changes, which occur several times a week, can be extremely painful. Venous ulcers from deep venous CVI are very difficult to
heal, and a significant percentage of venous ulcers remain unhealed for more than a year. Even if healed, recurrence rates for venous
ulcers are known to be high (20% to 40%) within the first year and as high as 60% after five years. Patients with severe CVI often become
housebound and experience social isolation due to difficulty with ambulation. As a result, studies have shown that patients with active
venous ulcers experience higher rates of anxiety and depression, with reported rates of anxiety of up to 30% and depression up to 40%.
Rates of depression caused by venous ulcers among the elderly are even higher, with 48% of elderly venous ulcer patients having severe
depressive symptoms.

We
estimate that there are approximately 3.5 million patients with severe deep venous CVI in the U.S. including approximately 1.5 million
patients that develop venous leg ulcers (C6 patients). The average patient seeking treatment of a venous ulcer spends as much as $30,000
a year on wound care, and the total direct medical costs from venous ulcer sufferers in the U.S. has been estimated to exceed $20 billion
a year.

enVVe
System

The
enVVe System is designed to treat severe deep chronic venous insufficiency (“CVI”) through a minimally invasive, catheter-based
approach. The procedure is performed without the need for open surgery or an overnight hospital stay. Built on the clinical foundation
of the VenoValve program, the enVVe Valve incorporates design enhancements intended to improve performance, strength and long-term durability.
The enVVe System directly addresses prior FDA concerns related to venous valves implanted via open surgical procedures. In addition to
eliminating open surgical complications, its transcatheter approach is expected to broaden adoption by appealing to a wider range of
implanting physicians including vascular surgeons, interventional radiologists, and interventional cardiologists.

The
Company has completed pre-clinical testing on the enVVe System and has begun discussions with the FDA regarding the enVVe pivotal trial,
which it expects to begin in 2026.

VenoValve

In
March 2021, the Company received FDA investigational device exemption (“IDE”) approval to initiate the SAVVE® (Surgical
Anti-reflux Venous Valve Endoprosthesis) U.S. pivotal clinical study evaluating the VenoValve. The prospective, multi-center, single-arm
study enrolled 75 patients with severe CVI. An application seeking pre-market approval for the VenoValve was filed in November of 2024.
In August of 2025 the Company received a non-approvable letter from the FDA for the VenoValve and a subsequent appeal was unsuccessful.

Most
medical devices start out as surgical iterations and transition to less invasive, trans-catheter delivered versions over time. The Company’s
strategy was to first develop the VenoValve, and then to transition to enVVe. That strategy remains intact. The enVVe System could not
have been developed without the experience gained from the VenoValve. Because the VenoValve was not approved by the FDA, the Company
has elected to forego any potential approval and commercialization efforts outside of the U.S. for the VenoValve and to instead focus
its resources on bringing enVVe to market.

Data
from the SAVVE pivotal study has been presented at vascular conferences throughout the world and has been very well received. Clinicians
recognize the need for a replacement venous valve for patients suffering from deep venous CVI and both the short-term and long-term VenoValve
efficacy data has been extremely promising for this difficult to treat patient population. Although interest in a surgical replacement
venous valve has been strong, clinicians recognize that long-term the large potential market is best served via a trans-catheter delivered
iteration of the device. There continues to be significant interest from clinicians wanting to participate in the enVVe pivotal study.

Government
Regulation

Our
product candidates and our 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. Our 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. The FDA regulates the development, design, non-clinical and clinical research, manufacturing, safety, efficacy, labeling, packaging,
storage, installation, distribution, servicing, recordkeeping, premarket clearance or approval, adverse event reporting, advertising,
promotion, marketing, and import and export of medical devices to ensure that medical devices distributed domestically are safe and effective
for their intended uses and otherwise meet the requirements of the FDCA.

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PMA
Approval Pathway

Class
III devices such as enVVe generally require pre-market approval (“PMA”) before they can be marketed in the U.S. The PMA review
and approval process is more demanding than the 510(k) premarket notification process. The PMA application consists of multiple parts,
sometimes referred to as “modules”. Modules typically include testing such as sterilization, packaging and shelf-life testing,
biocompatibility, manufacturing, and clinical data. All modules are reviewed by the FDA to ensure that the device is safe and effective.
In certain instances, the sponsor may elect a modular PMA, where certain sections are submitted for approval by the FDA in advance of
the clinical data. . Following receipt of a PMA, the FDA determines whether the application is sufficiently complete to permit a substantive
review. If the FDA accepts the application for review, it has 180 days under the FDCA to complete its review of a PMA. With the recent
reduction in workforce that has taken place within the federal government, including at the FDA, we may experience longer review periods
from the FDA for any applicable regulatory approvals. An advisory panel of experts from outside the FDA may be convened to review and
evaluate the application and provide recommendations to the FDA as to the approvability of the device. The FDA may or may not accept
the panel’s recommendation. In addition, the FDA generally will conduct a pre-approval inspection of the applicant or its third-party
manufacturers’ manufacturing facility or facilities to ensure compliance with the QSR. The FDA will generally approve the new device
for commercial distribution if it determines that the data and information in the PMA constitute valid scientific evidence and that there
is reasonable assurance that the device is safe and effective for its intended use(s).

The
FDA may approve a PMA with post-approval conditions intended to ensure the safety and effectiveness of the device, including, among other
things, restrictions on labeling, promotion, sale and distribution, and collection of long-term follow-up data from patients in the clinical
study that supported PMA approval, or requirements to conduct additional clinical studies post-approval. The FDA may condition PMA approval
on some form of post-market surveillance when deemed necessary to protect the public health or to provide additional safety and efficacy
data for the device in a larger population or for a longer period of use. In such cases, the manufacturer might be required to follow
certain patient groups for a number of years and to make periodic reports to the FDA on the clinical status of those patients. Failure
to comply with the conditions of approval can result in material adverse enforcement action, including withdrawal of the PMA approval.
Certain changes to an approved device, such as changes in manufacturing facilities, methods or quality control procedures, or changes
in the design performance specifications, which affect the safety or effectiveness of the device, require submission of a PMA supplement.
PMA supplements often require submission of the same type of information as a PMA, except that the supplement is limited to information
needed to support any changes from the device covered by the original PMA and may not require as much clinical data or the convening
of an advisory panel. Certain other changes to an approved device require the submission of a new PMA, such as when the design change
causes a different intended use, mode of operation and technical basis of operation, or when the design change is so significant that
a new generation of the device will be developed, and the data that were submitted with the original PMA are not applicable for the change
in demonstrating a reasonable assurance of safety and effectiveness. The enVVe System will require PMA approval before it can be market
and sold in the U.S.

Clinical
Trials in Support of PMA

Clinical
trials are almost always required to support a PMA submission. All clinical investigations of devices to determine safety and effectiveness
must be conducted in accordance with the IDE regulations, which govern investigational device labeling, prohibit promotion of the investigational
device and specify an array of recordkeeping, reporting and monitoring responsibilities of study sponsors and study investigators. If
the device presents a “significant risk,” to human health, as defined by the FDA, the FDA requires the device sponsor to
submit an IDE application to the FDA, which must become effective prior to commencing human clinical trials. A Class III medical device
is one that presents a potential for serious risk to the health, safety or welfare of a patient and either is implanted, used in supporting
or sustaining human life, substantially important in diagnosing, curing, mitigating or treating disease or otherwise preventing impairment
of human health, or otherwise presents a potential for serious risk to a subject. The enVVe System will require IDE approval before human
testing in the United States.

An
IDE application must be supported by appropriate data, such as animal and laboratory test results, showing that it is safe to test the
device in humans and that the testing protocol is scientifically sound. The IDE will automatically become effective 30 days after receipt
by the FDA unless the FDA notifies the company that the investigation may not begin. If the FDA determines that there are deficiencies
or other concerns with an IDE for which it requires modification, the FDA may permit a clinical trial to proceed under a conditional
approval.

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In
addition to IDE approval, a human study must be approved by, and conducted under the oversight of, an Institutional Review Board, or
IRB, for each clinical site. The IRB is responsible for the initial and continuing review of the study, and may pose additional requirements
for the conduct of the study. If an IDE application is approved by the FDA and one or more IRBs, human clinical trials may begin at a
specific number of investigational sites with a specific number of patients, as approved by the FDA. Acceptance of an IDE application
for review does not guarantee that the FDA will allow the IDE to become effective and, if it does become effective, the FDA may or may
not determine that the data derived from the trials support the safety and effectiveness of the device or warrant the continuation of
clinical trials. An IDE supplement must be submitted to, and approved by, the FDA before a sponsor or investigator may make a change
to the investigational plan that may affect its scientific soundness, study plan or the rights, safety or welfare of human subjects.
During a study, the sponsor is required to comply with the applicable FDA requirements, including, for example, trial monitoring, selecting
clinical investigators and providing them with the investigational plan, ensuring IRB review, adverse event reporting, record keeping
and prohibitions on the promotion of investigational devices or on making safety or effectiveness claims for them. The clinical investigators
in the clinical study are also subject to FDA’s regulations and must obtain patient informed consent, rigorously follow the investigational
plan and study protocol, control the disposition of the investigational device and comply with all reporting and recordkeeping requirements.
Additionally, after a trial begins, we, the FDA or the IRB could suspend or terminate a clinical trial at any time for various reasons,
including a belief that the risks to study subjects outweigh the anticipated benefits.

Post-market
Regulation

After
a device is cleared or approved for marketing, numerous and pervasive regulatory requirements continue to apply. These include: establishing
registration and device listing with the FDA; QSR requirements, which require manufacturers, including third-party manufacturers, to
follow stringent design, testing, control, documentation and other quality assurance procedures during all aspects of the design and
manufacturing process; labeling regulations and FDA prohibitions against the promotion of investigational products, or “off-label”
uses of cleared or approved products; requirements related to promotional activities; clearance or approval of product modifications
that could significantly affect safety or effectiveness or that would constitute a major change in intended use of one of our cleared
devices; medical device reporting regulations, which require that a manufacturer report to the FDA if a device it markets may have caused
or contributed to a death or serious injury, or has malfunctioned and the device or a similar device that it markets would be likely
to cause or contribute to a death or serious injury, if the malfunction were to recur; correction, removal and recall reporting regulations,
which require that manufacturers report to the FDA field corrections and product recalls or removals if undertaken to reduce a risk to
health posed by the device or to remedy a violation of the FDCA; and post-market surveillance activities and regulations.

Regulation
Outside of the U.S.

Each
country or territory outside of the U.S. has its own rules and regulations with respect to the manufacture, marketing and sale of medical
devices, including, but not limited to the European Medicines Agency in the European Union. For example, in December of 2018, we received
regulatory approval from Instituto Nacional de Vigilancia de Medicamentos y Alimentos, the Colombian equivalent of the U.S. Food and
Drug Administration, for our first-in-human study for the VenoValve in Colombia. At this time, other than the first-in-human trial in
Colombia, we have not determined which countries outside of the U.S., if any, we will seek approval for our product candidates.

Our
Competitive Strengths

We
believe we will offer the venous disease treatment market a compelling value proposition with the launch of our product candidates, if
approved, for the following reasons:

●
We have extensive experience
of proprietary processing and manufacturing methodology specifically applicable to the design, processing, manufacturing and sterilization
of our biologic tissue devices.

●
We operate a 14,507 square
foot manufacturing facility in Irvine, California. Our facility is designed expressly for the manufacture of Class III tissue based
implantable medical devices and is equipped for research and development, prototype fabrication, current good manufacturing practices
(cGMP), and manufacturing and shipping for Class III medical devices, including biologic cardiovascular devices.

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●
We have attracted senior
executives who are experienced in research and development and who have worked on numerous medical devices that have received FDA
approval or CE marking. We also have the advantage of an experienced board of directors and scientific advisory board who will provide
guidance as we move towards market launch.

Intellectual
Property

We
possess an extensive proprietary processing and manufacturing methodology specifically applicable to the design, processing, manufacturing
and sterilization of biologic devices. This includes FDA compliant quality control and assurance programs, proprietary tissue processing
technologies demonstrated to eliminate recipient immune responses, trusted relationship with abattoir suppliers, and a combination of
tissue preservation and gamma irradiation that enhances device functions and guarantees sterility. We have filed numerous patent applications
for the VenoValve and enVVe System with the U.S. Patent and Trademark Office (“USPTO”) and throughout the world. We currently
have forty-two (42) patents granted from agencies around the world including nine (9) from the USPTO.

Employees

As
of March 24, 2026, we had thirty-three (33) full-time employees. None of our employees are represented by a collective bargaining agreement,
and we have never experienced any work stoppage. We believe we have good relations with our employees.

Corporate
Information

We
were incorporated in Delaware on December 22, 1999. Our principal executive offices are located at 70 Doppler, Irvine, California, 92618,
and our telephone number is (949) 261-2900. Our corporate website address is www.envveno.com. The information contained on or accessible
through our website is not a part of this Annual Report, and the inclusion of our website address in this Annual Report is an inactive
textual reference only.